REFERENCIAS BIBLIOGRÁFICAS / BIBLIOGRAPHICAL REFERENCES

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1.) [Ginkgo biloba extract (EGb 761). State of knowledge in the dawn of the year 2000] 

2.)[Preparation and definition of Ginkgo biloba extract]. 

3.) Subarachnoid haemorrhage associated with Ginkgo biloba. 

4.) Extracts of Ginkgo biloba and bleeding or haemorrhage. 

5.) Association of Ginkgo biloba with intracerebral hemorrhage. 

6.) Spontaneous hyphema associated with ingestion of Ginkgo biloba extract. 

7.) Spontaneous bilateral subdural hematomas associated with chronic Ginkgo biloba ingestion. 

8.) Antiplatelet and antithrombotic effects of a combination of ticlopidine and ginkgo biloba ext (EGb 761). 

9.) [Paroxysmal non-hereditary angioedema]. 

10.)Dietary supplement-drug interactions. 

11.)Herbal remedies: adverse effects and drug interactions. 

12.)Herbal medicinals: selected clinical considerations focusing on known or potential drug-herb interactions. 

13.)The protective effect of Ginkgo biloba extract on CCl4-induced hepatic damage. 

14.)Ginkgo biloba for antidepressant-induced sexual dysfunction. 

15.)The efficacy of Ginkgo biloba on cognitive function in Alzheimer disease. 

16.) Medicinal plants and Alzheimer's disease: from ethnobotany to phytotherapy. 

17.)Free radicals in Alzheimer's dementia: currently available therapeutic strategies. 

18.)Proof of efficacy of the ginkgo biloba special extract EGb 761 in outpatients suffering from mild to moderate primary degenerative dementia of the Alzheimer type or multi-infarct dementia. 

19.)The relevance of herbal treatments for psychiatric practice. 

20.)[The effect of ginkgo biloba on cochleovestibular pathology of vascular origin]. 

21.)Effects of Ginkgo biloba extract on the cochlear damage induced by local gentamicin installation in guinea pigs. 

22.)Ginkgo biloba for tinnitus: a review. 

23.)[Contribution of a combination of alpha and beta benzopyrones, flavonoids and natural terpenes in the treatment of lymphedema of the lower limbs at the 2d stage of the surgical classification]. 

24.)[ Ginkgo biloba extract EGb 761 and pentoxifylline in intermittent claudication. Secondary analysis of the clinical effectiveness]. 

25.)[Placebo-controlled double-blind study of the effectiveness of Ginkgo biloba special extract EGb 761 in trained patients with intermittent claudication] 

26.)[Ginkgo biloba in treatment of intermittent claudication. A systematic research based 

on controlled studies in the literature] 

27.)Effect of Ginkgo biloba extract (EGb 761) on chloroquine induced retinal alterations. 

28.)Ginkgo biloba extract increases ocular blood flow velocity. 

29.)Pretreatment of skin with a Ginkgo biloba extract/sodium carboxymethyl-beta-1,3-glucan formulation appears to inhibit the elicitation of allergic contact dermatitis in man. 

30.)The effect of Ginkgo biloba extract (Egb 761) as a free radical scavenger on the survival of skin flaps in rats. A comparative study. 

31.)Induction of superoxide dismutase and catalase activity in different rat tissues and protection from UVB irradiation after topical application of Ginkgo biloba extracts. 

32.)In vivo regulation of peripheral-type benzodiazepine receptor and glucocorticoid synthesis by Ginkgo biloba extract EGb 761 and isolated ginkgolides. 

33.)Reactive oxygen metabolites, antioxidants and head and neck cancer. 

34.)Protective effects of Ginkgo biloba extract EGb 761 on myocardium of experimentally diabetic rats. I: ultrastructural and biochemical investigation on cardiomyocytes. 

45.)Identification of Ginkgo biloba flavonoid metabolites after oral administration to humans. 

46.)Solid-phase extraction and gas chromatography-mass spectrometry determination of kaempferol and quercetin in human urine after consumption of Ginkgo biloba tablets. 

47.)Ginkgo biloba extract (EGb 761) independently improves changes in passive avoidance learning and brain membrane fluidity in the aging mouse. 

48.)Lipid peroxidation in experimental spinal cord injury. Comparison of treatment with Ginkgo biloba, TRH and methylprednisolone. 

49.)A Ginkgo biloba extract (EGb 761) prevents mitochondrial aging by protecting against oxidative stress. 

50.)The correlation of cyto photometrically and biochemically measured enzyme activities: changes in the myocardium of diabetic and hypoxic diabetic rats, with and without Ginkgo biloba extract treatment. 

51.)Enhancement of radiation effect by Ginkgo biloba extract in C3H mouse fibrosarcoma. 

52.)Platelet-activating factor is an important mediator in hypoxic ischemic brain injury in the newborn rat. Flunarizine and Ginkgo biloba extract reduce PAF concentration in the brain. 

53.)The effect of meclofenoxate with ginkgo biloba extract or zinc on lipid peroxide, some free radical scavengers and the cardiovascular system of aged rats. 

54.)Effects on skeletal muscle fibres of diabetes and Ginkgo biloba extract treatment. 

55.)The effects of prostaglandin E2 indomethacin & Ginkgo biloba extract on resistance to experimental sepsis. 

56.)Ginkgo biloba extract protects brain neurons against oxidative stress induced by hydrogen peroxide. 

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1.) [Ginkgo biloba extract (EGb 761). State of knowledge in the dawn of 

the year 2000] 

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Author 

Clostre F 

Address 

Institut Henri Beaufour, Les Ulis. 

Source 

Ann Pharm Fr, 57 Suppl 1():1S8-88 1999 Jul 

Abstract 

EGb 761 is a standardized extract of dried leaves of Ginkgo biloba  containing 24%  ginkgo-flavonol glycosides, 6% terpene lactones such as ginkgolides A,  B, C, J and  bilobalide. Its broad spectrum of pharmacological activities allows it  to be in adequacy to the  numerous pathological requirements--hemodynamic, hemorheological,  metabolic--which  occur in cerebral, retinal, cochleovestibular, cardiac or peripheral  ischemia. Moreover, EGb  761 has direct effects against necrosis and apoptosis of neurons and  improves neural plasticity  as evidenced in vestibular compensation.

At the molecular and the  cellular levels, some  evidence obtained with animal models indicates that EGb 761 can  interact as a free  radical-scavenger and a inhibitor of lipid peroxidation with all, or  nearly all reactive oxygen  species; maintains ATP content by a protection of mitochondrial  respiration and preservation  of oxidative phosphorylations; exerts arterial and venous  vasoregulator effects involving the  release of endothelial factors and the catecholaminergic system.  Moreover, EGb 761  regulates ionic balance in damaged cells and exerts a specific and  potent Platelet-activating  factor antagonist activity.

Numerous well-controlled clinical studies,  realized in Europe and in  USA, have revealed that EGb 761 is an effective therapy for a wide  variety of disturbances of  cerebral function, ranging from cerebral impairment of ischemic  vascular origins (i.e. multi  infarct dementia), early cognitive decline to mild-to-moderate cases  of the more severe types  of senile dementias (including Alzheimer's disease) or mixed origins  (i.e. psychoorganic origin).  Improvement of signs and symptoms have been demonstrated for cognitive  functions,  particularly for memory loss, attention, alertness, vigilance, arousal  and mental fluidity. Some  clinical studies have showed that EGb 761 treatment may improve the  capacity of geriatric  patients to cope with the stressful demands of daily life. The  explanation is a dual  stress-alleviating action of EGb 761: its facilitates behavioral  adaptation to stress and may  decrease the excess of cortisol release to stress. Moreover, EGb 761  shows a specific  neuroprotective effects to hippocampic cells.

Regarding the visual  system, experimental  studies have shown that EGb 761 can inhibit or reduce the functional  retinal impairments  resulting from ischemia-reperfusion, photo-degeneration, diabetic or  proliferative retinopathy.  Clinical studies have revealed that EGb 761 may be useful in treating  visual activity  impairments and damages to the visual field associated with chronic  cerebrovascular  insufficiency, senile macular degeneration and diabete mellitus.  Regarding the vestibular and  auditory systems, experimental and clinical studies have shown the  efficacy of EGb 761 in  treating hypoacusis, tinnitus, vertigo, dizziness and other symptoms  of vestibulocochlear  disorders. At least, adequatly controlled studies in patients with  peripheral arterial occlusive  disease have provided good evidence for therapeutic efficacy in  intermittent claudication.

The  future of EGb 761 is undoubtedly in the promise in slowing the  progression of Alzheimer's  disease. Indeed, two recent american clinical studies have shown the  efficacy and safety of  EGb 761 in patients with mild to severe Alzheimer's disease and  multi-infarct dementia. In  clinical terms, progression of symptoms was delayed by approximately 6  months. Actually  new clinical studies are undertaken in USA and Europe. At the dawn of  the third millenium  (the Sixth for Ginkgo biloba) we propose a state of art about it. 

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2.)[Preparation and definition of Ginkgo biloba extract]. 

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Presse Med 1986 Sep 25;15(31):1455-7 

Drieu K 

Ginkgo biloba extract is a well-defined and complex product prepared from  green leaves of Ginkgo biloba. The leaves are harvested from trees growing  in plantations in South Corea, Japan and France. The mode of culture,  harvesting and extraction are perfectly standardized and controlled. 

Analysis of Ginkgo biloba extract makes it possible to confirm that  undesirable substances have been eliminated and to measure the amount of  active principles. The extract contains flavonoid substances, such as the  Ginkgo-flavone glycosides and terponoids which are characteristic of Ginkgo  and have a unique structure (ginkgolides, bilobalide). 

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3.) Subarachnoid haemorrhage associated with Ginkgo biloba. 

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Lancet 1998 Jul 4;352(9121):36 

Vale S 

Letter 

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4.) Extracts of Ginkgo biloba and bleeding or haemorrhage. 

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Lancet 1998 Oct 3;352(9134):1145-6 

Skogh M 

Publication Types: 

Letter 

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5.) Association of Ginkgo biloba with intracerebral hemorrhage. 

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Neurology 1998 Jun;50(6):1933-4 

Matthews MK Jr 

Publication Types: 

Letter 

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6.) Spontaneous hyphema associated with ingestion of Ginkgo biloba extract. 

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N Engl J Med 1997 Apr 10;336(15):1108 

Rosenblatt M, Mindel J 

Publication Types: 

Letter 

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7.) Spontaneous bilateral subdural hematomas associated with chronic Ginkgo 

biloba ingestion. 

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Neurology 1996 Jun;46(6):1775-6 

Rowin J, Lewis SL 

Department of Neurological Sciences, Rush-Presbyterian-St. Luke's Medical  Center, Chicago, IL 60612, USA. 

Comment in: Neurology 1997 Mar;48(3):789-90 

Comment in: Neurology 1997 Apr;48(4):1137 

Comment in: Neurology 1998 Jun;50(6):1933-4 

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8.) Antiplatelet and antithrombotic effects of a combination of ticlopidine and ginkgo  biloba ext (EGb 761). 

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Thromb Res 1998 Jul 1;91(1):33-8 

Kim YS, Pyo MK, Park KM, Park PH, Hahn BS, Wu SJ, Yun-Choi HS  Natural Products Research Institute, Seoul National University, Korea. 

The antiplatelet and antithrombotic effects of the oral combination  treatment of ticlopidine and Ginkgo biloba extract (EGb 761) were studied  in normal and thrombosis-induced rats.

The ex vivo inhibitory effect on  ADP-induced platelet aggregation of a small dose of ticlopidine (50  mg/kg/day) in combination with EGb 761 (40 mg/kg/day) was comparable to a  larger dose of only ticlopidine (200 mg/kg/day). Bleeding time was also  prolonged by 150%.

Thrombus weight was also consistently decreased by a  combination of ticlopidine and EGb 761 in an arterio-venous shunt model at  two doses of ticlopidine (50 mg/kg) plus EGb 761 (20 mg/kg) and ticlopidine  (50 mg/kg) plus EGb 761 (40 mg/kg). A combinatory treatment in acute  thrombosis model in mice also showed a higher recovery than a single  treatment. 

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9.) [Paroxysmal non-hereditary angioedema]. 

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Dtsch Med Wochenschr 1990 Oct 19;115(42):1586-90 

[Article in German] 

Steurer J, Siegenthaler-Zuber G, Siegenthaler W, Suter S, Kessler FJ,  Vahlensieck M, Streuli R, Lingg G 

Departement fur Innere Medizin, Universitatsspital Zurich. 

Recurrent hypovolaemic shock had been occurring over the last five and four  years, respectively, in a 53-year-old woman and a 46-year-old man who had  previously been healthy.

The attacks were characterized by a tension  feeling and sometimes oedema in the limbs, as well as increased thirst.  Within a few hours sweating, tachycardia, orthostatic complaints and shock  would occur. The woman's systolic blood pressure would fall to 70 mm Hg and  the pulse rate rise to 150/min.

The man's blood pressure was not measurable  by sphygmomanometer during his first attack. Haematocrit rose to 61 and  71.5%, haemoglobin concentration to 20.7 and 21.3 g/dl, respectively. On  administration of plasma expanders all abnormal clinical and biochemical  changes quickly disappeared, only to recur within weeks or months. The  cause of the condition is an increased permeability of the tissue  capillaries, while renal, pulmonary and cerebral vessels apparently are  unaffected.

During ketotifen and tebonin (gingko biloba extract)  administration to the man, he required no further hospitalization for nine  months, after which he had three severe attacks. The woman had a severe  attack of hypovolaemic shock one month on this treatment. The prognosis of  capillary leak syndrome is bad. 

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10.)Dietary supplement-drug interactions. 

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J Am Med Womens Assoc 1999 Fall;54(4):191-2 

Smolinske SC 

Children's Hospital of Michigan Regional Poison Control Center, USA. 

Recent surveys show that 18% of adults in the United States use  prescription drugs concurrently with herbal or vitamin products, placing an  estimated 15 million patients at risk of potential drug-supplement  interactions.

Despite this widespread concurrent use of conventional and  alternative medicines, documented drug-herb interactions are sparse. This  review focuses on possible interactions between drugs and herbal medicines  used for phytoestrogen-hormone and antiplatelet-oral anticoagulant therapy. 

Interactions with phytoestrogens are purely speculative, based on  competitive estrogen-receptor binding or antiestrogenic effects. In  contrast, several case reports document bleeding complications with Ginkgo  biloba, with or without concomitant drug therapy.

Case reports are also  suggestive of interaction between warfarin and dong quai or Panax ginseng.  Recommendations for counseling patients at highest risk of adverse 

interactions are given. 

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11.)Herbal remedies: adverse effects and drug interactions. 

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Am Fam Physician 1999 Mar 1;59(5):1239-45 

Cupp MJ 

Drug Information Center, West Virginia University School of Pharmacy,  Morgantown 26506-9550, USA. 

A growing number of Americans are using herbal products for preventive and  therapeutic purposes. The manufacturers of these products are not required  to submit proof of safety and efficacy to the U.S. Food and Drug  Administration before marketing.

For this reason, the adverse effects and  drug interactions associated with herbal remedies are largely unknown.  Ginkgo biloba extract, advertised as improving cognitive functioning, has  been reported to cause spontaneous bleeding, and it may interact with  anticoagulants and antiplatelet agents. St. John's wort, promoted as a  treatment for depression, may have monoamine oxidase-inhibiting effects or  may cause increased levels of serotonin, dopamine and norepinephrine. 

Although St. John's wort probably does not interact with foods that contain  tyramine, it should not be used with prescription antidepressants.  Ephedrine-containing herbal products have been associated with adverse  cardiovascular events, seizures and even death. Ginseng, widely used for  its purported physical and mental effects, is generally well tolerated, but  it has been implicated as a cause of decreased response to warfarin. 

Physicians must be alert for adverse effects and drug interactions  associated with herbal remedies, and they should ask all patients about the  use of these products. 

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12.)Herbal medicinals: selected clinical considerations focusing on known or  potential drug-herb interactions. 

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Arch Intern Med 1998 Nov 9;158(20):2200-11 

Miller LG 

Department of Pharmacy Practice, Texas Tech University Health Sciences  Center, Amarillo 79121, USA. 

Herbal medicinals are being used by an increasing number of patients who  typically do not advise their clinicians of concomitant use. Known or  potential drug-herb interactions exist and should be screened for. If used  beyond 8 weeks, Echinacea could cause hepatotoxicity and therefore should  not be used with other known hepatoxic drugs, such as anabolic steroids,  amiodarone, methotrexate, and ketoconazole. However, Echinacea lacks the  1,2 saturated necrine ring associated with hepatoxicity of pyrrolizidine  alkaloids.

Nonsteroidal anti-inflammatory drugs may negate the usefulness  of feverfew in the treatment of migraine headaches. Feverfew, garlic,  Ginkgo, ginger, and ginseng may alter bleeding time and should not be used  concomitantly with warfarin sodium. Additionally, ginseng may cause  headache, tremulousness, and manic episodes in patients treated with  phenelzine sulfate.

Ginseng should also not be used with estrogens or  corticosteroids because of possible additive effects. Since the mechanism  of action of St John wort is uncertain, concomitant use with monoamine  oxidase inhibitors and selective serotonin reuptake inhibitors is ill  advised. Valerian should not be used concomitantly with barbiturates  because excessive sedation may occur.

Kyushin, licorice, plantain, uzara  root, hawthorn, and ginseng may interfere with either digoxin  pharmacodynamically or with digoxin monitoring. Evening primrose oil and  borage should not be used with anticonvulsants because they may lower the  seizure threshold.

Shankapulshpi, an Ayurvedic preparation, may decrease  phenytoin levels as well as diminish drug efficacy. Kava when used with  alprazolam has resulted in coma. Immunostimulants (eg, Echinacea and zinc)  should not be given with immunosuppressants (eg, corticosteroids and  cyclosporine). Tannic acids present in some herbs (eg, St John wort and saw  palmetto) may inhibit the absorption of iron. Kelp as a source of iodine  may interfere with thyroid replacement therapies.

Licorice can offset the  pharmacological effect of spironolactone. Numerous herbs (eg, karela and  ginseng) may affect blood glucose levels and should not be used in patients  with diabetes mellitus. 

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13.)The protective effect of Ginkgo biloba extract on CCl4-induced hepatic  damage. 

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Author 

Ozenirler S; Din¸cer S; Akyol G; Ozo¨gul C; Oz E 

Address 

Department of Gastroenterology, Gazi University Faculty of Medicine,  Be¸sevler, Ankara,  Turkey. 

Source 

Acta Physiol Hung, 85(3):277-85 1997-98 

Abstract 

The aim of this study was to evaluate the protective effect of Ginkgo  biloba extract on  CCl4-induced hepatic damage in rats. Hepatic malondialdehyde,  glutathione and  hydroxyproline levels and histopathologic alterations in liver  specimens were assessed. 200  mg/kg/day Ginkgo biloba extract were given orally to the animals for  10 days, then a single  dose of 2 ml/kg b.w. carbon tetrachloride was, administered  intraperitoneally.

Ginkgo biloba  extract treatment reduced hepatic malondialdehyde levels significantly  (p < 0.05), but did not  alter glutathione (p > 0.05) and hydroxyproline levels (p > 0.05). The  light and electron  microscopic findings showed that Ginkgo biloba extract limited the  CCl4-induced hepatocyte  necrosis and atrophy. These results suggest that this extract may  protect the hepatocytes from  carbon tetrachloride-induced liver injury. 

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14.)Ginkgo biloba for antidepressant-induced sexual dysfunction.  Author 

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Cohen AJ; Bartlik B 

Address 

University of California, San Francisco, California, USA. 

Source 

J Sex Marital Ther, 24(2):139-43 1998 Apr-Jun 

Abstract 

In an open trial ginkgo biloba, an extract derived from the leaf of  the Chinese ginkgo tree and  noted for its cerebral enhancing effects, was found to be 84%  effective in treating  antidepressant-induced sexual dysfunction predominately caused by  selective serotonin  reuptake inhibitors (SSRIs, N = 63). Women (n = 33) were more  responsive to the sexually  enhancing effects of ginkgo biloba than men (N = 30), with relative  success rates of 91%  versus 76%.

Ginkgo biloba generally had a positive effect on all 4  phases of the sexual  response cycle: desire, excitement (erection and lubrication), orgasm,  and resolution  (afterglow).

This study originated from the observation that a  geriatric patient on ginkgo  biloba for memory enhancement noted improved erections. Patients  exhibited sexual  dysfunction secondary to a variety of antidepressant medications  including selective serotonin  reuptake inhibitor (SSRIs), serotonin and nonrepinephrine reuptake  inhibitor (SNRIs)  monoamine oxidase inhibitor (MAOIs), and tricyclics.

Dosages of ginkgo  biloba extract  ranged from 60 mg qd to 120 mg bid (average = 209mg/d). The common  side effects were  gastrointestinal disturbances, headache, and general central nervous  system activation. The  article includes a discussion of presumed pharmacologic mechanisms,  including effects on  platelet activating factor, prostaglandins, peripheral vasodilatation,  and central serotonin and  norepinephrine receptor factor modulation. 

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15.)The efficacy of Ginkgo biloba on cognitive function in Alzheimer disease. 

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Arch Neurol 1998 Nov;55(11):1409-15 

Oken BS, Storzbach DM, Kaye JA 

Department of Neurology, Oregon Health Sciences University, Portland 97201,  USA. oken@ohsu.edu 

OBJECTIVE: To determine the effect of treatment with Ginkgo biloba extract  on objective measures of cognitive function in patients with Alzheimer  disease (AD) based on formal review of the current literature.

METHODS: An  attempt was made to identify all English and non-English-language articles  in which G. biloba extract was given to subjects with dementia or cognitive  impairment. Inclusion criteria for the meta-analysis were

(1) sufficiently  characterized patients such that it was clearly stated there was a  diagnosis of AD by either Diagnostic and Statistical Manual of Mental  Disorders, Revised Third Edition, or National Institute of Neurological  Disorders and Stroke-Alzheimer's Disease and Related Disorders Association  criteria, or there was enough clinical detail to determine this by our  review;

(2) clearly stated study exclusion criteria, ie, those studies that  did not have stated exclusions for depression, other neurologic disease,  and central nervous system-active medications were excluded;

(3) use of  standardized ginkgo extract in any stated dose;

(4) randomized,  placebo-controlled and double-blind study design;

(5) at least 1 outcome  measure was an objective assessment of cognitive function; and (6)  sufficient statistical information to allow for meta-analysis.

RESULTS: Of  more than 50 articles identified, the overwhelming majority did not meet  inclusion criteria, primarily because of lack of clear diagnoses of  dementia and AD.

Only 4 studies met all inclusion criteria. In total there  were 212 subjects in each of the placebo and ginkgo treatment groups.  Overall there was a significant effect size of 0.40 (P<.0001). This modest  effect size translated into a 3% difference in the Alzheimer Disease  Assessment Scale-cognitive subtest.

CONCLUSIONS: Based on a quantitative  analysis of the literature there is a small but significant effect of 3- to  6-month treatment with 120 to 240 mg of G. biloba extract on objective  measures of cognitive function in AD. The drug has not had significant  adverse effects in formal clinical trials but there are 2 case reports of  bleeding complications.

In AD, there are limited and inconsistent data that  preclude determining if there are effects on noncognitive behavioral and  functional measures as well as on clinician's global rating scales.

Further  research in the area will need to determine if there are functional  improvements and to determine the best dosage. Additional research will be  needed to define which ingredients in the ginkgo extract are producing its  effect in individuals with AD. 

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16.) Medicinal plants and Alzheimer's disease: from ethnobotany to

phytotherapy. 

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J Pharm Pharmacol 1999 May;51(5):527-34 

Perry EK, Pickering AT, Wang WW, Houghton PJ, Perry NS 

Medical Research Council, Newcastle General Hospital, Newcastle upon Tyne.  e.k.perry@ncl.ac.uk 

The use of complementary medicines, such as plant extracts, in dementia  therapy varies according to the different cultural traditions. In orthodox  Western medicine, contrasting with that in China and the Far East for  example, pharmacological properties of traditional cognitive- or  memory-enhancing plants have not been widely investigated in the context of  current models of Alzheimer's disease.

An exception is Gingko biloba in  which the gingkolides have antioxidant, neuroprotective and cholinergic  activities relevant to Alzheimer's disease mechanisms. The therapeutic  efficacy of Ginkgo extracts in Alzheimer's disease in placebo controlled  clinical trials is reportedly similar to currently prescribed drugs such as  tacrine or donepezil and, importantly, undesirable side effects of Gingko  are minimal.

Old European reference books, such as those on medicinal  herbs, document a variety of other plants such as Salvia officinalis (sage)  and Melissa officinalis (balm) with memory-improving properties, and  cholinergic activities have recently been identified in extracts of these  plants.

Precedents for modern discovery of clinically relevant  pharmacological activity in plants with long-established medicinal use  include, for example, the interaction of alkaloid opioids in Papaver  somniferum (opium poppy) with endogenous opiate receptors in the brain.  With recent major advances in understanding the neurobiology of Alzheimer's  disease, and as yet limited efficacy of so-called rationally designed  therapies, it may be timely to re-explore historical archives for new  directions in drug development.

This article considers not only the value  of an integrative traditional and modern scientific approach to developing  new treatments for dementia, but also in the understanding of disease  mechanisms. Long before the current biologically-based hypothesis of  cholinergic derangement in Alzheimer' s disease emerged, plants now known  to contain cholinergic antagonists were recorded for their amnesia- and  dementia-inducing properties. 

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17.)Free radicals in Alzheimer's dementia: currently available therapeutic  strategies. 

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J Neural Transm Suppl 1998;54:211-9 

Rosler M, Retz W, Thome J, Riederer P 

Psychiatric Department, University of Wurzburg, Federal Republic of Germany. 

Substantial evidence now exists that oxidative stress may play an important  role in the etiopathogenesis of DAT. The different sources of oxidative  stress in DAT are suggesting several pharmacological opportunities for  influencing the disease.

It is possible to distinguish 2 major types of  possible therapeutic agents according to their pharmacological point of  attack.

1. Radical scavengers, agents directly interacting with free  radicals. Candidates of this type are gingko biloba, vitamins A, C, E and  estrogen.

2. Antioxidants, which are able to prevent or decrease the  production of free radicals by use of specific neuropharmacological  properties.

Candidates are selegiline, a MAO-B inhibitor well established  in the therapy of Parkinson's disease, and tenilsetam, which is believed to  be an AGE-inhibitor. Recent in vitro studies have demonstrated the efficacy  of both types of therapeutic agents by preventing or delaying oxidative  neural damage. Some clinical data exist regarding the antidementive  properties particularly in terms of gingko biloba, selegiline and vitamin  E.

The efficacy studies about these compounds seem to indicate a promising  future strategy in the therapy of DAT. But it is too early to draw definite  conclusions since it is well known that all of our candidate substances do  not act specifically as radical scavengers or antioxidants. 

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18.)Proof of efficacy of the ginkgo biloba special extract EGb 761 in  outpatients suffering from mild to moderate primary degenerative dementia  of the Alzheimer type or multi-infarct dementia. 

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Author 

Kanowski S; Herrmann WM; Stephan K; Wierich W; H¨orr R 

Address 

Department of Gerontopsychiatry, Free University Berlin, Germany. 

Source 

Pharmacopsychiatry, 29(2):47-56 1996 Mar 

Abstract 

The efficacy of the ginkgo biloba special extract EGb 761 in outpatients  with presenile and senile primary degenerative dementia of the Alzheimer  type (DAT) and multi-infarct dementia (MID) according to DSM-III-R was  investigated in a prospective, randomized, double-blind,  placebo-controlled, multi-center study.

After a 4-week run-in period, 216  patients were included in the randomized 24-week treatment period. These  received either a daily oral dose of 240 mg EGb 761 or placebo. In  accordance with the recommended multi-dimensional evaluation approach,  three primary variables were chosen: the Clinical Global Impressions (CGI  Item 2) for psychopathological assessment, the Syndrom-Kurztest (SKT) for  the assessment of the patient's attention and memory, and the N¨urnberger  Alters-Beobachtungsskala (NAB) for behavioral assessment of activities of  daily life.

Clinical efficacy was assessed by means of a responder  analysis, with therapy response being defined as response in at least two  of the three primary variables. The data from the 156 patients who  completed the study in accordance with the study protocol were taken into  account in the confirmatory analysis of valid cases.

The frequency of  therapy responders in the two treatment groups differed significantly in  favor of EGb 761, with p < 0.005 in Fisher's Exact Test.

The  intent-to-treat analysis of 205 patients led to similar efficacy results.  Thus, the clinical efficacy of the ginkgo biloba special extract EGb 761 in  dementia of the Alzheimer type and multi-infarct dementia was confirmed.  The investigational drug was found to be well tolerated. 

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19.)The relevance of herbal treatments for psychiatric practice. 

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Aust N Z J Psychiatry 1999 Aug;33(4):482-9; discussion 490-3 

Walter G, Rey JM 

Department of Psychological Medicine, University of Sydney, New South  Wales, Australia. gwalter@mail.usyd.edu.au 

OBJECTIVE: The aim of this paper is to inform psychiatrists about the basic  priniciples, terminology, schools of thought, efficacy, safety and  regulatory issues regarding herbal treatments for mental illness.

METHOD:  Information was obtained by computerised and manual searching of medical  and botanical data bases, and by discussions with experts in herbal  medicine and regulatory aspects of the pharmaceutical industry.

RESULTS:  Herbal medicines are commonly used in developed and developing countries  for psychiatric illness.

The main schools of herbal medicine in Australia  are Western herbal medicine, traditional Chinese medicine and 'Ayurveda'  (Indian herbal medicine). Herbs used for psychiatric or neurological  disorders are termed 'nervines'.

Three nervines which have attracted  considerable attention recently are St John's Wort, Gingko biloba and  Valeriana officinalis.

In Australia, most herbal drugs are classed as  'listed drugs' which are required to satisfy less rigorous safety and  efficacy criteria than 'registered drugs'. The popularity of herbal  remedies has a number of clinical and research implications for psychiatry. 

CONCLUSIONS: Psychiatrists should not endorse treatments that are  unsupported by sound research, nor remain ignorant about alternative  approaches to mental illness.

The extent of use of herbal treatments for  mental illness suggests that psychiatrists should become more knowledgeable  about developments in this area. 

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20.)[The effect of gingko biloba on cochleovestibulary pathology of vascular  origin]. 

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An Otorrinolaringol Ibero Am 1995;22(6):619-29 

[Article in Spanish] 

Cano Cuenca B, Marco Algarra J, Perez del Valle B, Pellicer Pascual FJ 

The AA. of the present paper recall the clinical and functional results of  this therapy in a group of 70 patients complaining of vertigo. The Gingko  biloba extract (4 ml/12 h per mouth) has been continued during 6 months.  Neck and vertebrobasilar insufficiency were predominant causes.

Six months  later statistically significant changes regarding the decrease of intensity  of tinnitus and vertigo crises were confirmed. Besides favorable  alterations in the peripherical symptomatology as a relative hearing  improvement turned up. 

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21.)Effects of Ginkgo biloba extract on the cochlear damage induced by local  gentamicin installation in guinea pigs. 

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Author 

Jung HW; Chang SO; Kim CS; Rhee CS; Lim DH 

Address 

Department of Otorhinolaryngology - Head & Neck Surgery, Seoul National  University College of Medicine, Korea. 

Source 

J Korean Med Sci, 13(5):525-8 1998 Oct 

Abstract 

Investigations evaluating the protective effect of Ginkgo biloba extract  (EGb) on gentamicin (GM) ototoxicity were undertaken. Guinea pigs treated  with 5 mg/kg gentamicin sulfate on the round window niche (RWN) showed  acute changes on electrocochleogram and hair cell or microvilli damage on  scanning electron microscopy (SEM).

There was accumulation of GM in the  whole cochlea, especially in the organ of Corti, stria vascularis, and type  III fibrocyte on immunohistochemical study. However, the guinea pigs  pretreated with local or systemic EGb revealed no significant changes by  local GM installation. From these results, we concluded that EGb has a  protective effect on the development of GM ototoxicity in the cochlea.  Language 

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22.)Ginkgo biloba for tinnitus: a review. 

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Clin Otolaryngol 1999 Jun;24(3):164-7 

Ernst E, Stevinson C 

Department of Complementary Medicine, School of Postgraduate Medicine and  Health Sciences, University of Exeter, UK. E.Ernst@exeter.ac.uk 

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23.)[Contribution of a combination of alpha and beta benzopyrones, flavonoids  and natural terpenes in the treatment of lymphedema of the lower limbs at  the 2d stage of the surgical classification]. 

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Minerva Cardioangiol 1996 Sep;44(9):447-55 

[Article in Italian] 

Vettorello G, Cerreta G, Derwish A, Cataldi A, Schettino A, Occhionorelli  S, Donini I 

Istituto di Clinica Chirurgica, Universita degli Studi, Ferrara. 

HYPOTHESIS: To create a phlebolymphologic therapy in order: to activate  venous system; to activate lymphatic system; to activate macrophagic  system; to reduce the proteic lymphatic load.

EXPERIMENTAL: A study was  performed on the use of an ideal phlebolymphological association (Tonka  Beans, Gingko Biloba, Melilotus Officinalis) as a practical standpoint in  the treatment of lymphedema of lower limbs in order to create an  efficacious dose of Coumarin, Benzopyrones and Ginkolidi.

CLINICAL: We  investigated a population of 76 patients treated in an open-label study for  six-eight months with a dosage of Coumarin 60 mg/daily + Gingko Biloba 40  mg/daily + Melilotus 40 mg/daily.

CONCLUSION: This trilogy induced a very  significant improvement in lymphedema (centimeter-aspect) both in  functional symptoms (pain heaviness in affected limbs) and physical signs  (edema, episodes of infection).

Tolerance of long term treatment was good  and the improvement was observed from the third month of treatment. 

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24.)[Gingko biloba extract EGb 761 and pentoxifylline in intermittent  claudication. Secondary analysis of the clinical effectiveness]. 

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Vasa 1992;21(4):403-10 

Letzel H, Schoop W 

Clinical trials on the efficacy of EGb 761 and pentoxifylline are  summarized in the context of their methods and results and compared with  each other.

All placebo-controlled, randomized and double-blind studies  with the major target objective of "pain-free walking distance" were  selected. The pentoxifylline studies were adopted from a survey of the  existing literature in the English language, which has been brought up to  date via DIMDI research.

The studies on both active substances are fraught  with similar difficulties as to method, and are not different as regards  their quality. The increase in walking distance is highly variable,  especially in the pentoxifylline studies.

On average through each and all  of the studies on both preparations, an increase of 45% (EGb 761) or 57%  (pentoxifylline) in relation to initial values is here found.

No  differences in the documentation of efficacy and the clinical efficacy were  discovered between the two substances, both of which are registered as  effective substances in the treatment of peripheral arterial occlusion  (pAO) in accordance with the Federal German Drugs Law (Arzneimittelgesetz,  AMG) of 1976. 

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25.)[Placebo-controlled double-blind study of the effectiveness of Ginkgo  biloba special extract EGb 761 in trained patients with intermittent claudication] 

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Author 

Blume J; Kieser M; H¨olscher U 

Address 

Angiologische Gemeinschaftspraxis, Aachen. 

Source 

Vasa, 25(3):265-74 1996 

Abstract 

This monocenter, randomized, placebo-controlled double-blind study  with parallel-group  comparison was carried out in order to demonstrate the efficacy of  Ginkgo biloba special  extract EGb 761 on objective and subjective parameters of the walking  performance in  trained patients suffering from peripheral arterial occlusive disease  in Fontaine stage IIb. In  total 60 patients were recruited (42 men; aged 47-82 years) with  angiographically proven  peripheral arterial occlusive disease of the lower extremities and an  intermittent claudication  existing for at least 6 months.

No improvement had been shown despite  consistent walking  training and a maximum pain-free walking distance on the treadmill of  less than 150 m was  recorded at the beginning of the study. The therapeutic groups were  treated with either  Ginkgo biloba special extract EGb 761 at a dose of 3 times 1  film-coated tablet of 40 mg  per day by oral route or placebo over a duration of 24 weeks following  a two-week placebo  run-in phase. The main outcome measure was the difference of the  walking distance between  the start of treatment and after 8, 16 and 24 weeks of treatment as  measured on the treadmill  (walking speed 3 km/h and slope of 12%).

As secondary parameters the  corresponding  differences for the maximum walking distance, the relative increase of  the pain-free walking  distance, the Doppler index and the subjective evaluation of the  patients were analyzed. The  absolute changes in the pain-free walking distance in treatment weeks  8, 16 and 24 as against  the treatment beginning (median values with 95% confidence interval)  led to the following  values for the patients treated with Ginkgo biloba special extract EGb  761:19 m (14, 33), 34  m (18, 50) and 41 m (26, 64).

The corresponding values in the placebo  group were as  follows: 7 m (-4, 12), 12 m (5, 22) and 8 m (-1, 21). The advantage of  the EGb 761-treated  group as compared to the placebo group could be verified statistically  at the 3 time points  with p < 0.0001, p = 0.0003 and p < 0.0001. The test for the presence  of a clinically relevant  difference of 20% between EGb 761 and placebo also produced a  statistically significant  result (p = 0.008).

The Doppler index remained unchanged in both  therapeutic groups: A  corresponding statistically significant advantage for the EGb 761  group was observed on a  descriptive level for the other parameters tested. The tolerance of  the treatment was very  good. The results of this placebo-controlled study show that treatment  with Ginkgo biloba  special extract EGb 761 produces a statistically highly significant  and clinically relevant  improvement of the walking performance in trained patients suffering  from intermittent  claudication with very good tolerance of the study preparation. 

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26.)[Ginkgo biloba in treatment of intermittent claudication. A systematic  research based on controlled studies in the literature] 

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Author 

Ernst E 

Address 

Postgraduate Medical School, University of Exeter/UK. 

Source 

Fortschr Med, 114(8):85-7 1996 Mar 20 

Abstract 

The aim of this systematic review was to evaluate the effectiveness of  ginkgo biloba in the  treatment of intermittent claudication. A Medline-search identified  ten controlled trials on the  subject. These were heterogeneous in all respects and, with only few  exceptions, of poor  methodological quality.

All the studies implied that ginkgo biloba is  an effective therapy for  intermittent claudication. This hypothesis should be confirmed in  further trials employing  meticulous methodology. Furthermore it would also be important to  determine whether oral  ginkgo biloba can be usefully combined with walking exercise. 

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27.)Effect of Gingko biloba extract (EGb 761) on chloroquine induced retinal  alterations. 

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Lens Eye Toxic Res 1992;9(3-4):521-8 

Droy-Lefaix MT, Vennat JC, Besse G, Doly M 

Laboratoire de Biophysique, Unite INSERM U71, Facultes de Medecine et de  Pharmacie, Clermont-Ferrand, France. 

Electroretinography was used to investigate the preventive action of Ginkgo  biloba extract (EGb 761) in experimental chloroquine-induced retinopathy in  rats. EGb 761 contains flavones and anthocyanosides known for their  oxygenated radical scavenging properties.

Chronic administration of  chloroquine (20 days) caused an overall lengthening of the duration of the  ERG b-wave, together with delayed peaking. These anomalies became more  marked with increased duration of treatment.

In rats treated simultaneously  with chloroquine and EGb 761 no such modification of the electroretinogram  (ERG) was observed.

These results suggest that retinal toxicity may be  related to a localized inflammation releasing oxygenated free radicals  and/or PAF. EGb 761 may thus afford a useful preventive treatment for  chloroquine-induced retinopathy, and generally for xenobiotic  retinotoxicities. 

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28.)Ginkgo biloba extract increases ocular blood flow velocity.  =========================================================== 

Author 

Chung HS; Harris A; Kristinsson JK; Ciulla TA; Kagemann C; Ritch R 

Address 

Glaucoma Research and Diagnostic Center, Department of Ophthalmology, 

Indiana University Medical Center, Indianapolis 46202, USA. 

Source J Ocul Pharmacol Ther, 15(3):233-40 1999 Jun 

Abstract 

We evaluated a possible therapeutic effect of Ginkgo biloba extract  (GBE) on glaucoma patients that may benefit from improvements in ocular blood flow. A  Phase I cross-over trial of GBE with placebo control in 11 healthy volunteers (8 women,  3 men: Age; 34 +/- 3 years, mean +/- SE) was performed.

Patients were treated with  either GBE 40 mg or placebo three  times daily orally, for 2 days.

Color Doppler imaging (Siemens Quantum  2000) was used to measure ocular blood flow before and after treatment. There was a  two week washout period between GBE and placebo treatment.

Ginkgo biloba extract  significantly increased end diastolic velocity (EDV) in the ophthalmic artery (OA)  (baseline vs GBE-treatment; 6.5 +/- 0.5 vs 7.7 +/- 0.5 cm/sec, 23% change, p=0.023),  with no change seen in placebo (baseline vs GBE-treatment; 7.2 +/- 0.6 vs 7.1 +/- 0.5  cm/sec, 3% change,  p=0.892).

No side effects related to GBE were found. Ginkgo biloba extract did not alter  arterial blood pressure, heart rate, or IOP. Ginkgo biloba extract significantly increased  EDV in the OA and deserves further investigation in ocular blood flow and  neuroprotection for possible application to the treatment of glaucomatous optic  neuropathy as well as other ischemic ocular diseases. 

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29.)Pretreatment of skin with a Ginkgo biloba extract/sodium  carboxymethyl-beta-1,3-glucan formulation appears to inhibit the  elicitation of allergic contact dermatitis in man. 

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Author 

Castelli D; Colin L; Camel E; Ries G 

Address 

RoC Laboratoires de Dermo-esth´etique, Colombes, France. 

Source 

Contact Dermatitis, 38(3):123-6 1998 Mar 

Abstract 

The clinical efficiency of mitigating contact dermatitis with a Ginkgo  biloba extract and carboxymethyl-beta-1,3-glucan formulation was  investigated in a double-blind versus placebo study using 22 subjects  (Caucasian women aged 22-55 years) with allergic contact dermatitis from  various substances in the European standard series. The formulation was  applied to intact skin 2X a day for 2 weeks ("in use" application) prior to  a single application of a selected contact allergen under a Finn Chamber  for 24 h. Readings were carried out in a blind study by a dermatologist 2  and 3 days after patch removal. Representative photographs were taken of  treated, placebo and untreated test areas. 68.2% of the panelists showed  significantly reduced skin reactivity (p = 0.037*) on the treated site 2  days after patch removal, versus untreated and/or placebo sites. This  finding indicates that the Ginkgo biloba/carboxymethyl-beta-1,3-glucan  formulation can mitigate against allergic contact dermatitis.  Language 

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30.)The effect of Gingko biloba extract (Egb 761) as a free radical scavenger 

on the survival of skin flaps in rats. A comparative study. 

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Scand J Plast Reconstr Surg Hand Surg 1998 Jun;32(2):135-9 

Bekerecioglu M, Tercan M, Ozyazgan I 

Department of Plastic and Reconstructive Surgery, Faculty of Medicine,  Yuzuncu Yil University, Van, Turkey. 

Free radicals may have a role in pedicle flap necrosis. We undertook this  study to compare the effect of various antioxidants and scavengers of free  radicals such as vitamin E, vitamin C, deferoxamine, and Gingko biloba  extract (Egb 761) on McFarlane caudal-based dorsal rat flaps. Fifty rats  were divided into five groups of 10 animals each. One group served as a  control (saline) group.

The remaining four groups were given vitamin C 340  mg/kg, deferoxamine 150 mg/kg, Egb 761 100 mg/kg, and vitamin E 20 mg/kg.  The necrosed area of flap was significantly reduced in the deferoxamine (p  < 0.001), Egb 761 (p < 0.001), and vitamin C (p < 0.05) groups compared  with the control group. Vitamin E had no effect on distal flap necrosis (p  = 0.20). 

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31.)Induction of superoxide dismutase and catalase activity in different rat  tissues and protection from UVB irradiation after topical application of  Ginkgo biloba extracts. 

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Author 

Lin SY; Chang HP 

Address 

Department of Medical Research and Education, Veterans General Hospital,  Taipei, Taiwan, Republic of China. 

Source 

Methods Find Exp Clin Pharmacol, 19(6):367-71 1997 Jul-Aug 

Abstract 

Ginkgo biloba extract (GBE) prepared from the leaves of Ginkgo biloba with  50% diluted alcohol was found to locally induce superoxide dismutase (SOD)  and catalase (CAT) enzyme activity in epidermis after topical application,  and also to systemically increase the activity of both enzymes in the  liver, heart and kidney of Sprague Dawley rats.

Skin pretreated with 50%  diluted alcohol-extracted liquid formulation was protected from  exacerbation of UVB damage. Changes in the lipid structure of the skin of  rats determined by ATR/FT-IR spectroscopy demonstrated penetration of  active components from GBE dosage formulations. 

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32.)In vivo regulation of peripheral-type benzodiazepine receptor and  glucocorticoid synthesis by Ginkgo biloba extract EGb 761 and isolated  ginkgolides. 

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Author 

Amri H; Ogwuegbu SO; Boujrad N; Drieu K; Papadopoulos V 

Address 

Department of Cell Biology, Georgetown University Medical Center,  Washington, District of Columbia 20007, USA. 

Source 

Endocrinology, 137(12):5707-18 1996 Dec 

Abstract 

Glucocorticoid excess has broad pathogenic potential including  neurotoxicity, neuroendangerment, and immunosuppression. Glucocorticoid  synthesis is regulated by ACTH, which acts by accelerating the transport of  the precursor cholesterol to the mitochondria where steroidogenesis begins.  Ginkgo biloba is one of the most ancient trees, and extracts from its  leaves have been used in traditional medicine. A standardized extract of  Ginkgo biloba leaves, termed EGb 761 (EGb), has been shown to have  neuroprotective and antistress effects.

In vivo treatment of rats with EGb,  and its bioactive components ginkgolide A and B, specifically reduces the  ligand binding capacity, protein, and messenger RNA expression of the  adrenocortical mitochondrial peripheral-type benzodiazepine receptor (PBR),  a key element in the regulation of cholesterol transport, resulting in  decreased corticosteroid synthesis. As expected, the ginkgolide-induced  decrease in glucocorticoid levels resulted in increased ACTH release, which  in turn induced the expression of the steroidogenic acute regulatory  protein.

Because ginkgolides reduced the adrenal PBR expression and  corticosterone synthesis despite the presence of high levels of  steroidogenic acute regulatory protein, these data demonstrate that PBR is  indispensable for normal adrenal function.

In addition, these results  suggest that manipulation of PBR expression could control circulating  glucocorticoid levels, and that the antistress and neuroprotective effects  of EGb are caused by to its effect on glucocorticoid biosynthesis. 

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33.)Reactive oxygen metabolites, antioxidants and head and neck cancer. 

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Author 

Seidman MD; Quirk WS; Shirwany NA 

Address 

Department of Otolaryngology-Head and Neck Surgery, Henry Ford Hospital, 

6777 W. Maple Road, W. Bloomfield, MI 48323, USA. 

Source 

Head Neck, 21(5):467-79 1999 Aug 

Abstract 

This manuscript will review the probable role of reactive oxygen  metabolites (ROM) in the etiopathogenesis of head and neck cancer (HNC).  Cancer is a heterogeneous disorder with multiple etiologies including  somatic and germ-line mutations, cellular homeostatic disturbances, and  environmental triggers.

Certain etiologies are characteristic of HNC and  include infectious agents such as the Epstein-Barr virus, the use of  tobacco, and consumption of alcohol. A large body of evidence implicates  ROM in tumor formation and promotion. ROM species are formed in the process  of cellular respiration, specifically during oxidative phosphorylation. 

These ubiquitous molecules are highly toxic in the cellular environment. Of  the many effects of ROM, especially important are their effect on DNA.  Specifically, ROM cause a variety of DNA damage, including insertions,  point mutations, and deletions. Thus, it is hypothesized that ROM may be  critically involved in the etiology of malignant disease through their  possible impact on protooncogenes and tumor suppressor genes. Additionally,  empirical evidence suggests that ROM may also affect the balance between  apoptosis and cellular proliferation.

If apoptotic mechanisms are  overwhelmed, uncontrolled cellular proliferation may follow, potentially  leading to tumor formation. Thus, this manuscript will critically review  the evidence that supports the role of ROM in tumorigenesis. ROM scavengers  and blockers have shown both in vivo and in vitro effects of attenuating  the toxicity of ROM.

Such compounds include the antioxidant vitamins (A, C,  and E), nutrient trace elements (selenium), enzymes (superoxide dismutase,  glutathione peroxidase, and catalase), hormones (melatonin), and a host of  natural and synthetic compounds (lazaroids, allopurinol, gingko extract).  Thus, this paper will also review the possible benefit derived from the use  of such scavengers/blockers in the prevention of HNC. Copyright 1999 John  Wiley & Sons, Inc. Head Neck 21: 467-479, 1999. 

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34.)Protective effects of Gingko biloba extract EGb 761 on myocardium of  experimentally diabetic rats. I: ultrastructural and biochemical  investigation on cardiomyocytes. 

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Exp Toxicol Pathol 1999 May;51(3):189-98 

Fitzl G, Martin R, Dettmer D, Hermsdorf V, Drews H, Welt K 

Institute of Anatomy, University Leipzig, Germany. 

Chronic diabetes in man and animal models develops cardiomyopathic  alterations which cannot be absolutely avoided by insuline therapy. Since  diabetic damage is partly attributed to oxidative stress antioxidative  treatment could be able to reduce the alterations.

Aim of this study was to  investigate the cardioprotective effects of EGb 761, known as a radical  scavenger, against diabetic alterations in rats. The diabetes was induced  by i.p. injection of 60 mg/kg body weight streptozotocin. Duration of  diabetes was 4 months, the protected group received 100 mg/kg body weight  EGb 761 with the drinking water over 3 months.

Electron and light  microscopic morphometry of left-ventricular samples revealed typical  diabetic alterations consisting in decrease of volume fraction of  myofibrils, SR and t-tubules and diminishing of cardiomyocyte diameter,  increase of interstitial volume, mitochondrial size and volume fraction,  and of vacuoles and of lipid drops.

EGb treatment could gradually prevent  the loss of myofibrils and reduction of myocyte diameter but has only  little influence on interstitial and mitochondria volume. The  diabetic-induced increase of lipid and vacuoles and the decrease of SR and  t-tubules were not influenced.

Biochemical parameters of oxidative stress:  malondialdehyde (MDA) was only insignificantly altered by diabetes and EGb.  The superoxide dismutase (SOD) activity was increased by diabetes and more  increased by EGb treatment. Creatine kinase (CK) activity was diminished by  diabetes but slightly increased by EGb. The polymerase chain reaction (PCR)  of i-NOS was not different between the diabetic and protected diabetic  groups. 

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45.)Identification of Gingko biloba flavonol metabolites after oral  administration to humans. 

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J Chromatogr B Biomed Sci Appl 1997 May 23;693(1):249-55 

Pietta PG, Gardana C, Mauri PL 

CNR-ITBA, Milan, Italy. 

An extract of Ginkgo biloba leaves (EGb) was given to healthy volunteers.  Urine samples were collected for 3 days, and blood samples were withdrawn  every 30 min for 5 h. The samples were purified through SPE C18 cartridges  and analyzed by reversed-phase LC-diode array detection for the presence of  EGb metabolites.

Only urine samples contained detectable amounts of  substituted benzoic acids, i.e., 4-hydroxybenzoic acid conjugate,  4-hydroxyhippuric acid, 3-methoxy-4-hydroxyhippuric acid,  3,4-dihydroxybenzoic acid, 4-hydroxybenzoic acid, hippuric acid and  3-methoxy-4-hydroxybenzoic acid (vanillic acid).

In contrast to rats no  phenylacetic acid or phenylpropionic acid derivatives were found in urine,  thus indicating that in humans a more extensive metabolism takes place. As  for rats the metabolites found in human urines accounted for less than 30%  of the flavonoids given. The same procedure was applied to blood samples,  and no metabolites could be detected. 

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46.)Solid-phase extraction and gas chromatography-mass spectrometry  determination of kaempferol and quercetin in human urine after consumption  of Ginkgo biloba tablets. 

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Author 

Watson DG; Oliveira EJ 

Address 

Department of Pharmaceutical Sciences, University of Strathclyde,  Strathclyde Institute of Biomedical Sciences, Glasgow, UK. 

d.g.watson@strath.ac.uk 

Source 

J Chromatogr B Biomed Sci Appl, 723(1-2):203-10 1999 Feb 19 

Abstract 

A method was developed for the quantification of the flavonoids quercetin  and kaempferol in human urine using a solid-phase extraction procedure  followed by gas chromatography-mass spectrometry. Deuterated internal  standards of the analytes were spiked into the samples prior to extraction. 

The limit of detection of the method was ca. 10 pg on column and precision  of the method for quantification in a sample of urine was +/-9.40% for  kaempferol and +/-7.34% for quercetin (n = 6). The levels of quercetin and  kaempferol found in urine samples were only a small fraction of the amount  ingested.

The treatment of urine samples with beta-glucuronidase markedly  increased the levels of flavonoids detected, supporting the view that  kaempferol and quercetin are eliminated in the urine as glucuronides.  Language 

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47.)Ginkgo biloba extract (EGb 761) independently improves changes in passive  avoidance learning and brain membrane fluidity in the aging mouse. 

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Pharmacopsychiatry 1996 Jul;29(4):144-9 

Stoll S, Scheuer K, Pohl O, Muller WE 

Central Institute for Mental Health, Section Psychopharmacology, Mannheim,  Germany. 

Decreases in cell membrane fluidity may be a major mechanism of age-related  functional decline. A prime cause for the decline of membrane fluidity may  be the presence of free radicals. Gingko biloba extract EGb 761 protects  neuronal cell membranes from free radical damage in vitro. Further, EGb 761  has repeatedly been shown to improve cognitive functions in man and in  laboratory animals.

To test if there is a link between these two actions we  assessed the effects of EGb 761 on passive avoidance learning and on  neuronal membrane fluidity in vivo in young (three-month-old), middle-aged  (12-month-old) and aged (22 to 24-month-old) female NMRI mice.

The animals  were treated daily with 100 mg/kg EGb 761 for three weeks. There was a  significant improvement in short-term memory, measured by the avoidance  latency 60 seconds after the aversive stimulus (p < 0.0311), and of  membrane fluidity (p < 0.01) in the aged animals, but no improvement in  long-term memory as measured by the avoidance latency 24 hours after shock. 

However, no significant correlation between membrane fluidity and  short-term memory performance was found. Taken together, these results  indicate that EGb 761 independently improves changes in passive avoidance  learning and brain membrane fluidity. 

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48.)Lipid peroxidation in experimental spinal cord injury. Comparison of  treatment with Ginkgo biloba, TRH and methylprednisolone. 

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Res Exp Med (Berl) 1995;195(2):117-23 

Koc RK, Akdemir H, Kurtsoy A, Pasaoglu H, Kavuncu I, Pasaoglu A, Karakucuk I 

Department of Neurosurgery, Erciyes University, School of Medicine,  Kayseri, Turkey. 

Ischaemia-induced lipid peroxidation is one of the most important factors  producing tissue damage in spinal cord injury. In our study, the protective  effects of Ginkgo biloba, thyroid releasing hormone (TRH) and  methylprednisolone (MP) on compression injury of the rat spinal cord were  investigated. For this study 45 rats in four groups, including control, MP,  TRH and Gingko biloba, were used to determine the formation of  malondialdehyde (MDA).

All the animals were made paraplegic by the  application clip method of Rivlin and Tator. Rats were divided randomly and  blindly to one of four treatment groups (ten animals in each). MP and  Ginkgo biloba treatments significantly decreased MDA levels (F = 54.138, P  < 0.01).

These results suggest that MP and Ginkgo biloba may have a  protective effect against ischaemic spinal cord injury by the antioxidant  effect. 

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49.)A Ginkgo biloba extract (EGb 761) prevents mitochondrial aging by  protecting against oxidative stress. 

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Author 

Sastre J; Mill´an A; Garc´ia de la Asunci´on J; Pl´a R; Juan G; Pallard´o;  O'Connor E; Martin JA; Droy-Lefaix MT; Vi~na J 

Address 

Departamento de Fisiolog´ia, Facultad de Medicina, Univ. Valencia, Spain. 

Source 

Free Radic Biol Med, 24(2):298-304 1998 Jan 15 

Abstract 

The effect of aging on indices of oxidative damage in rat mitochondria and  the protective effect of the Ginkgo biloba extract EGb 761 was  investigated. Mitochondrial DNA from brain and liver of old rats exhibited  oxidative damage that is significantly higher than that from young rats.  Mitochondrial glutathione is also more oxidized in old than in young rats.  Peroxide formation in mitochondria from old animals was higher than in  those from young ones.

According to morphological parameters (size and  complexity), there are two populations of mitochondria. One is composed of  large, highly complex mitochondria, and the other population is smaller and  less complex. Brain and liver from old animals had a higher proportion of  the large, highly complex mitochondria than seen in organs from young  animals.

Treatment with the Ginkgo biloba extract EGb 761 partially  prevented these morphological changes as well as the indices of oxidative  damage observed in brain and liver mitochondria from old animals. 

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50.)The correlation of cytophotometrically and biochemically measured enzyme  activities: changes in the myocardium of diabetic and hypoxic diabetic  rats, with and without Ginkgo biloba extract treatment. 

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Author 

Punkt K; Adams V; Linke A; Welt K 

Address 

Institute of Anatomy, University of Leipzig, Germany. 

Source 

Acta Histochem, 99(3):291-9 1997 Aug 

Abstract 

Changes of enzyme activities in the myocardium of rats from 6 different  experimental groups (normal rats, diabetic rats, hypoxic diabetic rats,  each with and without Ginkgo biloba extract treatment) were measured by  using both cytophotometric and biochemical methods.

The activity of  succinate dehydrogenase, a marker of oxidative capacity, and of  menadione-dependent glycerol-3-phosphate dehydrogenase and total lactate  dehydrogenase, both markers of glycolytic capacity were measured to  characterize changes of the metabolic profile in myocardium.

A strong  correlation between cytophotometric and biochemical data were found by  linear regression analysis, justifying the use of cytophotometrical enzyme  activity measurements in cells of organized tissue, where biochemistry  cannot provide topographical information.

The comparison of the results  obtained from the different groups revealed the following: Enzyme  activities in the myocardium of rats with streptozotocin-induced diabetes  were significantly increased by 10-30% as compared to the normal  myocardium.

This effect was interpreted as a metabolic compensation of the  diabetic heart with reduced performance. When diabetic rats were exposed to  acute hypoxia of 20 min duration, enzyme activities decreased under the  normal level, to 56% of the succinate dehydrogenase activity, to 87% of  glycerol-3-phosphate dehydrogenase activity and to 69% of lactate  dehydrogenase activity.

Treatment of rats with the oxygen radical scavenger  Ginkgo biloba extract (EGb 761) over 3 months resulted primarily in an  increase by 10% of oxidative capacity and in a decrease by 30% of  glycolytic capacity. Under diabetic conditions a shift to more glycolytic  metabolism was observed by increasing the glycolytic activity by 39% and  remaining the oxidative activity. 

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51.)Enhancement of radiation effect by Ginkgo biloba extract in C3H mouse  fibrosarcoma. 

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Author 

Ha SW; Yi CJ; Cho CK; Cho MJ; Shin KH; Park CI 

Address 

Laboratory of Radiation Biology, Seoul National University Medical College,  South Korea. 

Source 

Radiother Oncol, 41(2):163-7 1996 Nov 

Abstract 

BACKGROUND AND PURPOSE: Ginkgo biloba leaf extract (GBE) is known to  increase peripheral blood circulation. The hypothesis that GBE may be able  to enhance radiosensitivity of tumor by improving tumor blood flow and thus  decreasing hypoxic fraction was tested.

MATERIALS AND METHODS: Fibrosarcoma  (FSaII) growing in C3H mouse leg muscle was used as a tumor model. GBE was  given i.p. 1 h before irradiation with or without priming dose given 1 day  earlier. Effect on tumor and normal tissue radiation reaction was  investigated.

RESULTS: Tumor growth delay by radiation was more elongated  after two doses (1-day interval) of GBE than after a single dose. Radiation  dose for 3-day tumor growth delay was decreased from 12.45 (10.97-13.93) Gy  to 6.06 (3.89-8.22) Gy by two doses of GBE [enhancement ratio = 2.06  (1.32-2.79)].

Hypoxic cell fraction was 10.6% (6.3-18.2%) for control, 7.2%  (3.8-14.0%) after a single dose (P = 0.18) and 2.7% (1.5-5.0%) after two  doses (P < 0.001). Radiation effect on normal tissue, estimated by acute  skin reaction and jejunal crypt assay, was not affected by GBE.

CONCLUSION:  Ginkgo biloba extract enhances radiation effect on tumor without increasing  acute normal tissue radiation damage in this model system probably by  increasing tumor blood flow and further investigation for this possible  radiosensitizer is needed. 

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52.)Platelet-activating factor is an important mediator in hypoxic ischemic  brain injury in the newborn rat. Flunarizine and Ginkgo biloba extract  reduce PAF concentration in the brain. 

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Author 

Akis¨u M; K¨ult¨ursay N; Coker I; H¨useyinov A 

Address 

Department of Pediatrics, Ege University Medical School, Izmir, Turkey. 

makisu@med.ege.edu.tr 

Source 

Biol Neonate, 74(6):439-44 1998 Dec 

Abstract 

Hypoxic-ischemic encephalopathy is still a very important cause of neonatal  mortality and morbidity. Recently, platelet-activating factor (PAF) has  been accused of being responsible for the neuronal damage in  hypoxic-ischemic brain.

We investigated tissue PAF concentrations in  hypoxic-ischemic brain injury in immature rats. Endogenous PAF  concentration in brain tissue showed a marked increase in hypoxic-ischemic  pups (85.6 +/- 15.5 pg/mg protein) when compared to that of control (9.05  +/- 3.1 pg/mg protein).

In addition, we examined the effects of  flunarizine, a selective calcium channel blocker, and Ginkgo biloba extract  (EGb 761) on endogenous PAF concentration in hypoxic-ischemic brain injury.  Endogenous PAF concentrations in both flunarizine-pretreated (16.6 +/- 4.8  pg/mg protein) and EGb 761-pretreated (33.5 +/- 8.9 pg/mg protein) pups  were significantly lower than the untreated group.

These results indicate  that PAF is an important mediator in immature rat model of cerebral  hypoxic-ischemic injury. The suppressor effect of flunarizine and EGb 761  on PAF production may open new insight into the treatment of  hypoxic-ischemic brain injury. 

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53.)The effect of meclofenoxate with ginkgo biloba extract or zinc on lipid  peroxide, some free radical scavengers and the cardiovascular system of  aged rats. 

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Author 

al-Zuhair H; Abd el-Fattah A; el-Sayed MI 

Address 

Pharmacology Department, Faculty of Pharmacy, King Saud University, Riyadh,  Saudi Arabia. 

Source 

Pharmacol Res, 38(1):65-72 1998 Jul 

Abstract 

Aged rats are highly prone to many physiological changes such as blood  pressure and heart rate. These changes could be due to modification in  membrane phospholipid composition of their blood vessels. Lipid peroxide in  vivo has been identified as a basic deteriorative reaction in cellular  mechanisms of aging in human.

The effect of a nootropic drug, meclofenoxate  (MF) or its combination with extract of ginkgo biloba (EGb-761) or zinc  (Zn) on malondialdehyde (MDA) product as an index of endogenous lipid  peroxidation; phospholipid; glutathione (GSH) and protein thiols (PrSHs)  contents as well as superoxide dismutase (SOD) activity in blood, brain,  heart and liver of 24-month-old male rats was investigated. Aged rats were  treated with MF once daily at oral doses of 100 mg kg-1 body wt. alone or  with either EGb at a dose of 150 mg kg-1 body wt. or Zn at 10.5 mg kg-1  body wt. for 4 weeks.

This study showed that aging caused a higher  increment in MDA level of brain and heart than liver and plasma accompanied  with reduction in brain and heart phospholipid contents as well as  alteration of the antioxidant systems as compared to 4-month-old rats.  Treatment of aged rats with MF alone or combined with either EGb or Zn  caused improvement in the measured free radical scavengers especially in  brain and heart tissues.

Our results also showed that both EGb and Zn  induced a significant potential effect of MF action on blood pressure and  heart rate. The results were explained in the light of the antioxidant  properties of EGb and Zn. Thus it is concluded that EGb and Zn have a  beneficial role with MF in diminishing cumulative oxidative changes in aging. 

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54.)Effects on skeletal muscle fibres of diabetes and Ginkgo biloba  extract treatment. 

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Author 

Punkt K; Psinia I; Welt K; Barth W; Asmussen G 

Address 

Institute of Anatomy, University of Leipzig, Germany. 

Source 

Acta Histochem, 101(1):53-69 1999 Feb 

Abstract 

Combined cytophotometric and morphometric analysis of muscle fibre  properties and myosin  heavy chain electrophoresis were performed on extensor digitorum  longus and soleus muscles  from healthy rats and rats with streptozotocin-induced diabetes.  Moreover, the protective  effect of Ginkgo biloba extract, a potent oxygen radical scavenger, on  diabetic muscles was  investigated.

Changes in fibre type-related enzyme activities, fibre  type distribution, fibre cross  areas and myosin isoforms were found. In muscles of diabetic rats, a  metabolic shift was  measured mainly in fibres with oxidative metabolism. Fast-oxidative  glycolytic fibres showed a  shift to more glycolytic metabolism and about a third transformed into  fast-glycolytic fibres.  Slow-oxidative fibres became more oxidative. Fibre atrophy was  measured in diabetic  muscles dependent on fibre type and muscle. Different fibre types  atrophied to a different  degree.

Therefore, a decreased area percentage of slow fibres and an  increased area  percentage of fast fibres of the whole muscle cross section in both  muscles were found. This is  supported by reduced slow and increased fast myosin heavy chain  isoforms. These alterations  of diabetic muscle fibres could be due to less motion of diabetic rats  and diabetic neuropathy. 

After treatment with Ginkgo biloba extract, enzyme activities were  increased mainly in  oxidative fibres of diabetic muscles, which was interpreted as  protective effect. Generally, the  soleus muscle with predominant oxidative metabolism was more  vulnerable to diabetic  alterations and Ginkgo biloba extract treatment than the extensor  digitorum longus muscle  with predominant glycolytic metabolism. 

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55.)The effects of prostaglandin E2 indomethacin & Ginkgo biloba extract  on resistance to experimental sepsis. 

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Author 

Cant¨urk NZ; Utkan NZ; Cant¨urk Z; Yenisey C; Yildirir C; D¨ulger M 

Address 

Kocaeli University, Faculty of Medicine, Department of Surgery,  Kocaeli, Turkey. 

Source 

Indian J Med Res, 108():88-92 1998 Sep 

Abstract 

We investigated the effect of 16,16-dimethyl prostaglandin E2  indomethacin and Ginkgo  biloba extract on the survival in two experimental sepsis models in  rats due to administration  of 1 x 10(7) cfu and 1 x 10(9) cfu Escherichia coli.

Animals in each  model were then  randomly divided (10/group) into four groups, administered saline,  indomethacin, G. biloba  extract and prostaglandin E2 respectively. When compared, there was no  significant  difference in the survival period between the two sepsis models (P >  0.05). The best survival  rate was observed in the PGE2-administered animals in the first major  model (P < 0.05). 

Indomethacin appeared not to decrease the mortality rates. There was  no significant  difference in PGE2 levels between two sepsis models (P > 0.05). Our  results suggest that  elevated prostaglandin E2 levels following major trauma are not  responsible for the postinjury  increased susceptibility to infectious complications.

Our observations  should also discourage  aggressive use of cyclo-oxygenase inhibitors for protection against  infectious complications  after major trauma. 

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56.) Ginkgo biloba extract protects brain neurons against oxidative stress  induced by hydrogen peroxide. 

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Author 

Oyama Y; Chikahisa L; Ueha T; Kanemaru K; Noda K 

Address 

Laboratory of Cell Signaling (Pharmacology), Faculty of Integrated  Arts and Sciences,  University of Tokushima, Japan. 

Source 

Brain Res, 712(2):349-52 1996 Mar 18 

Abstract 

Effect of Ginkgo biloba extract was examined on dissociated rat  cerebellar neurons suffering  from oxidative stress induced by hydrogen peroxide using a flow  cytometer and ethidium  bromide.

Hydrogen peroxide at a concentration of 3 mM increased the  number of neurons  stained with ethidium (presumably dead neurons) in a time-dependent  manner. Pretreatment  of neurons with G. biloba extract (10 micrograms/ml) greatly delayed a  time-dependent  increase in number of dead neurons during exposure to hydrogen  peroxide.

It was true, but  less effective, in the case of treatment with G. biloba extract  immediately or 60 min after start  of oxidative stress.

Results implicate G. biloba extract as a  potential agent in protecting the  neurons suffering from oxidative stress induced by hydrogen peroxide. 

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DATA-MÉDICOS/DERMAGIC-EXPRESS No 2-(78) 03/11/99 DR. JOSÉ LAPENTA R. 

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A.- HLA-DR Association With the Genetic Susceptibility to Develop Ashy Dermatosis in Mexican Mestizo Patients (2007).

B.- Ashy dermatosis: a review (2019). 

C.- Ashy dermatosis with involvement of mucous membranes (2017).

D. - Skin Weathering and Ashiness in Black Africans (2003).

E. Rare ashy dermatosis-like hyperpigmentation associated with osimertinib (2022). 

F.- A retrospective clinico-pathological study comparing lichen planus pigmentosus with ashy dermatosis (2018). 

G.- Ashy Dermatosis and Lichen Planus Pigmentosus: The Histopathological Differences (2019). 

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1.) "Los cenicientos. Problema Clinico". (The Ashy. Clinical problem) 

2.) "Eritema Discromico Perstans" (Eritema figurado cronico con melanodermia).(Chronic Figured Erythema with Melanodermia) 

3.) Sobre la Etiopatogenia del eritema discrómico perstans (Dermatosis Cenicienta). Posibilidad de una Melanosis Neuro-cutánea 

4.) The ashy dermatosis (erythema dyschromicum perstans) 

5.) Ashy dermatosis or lichen planus pigmentosus: what is in a name? 

6.) ERYTHEMA DYSCHROMICUM PERSTANS (ASHY DERMATOSIS) THE ENTITY 

7.) [Ashy dermatitis. Comments on 2 clinical forms]. 

8.) Unilateral ashy dermatosis occurring in a child. 

9.) [Current status of ashy dermatosis. Synonym--erythema dyschromicum perstans]. 

10.) [Ashy-dermatosis--a case with spontaneous disappearance of the cutaneous lesions]. 

11.) Erythema dyschromicum perstans and lichen planus. 

12.) Ashy dermatosis. An apoptotic disease? 

13.) Ashy dermatosis--a variant of lichen planus? 

14.) Erythema dyschromicum perstans in early childhood. 

15.) Fixed drug eruption presenting as erythema dyschromicum perstans: a flare without taking any medications. 

16.) Reticulate postinflammatory hyperpigmentation with band-like mucin deposition. 

17.) Erythema dyschromicum perstans: report of a new case and critical review of the literature. 

18.) Involvement of cell adhesion and activation molecules in the pathogenesis of erythema dyschromicum perstans (ashy dermatitis). The effect of clofazimine therapy. 

19.) Periorbital hyperpigmentation and erythema dyschromicum perstans. 

20.) Erythema dyschromicum perstans and lichen planus: are they related? 

21.) Erythema dyschromicum perstans. Immunopathologic studies. 

22.) Simultaneously active lesions of vitiligo and erythema dyschromicum perstans. 

23.) Mononuclear cell subpopulations and infiltrating lymphocytes in erythema dyschromicum perstans and vitiligo. 

24.) Chlorothalonil, a possible cause of erythema dyschromicum perstans (ashy dermatitis). 

25.) Lichen planus pigmentosus presenting in zosteriform pattern. 

26.) [Erythema dyschromicum perstans versus lichen planus]. 

27.) Erythema dyschromicum perstans. 

28.) Erythema dyschromicum perstans. 

29.) [Erythema cinitiensis perstans]. 

30.) [Idiopathic eruptive macular pigmentation]. 

31.) [Erythema dyschromicum perstans]. 

32.) Erythema dyschromicum perstans. A follow-up study from northern Finand. 

33.) Ingestion of ammonium nitrate as a possible cause of erythema dyschromicum perstans (ashy dermatosis). 

34.) [Erythema dischromicum perstans (ashy dermatosis). Report of two cases]. Pathologica 1993 Sep-Oct;85(1099):533-41 

35.) [Ashy dermatosis]. 

36.) [Ashy dermatosis. Review of the literature and report of a case]. 

37.) [Ashy dermatosis (erithema dyschromicum perstans): prospective study of 23 patients]. 

38.) Reticulate, patchy and mottled pigmentation of the neck. Acquired forms. 

39.) Lichen planus pigmentosus associated with acrokeratosis of Bazex. 

40.) Ashy dermatosis and lichen planus pigmentosus: a clinicopathologic study of 31 cases. 

41.) [Lichen ruber exanthematicus et pigmentosus in mercury poisoning. A contribution to individual pathology in occupational medicine]. 

42.) [Lichen planus and lichen planus pigmentosus following gold therapy--case reports and review of the literature]. 

43.) Lichen planus pigmentosus of the oral mucosa: a rare clinical variety. 

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1.) "Los cenicientos. Problema Clinico". (The Ashy. Clinical problem) Memoria del Primer Congreso Centro Americano de Dermatologia, San salvador, 

1957:122-130 Ramirez, C.O 

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2.) "Eritema Discromico Perstans" (Eritema figurado cronico con melanodermia).(Chronic Figured Erythema with Melanodermia) 

Dermat. Venezolana, 1961, 2:118-164 

Convit, J., Kerdel-Vegas, F., Rodriguez, G. 

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3.) Sobre la Etiopatogenia del eritema discrómico perstans (Dermatosis Cenicienta). Posibilidad de una Melanosis Neuro-cutánea Derm Venez 1995; 

33:149-151 

Homez-Chacin, 1. Barroso T. 

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4.) The ashy dermatosis (erythema dyschromicum perstans): epidemiological study and report of 139 cases. 

Ramirez C.O. Cutis 1967; 3:244-7 

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5.) Ashy dermatosis or lichen planus pigmentosus: what is in a name? 

Arch Dermatol 1986 Feb;122(2):133 

Bhutani LK 

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6.) ERYTHEMA DYSCHROMICUM PERSTANS (ASHY DERMATOSIS) THE ENTITY 

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SOURCE: Sobre la Etiopatogenia del eritema discrómico perstans (Dermatosis Cenicienta). Posibilidad de una Melanosis Neuro-cutánea 

Derm Venez 1995;33:149-151 Homez-Chacin, 1. Barroso T. 

ABSTRACT 

In 1957 Oswaldo Ramírez, during the First Central-American DermatoIogy  Congress in El Salvador; described for the first time a dermatosis found in  his country wjth the name "The Ashy. Clinical problem". In 1961, Convit et  al. consider this disease as a variant ot erythema perstans and name it  "Chronic Figured Erythema with Melanodermia". this disease was accepted as  new nosologic entity in the Fifth Congress of the Ibero-Latin-American  College of Dermatology in Buenos Aires in 1963 with the name of "Erythema Dyschromicum Perstans". 

According to O. Ramírez. "Erythema Discromicum Perstans (Ashy Dermatosis)  is a chronic skin disease characterized by typical and marked changes in  color of the skin (hyperpigmented macules, black-board gray, variable), of  slow evolution, persistent, with no concomitant local alterations, but  which sometimes have repercussions on the psychic state of the patient,  according to the size of the lesion. It is not accompanied by any other  cutaneous or symptomatic abnormality. It is not influenced by climate,  racial, dietary or occupational factors". This dermatosis can appear at any  age, from one to eighty years. Either sex can be equally affected, even  though it is more frequent in females. lnitially lesions are localized,  but they can become generalized, not involving scalp, annexes or  palmo-plantar regions. 

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7.) [Ashy dermatitis. Comments on 2 clinical forms]. 

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Med Cutan Ibero Lat Am 1986;14(2):95-9 

Carvajal Huerta L, Uraga Pazmino E, Loayza Vivanzo E, Sabando Sanchez R,  Garcia Atiaga I, Jeny E 

The typical clinical characteristic of the ashy dermatitis is the fact that  in case of light colored skin, the grey colour remains invariable. There is  a new clinical form which is called the Brown Cinder Dermatitis which is  characterized by a disciplined localization in the center of the face,  trunk or upper extremities together with an inexorable change of the grey  colour at the beginning to a brown colour at the end on the other it, has  be enhanced the existence of the nummular form which is characterized by  the existence of many greyish independent spots of circular or oval form  mainly at the level of the trunk. 

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8.) Unilateral ashy dermatosis occurring in a child. 

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Arch Dermatol 1984 Nov;120(11):1491-3 

Urano-Suehisa S, Tagami H, Iwatsuki K 

An unusual case of ashy dermatosis of Ramirez occurred in a 5-year-old-girl  who had ash-colored hyperpigmented macules and plaques on the left leg and  the left side of the trunk. These unilateral lesions showed histopathologic  changes of a lichenoid tissue reaction. Although the exact cause of ashy  dermatosis remains unknown, the positive test result for serum rheumatoid  factor and the granular deposition of IgM at the dermoepidermal junction  found in our case has immunologic implications. 

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9.) [Current status of ashy dermatosis. Synonym--erythema dyschromicum perstans]. 

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Med Cutan Ibero Lat Am 1984;12(1):11-8 

[Article in Spanish] 

Ramirez O, Lopez Lino DG 

A clinical, histopathological, therapeutical and epidemiologic review of  Ashy Dermatosis is done. This research has been taken from scientific  publications, computers and personal communications. In twenty five years  of scientific medical investigations it has not been determined its truth  etiology , nor its therapeutic; this confirms it, as a new nosologic entity  well defined.

The epidemiologic researches are concludent that this is not  a tropical disease exclusively, but one of all over the world. We hope to  obtain more references on this dermatosis throughout the Sessions of 

Specialties of CILAD regarding this disease. 

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10.) [Ashy-dermatosis--a case with spontaneous disappearance of the cutaneous  lesions]. 

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Z Hautkr 1983 Jan 15;58(2):113-20 

[Article in German] 

Schneider I, Varga M, Zombai E, Husz S 

A 14-years-old girl suddenly developed typical dermal signs of  ashy-dermatosis at the time of menarche. After one year, the signs began to  fade and had disappeared completely two years later. The direct  immunofluorescence and the ultrastructure resemble lichen planus. Endocrine  factors may have played a part in the presented case, considering the  sudden onset at the time of menarche. 

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11.) Erythema dyschromicum perstans and lichen planus. 

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Arch Dermatol 1982 Sep;118(9):683-5 

Naidorf KF, Cohen SR 

Erythema dyschromicum perstans (EDP) is a cutaneous pigmentary disturbance  originally considered to be a variant of erythema perstans. The nosologic  identity of EDP has been challenged repeatedly as the number of patients  with concurrent EDP-like eruptions and lichenoid disorders has increased.  In this report, we describe a woman who had EDP for two years before the  onset of classic lichen planus (LP).

The active lesions of LP gradually  evolved into typical ashy-gray macules of EDP. This case provides further  support for the concept that EDP and EDP-like conditions should be  classified, in certain instances, as erythema dyschromicum variants of LP. 

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12.) Ashy dermatosis. An apoptotic disease? 

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Arch Dermatol 1981 Nov;117(11):701-4 

Person JR, Rogers RS 3d 

Of nine patients with ashy dermatosis, eight were women; most were young  adults when the dermatosis began. The incidences of atopy (five patients)  and thyroid disease (three patients) were striking.

Although some of the  patients were clinically atypical, histologic study in all cases showed  basal cell vacuolation, Civatte bodies, pigmentary incontinence, and a mild  perivascular lymphohistiocytic infiltrate. Direct immunofluorescence  microscopy, performed in four cases, showed igM cytoid bodies. We  hypothesize that the postinflammatory hyperpigmentation in ashy dermatosis  and, perhaps, in other dermatoses may occur on the basis of basal cell 

apoptosis. 

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13.) Ashy dermatosis--a variant of lichen planus? 

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Cutis 1980 Jun;25(6):631-3 

Kark EC, Litt JZ 

Immunofluorescence studies on a patient with clinical and histological  evidence of ashy dermatosis revealed a pattern commonly associated with  lichen planus. In view of these findings, the possibility of a relationship  between ashy dermatosis and lichen planus is suggested. 

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14.) Erythema dyschromicum perstans in early childhood.  J Dermatol 1999 Feb;26(2):119-21 

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Lee SJ, Chung KY 

Department of Dermatology, Yonsei University College of Medicine, Seoul,  Korea. 

Erythema dyschromicum perstans (EDP) is a rare disorder characterized by  asymptomatic, slowly progressive, ash-gray macular pigmentation of the skin  which usually occurs from age 5 through adult life.

We have experienced two  cases of EDP in children aged 2 and 3, both exceptionally younger than the  previously reported cases. We therefore suggest that EDP should be included  in the differential diagnosis of pigmentary disorders occurring at an early  age. 

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15.) Fixed drug eruption presenting as erythema dyschromicum perstans: a flare  without taking any medications. 

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Dermatology 1998;197(4):383-5 

Mizukawa Y, Shiohara T 

Department of Dermatology, Kyorin University School of Medicine, Tokyo,  Japan. 

Fixed drug eruption (FDE) can present as multiple pigmented macules that  flare at fixed sites even when the patient has taken no medications.  Although this presentation is not characteristic of FDE, it must be borne  in mind in order to make a correct diagnosis. We describe such a patient  whose condition was initially diagnosed as erythema dyschromicum perstans  (EDP). Immunohistochemically intraepidermal T cells were distributed  between basal and suprabasal keratinocytes in the lesional skin, a finding  suggestive of FDE.

A flare occurred not only with exposure to theophylline  but also without exposure. A flare has never recurred and pigmented macules  faded gradually after avoiding theophylline. On the basis of these  findings, we recommend that patients with an EDP-like presentation be  examined completely for causes such as drugs before labeling the cutaneous  lesions. 

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16.) Reticulate postinflammatory hyperpigmentation with band-like mucin deposition. 

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Int J Dermatol 1998 Nov;37(11):829-32 

Noto G, Pravata G, Arico M 

Department of Dermatology, University of Palermo, Policlinico P. Giaccone,  Italy. 

BACKGROUND: Mucinoses of the skin are a group of disorders sharing  accumulation of mucin in the skin or hair follicles. Postinflammatory  hyperpigmentation, with pigmentary incontinence, is due to loss of melanin  from epidermal basal cells and its accumulation in dermal macrophages.  METHODS: We describe clinicopathologic features of two patients presenting  with the association of pigmentary incontinence with an unusual diffuse,  band-like dermal deposition of mucin, clinically presenting with reticular  pigmented macular lesions.

RESULTS: Two patients were observed with  asymptomatic, persistent, reticular, pigmented patches located in the  flexures, thighs, neck and back. Histology showed melanophages with a  diffuse, band-like dermal deposition of mucin, an increased number of  fibroblasts, a slight T-cell infiltrate and scattered mast cells. Blood  markers of lupus erythematosus were negative.

CONCLUSIONS: These findings  may draw attention to pigmentary disorders such as lichen planus  pigmentosus, erythema dyschromicum perstans, pigmentatio maculos eruptiva  idiopathica, dermatopathia pigmentosa reticularis, prurigo pigmentosa and  frictional melanosis.

None of these entities, however, includes mucin  deposition among its microscopic features. Macules were not preceded by  erythema or any other lesions. We suggest that our cases could belong to  group II of Rongioletti and Rebora's classification, i.e. they could be  cases of secondary mucin deposition in postinflammatory hyperpigmentation,  possibly in an unusual form of lichen planus pigmentosus or, less likely,  frictional melanosis. 

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17.) Erythema dyschromicum perstans: report of a new case and critical review of  the literature. 

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J Dermatol 1998 Nov;25(11):747-53 

Combemale P, Faisant M, Guennoc B, Dupin M, Heyraud JD 

Department of Dermatology, Military Hospital Desgenettes, Lyon, France. 

Erythema dyschromicum perstans (EDP), described by Convit et al. in 1961,  is a rare dermatosis. Its relationship with ashy dermatosis (AD), described  by Ramirez in 1957, is still a matter of debate.

We report a typical case  of EDP. The patient, of North African origin, had a dyschromic (hypo- and  hyperpigmented) eruption on the chest and limbs for 2 years. The lesions  were occasionally surrounded by a papular border which spread slowly and  centrifugally. Histological examination showed a lichenoid infiltrate. A  carcinoma of the lung was simultaneously discovered.

No treatment was  given, EDP is infrequent and often considered identical to ashy dermatosis  in the literature. However, the clinical aspects of the two diseases  differ. The main features of these two diseases are reviewed and compared  on the basis of a literature review. We conclude that EDP and AD are  distinct clinical entities. 

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18.) Involvement of cell adhesion and activation molecules in the pathogenesis  of erythema dyschromicum perstans (ashy dermatitis). The effect of  clofazimine therapy. 

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Arch Dermatol 1997 Mar;133(3):325-9 

Baranda L, Torres-Alvarez B, Cortes-Franco R, Moncada B, Portales-Perez DP,  Gonzalez-Amaro R 

Department of Immunology, School of Medicine, University of San Luis  Potosi, Mexico City, Mexico. 

OBJECTIVES: To assess the expression of several cell adhesion and  lymphocyte activation molecules in erythema dyschromicum perstans lesions,  and to evaluate the effect of clofazimine therapy on the expression of  these molecules.

DESIGN AND METHODS: A prospective study. Skin biopsy  samples were obtained from patients before and after 3 months of  clofazimine therapy, and the expression of cell adhesion and activation  molecules was assessed by an immunohistochemical technique.

SETTING: This  study was performed in a clinical referral center and an immunology  research laboratory.

PATIENTS: We studied 6 patients with erythema  dyschromicum perstans. A diagnosis was made on the basis of clinical and  histological criteria. Two patients discontinued participation in the  study: one because of adverse effects and the other for unknown reasons. 

INTERVENTIONS: Patients were treated with clofazimine, 100 mg/d, for 3  months.

MAIN OUTCOME MEASURES: Expression of cell adhesion and lymphocyte  activation molecules in skin biopsy specimens before and after clofazimine  therapy. RESULTS: Before clofazimine therapy, we detected a noticeable  expression of intercellular adhesion molecule 1 and major  histocompatibility complex class II molecules (HLA-DR) in the keratinocyte  basal cell layer. In addition, CD36, a thrombospondin receptor that is not  expressed by normal skin, was detected in the strata spinosum and  granulosum. The dermal cell infiltrate expressed the activation molecule  AIM/CD69 and the cytotoxic cell marker CD94. After clofazimine therapy, the  expression of intercellular adhesion molecule 1 and HLA-DR disappeared, as  well as the mononuclear cell infiltrate.

CONCLUSIONS: Our results suggest  that some cell adhesion and activation molecules are involved in the  pathogenesis of erythema dyschromicum perstans. Clofazimine appears to have  an important effect on the inflammatory phenomenon of erythema dyschromicum  perstans. 

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19.) Periorbital hyperpigmentation and erythema dyschromicum perstans. 

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Can J Ophthalmol 1992 Dec;27(7):353-5 

Ing EB, Buncic JR, Weiser BA, de Nanassy J, Boxall L 

University of Toronto, ON. 

Erythema dyschromicum perstans is a rare idiopathic dermatosis  characterized by ash-grey, well-demarcated skin lesions, which may involve  the face.

We describe an 8-year-old girl with erythema dyschromicum  perstans presenting as bilateral acquired periorbital hyperpigmentation.  The changes seen on histologic study of a skin biopsy specimen were  consistent with the clinical diagnosis. The various causes of periorbital  hyperpigmentation and characteristics of erythema dyschromicum perstans are  reviewed. 

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20.) Erythema dyschromicum perstans and lichen planus: are they related? 

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J Am Acad Dermatol 1989 Aug;21(2 Pt 2):438-42 

Berger RS, Hayes TJ, Dixon SL 

Wilford Hall USAF Medical Center, Lackland Air Force Base, Texas. 

A 53-year-old woman initially had lichen planus primarily on her  extremities. Approximately 1 year later, lesions consistent with erythema  dyschromicum perstans were observed. Both diseases cleared with  griseofulvin therapy but returned after discontinuation of the drug.  Retreatment with griseofulvin again resulted in clearing. 

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21.) Erythema dyschromicum perstans. Immunopathologic studies. 

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J Am Acad Dermatol 1989 May;20(5 Pt 2):882-6 

Miyagawa S, Komatsu M, Okuchi T, Shirai T, Sakamoto K 

Department of Dermatology, Nara Medical University, Japan. 

Immunopathologic studies of a patient with clinical and histologic evidence  of erythema dyschromicum perstans revealed Ia antigen expression on  epidermal keratinocytes, pronounced OKT4 and OKT6 staining of epidermal  dendritic cells, and dermal infiltration of T lymphocytes of both  helper-inducer (OKT4) and suppressor-cytotoxic (OKT8) phenotypes--a pattern  commonly associated with lichen planus. These findings, taken in  conjunction with positive IgG staining on colloid bodies, suggest the  possibility that erythema dyschromicum perstans and lichen planus have  similar disease processes. 

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22.) Simultaneously active lesions of vitiligo and erythema dyschromicum perstans. 

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Arch Dermatol 1988 Aug;124(8):1258-60 

Henderson CD, Tschen JA, Schaefer DG 

Departments of Pathology, Baylor College of Medicine, Houston, Tex. 

Recently, a patient presented to us with skin that had areas of normal  pigmentation, hyperpigmentation, and depigmentation. Workup eventually  showed him to have simultaneously active lesions of a depigmenting  disorder, vitiligo, and a hyperpigmenting disorder, erythema dyschromicum  perstans. 

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23.) Mononuclear cell subpopulations and infiltrating lymphocytes in erythema  dyschromicum perstans and vitiligo. 

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Histol Histopathol 1987 Jul;2(3):277-83 

Gross A, Tapia FJ, Mosca W, Perez RM, Briceno L, Henriquez JJ, Convit J 

Institut of Biomedicine, Caracas, Venezuela. 

Erythema dyschromicum perstans (EDP) and vitiligo are two cutaneous  pigmentary dermatoses of unknown etiology. In the present study, the  leukocyte infiltrates in the affected skin of EDP and vitiligo patients  were studied using the avidin-biotin (ABC) immunoperoxidase technique and  monoclonal antibodies which recognise the following mononuclear cell  subgroups: T-suppressor/cytotoxic (CD8-Leu-2), T-helper (CD4 = OKT4),  T-suppressor + macrophages (Leu-15), Pan T (CD3 = Leu-4), macrophages  (Leu-M3) and Langerhans cells (CD1 = Leu-6), and other cellular markers  such as Ia antigens and the Interleukin-2 receptor (CD25 = TAC).

The  immunocytochemical analysis showed a selective accumulation of CD3+, CD8+,  Leu-15-, T-cytotoxic cells in the epidermis of both EDP and early lesions  of vitiligo.

In addition, an increase in the number of epidermal Langerhans  cells (CD1+) was observed in some cases of EDP and vitiligo. The CD4/CD8  ratios in affected and uninvolved skin for both disorders were not  significantly different, although values lower than unity were only  observed in the infiltrates of affected skin. Ia antigen positivity was  observed in the dendritic cells of the dermis and epidermis, as well as in  most of the lymphoid cells within the infiltrates for both diseases.  Macrophages (Leu-M3) in EDP dermal infiltrates were generally found  adjacent to extracellular melanin pigment.

Lymphocytes expressing TAC  (CD25) surface antigens were also present in the dermal infiltrates. These  morphological observations suggest a possible immune cell participation in  the dyschromia of such cutaneous disorders. 

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24.) Chlorothalonil, a possible cause of erythema dyschromicum perstans (  ashy dermatitis). 

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Penagos H; Jimenez V; Fallas V; O'Malley M; Maibach HI 

Occupational Dermatology Service, Social Security Hospital, Panama. 

Contact Dermatitis (DENMARK) Oct 1996 35 (4) p214-8 ISSN: 0105-1873 

Language: ENGLISH 

Document Type: JOURNAL ARTICLE 

Journal Announcement: 9705 

Subfile: INDEX MEDICUS 

We studied 39 patients with erythema-dyschromicum-perstans-like  dermatitis seen at Changuinola Hospital in Panama. They were compared  with 41 controls.

The 2 groups were native field workers of the banana  plantations exposed to many pesticides. In 34 patients, there was a  positive patch test reaction to 2,4,5,6-1,3-  tetrachloroisophthalonilnitrile (chlorothalonil, TCPN) 0.001% in acetone.  In 39 cases, biopsies showed a lichenoid tissue reaction compatible with a  chronic pigmented dermatitis or erythema-dyschromicum-perstans-like  dermatitis.

Chlorothalonil is possibly the cause of the pigmented  dermatitis observed in the 39 banana farm workers studied. Until  additional studies are carried out, we consider this a possible rather  than definite cause-and-effect relationship. 

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25.) Lichen planus pigmentosus presenting in zosteriform pattern. 

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Cho S; Whang KK 

Department of Dermatology, College of Medicine, Ewha Womans University, 

Seoul, Korea. 

J Dermatol (JAPAN) Mar 1997 24 (3) p193-7 ISSN: 0385-2407 

Language: ENGLISH 

Document Type: JOURNAL ARTICLE 

Journal Announcement: 9709 

Subfile: INDEX MEDICUS 

Lichen planus pigmentosus (LPP) has thus far been described as a  condition of unknown etiology which clinically differs from the classical  lichen planus (LP) by exhibiting dark brown macules and/or papules mostly  in exposed areas and flexural folds and a longer clinical course without  pruritus or scalp, nail or mucosal involvement.

Histopathologically, LPP  shows the typical changes seen in LP, but with thinning of epidermis. We  report a case of LPP that developed in a unilateral, zosteriform pattern  on the left flank of a 49-year-old man.

This case seems to lie in the  middle of the spectrum between classical LP and ashy dermatosis, and, to  the best of our knowledge, is the first report of LPP presenting in the  zosteriform pattern. 

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26.) [Erythema dyschromicum perstans versus lichen planus]. 

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Med Cutan Ibero Lat Am 1987;15(1):89-92 

Leonforte JL, Pelaez de di Bari O 

Erythema dyschromicum perstans and lichen planus have been regarded as  related. We describe the case of a 41 year old man presenting a relapsing  dermatitis consisting of erythematous patches leaving behind ashy-gray  macules. The lesions of lichen planus were atypical and the ashy dermatosis  was transient. The possibility that some cases of lichen planus lead to an  erythema dyschromicum perstans is discussed. 

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27.) Erythema dyschromicum perstans. 

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Cutis 1986 Jan;37(1):42-4 

Lambert WC, Schwartz RA, Hamilton GB 

A 29-year-old woman from Trinidad experienced the rapid onset of extensive  lesions characteristic of erythema dyschromicum perstans following an x-ray  study using orally administered contrast.

Eleven months later a skin biopsy  specimen showed few epidermal changes but extensive incontinence of melanin  pigment and marked dilatation of lymphatics in the superficial dermis.  Results of a systemic evaluation were normal. The available data on this  disease are analyzed and conclusions offered regarding its nature and causes. 

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28.) Erythema dyschromicum perstans. 

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J Am Acad Dermatol 1980 Apr;2(4):295-302 

Tschen JA, Tschen EA, McGavran MH 

Erythema dyschromicum perstans (EDP) was first described in 1957, and  electron microscopic studies were reported in 1969. Herein, we describe  five cases and compare light and electron microscopic findings, direct and  indirect immunofluorescence, and dopa-positive melanocyte counts between  normal and affected skin.

The results indicate that EDP is a clinically  characteristic disorder with a lichenoid reaction in its active phase. This  lichenoid reaction leads to a pronounced incontinence of pigment and to  decreased numbers of melanocytes and of tyrosinase activity in the involved  epidermis. These findings support the suggestion that EDP and lichen planus  pigmentosus are possible the same entity.

Direct inmunofluorescence and  fine structural studies show similar findings to lichen plunus. Patients  have low-titer antibodies to extranuclear basal cell components. 

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29.) [Erythema cinitiensis perstans]. 

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Med Cutan Ibero Lat Am 1980;8(1-3):11-4 

Sittart JA, Tayah M 

The authors report a case of Erythema Cinitiensis Perstans, in a thirty-one  years old white man. This dermatosis, reported in the literature also es  Ashy Dermatitis and Erythema Dyschromicum Perstans, is here in Brazil  exceptional. Clinically this dermatosis is characterized by the presence of  gray patches in a sometimes surrounded by an erythematous active border.  The lesions may occur on any area of the integument, sparing the hair  scalp, palms, soles and nails.

The therapy has been ineffective in all the  cases, but one reported by Stevenson and Miura and in our case, where the  patients have improved after Dithiazanine iodide treatment due to  intestinal parasitoses by the Tricocephalus trichiurus. 

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30.) [Idiopathic eruptive macular pigmentation]. 

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Ann Dermatol Venereol 1978 Feb;105(2):177-82 PORTUGAL 

Degos R, Civatte J, Belaich S 

The feeling of the authors is that their seven reported cases of a  pigmented dermatosis are different from the ashy dermatosis and from the  erythema dyschromicum perstans.

This disease, which affects children and  teenagers, males as well as females, is characterized by pigmented macules  5-25 mm in diameter, affecting the neck, the trunk and the limbs. The first  symptom is whether a pigmented spot, or an erythematous, papular or  achromic lesion; in the latter instance the pigmentation occurs only  secundarily. In most of the cases this dermatose is slowly and  spontaneously regressive.

The histological picture is not really specific.  In one case there was a marked intraepidermal dyskeratosis of the sweat  duct openings. The etiology remains unknown. 

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31.) [Erythema dyschromicum perstans]. 

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Hautarzt 1977 Oct;28(10):539-41 

Moller-Vietheer M, Goos M 

The case of a 4 1/2 year old girl with the typical clinical picture of  erythema dyschromicum perstans is presented. A survey of the literature on  this dermatosis is described. 

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32.) Erythema dyschromicum perstans. A follow-up study from northern Finand. 

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Dermatologica 1977;155(1):40-4 

Palatsi R 

Four patients with ashy dermatosis are described. Their ages varied from 8  to 12 years. Three had typical widespread macular eruptions and one had a  linear lesion not described before. The follow-up investigation revealed  that the eruption disappeared within 2 years in three of the patients. One  patient could not be followed. The duration of the disease and the  linearity of one lesion resembled lichen ruber planus. 

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33.) Ingestion of ammonium nitrate as a possible cause of erythema dyschromicum  perstans (ashy dermatosis). 

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Dermatologica 1975;150(5):287-91 

Jablonska S 

Clinically and histologically typical erythema dyschromicum perstans has  been provoked by repeated ingestion of very small amounts of a fertilizer,  ammonium nitrate.

It has been used by a boy who has noticed accidentally  that after licking the fertilizer he developed hyperpigmentations. His main  purpose was to avoid school attendance, and he developed a very ingenious  method of licking the fertilizer once in several weeks in such a way that  it did not produce any digestive or other troubles.

His brother, an  uniovular twin who had no contact with ammonium nitrate, was healthy. The  case supports Pinkus' hypothesis that this type of lesions may be related  to some environmental contaminant. Attention is called to a possible food  contamination by ammonium nitrate. 

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34.) [Erythema dischromicum perstans (ashy dermatosis). Report of two cases].  Pathologica 1993 Sep-Oct;85(1099):533-41 

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[Article in Italian] 

Paradisi M, Mostaccioli S, Celano G, Angelo C, Ruatti P, Ferranti G, Onetti 

Muda A, Faraggiana T 

IV Divisione e Dermatologia Pediatrica, IDI-IRCCS, Roma. 

Clinical, histological and ultrastructural investigations of two cases of  Erythema Dischromicum Perstans (EDP) are reported. EDP is a chronic  pigmented lesion of the skin, and its etiology is still unknown. The  reported cases showed clinical and ultrastructural differences from what  already described in the literature.

EDP is also difficult to differentiate  from other cutaneous pigmented lesions: clinical and morphologic  differences and/or similarities are therefore discussed and compared. The  usefulness for a correct diagnosis of the co-existence of optical and  ultrastructural lesions which are not pathognomonic per se, is also stressed. 

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35.) [Ashy dermatosis]. 

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Vestn Dermatol Venerol 1989;(11):57-8 

[Article in Russian] 

Kasimov N, Kiiamov FA, Naimova MR 

Five patients with ashy dermatitis are described, aged 6 to 14, one boy and  four girls. The process is characterized by dirty grayish or  ash-gray-colored maculae on the skin of the trunk and limbs.

These maculae  do not tend to fuse, nor exfoliate; they are not associated with any  subjective sensations. Thorough examinations have not revealed any  osteomuscular or visceral abnormalities.

The disease runs a benign course,  and only the cosmetic defect worries the patients. 

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36.) [Ashy dermatosis. Review of the literature and report of a case]. 

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Med Cutan Ibero Lat Am 1988;16(1):31-6 

[Article in Portugese] 

de Azevedo LM, Porto JA 

Servico de Dermatologia do Hospital Universitario Pedro Ernesto, da  Universidade do Estado do Rio de Janeiro. 

The authors make a review of the epidemiologic, etiopathogenic, clinical,  laboratory and therapeutic aspects of ashy dermatosis, described in 1957 by  Ramirez in El Salvador, of which more than 150 cases have been described up  to now in different continents. The disease is exclusively cutaneous,  presents peculiar clinical features with a lichenoid tissue reaction, and  has no specific treatment or known etiology.

The authors report a case in a  Brasilian man, followed up for three years. The treatment of a T. trichiura  infestation did not change the cutaneous features, as opposed to what has  been reported. 

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37.) [Ashy dermatosis (erithema dyschromicum perstans): prospective study of 23  patients]. 

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Med Cutan Ibero Lat Am 1988;16(5):407-12 

[Article in Spanish] 

Navarro Jimenez BR, Sanchez Navarro LM 

Servicio de Dermatologia, Universidad Autonoma, Benito Juarez, Oaxaca,  Mexico. 

During the period between january 1984 to july 1987 in the Hospital Unit  "Presidente Juarez" ISSSTE, Oaxaca (Mexico), for the first time was given  dermatology consult to 2,683 patients among them, 23 who had ashy  dermatosis (Erithema dyschromicum perstans), a study was done for the  present time and the future of the same, discarding it as possible cause of  that nosological entity: treponemal disease, parasitic, infectious, hepatic  and renal.

It is commented in relation with the ashy dermatosis and lichen  planus, the clinicals variants and the possible sun etiology. 

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38.) Reticulate, patchy and mottled pigmentation of the neck. Acquired forms. 

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Dermatology 1998;197(3):291-6 

Lautenschlager S, Itin PH 

Outpatient Clinic of Dermatology, Triemli Hospital, Zurich, Switzerland. 

Besides the inherited forms of mottled and reticulate pigmentation, a vast  number of diseases and trigger mechanisms can lead to acquired pigmentation  of the neck. Nonhereditary variants of reticulate and mottled pigmentation  can affect the neck as a typical site and therefore may give a diagnostic  clue or it can occur sporadically on the neck as well as on other sites. A  well-known and important factor in the pathogenesis is exposure to  sunlight.

Sun-induced pigmentation often presents on the neck and may  result from phototoxic, photoallergic and cumulative actinic damage.  Frequent forms comprise berloque dermatitis, Riehl's melanosis,  poikiloderma of Civatte and tanning bed lentigines. Different infections  may also lead to this distinct skin alteration as pediculosis capitis,  pityriasis versicolor and syphilis II.

Treatment-induced irregular  pigmentations may occur after applications of topical agents (e.g.  diphenylcyclopropenone), systemic medication (e.g. 5-fluorouracil,  chlorpromazine), as a complication of laser resurfacing or as a chronic  graft-versus-host reaction. Different neoplasms may also involve the neck.  Widespread pigmented basal cell carcinoma, cutaneous T-cell lymphoma,  syringolymphoid hyperplasia and histiocytic diseases may lead to  reticulated pigmentation.

Various other infrequent conditions as connective  tissue diseases, malnutrition, lichen planus pigmentosus and others are  summarized. The neck, a readily accessible site to medical inspection, may  have an underestimated value for the diagnosis of different skin diseases. 

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39.) Lichen planus pigmentosus associated with acrokeratosis of Bazex. 

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Clin Exp Dermatol 1994 Jan;19(1):70-3 

Sassolas B, Zagnoli A, Leroy JP, Guillet G 

Department of Dermatology, C.H.U. Brest, France. 

A patient with an acquired pigmentation related to lichen planus  pigmentosus is described. Features of acrokeratosis of Bazex were  associated, related to a head and neck carcinoma. Both cutaneous conditions  disappeared after treatment of the neoplasia. Diagnostic criteria of lichen  planus pigmentosus are reviewed. The paraneoplastic nature of this original  observation of lichen planus pigmentosus is discussed. 

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40.) Ashy dermatosis and lichen planus pigmentosus: a clinicopathologic study of  31 cases. 

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Int J Dermatol 1992 Feb;31(2):90-4 

Vega ME, Waxtein L, Arenas R, Hojyo T, Dominguez-Soto L 

Department of Dermatology, Hospital General Dr. Manuel Gea Gonzalez, Mexico  City, Mexico. 

The clinical and histopathologic characteristics of patients with ashy  dermatosis (n = 20) and lichen planus pigmentosus (n = 11) were analyzed.  We found significant clinical differences between both dermatoses,  supporting our opinion that they are two separate conditions. Both  dermatoses were histologically similar. 

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41.) [Lichen ruber exanthematicus et pigmentosus in mercury poisoning. A  contribution to individual pathology in occupational medicine]. 

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Z Hautkr 1990 Nov;65(11):1013-8, 1021 

[Article in German] 

Marsch WC, Groebe G 

Zentrum der Dermatologie und Venerologie, Abteilung I, Johann Wolfgang  Goethe-Universitat, Frankfurt am Main. 

We report on a 21-year-old man professionally exposed to mercury, who  developed lichen planus. This case must be regarded as a dispositional  reaction and is in Germany entitled to indemnification in terms of a  "quasi-occupational disease".

The clinical signs and the probably  non-allergic pathomechanism are comparable with those of lichen planus  induced by gold. In diseases due to occupational intoxication, we face an  individual disposition regarding the degree of clinical symptoms, which has  to underly any expert opinion on indemnity. 

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42.) [Lichen planus and lichen planus pigmentosus following gold therapy--case  reports and review of the literature]. 

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Z Hautkr 1986 Mar 1;61(5):315-9 

[Article in German] 

Ingber A, Weissmann-Katzenelson V, David M, Bialowons M, Feuerman EJ  We report on two typical cases of lichen planus and lichen pigmentosus  appearing after gold therapy. The characteristics of lichen planus induced  by drugs are emphasized, and the literature is reviewed. 

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43.) Lichen planus pigmentosus of the oral mucosa: a rare clinical variety. 

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Dermatologica 1981;162(1):61-3 

Laskaris GC, Papavasiliou SS, Bovopoulou OD, Nicolis GD 

In this paper, we describe a case of lichen planus of the mouth with  intense melanosis, in a middle-aged white male. Due to its unusual clinical  characteristics, we believe that this case represents a rare variant of  lichen planus of the oral mucosa. The histopathologic findings,  differential diagnosis and its possible connection with lichen planus  pigmentosus of the skin are discussed. 

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DATA-MÉDICOS/DERMAGIC-EXPRESS No 2-(78) 03/11/99 DR. JOSÉ LAPENTA R. 

UPDATED 15 JUNE 2025

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Produced by Dr. José Lapenta R. Dermatologist

Venezuela 1.998-2.025

Producido por Dr. José Lapenta R. Dermatólogo Venezuela 1.998-2.025

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