EDITORIAL ESPANOL:

====================

Saludos, amigos de la red, DERMAGIC en esta ocasión con una revisión de LA PENTOXIFILINA (TRENTAL), medicamento muy utilizado en numerosas patologías dermatológicas y no dermatológicas. Estas 56 referencias nos hablan sobre sus mecanismos de acción y algunas de las enfermedades donde se esta utilizando. Al final una monografía del producto.

Bienvenidos a DERMAGIC: Dr. pedro Pinto, (ESPAñA), Armando Mocci (PANAMÁ), David Rosenfeld (PARAGUAY),

Saludos a TODOS,,, 

PRÓXIMA EDICIÓN: CARCINOMA DE MERKEL !!

Dr. José Lapenta R.,,,

 EDITORIAL ENGLISH:

===================

Hello Friends of the DERMA Cyber, DERMAGIC with the first delivery of the

year brings this interesting topic on THE ANDROGENIC ALOPECIA. I found 43

references that illustrate us very well this topic that never left of

being of interest for all. 

Some years ago it was said in the jargon: "alone the floor stops the fall

of the hair". Today we can say that with a pill (finasteride) and a lotion

(minoxidil), the thing change radically. 

Happy New year for all !!!! 

Dr. José Lapenta R. 

======================================================================

DERMAGIC/EXPRESS(37)

======================================================================

LA PENTOXIFILINA / THE PENTOXIFYLLINE

======================================================================

1.) New developments in the treatment of systemic vasculitis. 

2.) Chilblain lupus erythematosus (lupus pernio): clinical review of the

Mayo Clinic experience and proposal of diagnostic criteria. 

3.) [Vernet's syndrome as an early manifestation of systemic erythematous

lupus] 

4.) [Favorable in vitro effect of pentoxifylline on damaged lymphocyte

migration in arteriosclerosis obliterans and systemic lupus erythematosus

(see comments)] 

5.) Effect of pentoxifylline on decreased in vitro mononuclear leucocyte

chemotaxis in vascular and polysystemic autoimmune diseases. 

6.) Effect of pentoxifylline on the course of systemic Candida albicans

infection in mice. 

7.) [Current status and trends in treatment of scleroderma] 

8.) [New properties of trental as an inhibitor of viral activity with a

wide range of activity] 

9.)[Lymphotropic therapy with trental in the treatment of chronic herpetic

stomatitis] 

10.) A double-blind, randomized, placebo-controlled, crossover trial of

pentoxifylline for the prevention of chemotherapy-induced oral mucositis. 

11.) Vasculitis. 

12.) Improvement of acral circulation in a patient with systemic sclerosis

with stellate blocks. 

13.) Effects of pentoxifylline on hemodynamics and oxygenation in septic

and nonseptic patients. 

14.) Antiproliferative effect of pentoxifylline on psoriatic and normal

epidermis. In vitro and in vivo studies. 

15.) Antineoplastic effect of the xanthine derivative Trental. 

16.) Treatment of experimental frostbite with pentoxifylline and aloe vera

cream.

17.) High-dose pentoxifylline in patients with AIDS: inhibition of tumor

necrosis factor production. National Institute of Allergy and Infectious

Diseases AIDS Clinical Trials Group.

18.) Pentoxifylline as a supportive agent in the treatment of cerebral

malaria in children.

19.) Pentoxifylline inhibits tumor necrosis factor-alpha (TNF

alpha)-induced T-lymphoma cell adhesion to endothelioma cells.

20.) Pharmacotherapy of Raynaud's phenomenon. 

21.) Severe idiopathic recurrent aphthous stomatitis: treatment with

pentoxifylline [letter]

22.) Pentoxifylline for Sweet's syndrome [letter; comment]

23.) Urticarial vasculitis syndrome effectively treated with dapsone and

pentoxifylline.

24.) Schamberg's purpura: association with persistent hepatitis B surface

antigenemia and treatment with pentoxifylline.

25.) The use of pentoxifylline in the treatment of systemic sclerosis and

lipodermatosclerosis: a unifying hypothesis? [letter; comment]

26.) Pentoxifylline [see comments]

27.) Toxic epidermal necrolysis. Treatment with pentoxifylline [letter]

28.) Pentoxifylline for the treatment of infection with human

immunodeficiency virus.

29.) Inhibition of collagen lattice contraction by pentoxifylline and

interferon-alpha, -beta, and -gamma.

30.) Long-term pretreatment with pentoxifylline increases random skin flap

survival.

31.) Angiolymphoid hyperplasia with eosinophilia may respond to

pentoxifylline.

32.) Chronic balanitis with palisading granuloma: an atypical genital

localization of necrobiosis lipoidica responsive to pentoxifylline.

33.) Pentoxifylline for ischemic pain in pseudoxanthoma elasticum.

34.) Pentoxifylline suppresses irritant and contact hypersensitivity

reactions.

35.) Ulcerating necrobiosis lipoidica effectively treated with pentoxifylline.

36.) Generalised granuloma annulare successfully treated with pentoxifylline.

37.) Intractable chronic furunculosis: prevention of recurrences with

pentoxifylline.

38.) Successful treatment of Kasabach-Merritt syndrome with pentoxifylline.

39.) Pentoxifylline inhibits the proliferation of human fibroblasts derived

from keloid, scleroderma and morphoea skin and their production of

collagen, glycosaminoglycans and fibronectin.

40.) Effects and limitations of pentoxifylline therapy in various stages of

peripheral vascular disease of the lower extremity.

41.) Enhancement of the treatment of experimental candidiasis with vascular

decongestants.

42.) Treatment of sickle cell leg ulcers with pentoxifylline.

43.) Oxpentifylline treatment of venous ulcers of the leg [see comments]

44.) Oxpentifylline in endotoxaemia [see comments]

45.) Pentoxifylline inhibits normal human dermal fibroblast in vitro

proliferation, collagen, glycosaminoglycan, and fibronectin production, and

increases collagenase activity.

46.) Pentoxifylline increases extremity blood flow in diabetic

atherosclerotic patients.

47.) Treatment of peripheral gangrene due to systemic sclerosis with

intravenous pentoxifylline.

48.) Therapy of livedo vasculitis with pentoxifylline.

49.) Pentoxifylline therapy in dermatology. A review of localized

hyperviscosity and its effects on the skin.

50.) Augmentation of skin flap survival by parenteral pentoxifylline.

51.) Synergistic effects of pentoxifylline and hyperbaric oxygen on skin

flaps.

52.) Pentoxifylline inhibits granulocyte and platelet function, including

granulocyte priming by platelet activating factor.

53.) Livedo vasculitis. Therapy with pentoxifylline [published erratum 

54.) Pentoxifylline inhibits T-cell adherence to keratinocytes.

55.) Pentoxifylline promotes replication of human cytomegalovirus in vivo

and in vitro. 

56.) Efficacy, Safety, Tolerability, and Satisfaction of N-Acetylcysteine and Pentoxifylline in Lichen 

Planopilaris Patients Under Treatment With Topical Clobetasol: A Triple Arm Blinded Randomized Controlled Trial.

57.) PENTOXIFYLLINE (Systemic), the product

========================================================================

1.) New developments in the treatment of systemic vasculitis. 

========================================================================

Author 

Gross WL 

Address 

Universit¨at zu L¨ubeck, Germany. 

Source 

Curr Opin Rheumatol, 6(1):11-9 1994 Jan 

Abstract 

Although precise diagnosis of the systemic vasculitides can provide general

prognostic information and help to guide initial therapy, recent studies on

the long-term clinical course have revealed considerable variation in

clinical severity. Therefore, anatomic distribution of involvement and

speed of progression should be the principle determinants of the intensity

of immunosuppressive therapy. In progressive pulmonary or renal disease,

eg, Wegener's granulomatosis, aggressive "standard" therapy is obligatory,

eg, daily cyclophosphamide and glucocorticoids. Such regimens, however,

should be applied with caution in chronic or indolent and abortive forms of

systemic vasculitis, because follow-up studies (eg, in Wegener's

granulomatosis) have revealed treatment-associated morbidity rates of up to

42%, disease-related morbidity, and a high incidence of relapse under

treatment. Moreover, less toxic therapeutic strategies are being pursued

with remarkable success: low-dose weekly methotrexate, monthly intravenous

or oral pulses of cyclophosphamide plus glucocorticoids, and high-dose

intravenous immunoglobulin. Long-term remission of intractable

(non-antineutrophil cytoplasmic antibody-associated) systemic vasculitis

has been achieved using humanized monoclonal antibodies (ie,

anti-CD4/anti-CDw52); and amelioration of glomerulonephritis in immune

complex diseases (eg, systemic lupus erythematosus) has been achieved with

nafamostat mesilate, an inhibitor of complement serine proteases. In

addition, leukocytoclastic vasculitis has been effectively controlled with

pentoxifylline, presumably by neutralizing proinflammatory cytokines, and

hepatitis C virus-associated mixed cryoglobulinemia has been successfully

treated with interferon alfa. 

========================================================================

2.) Chilblain lupus erythematosus (lupus pernio): clinical review of the

Mayo Clinic experience and proposal of diagnostic criteria. 

========================================================================

Author 

Su WP; Perniciaro C; Rogers RS 3rd; White JW Jr 

Address 

Department of Dermatology, Mayo Clinic, Rochester, Minnesota 55905. 

Source 

Cutis, 54(6):395-9 1994 Dec 

Abstract 

Five cases of chilblain lupus erythematosus were retrospectively reviewed

regarding their clinical, histopathologic, serologic, and

immunofluorescence findings. Ages at onset of chilblain lupus erythematosus

varied from 26 to 73 years, with a female-to-male ratio of 3:2. Since other

entities can be confused with this disorder, we propose the following

diagnostic criteria. The two major criteria are skin lesions in acral

locations induced by exposure to cold or a drop in temperature, and

evidence of lupus erythematosus in the skin lesions by results of

histopathologic examination or direct immunofluorescence study. The three

minor criteria are coexistence of systemic lupus erythematosus or other

skin lesions of discoid lupus erythematosus, response to anti-lupus

erythematosus therapy, and negative results of cryoglobulin and cold

agglutinin studies. We conclude that chilblain lupus erythematosus can be

diagnosed and treated. Discoid lupus erythematosus lesions respond more

quickly to treatment than chilblain lupus erythematosus lesions. Treatment

with antimalarial agents, prednisone, pentoxifylline, or dapsone was of

benefit to our patients. 

========================================================================

3.) [Vernet's syndrome as an early manifestation of systemic erythematous

lupus] 

========================================================================

Author 

Leache Pueyo JJ; Campos del Alamo MA; Gil Para´iso P; Ortiz Garc´ia A 

Address 

Servicio de O.R.L., Hospital Miguel Servet, Z´aragoza. 

Source 

An Otorrinolaringol Ibero Am, 24(2):135-41 1997 

Abstract 

Report of one case of Vernet's syndrome (involving the IX, X and XIth

cranial nerves) in a young woman, as early sing of SEL. The patient

presented the 4 criteria suggested by the American Society in order to

diagnose SEL: arthritis, serositis, positive anti-nuclear antibodies and

anemia. The AA. carry out a study in search of other cases sitting in the

larynx and a perusal about etiopathogenical theories as well. Hinting, for

the clinical picture, of being it due to a localised vasculitis of vasa

nervorum, a treatment with corticoids and pentoxifylline was ordered, being

the outcome, after 3 weeks, the eradication of ENT syndrome. 

========================================================================

4.) [Favorable in vitro effect of pentoxifylline on damaged lymphocyte

migration in arteriosclerosis obliterans and systemic lupus erythematosus

(see comments)] 

========================================================================

Author 

Szekanecz Z; Szab´o G; Sonkoly I; Bed¨o Z; Szegedi G 

Address 

Debreceni Orvostudom´anyi Egyetem III. sz. Belgy´ogy´azati Klinika. 

Source 

Orv Hetil, 134(7):349-53 1993 Feb 14 

Abstract 

Decreased blood cell--e.g. lymphocyte--motility is seen in a number of

vascular and autoimmune diseases. Pentoxifylline (Pf) shows a well-known

therapeutic effect in several vascular alterations by causing the

redistribution of blood cell cytoskeleton and increased microcirculation.

As most literary data on Pf concern red blood cells and granulocytes

authors here investigated the effect of Pf on previously decreased

lymphocyte migration and chemotaxis. Results of in vitro studies suggest

that Pf enhances impaired lymphocyte motility in obliterative

arteriosclerosis and systemic lupus erythematosus and thus may also be

introduced in the treatment of polysystemic autoimmune diseases. 

========================================================================

5.) Effect of pentoxifylline on decreased in vitro mononuclear leucocyte

chemotaxis in vascular and polysystemic autoimmune diseases. 

========================================================================

Author 

Szekanecz Z; Szab´o G; Sonkoly I; Bed¨o Z; Szegedi G 

Address 

3rd Department of Medicine, University Medical School of Debrecen, Hungary. 

Source 

Agents Actions, 33(3-4):254-9 1991 Jul 

Abstract 

Impaired mononuclear leucocyte (MNL) motility can be found both in vascular

and autoimmune diseases. Pentoxifylline (PTX) has a well-known therapeutic

effect in vascular diseases, which is based on the rearrangement of blood

cell cytoskeleton and thus increased microcirculatory flow. Most data on

PTX concern red blood cells and granulocytes so now the effect of PTX on

previously decreased MNL migration and chemotaxis was investigated in

vitro. The results of MNL chemotaxis studies described here suggest that

this drug enhances impaired MNL motility in obliterative atherosclerosis

and systemic lupus erythematosus and thus may also be introduced in the

treatment of certain polysystemic autoimmune diseases with decreased in

vitro MNL chemotaxis. 

========================================================================

6.) Effect of pentoxifylline on the course of systemic Candida albicans

infection in mice. 

========================================================================

Author 

Louie A; Baltch AL; Franke MA; Ritz WJ; Smith RP; Singh JK; Gordon MA 

Address 

Infectious Disease Section, Stratton Veterans Affairs Medical Center,

Albany, New York 12208, USA. 

Source 

J Antimicrob Chemother, 37(5):943-54 1996 May 

Abstract 

Pentoxifylline can decrease the production of tumour necrosis factor alpha

(TNF alpha) by endotoxin-stimulated macrophages and may improve survival in

animals with overwhelming bacterial sepsis. In this study various doses of

pentoxifylline were administered to mice with systemic Candida albicans

infection to determine its effect on serum TNF alpha levels, organ fungal

burden, and host survival. Intraperitoneal injections of pentoxifylline at

20 mg/kg every 8 h did not affect these endpoints. However, fungal counts

were significantly higher in kidneys of animals that received 30 and 60

mg/kg of pentoxifylline every 8 h when compared to controls. Injection of

60 mg/kg of pentoxifylline at 8 h intervals also significantly shortened

mean survival from 5.8 to 3.8 days (P = 0.01). Pentoxifylline did not

affect peripheral WBC counts, serum TNF alpha and interleukin-6 levels, or

the density of neutrophils in tissues. In vitro, pentoxifylline decreased

the production of TNF alpha by C. albicans-stimulated macrophages in a

dose-dependent manner, but only at concentrations greater than 100 mg/L. In

contrast, pentoxifylline suppressed TNF alpha production by

endotoxin-stimulated macrophages at concentrations as low as 10 mg/L. Thus,

higher doses of pentoxifylline are detrimental in systemic C. albicans

infection. However, the detrimental effect is not mediated by alterations

in serum TNF alpha or interleukin-6 levels or the aggregation of

neutrophils in tissues. 

========================================================================

7.) [Current status and trends in treatment of scleroderma] 

========================================================================

Author 

Haustein UF 

Address 

Klinik f¨ur Hautkrankheiten, Universit¨at Leipzig. 

Source 

Hautarzt, 43(7):409-16 1992 Jul 

Abstract 

Owing to the wide variety of symptoms, the long clinical course, the

inadequate knowledge of the points at which therapeutic action is

appropriate and the difficulty of obtaining objective measurements of the

treatment results, therapy for systemic sclerosis has to be planned

individually. Besides basic recommendations (avoidance of noxious

substances, sensible diet, keeping warm, active exercises), physiotherapy

and psychological guidance, the therapy is directed at three pathogenetic

complexes. Among the vasoactive substances the prostacyclins, calcium

channel blockers and angiotensin-converting-enzyme inhibitors (in the case

of complicated renal involvement) are recommended. They inhibit the

thrombocyte hyperaggregation and lead to vasodilatation. The

anti-inflammatory substances prednisolone and azathioprine also exert

immunosuppressant (and cytotoxic) effect. Their use is indicated in

inflammatory, immunologically active forms of systemic sclerosis.

Antifibrotic agents inhibit cross-link formation, prolylhydroxylase,

extrusion of collagen from fibroblasts and, thus, collagen synthesis. In

addition, they favour the degradation of collagen via the activation of

collagenase. Good results have been reported with penicillamine and

penicillin G. Pentoxyphyllin leads to vasodilatation and also inhibits

collagen metabolism. Promising agents and procedures for future use include

cyclosporin A, CD4 antibodies, photopheresis, interferon gamma and factor

XIII. A critical attitude to therapy and a great deal of patience are

necessary to avoid harming the patients, especially as it is often some

months before any effects of the treatment are seen. 

========================================================================

8.) [New properties of trental as an inhibitor of viral activity with a

wide range of activity] 

========================================================================

Author 

Amvros'eva TV; Votiakov VI; Andreeva OT; Vladyko GV; Nikolaeva SN; Orlova

SV; Azarova IA; Zgirovskaia AA 

Source 

Vopr Virusol, 38(5):230-3 1993 Sep-Dec 

Abstract 

Experimental investigations on the spectrum and degree of the expression of

trental antiviral activity were carried out. The investigations were done

in cell cultures and laboratory animals using laboratory strains (including

drug-resistant ones) of 13 viruses, causative agents of human and animal

infections. The drug demonstrated its activity against 8 viruses of 7

families. It was highly active against 5 viruses: herpes simplex virus

(including its acyclovir-resistant strain), vaccinia virus (including its

methisazone-resistant strain), rotavirus and tick-borne encephalitis virus.

As regards other viruses, its activity was less pronounced (hepatitis JA

virus) or low (vesicular stomatitis virus, West Nile virus). It was

concluded that, being a cardiovascular drug, trental was an effective broad

spectrum virus inhibitor. 

========================================================================

9.)[Lymphotropic therapy with trental in the treatment of chronic herpetic

stomatitis] 

========================================================================

Author 

Shumski¨i AV 

Source 

Stomatologiia (Mosk), 76(1):15-7 1997 

Abstract 

Lymphotropic therapy with trental was administered to patients with chronic

herpetic stomatitis. Trental was injected near the mastoid process after

preinjection with lidase (total dose no more than 1 ml on each side, 6

sessions per course). The treatment normalized the immune status, clinical

symptoms regressed sooner than after treatment with an antiviral agent

bonafton, remissions were prolonged, and in 5 out of 18 patients no more

relapses occurred. 

========================================================================

10.) A double-blind, randomized, placebo-controlled, crossover trial of

pentoxifylline for the prevention of chemotherapy-induced oral mucositis. 

========================================================================

Author 

Verdi CJ; Garewal HS; Koenig LM; Vaughn B; Burkhead T 

Address 

Section of Hematology/Oncology, Tucson Veteran's Affairs Medical Center,

Ariz., USA. 

Source 

Oral Surg Oral Med Oral Pathol Oral Radiol Endod, 80(1):36-42 1995 Jul 

Abstract 

Oral mucositis is a frequent side effect of cancer therapy. No effective

method of prophylaxis is currently available. We conducted a randomized,

double-blind, placebo-controlled, crossover trial of pentoxifylline to

evaluate its potential in preventing mucositis in cancer patients receiving

chemotherapy. Ten cancer patients were randomized for treatment with a

15-day course of 400 mg of pentoxifylline given orally four times daily.

Concurrent chemotherapy consisted of bolus cisplatin and infusional

5-fluorouracil. Mucositis was evaluated with the use of the Oral Assessment

Guide developed at the University of Nebraska. Patients completing two

cycles of chemotherapy--one with pentoxifylline and one with placebo--were

evaluated for prophylaxis efficacy. Comparison of the oral assessment

scores of the two cycles with a two-sided Student's t test failed to

demonstrate a cytoprotective effect for pentoxifylline over placebo. We

conclude that pentoxifylline as given in this study is ineffective for

preventing mucositis in patients receiving cisplatin and 5-FU. 

========================================================================

11.) Vasculitis. 

========================================================================

Author 

Smith JG Jr 

Address 

University of South Alabama, Mobile, USA. 

Source 

J Dermatol, 22(11):812-22 1995 Nov 

Abstract 

Many cutaneous and systemic disorders are associated with inflammation and

necrosis of blood vessels. Several classifications of vasculitis have been

used. Internists tend to utilize the classification of Fauci with

modifications such as those by Cupps. Gibson and Ryan, who are

dermatopathologists, have classified vasculitis based on vessel size,

leukocyte type, and presence of granulomas. A more recent classification

has been developed by Jennette, a pathologist, and colleagues. The etiology

of vasculitis is varied; it includes bacteria, viruses, chemicals,

autoimmune disease, malignancy and abnormal exogenous and endogenous

proteins. Leukocytoclastic vasculitis can be experimentally reproduced by

the Arthus phenomenon. IgM and C3 are found in cutaneous blood vessels and

associated with circulating immune complexes. CH50, C3 and C4 may be

reduced in serum. Increased incidence of nasal carriage of staphylococci is

associated with higher relapse rates in Wegener's granulomatosis and toxic

shock syndrome toxin from staphylococci is associated with the Kawasaki

syndrome. Additionally, at least four systemic vasculitic drug reactions

can be confirmed with patch testing. Antineutrophil cytoplasmic antibodies

(ANCA) are found in association with certain systemic vasculitides. These

may be tested with indirect immunofluorescence and enzyme linked

immunosorbent assays (ELISA) with radioimmunoassays. Originally cytoplasmic

ANCA (cANCA) was identified with proteinase 3 as the antigen and

perinuclear ANCA (pANCA) was related to myeloperoxidase. While cANCA is

very specific for proteinase 3, pANCA is associated with a number of

antigens other than myeloperoxidase. pANCA is found with alcohol fixed but

not formalin-fixed neutrophils. cANCA is particularly sensitive and

specific for Wegener's granulomatosis and predicts prognosis and response

to therapy. pANCA is not so specific and is associated with a number of

other vasculitic syndromes. Cutaneous vasculitis is managed primarily with

colchicine, dapsone and prednisone, with recent studies indicating that

there may be a synergistic effect of pentoxifylline with dapsone. Systemic

vasculitis involves treatment with various agents. Recently it has been

observed that co-trimoxazole (trimethoprim/sulfamethoxazole) is useful in

many cases of Wegener's granulomatosis along with other more toxic

chemotherapeutic agents. 

========================================================================

12.) Improvement of acral circulation in a patient with systemic sclerosis

with stellate blocks. 

========================================================================

Author 

Klyscz T; J¨unger M; Meyer H; Rassner G 

Address 

Department of Dermatology, University of T¨ubingen, Germany. 

Source 

Vasa, 27(1):39-42 1998 Feb 

Abstract 

We report on a 77-year-old male patient with systemic sclerosis. He

suffered from secondary Raynaud's phenomenon on the basis of systemic

sclerosis. Medical treatment in the past, including the administration of

calcium-channel blockers, pentoxifylline and intravenous prostaglandin

therapy, was unsuccessful and the clinical situation became worse. In a

final effort stellate blocks were performed over a period of several weeks

and, for the first time, there was lasting clinical benefit. Complaints and

Raynaud's attacks abated significantly, as documented by local cold

exposure tests. Therapeutic benefit from stellate blocks in a patient with

systemic sclerosis is described here for the first time. 

========================================================================

13.) Effects of pentoxifylline on hemodynamics and oxygenation in septic

and nonseptic patients. 

========================================================================

Author 

Bacher A; Mayer N; Klimscha W; Oism¨uller C; Steltzer H; Hammerle A 

Address 

Department of Anesthesiology and General Intensive Care, University of

Vienna, Austria. 

Source 

Crit Care Med, 25(5):795-800 1997 May 

Abstract 

OBJECTIVE: To evaluate the effects of pentoxifylline on hemodynamics and

systemic oxygenation in septic and nonseptic critically ill patients.

DESIGN: Prospective clinical investigation. SETTING: Intensive care unit

(ICU) of a university hospital. PATIENTS: Nineteen critically ill patients

were included in the study 1 to 4 days after their admission to the ICU. A

systemic inflammatory response syndrome was present in 12 patients,

fulfilling at least two of the American College of Chest Physicians/

Society of Critical Care Medicine Consensus Conference criteria. The other

seven patients did not fulfill these criteria and were classified as

nonseptic. INTERVENTIONS: All patients were mechanically ventilated. The

dosage of catecholamines was kept constant during the entire study period

and at least during 15 mins before the start of the study. In both study

groups, pulmonary and radial artery catheters were inserted and 5 mg/kg of

pentoxifylline (diluted in 300 mL of physiologic saline) was intravenously

administered over a period of 180 mins at a rate of 100 mL/hr. MEASUREMENTS

AND MAIN RESULTS: Hemodynamic variables, oxygen transport (DO2), oxygen

uptake (VO2), and oxygen extraction ratio were determined before

pentoxifylline, after 2.5 mg/kg of pentoxifylline, after 5 mg/kg of

pentoxifylline, and 60 mins after the termination of pentoxifylline.

Repeated-measures analysis of variance and Mann-Whitney test were used for

statistical analysis. At baseline, there were significant differences

between the septic and the nonseptic groups in mean pulmonary arterial

pressure (septic: 31 +/- 5 mm Hg; nonseptic: 26 +/- 7 mm Hg, p < .05), and

pulmonary vascular resistance index (PVRI) (septic: 344 +/- 121 dyne.sec/

cm5.m2; nonseptic: 233 +/- 100 dyne.sec/cm5.m2, p < .05). In the septic

group, significant increases in heart rate and cardiac index were observed.

Systemic vascular resistance index and PVRI decreased. No significant

changes in hemodynamic variables occurred in the nonseptic group. In both

groups, DO2 and VO2 increased significantly, while oxygen extraction ratio

remained unchanged. CONCLUSIONS: The administration of pentoxifylline to

septic patients results in a significant improvement in hemodynamic

performance compared with critically ill nonseptic patients. The better

hemodynamic state is accompanied by an increase in DO2 and VO2 with

unchanged oxygen extraction ratio. 

========================================================================

14.) Antiproliferative effect of pentoxifylline on psoriatic and normal

epidermis. In vitro and in vivo studies. 

========================================================================

Author 

Gilhar A; Grossman N; Kahanovicz S; Reuveni H; Cohen S; Eitan A 

Address 

Skin Research Laboratory, Bruce Rappaport Faculty of Medicine,

Technion-Israel Institute of Technology, Haifa, Israel. 

Source 

Acta Derm Venereol, 76(6):437-41 1996 Nov 

Abstract 

Psoriasis is characterized by abnormal cell proliferation, inflammation and

increased biosynthesis of various cytokines. The inhibitory effect of

pentoxifylline on some cell functions has been reported widely. This

property of pentoxifylline prompted an investigation of its possible role

in controlling psoriasis. In the in vitro study normal human keratinocytes

proliferation was determined and formation of cornified envelopes was

assayed following treatment with pentoxifylline. The in vivo experiment

consisted of nude mice grafted with psoriatic or normal skin treated with

tetradecanyl phorbol 13 acetate. At the end of the treatment period, the

grafts were excised and assessed for acanthosis and labelling index. The in

vitro study showed that continuous exposure of normal human keratinocyte

cultures to pentoxifylline resulted in a significant dose-dependent

inhibition of proliferation, and in induction of cornified envelope

formation. The in vivo experiments showed a significant reduction of

epidermal thickness and of labeling index in psoriatic and tetradecanyl

phorbol 13 acetate-treated normal skin, as compared to the initial values. 

========================================================================

15.) Antineoplastic effect of the xanthine derivative Trental. 

========================================================================

Author 

Biddle W; Ambrus CM; Gastpar H; Ambrus JL 

Source 

J Med, 15(5-6):355-66 1984 

Abstract 

The xanthine derivative, Trental (pentoxifylline) was found to inhibit

several human leukemic and lymphoma cell lines in tissue cultures. Optimal

concentrations were less inhibitory for a normal B-lymphocyte cell line

then for the neoplastic cell lines. In fact, small concentrations

stimulated DNA synthesis in the normal cell line. Trental and

beta-interferon appeared to be additive synergists at certain dosages.

Possible mechanisms are discussed. 

========================================================================

16.) Treatment of experimental frostbite with pentoxifylline and aloe vera

cream.

========================================================================

SO - Arch Otolaryngol Head Neck Surg 1995 Jun;121(6):678-80

AU - Miller MB; Koltai PJ

AD - Division of Otolaryngology, Albany (NY) Medical College, USA.

AB - OBJECTIVE: To compare the therapeutic effects of systemic

pentoxifylline and topical aloe vera cream in the treatment of frostbite.

DESIGN: The frostbitten ears of 10 New Zealand white rabbits were assigned

to one of four treatment groups: untreated controls, those treated with

aloe vera cream, those treated with pentoxifylline, and those treated with

aloe vera cream and pentoxifylline. MAIN OUTCOME MEASURES: Tissue survival

was calculated as the percent of total frostbite area that remained after 2

weeks. RESULTS: The control group had a 6% tissue survival. Tissue survival

was notably improved with pentoxifylline (20%), better with aloe vera cream

(24%), and the best with the combination therapy (30%). CONCLUSION:

Pentoxifylline is as effective as aloe vera cream in improving tissue

survival after frostbite injury.

========================================================================

17.) High-dose pentoxifylline in patients with AIDS: inhibition of tumor

necrosis factor production. National Institute of Allergy and Infectious

Diseases AIDS Clinical Trials Group.

========================================================================

SO - J Infect Dis 1995 Jun;171(6):1628-32

AU - Dezube BJ; Lederman MM; Spritzler JG; Chapman B; Korvick JA; Flexner

C; Dando S; Mattiacci MR; Ahlers CM; Zhang L; et al

AD - Department of Medicine, Beth Israel Hospital, Boston, MA 02215, USA.

AB - Tumor necrosis factor-alpha (TNF) may activate human immunodeficiency

virus (HIV), antagonize zidovudine activity, and contribute to AIDS wasting

syndrome. Pentoxifylline decreases TNF production. In cell culture,

pentoxifylline decreases HIV replication and gene expression. Since an AIDS

Clinical Trial Group study suggested that pentoxifylline (400 mg thrice

daily) is safe in AIDS patients and decreases TNF mRNA levels in peripheral

blood mononuclear cells (PBMC), a second cohort received 800 mg thrice

daily for 8 weeks. During treatment, the median decrease in TNF production

by PBMC cultured with 0.1 microgram/mL lipopolysaccharide (LPS) was 40%.

The median change in TNF mRNA was a 34% decrease. Pentoxifylline did not

affect HIV levels as detected by quantitative microculture or serum p24

antigen measurements, nor did it alter zidovudine pharmacokinetics. The

most common toxicity was gastrointestinal. Pentoxifylline at dosages of

less than thrice-daily 800 mg is well tolerated and may decrease TNF mRNA

levels and LPS-induced TNF production.

========================================================================

18.) Pentoxifylline as a supportive agent in the treatment of cerebral

malaria in children.

========================================================================

SO - J Infect Dis 1995 May;171(5):1317-22

AU - Di Perri G; Di Perri IG; Monteiro GB; Bonora S; Hennig C; Cassatella

M; Micciolo R; Vento S; Dusi S; Bassetti D; et al

AD - Institute of Immunology, University of Verona, Italy.

AB - In an open, randomized, controlled therapeutic trial, 56 children

with cerebral malaria (CM) were randomly assigned to receive standard

quinine regimen with or without pentoxifylline (10 mg/kg/day by continuous

intravenous infusion). Pentoxifylline exerted an inhibitory effect on the

synthesis of tumor necrosis factor (TNF), a possible mediator of CM. The 26

children who received pentoxifylline had significantly shorter comas than

controls (median, 6 vs. 46 h; P .001) Pentoxifylline recipients showed a

trend toward a lower mortality, with a borderline significant difference (P

= .055). The better outcome in the pentoxifylline group was associated with

a decline in TNF serum levels on the third day of treatment in a few

subjects that was not seen in controls. While alternative or concurrent

mechanisms of action may be of some relevance, larger double-blind trials

are needed to determine whether pentoxifylline has a therapeutic role in CM.

========================================================================

19.) Pentoxifylline inhibits tumor necrosis factor-alpha (TNF

alpha)-induced T-lymphoma cell adhesion to endothelioma cells.

========================================================================

SO - J Invest Dermatol 1995 May;104(5):824-8

AU - Weiss JM; Vanscheidt W; Pilarski KA; Weyl A; Peschen M; Schopf E;

Vestweber D; Simon JC

AD - Department of Dermatology, University of Freiburg, Germany.

AB - Pentoxifylline, a methylxanthine derivative, has been shown to

inhibit T-cell-mediated cutaneous immune response by yet ill-understood

mechanisms. Because cell adhesion to endothelial cells is a critical step

in the initiation of such immune responses, we analyzed whether

pentoxifylline would affect this process. To address this issue, adhesion

of mouse T-lymphoma cells (TK-1) to mouse endothelioma cells (eEnd.2),

either untreated or stimulated with tumor necrosis factor-alpha (TNF

alpha), was studied. Pentoxifylline reduced the ability of endothelioma

cells stimulated with different concentrations of TNF alpha, but not of

untreated endothelioma cells, to bind T-lymphoma cells in dose-dependent

(10(-5)-10(-3) M) fashion. Selective incubation of either endothelioma

cells or T-lymphoma cells revealed that pentoxifylline acted exclusively on

the endothelioma cells, even when added after TNF alpha stimulation. We

questioned whether pentoxifylline suppressed T-lymphoma cell/endothelioma

cell interactions by interfering with adhesion molecules expressed by

either cell. However, as determined by flow cytometry, pentoxifylline did

not alter TNF alpha-induced upregulation of intercellular adhesion

molecule-1 or vascular cellular adhesion molecule-1 on endothelioma cells

nor did it affect constitutive CD11a, CD18, or alpha 4-integrin expression

on T-lymphoma cells, suggesting that rather than affecting quantitative

expression of these adhesion molecules, pentoxifylline might modulate their

avidity. We conclude that pentoxifylline in therapeutically achievable

concentrations is a potent inhibitor of TNF alpha-induced T-lymphoma cell

adhesion to endothelioma cells. This finding may account, at least in part,

for the recently discovered anti-inflammatory action of pentoxifylline.

========================================================================

20.) Pharmacotherapy of Raynaud's phenomenon. 

========================================================================

Author 

Belch JJ; Ho M 

Address 

Department of Vascular Medicine, Ninewells Hospital and Medical School, Dundee, Scotland. jjfbelch@dundee.ac.ulc 

Source 

Drugs, 52(5):682-95 1996 Nov 

Abstract 

Primary Raynaud's phenomenon is common, particularly in younger women, and may be familial. Vasospasm is not confined to the digits and may involve, for example, the tongue and nose, and also visceral organs like the heart, oesophagus or lung and cerebral circulation. Symptoms tend to be milder in primary compared with secondary Raynaud's phenomenon, which is associated with other disorders such as the connective tissue diseases. Indeed, the severity of symptoms often acts as the predictor for the much later onset of the associated systemic disease. Occupational Raynaud's phenomenon is related to the use of vibrating instruments, and a significant proportion of patients may be cured by an early change in job. In those over 60 years of age, Raynaud's phenomenon is commonly a result of atherosclerotic obstructive arterial disease, and screening for and treatment of the risk factors is appropriate. The best-studied mechanisms in Raynaud's phenomenon involve the blood and vascular endothelium. Microcirculatory flow may be impeded by activated platelet clumps, rigid red and white blood cells and damaged endothelium. These platelet clumps, white blood cells and damaged endothelium also release vasoactive/vasoconstrictive compounds which may additionally trigger the clotting cascade and thrombosis. Initial management for mild disease should focus on support and advice regarding avoidance of known precipitating factors, including vasospastic drugs. Cold protection with warming agents, 'Abel' shoes and also electrically heated gloves and socks is effective, but may be too cumbersome and inconvenient for some patients. Simple vasodilators like naftidrofuryl, inositol nicotinate and possibly pentoxifylline (oxpentifylline) are useful in mild disease, with adverse effects like headache and flushing being less problematic. The 'gold standard' of Raynaud's phenomenon treatment is nifedipine, a calcium channel antagonist/blocker. Full dosage, however, can be limited by ankle swelling, headache and flushing, but adverse effects may be reduced by using the 'retard' or long-acting preparations. Adverse effects are also reduced with the newer calcium channel antagonists like diltiazem but at the expense of efficacy. Useful, enhanced benefit is also achieved by combination therapy with vasodilators. Newer treatments include the prostaglandin analogues which are effective but disadvantaged by their parenteral route of administration, and lack of licence in some countries. Oral preparations are, however, being studied and are in the pipeline. Essential fatty acid supplementation is mildly effective, while ketanserin and calcitonin gene-related peptide both look promising. Lumbar sympathectomy retains its important role in the treatment of Raynaud's phenomenon involving the lower limbs. Satisfactory symptomatic relief is now possible for many patients with Raynaud's phenomenon and this should certainly be the aim for all patients seeking medical help. 

========================================================================

21.) Severe idiopathic recurrent aphthous stomatitis: treatment with

pentoxifylline [letter]

SO - Acta Derm Venereol 1995 Mar;75(2):157

AU - Wahba-Yahav AV

========================================================================

========================================================================

22.) Pentoxifylline for Sweet's syndrome [letter; comment]

CM - Comment on: J Am Acad Dermatol 1994 Apr; 30(4):603-21; Comment on: J

Am Acad Dermatol 1994 Apr; 30(4):639-42

SO - J Am Acad Dermatol 1995 Mar;32(3):533-5

AU - Cohen PR; Holder WR

========================================================================

========================================================================

23.) Urticarial vasculitis syndrome effectively treated with dapsone and

pentoxifylline.

========================================================================

SO - Acta Derm Venereol 1995 Jan;75(1):54-6

AU - Nurnberg W; Grabbe J; Czarnetzki BM

AD - Department of Dermatology, University Clinics Rudolf Virchow,

FU-Berlin, Germany.

AB - Urticarial vasculitis is difficult to treat. We report here on a

40-year-old woman with a 16-year history of idiopathic hypocomplementemic

urticarial vasculitis syndrome. Her disease had been resistant to treatment

with H1- and H2-blockers, indomethacin, dapsone and interferon alpha but

responded to 25 mg/day prednisolone. Monotherapy with pentoxifylline was

also of only minor benefit. Using a combination of dapsone (100 mg/day) and

pentoxifylline (1,200 mg/day), we observed a gradual improvement resulting

in a complete remission within 8 weeks. Complete control of symptoms could

be maintained for 18 months without any serious side-effects. This type of

treatment may be of benefit in other therapy-resistant cases of

hypocomplementemic urticarial vasculitis syndrome, particularly in view of

its excellent tolerance.

========================================================================

24.) Schamberg's purpura: association with persistent hepatitis B surface

antigenemia and treatment with pentoxifylline.

========================================================================

SO - Cutis 1994 Sep;54(3):205-6

AU - Wahba-Yahav AV

AB - A 54-year-old man experienced an extensive asymptomatic purpuric

eruption on both his legs consistent with Schamberg's purpura. Three months

before, he had had an episode of acute viral hepatitis. Nine months later,

the purpura was unchanged despite administration of a topical

corticosteroid. Results of serologic evaluation revealed hepatitis B

surface antigen. The patient was treated orally with pentoxifylline, 400 mg

three times daily. After one month of therapy, the purpuric elements of his

eruption had disappeared, and after two additional months most of the

pigmentation had also faded.

========================================================================

25.) The use of pentoxifylline in the treatment of systemic sclerosis and

lipodermatosclerosis: a unifying hypothesis? [letter; comment]

CM - Comment on: J Am Acad Dermatol 1993 Apr; 28(4):525-47; Comment on: J

Am Acad Dermatol 1993 Apr; 28(4):623-7

SO - J Am Acad Dermatol 1994 Jul;31(1):135-6

AU - Goldman MP

========================================================================

========================================================================

26.) Pentoxifylline [see comments]

========================================================================

CM - Comment in: J Am Acad Dermatol 1994 Apr; 30(4):639-42; Comment in: J

Am Acad Dermatol 1995 Mar; 32(3):533-5; Comment in: J Am Acad Dermatol 1995

Jul; 33(1):143

SO - J Am Acad Dermatol 1994 Apr;30(4):603-21

AU - Samlaska CP; Winfield EA

AD - Dermatology Service, Tripler Army Medical Center, Honolulu, Hawaii.

AB - Pentoxifylline (oxpentifylline) is a methylxanthine derivative with

potent hemorrheologic properties. In the United States it is marketed for

the treatment of intermittent claudication. Human and animal studies have

shown that pentoxifylline therapy results in a variety of physiological

changes at the cellular level, which may be important in treating a diverse

group of human afflictions. Immune modulation includes increased leukocyte

deformability and chemotaxis, decreased endothelial leukocyte adhesion,

decreased neutrophil degranulation and release of superoxides, decreased

production of monocyte-derived tumor necrosis factor, decreased leukocyte

responsiveness to interleukin 1 and tumor necrosis factor, inhibition of T

and B lymphocyte activation, and decreased natural killer cell activity.

Hypercoagulable states improve through decreased platelet aggregation and

adhesion, increased plasminogen activator, increased plasmin, increased

antithrombin III, decreased fibrinogen, decreased alpha 2-antiplasmin,

decreased alpha 1-antitrypsin, and decreased alpha 2-macroglobulin. Wound

healing and connective tissue disorders may respond to an increase in

fibroblast collagenases and decreased collagen, fibronectin, and

glycosaminoglycan production. Fibroblast responsiveness to tumor necrosis

factor is also diminished. Potential medical uses of pentoxifylline are

reviewed.

========================================================================

27.) Toxic epidermal necrolysis. Treatment with pentoxifylline [letter]

SO - Br J Dermatol 1994 May;130(5):688-9

AU - Redondo P; Ruiz de Erenchun F; Iglesias ME; Monedero P; Quintanilla E

========================================================================

========================================================================

28.) Pentoxifylline for the treatment of infection with human

immunodeficiency virus.

========================================================================

SO - Clin Infect Dis 1994 Mar;18(3):285-7

AU - Dezube BJ

AD - Department of Medicine, Beth Israel Hospital, Boston, Massachusetts

02215.

AB - Cytokine dysregulation in human immunodeficiency virus type 1 (HIV-1)

infection has been documented in numerous studies and has been cited as an

important component in the pathogenesis of this retroviral infection.

Pharmacological modification of cytokine dysregulation, therefore, has been

suggested as a therapeutic modality for HIV-1 infection. Dr. Dezube of Beth

Israel Hospital (Boston) concisely reviews the state of our knowledge

regarding the effects of pentoxifylline on expression of tumor necrosis

factor-alpha, a cytokine known to influence HIV-1 replication and to play a

possible role in the clinical manifestations of advanced infection with

this virus. Pentoxifylline, a trisubstituted xanthine derivative, has been

used to decrease blood viscosity and is reasonably well tolerated by most

recipients of the drug. Results of preliminary studies, many of which were

conducted by Dr. Dezube, suggest that use of this agent in combination with

antiretroviral compounds may prove useful in the treatment of patients with

HIV-1 infection.

========================================================================

29.) Inhibition of collagen lattice contraction by pentoxifylline and

interferon-alpha, -beta, and -gamma.

========================================================================

SO - J Invest Dermatol 1994 Jan;102(1):118-21

AU - Dans MJ; Isseroff R

AD - Department of Dermatology, University of California, Davis 95616.

AB - The ability to control wound contraction is important in preventing

disfiguring scarring in burn and trauma patients. Fibroblasts within the

wound generate the mechanical forces that cause this contraction, and their

interactions with various extracellular matrix components are thought to

regulate this process. Because pentoxifylline and the interferons are

believed to moderate fibroblast production of such matrix components, we

assessed the effects of these agents on wound contraction in vitro, using a

model wherein dermal fibroblasts are incorporated into a collagen lattice.

Pentoxifylline and interferon-alpha, -beta, and -gamma inhibited lattice

contraction in a dose-dependent manner and showed no effect on cell number

or cell viability. These results suggest that pentoxifylline and the

interferons may retard wound contraction in vivo and thus reduce scarring

associated with severely contracted wounds. Further study is needed to

determine the mechanism of action of these agents on the collagen lattice

model.

========================================================================

30.) Long-term pretreatment with pentoxifylline increases random skin flap

survival.

========================================================================

SO - Arch Otolaryngol Head Neck Surg 1994 Jan;120(1):65-71

AU - Williams PB; Hankins DB; Layton CT; Phan T; Pratt MF

AD - Department of Pharmacology, Eastern Virginia Medical School, Norfolk.

AB - Optimizing survival of random skin flaps is essential to ensure

successful rehabilitation of patients in whom flap reconstruction is

necessary. This study tested the hypothesis that pentoxifylline improves

random skin flap survival in porcine dorsal flank flaps when administered

for at least 2 weeks preoperatively. Specific aims included establishing

the mechanisms by which pentoxifylline enhanced survival. Treatment with

pentoxifylline (25 mg/kg per day) for 14 days before surgery and for 7 days

thereafter significantly increased mean flap survival to 73.2% +/- 4.5%

compared with mean flap survival of 49.6% +/- 2.2% in untreated pigs.

Increased flap survival was associated with a parallel increase in red

blood cell flexibility. Plasma concentration of pentoxifylline ranged from

92.9 to 122.7 ng/mL but did not correlate directly with the improved flap

survival. Likewise, pentoxifylline decreased platelet aggregation; there

was a trend toward increased flap survival in those pigs with the least

amount of aggregation. Thus, pentoxifylline improves random flap survival

but only after a sufficient pretreatment period of at least 14 days.

========================================================================

31.) Angiolymphoid hyperplasia with eosinophilia may respond to

pentoxifylline.

========================================================================

SO - J Am Acad Dermatol 1994 Jul;31(1):117-8

AU - Person JR

AD - Fallon Clinic, Worcester, Massachusetts.

========================================================================

32.) Chronic balanitis with palisading granuloma: an atypical genital

localization of necrobiosis lipoidica responsive to pentoxifylline.

========================================================================

SO - Dermatology 1994;188(3):222-5

AU - Espana A; Sanchez-Yus E; Serna MJ; Redondo P; Robledo A; Quintanilla E

AD - Department of Dermatology, University Clinic of Navarra, Pamplona,

Spain.

AB - We report a case of necrobiosis lipoidica located on the glans penis

of a patient without diabetes mellitus. Both clinical and histologic

features favor the diagnosis of necrobiosis lipoidica, even though the

location is unusual. Treatment with pentoxifylline was effective. The

differential diagnosis is discussed.

========================================================================

33.) Pentoxifylline for ischemic pain in pseudoxanthoma elasticum.

========================================================================

SO - West J Med 1993 Dec;159(6):689-90

AU - Takaro TK; Coodley GO

AD - Division of Internal Medicine, Oregon Health Sciences University

School of Medicine, Portland 97201-3098.

========================================================================

34.) Pentoxifylline suppresses irritant and contact hypersensitivity

reactions.

========================================================================

SO - J Invest Dermatol 1993 Oct;101(4):549-52

AU - Schwarz A; Krone C; Trautinger F; Aragane Y; Neuner P; Luger TA;

Schwarz T

AD - Department of Dermatology, University Munster, Germany.

AB - Pharmacologic suppression of the effector phase of contact

hypersensitivity appears to have major relevance with regard to treatment

of type IV reactions like contact dermatitis. Recently, tumor necrosis

factor alpha has been shown to be a critical mediator in hapten-induced

irritant and contact hypersensitivity reactions, thus offering new

possibilities, for therapeutic intervention. Pentoxifylline, a

methylxanthine derivative used in the treatment of vascular disorders,

currently has been found to suppress the production of tumor necrosis

factor alpha by human and murine leukocytes. Therefore, the effect of

pentoxifylline on the elicitation phase of contact hypersensitivity was

studied. Intraperitoneal injection of pentoxifylline into sensitized Balb/c

and C3H/HeN mice before application of the challenging hapten dose resulted

in a significant reduction of the outcome of the contact hypersensitivity

reaction. The suppressive effect of pentoxifylline was dose dependent and

maximally pronounced upon injection 3 h before hapten application. In

contrast to the effector phase of contact hypersensitivity, induction of

contact hypersensitivity was not affected by pentoxifylline when injected

into naive mice before performance of sensitization. In addition, irritant

dermatitis induced by 1% croton oil or 5% benzalkonium chloride was

suppressed by pentoxifylline as well. These data suggest a potential

pharmacologic intervention, with pentoxifylline as a means to treat contact

dermatitis.

========================================================================

35.) Ulcerating necrobiosis lipoidica effectively treated with pentoxifylline.

========================================================================

SO - Clin Exp Dermatol 1993 Jan;18(1):78-9

AU - Noz KC; Korstanje MJ; Vermeer BJ

AD - Department of Dermatology, Academic Hospital Leiden, The Netherlands.

AB - A 30-year-old man had suffered from persistent ulceration within an

area of necrobiosis lipoidica diabeticorum for 13 months. The ulcerating

necrobiosis lipoidica was resistant to topical therapy and oral therapy

with acetylsalicylic acid. However, the ulcers healed completely within 8

weeks of administration of 400 mg pentoxifylline twice daily.

========================================================================

36.) Generalised granuloma annulare successfully treated with pentoxifylline.

========================================================================

SO - Australas J Dermatol 1993;34(3):103-8

AU - Rubel DM; Wood G; Rosen R; Jopp-McKay A

AD - Department of Dermatology, Prince of Wales Hospital, Randwick, NSW.

AB - Generalised granuloma annulare (GA) is a chronic disease of unknown

aetiology and is recalcitrant to many treatment regimes. Some investigators

have suggested that an immune medicated vasculitis may be involved in the

pathogenesis of GA. We describe a patient with a ten year history of

generalised GA, who showed dramatic clearing of the majority of papules

after four weeks of treatment with pentoxifylline. This drug has shown

promising results in the treatment of many dermatologic disorders including

necrobiosis lipoidica diabeticorum, leukocytoclastic vasculitis and

Raynaud's phenomenon. Pentoxifylline is thought to reduce blood viscosity

via effects on all major blood components, and its clinical effectiveness

in generalised GA lends support to a model of immune-medicated vasculitis

in the pathogenesis of this disorder. Thus, pentoxifylline offers a

well-tolerated and effective alternative to the treatment options available

for patients with granuloma annulare.

========================================================================

37.) Intractable chronic furunculosis: prevention of recurrences with

pentoxifylline.

========================================================================

SO - Acta Derm Venereol 1992 Nov;72(6):461-2

AU - Wahba-Yahav AV

AB - A 60-year-old HIV-negative man with known noninsulin-dependent

diabetes mellitus and glucose 6-phosphate-dehydrogenase deficiency anemia

suffered from chronic recurrent furunculosis since the age of 30. In recent

years, his condition had become increasingly severe and the recurrences

increasingly frequent. Different measures including continuous therapy with

large doses of systemic antibiotics for a period of 6 months failed to

prevent the recurrences. Oral treatment with pentoxifylline 400 mg t.i.d.

was prescribed, and 2 months later the patient experienced a dramatic and

complete remission of his furunculosis. Six months later he was still

totally free of lesions while continuing to take the same medication.

Pentoxifylline may provide a new and effective approach to the previously

difficult and often disappointing problem of the management of patients

with chronic recurrent furunculosis.

========================================================================

38.) Successful treatment of Kasabach-Merritt syndrome with pentoxifylline.

SO - J Am Acad Dermatol 1991 Nov;25(5 Pt 1):854-5

AU - de Prost Y; Teillac D; Bodemer C; Enjolras O; Nihoul-Fekete C; de

Prost D

AD - Department of Dermatology, Hopital Necker Enfants Malades, Paris,

France.

========================================================================

========================================================================

39.) Pentoxifylline inhibits the proliferation of human fibroblasts derived

from keloid, scleroderma and morphoea skin and their production of

collagen, glycosaminoglycans and fibronectin.

========================================================================

SO - Br J Dermatol 1990 Sep;123(3):339-46

AU - Berman B; Duncan MR

AD - Department of Dermatology, University of California, Davis School of

Medicine.

AB - Pentoxifylline, an analogue of the methylxanthine theobromine,

inhibits the proliferation and certain biosynthetic activities of

fibroblasts derived from normal human skin. Fibroblasts from the skin of

patients with keloids, scleroderma and morphoea were cultured in vitro in

the presence and absence of pentoxifylline (100-1000 micrograms/ml) to

determine whether it inhibits fibroblast proliferation and the production

of collagen, glycosaminoglycans (GAG), fibronectin and collagenase

activity. The exposure of subconfluent fibroblast cultures to

pentoxifylline resulted in non-lethal, dose-dependent reductions in

serum-driven fibroblast proliferation, with 1000 micrograms/ml

pentoxifylline virtually negating the proliferative effect of serum on the

cells. The fibroblasts assayed as confluent cultures produced reduced

amounts, by up to 95%, of collagen and GAG, dependent on the concentration

of pentoxifylline, both in the presence and absence of serum.

Pentoxifylline similarly inhibited the fibronectin production by keloid and

scleroderma fibroblasts, but had no effect on collagenase activity.

========================================================================

40.) Effects and limitations of pentoxifylline therapy in various stages of

peripheral vascular disease of the lower extremity.

========================================================================

SO - Am J Surg 1990 Sep;160(3):266-70

AU - Abu Rahma AF; Woodruff BA

AD - Department of Surgery, West Virginia University Health Sciences

Center, Charleston.

AB - One hundred one patients with peripheral vascular disease of the

lower extremity were entered into a study of the efficacy of oral

pentoxifylline to determine if the response to therapy varied with the

severity of disease. Ninety-three patients were evaluated before and after

8 weeks of therapy with pentoxifylline, while 8 did not complete the entire

course due to adverse drug reactions. Resting and post-stress ankle/arm

Doppler indices (AAIs) were measured and, in those patients who could walk

on a treadmill, treadmill walking distances were measured. Patients were

classified according to pretreatment clinical and treadmill measurements

and according to pretreatment resting AAIs. Resting and post-stress AAIs,

as well as treadmill walking distances, increased in patients with

moderately severe claudication. Patients in this group responded better to

therapy than did patients with rest pain or ischemic ulcers, severe

claudication, or mild claudication. Patients with a pretreatment resting

AAI greater than or equal to 0.5 responded better than those with an AAI

less than 0.5. Only 5% of patients reported satisfaction with the results

of treatment. These results support the findings that pentoxifylline may be

useful only in selected patients with moderately severe peripheral vascular

disease of the lower extremity and may not be useful in those with severe

or mild disease.

========================================================================

41.) Enhancement of the treatment of experimental candidiasis with vascular

decongestants.

========================================================================

SO - J Infect Dis 1990 Jul;162(1):211-4

AU - Luke DR; Wasan KM; McQueen TJ; Lopez-Berestein G

AD - Department of Pharmaceutics, University of Houston.

AB - The mechanism of amphotericin B (AmB) nephrotoxicity may be related

to changes in vascular flow within the kidney, resulting in significant

decreases in glomerular filtration rate and tubular integrity. The toxic

and antifungal effects of AmB with and without the vascular decongestants

pentoxifylline (PTX) and a methylxanthine analog, HWA-138, were compared in

the murine model of candidiasis. At 48 h after inoculation with Candida

albicans, half of the rats received a single intravenous 0.8 mg/kg dose of

AmB whereas the others were administered sterile water. After 1 h, rats

were randomized to receive three doses of 45 mg/kg PTX intraperitoneally, 5

mg/kg HWA-138 intravenously, or saline every 12 h. Renal function and

Candida cell counts were estimated 24 h after AmB administration. Mean

inulin clearances were significantly greater in rats coadministered AmB and

PTX or HWA-138 than in AmB controls. Candida counts in kidneys of rats

administered HWA-138 were similar independent of AmB therapy and markedly

reduced compared with other groups. Whereas both vascular decongestants

prevented drug-associated renal toxicity, the coadministration of AmB with

HWA-138 resulted in a profound antifungal effect.

========================================================================

42.) Treatment of sickle cell leg ulcers with pentoxifylline.

========================================================================

SO - Int J Dermatol 1990 Jun;29(5):375-6

AU - Frost ML; Treadwell P

AD - Department of Dermatology, Indiana University Medical Center,

Indianapolis.

AB - A 58-year-old black man with leg ulcers of 43 years duration

responded to pentoxifylline 400 mg tid in 8 months. The ability of

pentoxifylline to increase erythrocyte flexibility and decrease blood

viscosity was the basis for our use of this agent. Oral pentoxifylline may

be a useful adjunct in healing sickle cell leg ulcers and preventing their

recurrence.

========================================================================

43.) Oxpentifylline treatment of venous ulcers of the leg [see comments]

========================================================================

CM - Comment in: BMJ 1990 Jun 9; 300(6738):1528; Comment in: BMJ 1990 Jun

30; 300(6741):1725

SO - BMJ 1990 Apr 14;300(6730):972-5

AU - Colgan MP; Dormandy JA; Jones PW; Schraibman IG; Shanik DG; Young RA

AD - Vascular Laboratories, St James's Hospital, Dublin.

AB - OBJECTIVE--To determine the effect of oxpentifylline on the healing

of venous ulcers of the leg. DESIGN--Double blind, randomised, prospective,

placebo controlled, parallel group study. SETTING--Four outpatient clinics

treating leg ulcers in England and the Republic of Ireland. PATIENTS--80

Consecutive patients with clinical evidence of venous ulceration of the leg

in whom appreciable arterial disease was excluded by the ratio of ankle to

brachial systolic pressure being greater than 0.8. INTERVENTIONS--All

patients received either oxpentifylline 400 mg three times a day by mouth

or a matching placebo for six months (or until their reference ulcer healed

if this occurred sooner) in addition to a locally standardised method of

compression bandaging. MAIN OUTCOME MEASURES--The primary end point was

complete healing of the reference ulcer within six months. The secondary

end point was the change in the area of the ulcer over the six month

observation period. RESULTS--Complete healing of the reference ulcer

occurred in 23 of the 38 patients treated with oxpentifylline and in 12 of

the 42 patients treated with a placebo. Life table analysis showed that the

proportion of ulcers healed at six months was 64% in the group treated with

oxpentifylline compared with 34% in the group treated with a placebo (log

rank test chi 2 = 4.78, p = 0.03), which was significant (odds ratio =

1.81, 95% confidence interval 1.20 to 2.71). CONCLUSION--Oxpentifylline

used in conjunction with compression bandaging improves the healing of

venous ulcers of the leg.

========================================================================

44.) Oxpentifylline in endotoxaemia [see comments]

========================================================================

CM - Comment in: Lancet 1990 Mar 3; 335(8688):543

SO - Lancet 1989 Dec 23-30;2(8678-8679):1474-7

AU - Zabel P; Wolter DT; Schonharting MM; Schade UF

AD - Forschungsinstitut Borstel, Medizinische Klinik, Federal Republic of

Germany.

AB - Oxpentifylline (pentoxifylline), which is known to have

pharmacological effects in animal models of respiratory distress syndrome,

multiorgan failure, and shock, was tested in human beings after injection

of endotoxin. Of ten healthy volunteers, nine met the inclusion criterion

of a rise in body temperature of at least 1.0 degrees C after 100 ng

endotoxin (Salmonella abortus equi) as a bolus injection. Serum levels of

tumour necrosis factor alpha (TNF) and interleukin-6 (IL-6) were both

significantly higher than baseline levels 2 h and 3 h after endotoxin

injection. 3 weeks later the nine volunteers were again injected with 100

ng endotoxin and oxpentifylline (500 mg over 4 h) was also infused. There

was no rise in TNF levels, though IL-6 levels rose in parallel with body

temperature. These data suggest that oxpentifylline blocks the

endotoxin-induced synthesis of TNF in man and, therefore, could possibly

have beneficial effects in clinical endotoxaemia.

========================================================================

45.) Pentoxifylline inhibits normal human dermal fibroblast in vitro

proliferation, collagen, glycosaminoglycan, and fibronectin production, and

increases collagenase activity.

========================================================================

SO - J Invest Dermatol 1989 Apr;92(4):605-10

AU - Berman B; Duncan MR

AD - Department of Dermatology, University of California, Davis School of

Medicine.

AB - Fibroblasts from normal human adult skin were cultured in vitro in

the presence and absence of different concentrations of pentoxifylline or a

pentoxifylline analog, A81-3138 (10(-1)-10(3) micrograms/ml). Similar

concentration dependent reductions in normal proliferation of fibroblasts

in fetal calf serum-driven subconfluent cultures were detected following

treatment with pentoxifylline or A81-3138. Fibroblasts assayed as confluent

cultures produced sub-normal amounts of collagen, glycosaminoglycans

(GAGs), and fibronectin in a fashion dependent upon the concentration of

pentoxifylline. In contrast, fibroblasts exposed to pentoxifylline

elaborated double the collagenase activity produced by normal, untreated

fibroblasts. The reduced proliferation and reduced synthetic activities

were not due to a lethal toxic effect on fibroblasts by pentoxifylline and

A81-3138, nor was the reduction in collagen synthesis simply due to an

inability to secrete newly synthesized intracellular collagen. Unlike

pentoxifylline-induced inhibition of collagen and fibronectin production,

which was detected only in cultures supplemented with serum, pentoxifylline

inhibits, to a similar degree, both constitutive and serum-driven

production of GAGs. The addition of IL1 beta (2.5 and 10.0 U/ml) to

serum-driven fibroblast cultures resulted in greater proliferation, which

was inhibitable by the presence of pentoxifylline and A81-3138 as

anti-fibrotic agents in certain disorders of fibrosis.

========================================================================

46.) Pentoxifylline increases extremity blood flow in diabetic

atherosclerotic patients.

========================================================================

SO - Arch Surg 1989 Apr;124(4):434-7

AU - Schwartz RW; Logan NM; Johnson PJ; Strodel WE; Fine JG; Kazmers A;

Hyde GL

AD - Department of Surgery, University of Kentucky, Chandler Medical

Center, Lexington 40536-0084.

AB - Pentoxifylline, a new trisubstituted methylxanthine derivative known

for its hemorrheologic action, has been shown to improve exercise tolerance

in atherosclerotic patients. We examined the responses of diabetic

atherosclerotic patients to pentoxifylline administration, measured by

Doppler waveform analysis and exercise tolerance. Standard exercise

tolerance and Doppler waveform analytic studies of the lower extremity,

specifically the right dorsalis pedis artery, were performed before and

after three months of pentoxifylline administration (400 mg three times a

day). The study group comprised ten subjects (six men and four women) with

a mean (+/- SD) age of 60 +/- 3.3 years. Data were analyzed using a paired

Student t test. All ten subjects showed a significant increase in exercise

tolerance after pentoxifylline treatment. Eight of ten subjects

demonstrated a significant increase in right dorsalis pedis arterial flow.

========================================================================

47.) Treatment of peripheral gangrene due to systemic sclerosis with

intravenous pentoxifylline.

========================================================================

SO - Clin Exp Dermatol 1989 Mar;14(2):161-2

AU - Goodfield MJ; Rowell NR

AB - Vascular problems are very common in systemic sclerosis with 95% of

patients suffering with Raynaud's phenomenon at some stage in their

illness. Acute ischaemic lesions are much less common, but when they occur

are a serious complication, and are often difficult to treat. Many drugs

have been used in this situation, including both oral and intravenous

vaso-dilators and low molecular weight dextran, each with varying degrees

of success. The phospho-diesterase inhibitor, pentoxifylline, is reported

to be useful in peripheral vascular disease, and in Raynaud's phenomenon,

and the intravenous form is indicated for acute peripheral ischaemia,

though its use in the context of connective tissue disease has not so far

been reported. We now report the use of intravenous pentoxifylline in two

patients with acute peripheral gangrene due to systemic sclerosis.

========================================================================

48.) Therapy of livedo vasculitis with pentoxifylline.

========================================================================

SO - Cutis 1988 Nov;42(5):448-53

AU - Ely H; Bard JW

AD - University of California, Davis.

AB - Two patients with idiopathic livedo vasculitis responded favorably to

therapy with pentoxifylline. One patient had responded to fibrinolytic

therapy with phenformin and ethylestrenol before phenformin was taken off

the market. Pentoxifylline (Trental) has multiple mechanisms of action,

including stimulation of prostacyclin synthesis, decreased aggregation of

platelets, increased deformability of red blood cells, increased mobility

of neutrophils, and increased fibrinolysis. All of these factors may

contribute to its successful use in the treatment of idiopathic livedo

vasculitis.

========================================================================

49.) Pentoxifylline therapy in dermatology. A review of localized 

hyperviscosity and its effects on the skin.

========================================================================

SO - Dermatol Clin 1988 Oct;6(4):585-608

AU - Ely H

AD - Department of Dermatology, University of California, Davis.

AB - The conditions treatable with PTX are limited only by our

understanding of disease pathogenesis. Surely the reader will think of new

applications. I would caution at this point that PTX is not the primary

treatment for any cutaneous condition but may be a valuable therapeutic

adjunct.

========================================================================

50.) Augmentation of skin flap survival by parenteral pentoxifylline.

========================================================================

SO - Br J Plast Surg 1988 Sep;41(5):515-20

AU - Roth AG; Briggs PC; Jones EW; Heckler FR

AD - Allegheny-Singer Research Institute, University of Pittsburgh,

Pennsylvania.

AB - One prime factor implicated in flap necrosis is diminished blood

flow. A known corollary of morbid ischaemia is an energy-dependent

reduction in red blood cell deformability associated with an increase in

whole blood viscosity. The newly available drug pentoxifylline is alleged

to improve this red cell membrane defect in the low flow state, thereby

improving the rheologic characteristics of blood. We studied its effect in

a flap model with an ischaemic component and also measured changes in blood

viscosity. A caudally-based dorsal flap in a rat model was used. Control

(saline-treated) animals exhibited 74.8 +/- 9.8% flap survival. Three

groups of animals were treated at different times with pentoxifylline with

respect to date of surgery; all groups showed a statistically significant

increase in flap survival compared to controls, ranging from 92.3 to 94.3%

(p less than .01). Simultaneous viscometric measurements with a cone-plate

viscometer were performed. The observed increase in flap survival did not,

as suggested by other investigators, correlate dependably with viscosity

reduction. Reasons for this are discussed.

========================================================================

51.) Synergistic effects of pentoxifylline and hyperbaric oxygen on skin

flaps.

========================================================================

SO - Arch Otolaryngol Head Neck Surg 1988 Sep;114(9):977-81

AU - Nemiroff PM

AD - Department of Surgery, Southern Illinois University School of

Medicine, Springfield.

AB - This study investigated the effects of pentoxifylline and hyperbaric

oxygen (HBO) on experimental skin flaps in rats under four conditions.

Sixty animals were randomly divided into one of four groups: (1) a control

group, (2) a pentoxifylline- or (3) an HBO-treated group, and (4) a

pentoxifylline- plus HBO-treated group. Cranially based skin flaps were

elevated on the dorsum. The surviving length was evaluated with fluorescein

dye seven days after the operation. Rats that were treated with

pentoxifylline received 20 mg/kg intraperitoneally at 24, 12, and 1 hour(s)

before flap elevation and every 12 hours after the operation for seven

days. Rats that were treated with HBO received a total of 14 two-hour

treatments at 2.5 absolute atmospheres in divided doses. Results indicated

that the surviving length of flaps in the pentoxifylline- or HBO-treated

groups was significantly greater than those in the control group, but were

not significantly different from each other. Animals treated with both

pentoxifylline and HBO had significantly greater flap survival than animals

in any of the other three groups. This reflected a 30% to 39% improvement

over pentoxifylline alone- or HBO alone-treated animals, and an 86%

improvement over control animals. Mechanisms of action for this apparent

synergistic effect on flap survival are discussed.

========================================================================

52.) Pentoxifylline inhibits granulocyte and platelet function, 

including granulocyte priming by platelet activating factor.

========================================================================

SO - J Lab Clin Med 1988 Aug;112(2):254-63

AU - Hammerschmidt DE; Kotasek D; McCarthy T; Huh PW; Freyburger G;

Vercellotti GM

AD - Department of Medicine, University of Minnesota Medical School,

Minneapolis.

AB - Pentoxifylline has been claimed to work a beneficial effect in

arterial insufficiency by improving erythrocyte deformability and thus

improving blood flow. A number of observations, including the drug

concentrations required to work the red cell effect, suggested that this

was not likely to be a complete explanation. We therefore examined the

effect of pentoxifylline on several granulocyte and platelet functions.

Pentoxifylline inhibited platelet aggregation in response to 4 mumol/L

adenosine diphosphate; although statistically significant inhibition was

seen at 1 mumol/L pentoxifylline, over 200 mumol/L was required for 50%

inhibition. The adherence of unstimulated platelets to cultured endothelial

cells was not strongly inhibited by pentoxifylline; however, the additional

increment in adherence seen in the presence of thrombin was strongly

inhibited (50% attenuative dose [AD50] = 18 mumol/L). Granulocyte

aggregation in response to C5a was modestly inhibited (AD30 approximately

equal to 8 mumol/L; AD50 greater than 1 mmol/L), and the adherence of

unstimulated polymorphonuclear neutrophils (PMNs) to endothelium was

uninhibited. The C5a-mediated augmentation of PMN adherence to endothelium

was mildly inhibited (AD50 = 240 mumol/L). Inhibition of PMN chemotaxis to

N-Formyl-methionyl-leucyl-phenylalanine (FMLP) or C5a (AD50 = 12 mumol/L)

and inhibition of superoxide production in response to FMLP-cytochalasin B

(AD50 = 24 mumol/L) were seen at more clinically credible concentrations.

Perhaps most important, pentoxifylline blocked the ability of platelet

activation factor to prime neutrophils for enhanced response to subsequent

stimuli (AD50 approximately equal to 8 mumol/L; AD60 = 10 mumol/L when

production was the indicator system); in vivo, this could broaden the

drug's effect to include functions that it does not inhibit potently in a

primary fashion. Although pentoxifylline is known to be a phosphodiesterase

inhibitor, and we found it to elevate intracellular cyclic adenosine

monophosphate in stimulated PMNs, we found it to be only marginally more

potent than theophylline in this regard; therefore, the failure of

theophylline to inhibit PMN priming suggests that this enzyme inhibition is

not a complete explanation of the pharmacologic action of pentoxifylline.

We suggest that the effects of pentoxifylline on platelet and granulocyte

function are likely to contribute to the drug's clinical efficacy.

========================================================================

53.) Livedo vasculitis. Therapy with pentoxifylline [published erratum

========================================================================

appears in Arch Dermatol 1989 Mar; 125(3):368]

SO - Arch Dermatol 1988 May;124(5):684-7

AU - Sams WM Jr

AD - Department of Dermatology, University of Alabama, Birmingham 35294.

AB - Eight patients with livedo vasculitis of four to 30 years' duration

that was unresponsive to a variety of medications were treated with

pentoxifylline. Three patients experiences complete healing and remained

free of active lesions while receiving the drug, four noted much

improvement, and one had no change.

========================================================================

54.) Pentoxifylline inhibits T-cell adherence to keratinocytes.

========================================================================

SO - J Invest Dermatol 1995 Jun;104(6):1004-7

AU - Bruynzeel I; van der Raaij LM; Stoof TJ; Willemze R

AD - Department of Dermatology, Free University Hospital, Amsterdam, The

Netherlands.

AB - In many inflammatory dermatoses leukocyte function-associated

antigen-1/intercellular adhesion molecule-1 mediated T-cell/keratinocyte

adhesion is considered to play an important role. Pentoxifylline (PTX), a

methylxanthine derivative widely used for the symptomatic treatment of

various vascular disorders, was recently found to have anti-inflammatory

effects. PTX can suppress tumor necrosis factor-alpha production and

function, and inhibits leukocyte-endothelial cell adherence. The aim of the

present study was to investigate whether PTX also interferes with

T-cell/keratinocyte binding. Peripheral blood T cells were activated with

phorbol myristate acetate and co-incubated with interferon-gamma- or tumor

necrosis factor-alpha-stimulated keratinocytes (SVK 14 cells) in the

presence or absence of PTX. Using an enzyme-linked immuno cell adhesion

assay PTX was found to inhibit T-cell/keratinocyte adhesion in a

dose-dependent manner. A similar inhibition was found when PTX was replaced

by isobutylmethylxanthine, another methylxanthine derivative, or by a

combination of two cyclic adenosine monophosphate analogues. No major

effect on T-cell/keratinocyte adherence was observed when PTX was present

during the pre-incubation of keratinocyte monolayers with tumor necrosis

factor-alpha or interferon-gamma prior to the adhesion assay. In

keratinocyte monolayers the interferon-gamma or tumor necrosis factor-alpha

induced intercellular adhesion molecule-1 expression could not be inhibited

by PTX. However, when PTX was added to short-term organ cultures of normal

human skin biopsies, the lipopolysaccharide- and tumor necrosis

factor-alpha-induced keratinocyte intercellular adhesion molecule-1

expression was blocked completely. The interferon-gamma-induced ICAM-1

expression was not blocked by PTX. The results presented herein suggest

that impaired T-cell/keratinocyte binding may be one of the mechanisms by

which PTX exerts a beneficial effect in certain inflammatory dermatoses.

========================================================================

55.) Pentoxifylline promotes replication of human cytomegalovirus in vivo

and in vitro. 

========================================================================

Author 

Staak K; Prosch S; Stein J; Priemer C; Ewert R; Docke WD; Kruger DH; Volk

HD; Reinke P 

Address 

Institute of Medical Virology, Medical Clinic V-Nephrology, Medical Faculty

(Charite), Humboldt Universitat zu Berlin, Germany. 

Source 

Blood, 89(10):3682-90 1997 May 15 

Abstract 

OKT3 monoclonal antibody (MoAb) therapy is well established in the

prevention and therapy of acute rejection in transplant patients.

Unfortunately, this therapy is associated with several short-term (cytokine

release syndrome) and long-term (infections, EBV-related lymphoma) side

effects. Recently, we were able to demonstrate an association between the

TNF alpha release following the first OKT3 MoAb infusions and the

appearance of human cytomegalovirus (HCMV) reactivation several days later.

In order to prevent this TNF alpha associated HCMV reactivation patients

were additionally treated with pentoxifylline (PTX), a methylxanthine

derivative that has been shown to suppress TNF alpha induction. Although

the TNF alpha peak plasma level following OKT3 MoAb treatment was markedly

reduced, the incidence of HCMV reactivation and HCMV disease was not

influenced. In transient transfection experiments using HCMV immediate

early enhancer/promoter CAT reporter gene constructs PTX enhanced the

promoter activity independently from TNF alpha in premonocytic cells.

Furthermore, PTX acted synergistically with TNF alpha. In virus-infected

human embryonal lung fibroblasts HCMV replication was triggered in the

presence of both PTX and TNF alpha, while either substance alone had only

marginal effects. The stimulatory effect of PTX on the immediate early (IE)

enhancer/promoter was mediated via CREB/ ATF, a eukaryotic transcription

factor that binds to the 19 bp sequence motif in the enhancer region, while

TNF alpha stimulation was mediated by activation of the transcription

factor NF-kappaB and its binding to the 18 bp sequence motif in the

enhancer. These data suggest a potential side effect of cAMP-elevating

drugs such as PTX. 

Language 

========================================================================

56.) intravenous and oral pentoxifylline in the treatment of peripheral vascular disease. A clinical trial.

==========================================================================

Int Angiol. 1990 Oct-Dec;9(4):266-70.

Thomson GJ1, Thomson S, Todd AS, Vohra RK, Carr MH, Walker MG.

Author information

1

Department of Vascular Surgery, Manchester Royal Infirmary, Gran Bretagna.

Abstract

Sixteen patients with severe occlusive vascular disease of the lower extremities were randomised to receive a five day course of combined intravenous and oral Pentoxifylline followed by three months oral treatment only, or identical treatment with a matching placebo. Nine patients received active Pentoxifylline, and 7 placebo, Follow-up by regular clinical examination and haemoreological assessment revealed a marked improvement in claudication distance and an increase in red cell deformability in those receiving Pentoxifylline, there being no change in those receiving placebo. Although both of the above parameters were improved by the treatment, there did not appear to be a direct correlation between red cell deformability and claudication distance in individual patients. A combination of intravenous and oral Pentoxifylline therapy results in an increase in both claudication distance and red cell deformability, but the former may not te a direct consequence of the latter.

==========================================================================

57.) Targeting inflammation in diabetic kidney disease: early clinical trials.

==========================================================================

Expert Opin Investig Drugs. 2016 Sep;25(9):1045-58. doi: 10.1080/13543784.2016.1196184. Epub 2016 Jun 13.

Perez-Gomez MV1,2, Sanchez-Niño MD1,2, Sanz AB1,2, Zheng B1, Martín-Cleary C1,2, Ruiz-Ortega M1,2, Ortiz A1,2, Fernandez-Fernandez B1,2.

Author information

1

a Division of Nephrology and Hypertension and FRIAT, IIS-Fundacion Jimenez Diaz, School of Medicine , UAM , Madrid , Spain.

2

b REDINREN , Madrid , Spain.

Abstract

INTRODUCTION:

The age-standardized death rate from diabetic kidney disease increased by 106% from 1990 to 2013, indicating that novel therapeutic approaches are needed, in addition to the renin-angiotensin system (RAS) blockers currently in use. Clinical trial results of anti-fibrotic therapy have been disappointing. However, promising anti-inflammatory drugs are currently on phase 1 and 2 randomized controlled trials.

AREAS COVERED:

The authors review the preclinical, phase 1 and 2 clinical trial information of drugs tested for diabetic kidney disease that directly target inflammation as a main or key mode of action. Agents mainly targeting other pathways, such as endothelin receptor or mineralocorticoid receptor blockers and vitamin D receptor activators are not discussed.

EXPERT OPINION:

Agents targeting inflammation have shown promising results in the treatment of diabetic kidney disease when added on top of RAS blockade. The success of pentoxifylline in open label trials supports the concept of targeting inflammation. In early clinical trials, the pentoxifylline derivative CTP-499, the CCR2 inhibitor CCX140-B, the CCL2 inhibitor emapticap pegol and the JAK1/JAK2 inhibitor baricitinib were the most promising drugs for diabetic kidney disease. The termination of trials testing the anti-IL-1β antibody gevokizumab in 2015 will postpone the evaluation of therapies targeting inflammatory cytokines.

==========================================================================

58.) Pentoxifylline for Diabetic Nephropathy: an Important Opportunity to Re-purpose an Old Drug?

===========================================================================

Curr Hypertens Rep. 2016 Jan;18(1):8. doi: 10.1007/s11906-015-0612-7.

Bhanot S1, Leehey DJ2,3.

Author information

1

George Washington University School of Medicine, Washington, DC, USA.

2

Loyola University Stritch School of Medicine, Maywood, IL, USA. david.leehey@va.gov.

3

Hines VA Hospital, 111L, Hines, IL, 60141, USA. david.leehey@va.gov.

Abstract

Diabetic nephropathy, or diabetic kidney disease (DKD), is the most serious complication of diabetes mellitus (DM). Despite recent advances in therapy, DKD still often progresses to end-stage renal disease (ESRD). Recent studies have suggested that pentoxifylline (PTX) may be efficacious in the treatment of DKD. PTX is a rheologic modifier approved for use in the USA for the symptomatic relief of claudication. It competitively inhibits phosphodiesterase (PDE), resulting in increased intracellular cyclic AMP (cAMP), activation of protein kinase A (PKA), inhibition of interleukin (IL) and tumor necrosis factor (TNF) synthesis, and reduced inflammation. PTX improves red blood cell deformability, reduces blood viscosity, and decreases platelet aggregation. In combination with renin-angiotensin-aldosterone (RAAS) blockers, PTX may help prevent progression to ESRD in patients with DKD. This review focuses on the possible mechanisms of action of PTX in DKD and studies suggesting possible efficacy of this old drug for a new indication.

==========================================================================

59.) Improvements in the Management of Diabetic Nephropathy.

==========================================================================

Rev Diabet Stud. 2015 Spring-Summer;12(1-2):119-33. doi: 10.1900/RDS.2015.12.119. Epub 2015 Aug 10.

Dounousi E1, Duni A1, Leivaditis K2, Vaios V2, Eleftheriadis T2, Liakopoulos V2.

Author information

1

University of Ioannina, School of Health Siences, Department of Internal Medicine, Division of Nephrology, Ioannina, Greece.

2

Division of Nephrology and Hypertension, 1st Department of Internal Medicine, AHEPA Hospital, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece.

Abstract

The burden of diabetes mellitus is relentlessly increasing. Diabetic nephropathy is the most common cause of end-stage renal disease (ESRD) worldwide and a major cause of morbidity and mortality in patients with diabetes. The current standard therapy of diabetic nephropathy involves intensive treatment of hyperglycemia and strict blood pressure control, mainly via blockade of the renin-angiotensin system (RAS). Attention has been drawn to additional beneficial effects of oral hypoglycemic drugs and fibrates on other aspects of diabetic nephropathy. On the other hand, antiproteinuric effects of RAS combination therapy do not seem to enhance the prevention of renal disease progression, and it has been associated with an increased rate of serious adverse events. Novel agents, such as bardoxolone methyl, pentoxifylline, inhibitors of protein kinase C (PKC), sulodexide, pirfenidone, endothelin receptor antagonists, vitamin D supplements, and phosphate binders have been associated with controversial outcomes or significant side effects. Although new insights into the pathogenetic mechanisms have opened new horizons towards novel interventions, there is still a long way to go in the field of DN research. The aim of this review is to highlight the recent progress made in the field of diabetes management based on the existing evidence. The article also discusses novel targets of therapy, with a special focus on the major pathophysiologic mechanisms implicated in the initiation and progression of diabetic nephropathy.

==========================================================================

60.) Improvements in the Management of Diabetic Nephropathy.

==========================================================================

Rev Diabet Stud. 2015 Spring-Summer;12(1-2):119-33. doi: 10.1900/RDS.2015.12.119. Epub 2015 Aug 10.

Dounousi E1, Duni A1, Leivaditis K2, Vaios V2, Eleftheriadis T2, Liakopoulos V2.

Author information

1

University of Ioannina, School of Health Siences, Department of Internal Medicine, Division of Nephrology, Ioannina, Greece.

2

Division of Nephrology and Hypertension, 1st Department of Internal Medicine, AHEPA Hospital, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece.

Abstract

The burden of diabetes mellitus is relentlessly increasing. Diabetic nephropathy is the most common cause of end-stage renal disease (ESRD) worldwide and a major cause of morbidity and mortality in patients with diabetes. The current standard therapy of diabetic nephropathy involves intensive treatment of hyperglycemia and strict blood pressure control, mainly via blockade of the renin-angiotensin system (RAS). Attention has been drawn to additional beneficial effects of oral hypoglycemic drugs and fibrates on other aspects of diabetic nephropathy. On the other hand, antiproteinuric effects of RAS combination therapy do not seem to enhance the prevention of renal disease progression, and it has been associated with an increased rate of serious adverse events. Novel agents, such as bardoxolone methyl, pentoxifylline, inhibitors of protein kinase C (PKC), sulodexide, pirfenidone, endothelin receptor antagonists, vitamin D supplements, and phosphate binders have been associated with controversial outcomes or significant side effects. Although new insights into the pathogenetic mechanisms have opened new horizons towards novel interventions, there is still a long way to go in the field of DN research. The aim of this review is to highlight the recent progress made in the field of diabetes management based on the existing evidence. The article also discusses novel targets of therapy, with a special focus on the major pathophysiologic mechanisms implicated in the initiation and progression of diabetic nephropathy.

==========================================================================

61.) Renoprotective effect of combining pentoxifylline with angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker in advanced chronic kidney disease.

==========================================================================

J Formos Med Assoc. 2014 Apr;113(4):219-26. doi: 10.1016/j.jfma.2014.01.002. Epub 2014 Feb 7.

Chen PM1, Lai TS2, Chen PY3, Lai CF1, Wu V1, Chiang WC4, Chen YM1, Wu KD1, Tsai TJ1.

Author information

1

Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.

2

Department of Internal Medicine, National Taiwan University Hospital, Bei-Hu Branch, Taipei, Taiwan.

3

Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Department of Internal Medicine, Chi Mei Medical Center, Chiali Campus, Tainan, Taiwan.

4

Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan. Electronic address: wcchiang@ntu.edu.tw.

Abstract

BACKGROUND/PURPOSE:

Several studies have shown the renoprotective effects of pentoxifylline in the treatment of chronic kidney disease (CKD). This study was conducted to examine whether there was an increased benefit of including pentoxifylline with angiotensin-converting enzyme inhibitor (ACEI) or angiotensin II receptor blocker (ARB) in the treatment of CKD.

METHODS:

A single-center retrospective analysis was conducted. A total of 661 Stage 3B-5 CKD patients who received ACEI or ARB treatment were recruited. The patients were divided into the pentoxifylline use group and the no pentoxifylline group. Renal survival analysis of the two groups was compared. Subgroup analysis was performed by dividing the patients into lower [urine protein to creatinine ratio (UPCR)<1 g/g] and higher (UPCR ≥ 1 g/g) proteinuria subgroups.

RESULTS:

There was no between-groups difference regarding mortality and cardiovascular events. Addition of pentoxifylline showed a better renal outcome (p = 0.03). The protective effect of add-on pentoxifylline was demonstrated in the higher proteinuria subgroup (p = 0.005). In the multivariate Cox regression model, pentoxifylline use also showed a better renal outcome [hazard ratio (HR): 0.705; 95% confidence interval (CI): 0.498-0.997; p = 0.048]. This effect was more prominent in the higher proteinuria subgroup (HR: 0.602; 95% CI: 0.413-0.877; p = 0.008).

CONCLUSION:

In the advanced stages of CKD, patients treated with a combination of pentoxifylline and ACEI or ARB had a better renal outcome than those treated with ACEI or ARB alone. This effect was more prominent in the higher proteinuria subgroup. More large randomized control trials are needed to provide concrete evidence of the add-on effect of pentoxifylline.

==========================================================================

62.) Diagnosis and Management of Alcoholic Liver Disease.

==========================================================================

J Clin Transl Hepatol. 2015 Jun 28;3(2):109-16. doi: 10.14218/JCTH.2015.00008. Epub 2015 Jun 15.

Dugum M1, McCullough A2.

Author information

1

Department of Internal Medicine, Medicine Institute, Cleveland Clinic, Cleveland, Ohio, USA;

2

Department of Gastroenterology and Hepatology, Digestive Disease Institute, Cleveland Clinic, Cleveland, Ohio, USA.

Abstract

Alcohol is a leading cause of liver disease and is associated with significant morbidity and mortality. Several factors, including the amount and duration of alcohol consumption, affect the development and progression of alcoholic liver disease (ALD). ALD represents a spectrum of liver pathology ranging from fatty change to fibrosis to cirrhosis. Early diagnosis of ALD is important to encourage alcohol abstinence, minimize the progression of liver fibrosis, and manage cirrhosis-related complications including hepatocellular carcinoma. A number of questionnaires and laboratory tests are available to screen for alcohol intake. Liver biopsy remains the gold-standard diagnostic tool for ALD, but noninvasive accurate alternatives, including a number of biochemical tests as well as liver stiffness measurement, are increasingly being utilized in the evaluation of patients with suspected ALD. The management of ALD depends largely on complete abstinence from alcohol. Supportive care should focus on treating alcohol withdrawal and providing enteral nutrition while managing the complications of liver failure. Alcoholic hepatitis (AH) is a devastating acute form of ALD that requires early recognition and specialized tertiary medical care. Assessment of AH severity using defined scoring systems is important to allocate resources and initiate appropriate therapy. Corticosteroids or pentoxifylline are commonly used in treating AH but provide a limited survival benefit. Liver transplantation represents the ultimate therapy for patients with alcoholic cirrhosis, with most transplant centers mandating a 6 month period of abstinence from alcohol before listing. Early liver transplantation is also emerging as a therapeutic measure in specifically selected patients with severe AH. A number of novel targeted therapies for ALD are currently being evaluated in clinical trials.

==========================================================================

63.) Advances in alcoholic liver disease: An update on alcoholic hepatitis.

==========================================================================

World J Gastroenterol. 2015 Nov 14;21(42):11893-903. doi: 10.3748/wjg.v21.i42.11893.

Liang R1, Liu A1, Perumpail RB1, Wong RJ1, Ahmed A1.

Author information

1

Randy Liang, Department of Medicine, Santa Clara Valley Medical Center, San Jose, CA 95128, United States.

Abstract

Alcoholic hepatitis is a pro-inflammatory chronic liver disease that is associated with high short-term morbidity and mortality (25%-35% in one month) in the setting of chronic alcohol use. Histopathology is notable for micro- and macrovesicular steatosis, acute inflammation with neutrophil infiltration, hepatocellular necrosis, perivenular and perisinusoidal fibrosis, and Mallory hyaline bodies found in ballooned hepatocytes. Other findings include the characteristic eosinophilic fibrillar material (Mallory's hyaline bodies) found in ballooned hepatocytes. The presence of focal intense lobular infiltration of neutrophils is what typically distinguishes alcoholic hepatitis from other forms of hepatitis, in which the inflammatory infiltrate is primarily composed of mononuclear cells. Management consists of a multidisciplinary approach including alcohol cessation, fluid and electrolyte correction, treatment of alcohol withdrawal, and pharmacological therapy based on the severity of the disease. Pharmacological treatment for severe alcoholic hepatitis, as defined by Maddrey's discriminant factor ≥ 32, consists of either prednisolone or pentoxifylline for a period of four weeks. The body of evidence for corticosteroids has been greater than pentoxifylline, although there are higher risks of complications. Recently head-to-head trials between corticosteroids and pentoxifylline have been performed, which again suggests that corticosteroids should strongly be considered over pentoxifylline.

==========================================================================

64.) Use of pentoxifylline and tocopherol in radiation-induced fibrosis and fibroatrophy.

==========================================================================

Br J Oral Maxillofac Surg. 2017 Apr;55(3):235-241. doi: 10.1016/j.bjoms.2016.11.323. Epub 2016 Dec 24.

Patel V1, McGurk M2.

Author information

1

Oral Surgery Dept, Floor 23, Guys Dental Hospital, London Bridge, London, SE1 9RT. Electronic address: Vinod.Patel@hotmail.co.uk.

2

Department of Oral and Maxillofacial Surgery, Atrium 3, 3rd Floor, Bermondsey Wing, Guy's Hospital, London, SE1 9RT. Electronic address: Mark.mcgurk@kcl.ac.uk.

Abstract

Radiation-induced fibrosis in the head and neck is a well-established pathophysiological process after radiotherapy. Recently pentoxifylline and tocopherol have been proposed as treatments to combat the late complications of radiation-induced fibrosis and a way of dealing with osteoradionecrosis. They both have a long history in the management of radiation-induced fibrosis at other anatomical sites. In this paper we review their use in sites other than the head and neck to illustrate the potential benefit that they offer to our patients.

==========================================================================

65.) Prophylactic use of pentoxifylline (Trental) and vitamin E to prevent capsular contracture after implant reconstruction in patients requiring adjuvant radiation.

==========================================================================

Cook M1, Johnson N2, Zegzula HD3, Schray M4, Glissmeyer M5, Sorenson L6.

Author information

1

Oncology Clinical Research, Legacy Health, Portland, OR, USA.

2

Legacy Medical Group- Surgical Oncology, NW 1040 22nd Ave, Portland, OR, 97210, USA. Electronic address: nemtipi@aol.com.

3

Portland Plastic Surgery Group, Portland, OR, USA.

4

Legacy Medical Group- Radiation Oncology, Portland, OR, USA.

5

Legacy Medical Group- Surgical Oncology, NW 1040 22nd Ave, Portland, OR, 97210, USA.

6

Oncology Clinical Research, Legacy Health, Portland, OR, USA; Legacy Medical Group- Surgical Oncology, NW 1040 22nd Ave, Portland, OR, 97210, USA.

Abstract

BACKGROUND:

The combination of pentoxifylline (Trental) and vitamin E has been reported to reverse significant consequences of radiation after mastectomy with immediate reconstruction, such as severe capsular contracture or loss of implants. We questioned whether prophylactic use could prevent these consequences.

METHODS:

Thirty women with implants or tissue expanders after mastectomy that underwent adjuvant radiation were treated with Trental and vitamin E for 180 days. All subjects then entered a 12-month observational phase.

RESULTS:

Of the 26 evaluable subjects, 3 subjects required implant revisions. One due to malposition of the nonradiated breast and 2 were due to contracture (7.7%). There were no implant losses.

CONCLUSIONS:

The combination of Trental and vitamin E can prevent severe contracture and implant losses allowing for immediate reconstruction with implant or tissue expander even if radiation is planned after mastectomy.

======================================================================

DATA-MÉDICOS/DERMAGIC-EXPRESS No (37) 09/02/99 DR. JOSE LAPENTA R. 

======================================================================

Produced by Dr. José Lapenta R. Dermatologist

Venezuela 1.998-2.024

Producido por Dr. José Lapenta R. Dermatólogo
Venezuela 1.998-2.024

Tlf: 0414-2976087 - 04127766810