|
The
Pentoxyfilline. La pentoxifilina.
***********************************
Estas 65 referencias nos hablan sobre sus mecanismos de
acción y algunas de las enfermedades donde se esta utilizando. Al final una
monografía del producto.
EDITORIAL ENGLISH:
These 65 references talk us about their action mechanisms and some of the illnesses where they are using it. At the end a monograph of the product.
NEXT EDITION: THE MERKEL CELL CARCIMONA !!! ==================================================================== 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. 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. 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. ======================================================================== 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. ======================================================================== 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. ======================================================================== 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. 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. ======================================================================== 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. 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. 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. 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. 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. 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. 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. ======================================================================== 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.
AB - A 60-year-old HIV-negative man with known noninsulin-dependentdiabetes 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. 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. ======================================================================== 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. 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. 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. 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. 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. 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.
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.
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. 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. ======================================================================== 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. 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. 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. ======================================================================== 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. ======================================================================== 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. ======================================================================== 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. Abstract INTRODUCTION: ========================================================================== ========================================================================== 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. ========================================================================== BACKGROUND/PURPOSE: 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. ========================================================================== 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. ========================================================================== ========================================================================== BACKGROUND:
==========================================================================
====================================================================== |
||||
|
|
|
|||
|
Produced by Dr. José Lapenta R.
Dermatologist
|
|
|||
|
|
||||