Pentoxifylline Treatment Research Articles

Covering the Cover

Covering the Cover

Pentoxifylline Treatment in Severe Acute Pancreatitis: A Pilot, Double-Blind, Placebo-Controlled, Randomized Trial

In acute pancreatitis (AP) tumor necrosis factor-α mediates multi-organ failure; in animal models its blockade with pentoxifylline ameliorates AP. The efficacy of pentoxifylline in predicted severe AP (pSAP) was tested in a double-blinded, randomized, control trial. Twenty-eight patients with pSAP were randomized within 72 hours of diagnosis to pentoxifylline or placebo. Baseline characteristics were similar in both groups. The pentoxifylline grouphad fewer intensive care unit admissions and shorter intensive care unit and hospital stays of longer than 4 days (all P < .05). Patients receiving pentoxifylline had no adverse effects. Pentoxifylline within 72 hours of pSAP is safe; a larger study of pentoxifylline in AP is needed to confirm efficacy. ClinicalTrials.gov number: NCT01292005.

Effects and clinical significance of pentoxifylline on the oxidative stress of rats with diabetic nephropathy.

Diabetic nephropathy (DN) is a common and serious clinical complication of diabetes and presently there are no effective ways to prevent its occurrence and progression. Recent studies show that pentoxifylline (PTX) can improve renal hemodynamics, reduce urinary protein excretion, and alleviate or delay renal failure in DN patients. In this study, we focused on the anti-oxidative stress effect of PTX on alleviating renal damages of DN using rat models. DN rats were established with injection of streptozotocin. Blood glucose, urinary protein excretion, serum cystatin C, renal biopsy, superoxide dismutase (SOD) and malondialdehyde (MDA) in serum and renal homogenate and renal nitrotyrosine levels were analyzed before and 12 weeks after the treatment of PTX. Before treatment, all the DN rats had elevated blood glucose, increased urinary protein excretion and elevated serum cystatin C. Morphologically, DN rats exhibited renal tissue damages, including swelling and fusions of foot processes of podocytes under electron microscope. Masson staining revealed blue collagen deposition in glomeruli and renal interstitium. With treatment of PTX, symptoms and renal pathological changes of DN rats were alleviated. Furthermore, the MDA levels were increased and the SOD levels were decreased in the serum and kidneys of DN rats, and these changes were reversed by PTX. The expression of nitrotyrosine was up-regulated in DN rat model and down-regulated by PTX, indicating that PTX was able to inhibit oxidative reactions in DN rats. PTX could alleviate renal damage in DN, which may be attributable to its anti-oxidative stress activity.

Pentoxifylline immunomodulation in the treatment of experimental chronic pulmonary paracoccidioidomycosis.

BackgroundPentoxifylline (PTX) is a methylxanthine compound with immunomodulatory and antifibrotic properties. The simultaneous use of PTX and antifungal therapy (itraconazole) has previously been evaluated in an experimental model of pulmonary paracoccidioidomycosis (PCM), a systemic fungal disease caused by the fungus Paracoccidioides brasiliensis (Pb) and characterized by chronic inflammation and lung fibrosis that appears even after a successful course of antifungal therapy. The results revealed prompt and statistically significant reductions in inflammation and fibrosis when compared to itraconazole alone. However, the effect of monotherapy with PTX on the host response to PCM has not been well-documented. Our aim was to determine the effect of PTX on the course of pulmonary lesions and on the local immune response.ResultsAt the middle and end of treatment, the Pb-infected-PTX-treated mice exhibited significant reductions in lung density compared to the Pb-infected-non-treated mice as assessed by the quantification of Hounsfield units on high-resolution computed tomography (HRCT) (p <0.05 by Kruskal-Wallis test); additionally, at the end of therapy, the lung areas involved in the inflammatory reactions were only 3 vs. 22 %, respectively, by histomorphometry (p <0.05 by Mann–Whitney test), and this reduction was associated with a lower fungal burden and limited collagen increment in the pulmonary lesions. PTX treatment restored the levels of IFN-γ, MIP-1β, and IL-3 that had been down-regulated by Pb infection. Additionally, IL-12p70, IL-10, IL-13, and eotaxin were significantly increased, whereas Regulated upon Activation, Normal T cell Expressed and Secreted (RANTES) levels were decreased in the lungs of the Pb-infected-PTX-treated mice compared to the non-treated group.Conclusions/significanceThis study showed that PTX therapy administered at an “early” stage of granulomatous inflammation controlled the progress of the PCM by diminishing the pulmonary inflammation and the fungal burden and avoiding the appearance of collagen deposits in the pulmonary lesions.

Pentoxifylline reduces the inflammatory process in diabetic rats: relationship with decreases of pro-inflammatory cytokines and inducible nitric oxide synthase.

Studies suggest that inflammation is a key factor in the pathogenesis of diabetes mellitus. Pro-inflammatory cytokines, such as IL-6 and TNF-alpha, are produced by adipose tissue in large quantities, in obese and especially in diabetic individuals. Pentoxifylline (PTX) is a non-selective phosphodiesterase inhibitor with anti-inflammatory and antioxidant actions that may contribute to alleviate diabetes side effects, as neuropathy, retinopathy and nephropathy. This study aims to investigate PTX anti-inflammatory effects on the carrageenan-induced paw edema model, in alloxan-induced diabetic rats. Diabetic animals (male Wistar rats, 200–250 g) were daily treated with PTX (25, 50, 100 mg/kg, p.o.), glibenclamide (GLI, 5 mg/kg, p.o., as reference) or water, for 5 days. Afterwards, carrageenan-treated paws were dissected, their skin removed and the tissue used for preparation of homogenates and measurements of IL-6 and TNF-alpha by Elisa. Serum levels of nitrite were also determined and paw slices used for iNOS immunohistochemistry assays. We showed that diabetic rats presented an amplification of the inflammatory response, as related to non-diabetic rats, what was evident 48 h after the edema-induction. The PTX-treatment of diabetic rats reduced glycemia (as related to untreated-diabetic ones) and the paw edema. It also brought edema volumes to values similar to those of non-diabetic rats, at the same observation time. The increased TNF-alpha and IL-6 levels in paws of untreated-diabetic rats were reduced in diabetic animals after PTX treatments. Besides, the increased levels of nitrite in the serum of diabetic rats were also decreased by PTX. Furthermore, a higher number of iNOS immunostained cells was demonstrated in paw tissues from untreated-diabetic rats, as related to those of PTX-treated diabetic animals. Our results show that PTX reduces inflammatory parameters, as pro-inflammatory cytokines and iNOS expression, indicating the potential benefit of the drug for the treatment of diabetes and related pathologic conditions.

Pentoxifylline for treatment of sepsis and necrotizing enterocolitis in neonates.

Mortality and morbidity due to neonatal sepsis and necrotizing enterocolitis (NEC) remain high despite the use of potent antimicrobial agents. Agents that modulate inflammation may improve outcomes. Pentoxifylline, a phosphodiesterase inhibitor, is one such agent. Our primary objectives were :1.To assess the effect of intravenous pentoxifylline as an adjunct to antibiotic therapy on mortality and morbidity in neonates with suspected or confirmed sepsis.2.To assess the effect of intravenous pentoxifylline as an adjunct to antibiotic therapy on mortality and morbidity in neonates with NEC. We searched the Cochrane Neonatal Review Group Specialized Register, CENTRAL (The Cochrane Library Issue 2, 2014), EMBASE (January 1980 to May 2014), PubMed (January 1966 to May 2014), CINAHL (January 1982 to May 2014), Science Citation Index (January 1990 to May 2014), and BIOSIS (January 1992 May 2014) in May 2014. We checked references and cross-references from identified studies. We handsearched abstracts from the proceedings of the Pediatric Academic Societies Meetings (from January 1990 to May 2014). We placed no restrictions on language. We included randomised or quasi-randomised trials assessing the efficacy of pentoxifylline as an adjunct to antibiotics for treatment of suspected or confirmed sepsis or NEC in neonates. We reported typical risk ratio (RR) and risk difference (RD) with 95% confidence intervals (CI) using fixed-effect model for dichotomous outcomes and mean difference (MD) for continuous outcomes. We calculated the number needed to treat for an additional beneficial outcome (NNTB) if there was a statistically significant reduction in RD. Pentoxifylline used as an adjunct to antibiotics in neonates with sepsis decreased all-cause mortality during hospital stay (typical RR 0.57, 95% CI 0.35 to 0.93; typical RD -0.08, 95% CI -0.14 to -0.01; NNTB 13, 95% CI 7 to 100; 6 studies, 416 participants, low-quality evidence). Subgroup analyses revealed decrease in mortality in preterm infants, infants with confirmed sepsis, and infants with gram-negative sepsis (low-quality evidence, four studies). Pentoxifylline decreased length of hospital stay (MD -7.59 days, 95% CI -11.65 to -3.52; 2 studies, 148 participants, low-quality evidence). Pentoxifylline did not change the risk of development of NEC, chronic lung disease, severe intraventricular haemorrhage, retinopathy of prematurity, or periventricular leukomalacia in neonates with sepsis (one to two studies, very low-quality evidence). Pentoxifylline therapy compared to pentoxifylline and immunoglobulin M-enriched intravenous immunoglobulin or immunoglobulin M-enriched intravenous immunoglobulin alone did not change mortality or development of NEC in neonates with sepsis (one study, very low-quality evidence). We noted no adverse effects due to pentoxifylline. We identified no trials evaluating pentoxifylline treatment for NEC. Low-quality evidence from six small studies suggests that pentoxifylline therapy as an adjunct to antibiotics in neonatal sepsis decreases mortality without any adverse effects. We encourage researchers to undertake large, well-designed multicentre trials to confirm or refute the effectiveness of pentoxifylline in reducing mortality and morbidity in neonates with sepsis or NEC.

Investigating the effects of Pentoxifylline on human breast cancer cells using Raman spectroscopy

Breast cancer is one of the leading causes of cancer-related deaths in a global scenario. In the present study, biochemical changes exerted upon Pentoxifylline (PTX) treatment had been appraised in human breast cancer cells using Raman spectroscopy. There are no clinically approved methods to monitor such therapeutic responses available. The spectral profiling is suggestive of changes in DNA, protein and lipid contents showing a linear relationship with drug dosage. Further, multivariate analysis using principal-component based linear-discriminant-analysis (PC-LDA) was employed for classifying the control and the PTX treated groups. These findings support the feasibility of Raman spectroscopy as an alternate/adjunct label-free, objective method for monitoring drug-induced modifications against breast cancer cells.

Immunotherapeutic effects of pentoxifylline in type 1 diabetic mice and its role in the response of T-helper lymphocytes.

Pentoxifylline is an immunomodulatory and anti-inflammatory agent and is used in vascular disorders. It has been shown that pentoxifylline inhibits proinflammatory cytokines production. The purpose of this study was to investigate the therapeutic effects of pentoxifylline on the treatment of autoimmune diabetes in mice. Diabetes was induced by multiple low dose of streptozotocin (MLDS) injection (40 mg/kg/day for 5 consecutive days) in male C57BL/6 mice. After induction of diabetes, mice were treated with pentoxifylline (100 mg/kg/day IP) for 21 days. Blood glucose levels and plasma levels of insulin were measured. Splenocytes were tested for proliferation by MTT test and cytokine production by ELISA. Pentoxifylline treatment prevented hyperglycemia and increased plasma insulin levels in the diabetic mice. Aside from reducing lymphocyte proliferation, pentoxifylline significantly inhibited the production of proinflammatory interleukin 17 (IL-17) as well as interferon gamma (IFN-γ), while increased anti-inflammatory cytokine IL-10 as compared with those in MLDS group (diabetic control group). These findings indicate that pentoxifylline may have therapeutic effect against the autoimmune destruction of the pancreatic beta-cells during the development of MLDS-induced type 1 diabetes in mice.

Is petoxifylline still an option in severe alcoholic hepatitis?

Abstract Background &amp; Aims: Both corticosteroids and pentoxifylline reduce short-term mortality in severe alcoholic hepatitis. However, few studies have directly compared the efficacy of pentoxifylline and corticosteroids in patients with this condition. Methods: In this multicentre, open-labelled, randomized non-inferiority trial, we assigned 121 patients with severe alcoholic hepatitis (Maddrey's discriminant function &gt;32) to receive either pentoxifylline (400 mg, three times daily, in 62 subjects) or prednisolone (40 mg daily, in 59 subjects). The primary end point was non-inferiority in survival at the 1 month time point for the pentoxifylline treatment compared with prednisolone. Results: The 1-month survival rate of patients receiving pentoxifylline was 75.8% (15 deaths) compared with 88.1% (7 deaths) in those taking prednisolone, for a treatment difference of 12.3% (95% confidence interval, −4.2% to 28.7%; p = 0.08). The 95% confidence interval for the observed difference exceeded the predefined margin of non-inferiority (15%) and included zero. The 6-month survival rate was not significantly different between the pentoxifylline and prednisolone groups (64.5% vs 72.9%; p = 0.23). At 7 days the response to therapy assessed by the Lille model was significantly lower in the prednisolone group (n = 58) than in the pentoxifylline group (n = 59): 0.35 vs 0.50 ( p = 0.012). Hepatitis complications, including hepatorenal syndrome and side effects such as infection and gastrointestinal bleeding, were similar in the two groups. Conclusions: The findings demonstrate that the efficacy of the pentoxifylline is not statistically equivalent to the efficacy of prednisolone, supporting the use of prednisolone as a preferred treatment option in patients with severe alcoholic hepatitis.

Artificial oocyte activation in intracytoplasmic sperm injection cycles using testicular sperm in human in vitro fertilization.

ObjectiveArtificial oocyte activation (AOA) is an effective method to avoid total fertilization failure in human in vitro fertilization-embryo transfer (IVF-ET) cycles. AOA performed using a calcium ionophore can induce calcium oscillation in oocytes and initiate the fertilization process. We evaluated the usefulness of AOA with a calcium ionophore in cases of total fertilization failure in previous cycles and in cases of severe male factor infertility patients with non-motile spermatozoa after pentoxifylline (PF) treatment.MethodsThe present study describes 29 intracytoplasmic sperm injection (ICSI)-AOA cycles involving male factor infertility at Cheil General Hospital from January 2006 to June 2013. Patients were divided into two groups (control, n=480; AOA, n=29) depending on whether or not AOA using a calcium ionophore (A23187) was performed after testicular sperm extraction-ICSI (TESE-ICSI). The AOA group was further split into subgroups according to sperm motility after PF treatment: i.e., motile sperm-injected (n=12) and non-motile sperm-injected (n=17) groups (total n=29 cycles).ResultsThe good embryo rate (52.3% vs. 66.9%), pregnancy rate (20.7% vs. 52.1%), and delivery rate (10.3% vs. 40.8%) were lower in the PF/AOA group than in the control group. When evaluating the effects of restoration of sperm motility after PF treatment on clinical outcomes there was no difference in fertilization rate (66.6% vs. 64.7% in non-motile and motile sperm, respectively), pregnancy rate (17.6% vs. 33.3%), or delivery rate (5.9% vs. 16.7%) between the two groups.ConclusionWe suggest that oocyte activation is a useful method to ensure fertilization in TESE-ICSI cycles regardless of restoration of sperm motility after PF treatment. AOA may be useful in selected patients who have a low fertilization rate or total fertilization failure.

Effect of various concentrations of caffeine, pentoxifylline, and kallikrein on hyperactivation of frozen bovine semen.

Caffeine, pentoxifylline, and kallikrein are substances that affect the efficiency of sperms in the fertilization process; however, they have not been adequately studied. The present study aimed to examine the influence of caffeine, kallikrein, and pentoxifylline on sperm motility in bovine as well as investigate their optimum concentrations for increasing the movement of sperms in bovine. Frozen bovine sperms were thawed in universal IVF medium supplemented with 1, 5, and 10 mM caffeine or pentoxifylline or 1, 4, and 8 U/mL kallikrein and were then incubated for 30 min. Treated semen parameters were analyzed using a computer assisted semen analyzer (CASA). Data analysis showed that the mean values concerning progression and motility of sperm increased in caffeine and pentoxifylline treatments when compared with the kallikrein group. The obtained results revealed that kallikrein is not necessary for the improvement of bovine sperm motility. Additionally, our results revealed that 5 mM from caffeine was the best concentration added to the medium, followed by 1 or 5 mM from pentoxifylline. Therefore, it is concluded from the present study that caffeine has hyperactivation efficacy at 5 mM concentration compared to other treatments.

Cellular and molecular mechanisms of pentoxifylline's beneficial effects in experimental polycystic ovary

Chronic low-grade inflammation and oxidative stress (OS) appear to be two main pathways involved in the pathogenesis of polycystic ovary (PCO) syndrome. Therefore, targeting these pathways by means of anticytokine and antioxidant agents might be a therapeutic alternative approach to the current treatments of PCO syndrome. In this study, we investigated the protective effects of pentoxifylline (PTX), a drug with antioxidant and anti–tumor necrosis factor alpha (TNF-α) properties, in hyperandrogenism-induced PCO rats. The inflammatory and OS responses and their connections with ovarian functionality in induced PCO rats were investigated through ovarian histopathologic examination and a series of biochemical measurements including serum estradiol, progesterone, testosterone, insulin, and TNF-α, ovarian and serum lipid peroxidation, total antioxidant power, and reactive oxygen species. Experimental PCO was induced in rats by oral administration of letrozole (1 mg/kg body weight) for 21 consecutive days. In a different group, PTX was administrated orally (50 mg/kg/d) for 21 days simultaneous with letrozole to assess its potential protective effects. The letrozole-induced PCOs were characterized by irregular cycles, high incidence of subcapsular ovarian cysts with diminished or scant granulosa cell layers, increased number of atretic preantral and antral follicles, and absence of CL. In addition, the letrozole-induced PCO rats exhibited notable increase in lipid peroxidation and reactive oxygen species of serum and ovary, serum testosterone, insulin, and TNF-α and significant decline in total antioxidant power, serum estradiol, and serum progesterone. Our results indicated that all the identified pathologic parameters and biochemical characteristics in letrozole-induced PCO rats in this study were preserved close to normal levels by simultaneous PTX treatments. Present results demonstrate that there is a direct connection between ovarian dysfunction and increased OS and inflammation in PCO. For the first time, the beneficial effects of PTX as a powerful antioxidant and TNF-α blocker in hyperandrogenism-induced PCO are reported.

Modulation of radiation-induced oral mucositis by pentoxifylline: preclinical studies.

Oral mucositis is a frequent early side effect of radio(chemo)therapy of head-and-neck malignancies. The epithelial radiation response is accompanied by inflammatory reactions; their interaction with epithelial processes remains unclear. The aim of the present study was to investigate the effect of pentoxifylline (PTX) on the oral mucosal radiation response in the mouse tongue model. Irradiation comprised fractionation (5 fractions of 3 Gy/week) over 1 (days 0-4) or 2 weeks (days 0-4, 7-11), followed by graded local top-up doses (day 7/14), in order to generate complete dose-effect curves. PTX (15 mg/kg subcutaneously) was applied once daily over varying time intervals. Ulceration of mouse tongue epithelium, corresponding to confluent mucositis, was analyzed as the clinically relevant endpoint. With fractionated irradiation over 1 week, PTX administration significantly reduced the incidence of mucosal reactions when initiated before (day-5) the onset of fractionation; a trend was observed for start of PTX treatment on day 0. Similarly, PTX treatment combined with 2 weeks of fractionation had a significant effect on ulcer incidence in all but one experiment. This clearly illustrates the potential of PTX to ameliorate oral mucositis during daily fractionated irradiation. PTX resulted in a significant reduction of oral mucositis during fractionated irradiation, which may be attributed to stimulation of mucosal repopulation processes. The biological basis of this effect, however, needs to be clarified in further, detailed mechanistic studies.

PO-0400 Neuroprotective Effect Of Pentoxifylline In Rat Pups With Hypoxic-ischaemic Encephalopathy

Background and aims Hypoxic-ischaemic (H-I) brain injury in the human perinatal period often leads to significant long-term neurobehavioral dysfunction in the cognitive and sensory-motor domains. The aim of the present study investigated that effect neuroprotective of different dosages of pentoxifylline in neonatal rat model of HIE. Methods H/I was performed according to the Levine-Rice model on postnatal seven-day-old. Wistar rat pups were randomly divided into four groups as: sham-operated group (n = 17), H/I(n = 16), H/I and intraperitoneal Pentoxifylline 60 mg/kg-treated group (n = 17) and HI and intraperitoneal Pentoxifylline 100 mg/kg-treated group (n = 17). Twenty-three rat pups, twenty-four hours after hypoxia, the animals were killed for histopathological evaluation to detect apoptosis by caspase-3 immunohistochemistry method. The other rat pups were grown to 11 weeks. The synaptic plasticity and cognitive function of rats were evaluated using long term potentiation (LTP) and Morris water maze (MWM) test on D77–D82, respectively. Results Pentoxifylline 60 mg/kg two doses treatment decreased the number of caspase-3 positive cells that showed the typical morphological features of apoptosis in only hippocampus (p0.05) but, total numbers of degenerative cell significantly diminished. Conclusions Low dose pentoxifylline treatment is protective against both brain injury and memory impairment and synaptic plasticity.

An Evaluation of Chitinase Inhibitors, Psammaplin A and Pentoxifylline, Treated Diets against the Eastern Subterranean Termite (Isoptera: Rhinotermitidae)

Abstract Psammaplin A and pentoxifylline, two chitinolytic enzyme inhibitors, were evaluated for their palatability, feeding deterrence, consumption, and subsequent mortality against the eastern subterranean termite, Reticulitermes flavipes (Kollar). Psammaplin A and pentoxifylline were incorporated into filter paper diets at 0.0375, 0.075, 0.15, and 0.3%, and 0.01, 0.02, 0.04, 0.08, and 0.21% active ingredient (w/w), respectively. The treated filter papers served as food source or bait for termite workers used in this study. No-choice and two-choice feeding bioassays assessed bait consumption, palatability, repellency, and biological activity over a period of 1 - 5 wk (no-choice assay) and 3 - 5 wk (two-choice assay) of feeding. Neither psammaplin A nor pentoxifylline treatment repelled eastern subterranean termite diet consumption (in both nochoice and two-choice feeding arenas) as feeding commenced on both diet types within 48 h. In no-choice feeding tests, diet consumption was significantly decreased ...

Pentoxifylline alleviates cardiac ischemia and dysfunction following experimental angina in insulin resistance.

We have previously shown that pentoxifylline (PTX) protects from vascular complications associated with insulin resistance (IR). Here, we investigated the protective effect of PTX against cardiac ischemia and dysfunction following experimental angina in IR. IR, along with its accompanying cardiac dysfunction, was induced in rats by a high-fructose (10% in drinking water) high-fat diet for 12 weeks. PTX was administered daily (30 mg⋅kg−1) during the last 4 weeks of the study. Experimental angina was induced by isoproterenol (10 µg⋅kg−1) administered by intravenous injection. Both before (baseline) and after the experimental angina, cardiac contractility was assessed by continuous recording in anesthetized rats via a microtip catheter inserted in the left ventricle, and cardiac conductivity was determined by a surface electrocardiograph. Serum glucose, insulin, tumor necrosis factor-α (TNFα), and adiponectin levels and lipid profile were also determined. Feeding the rats a high-fructose high-fat diet produced IR, as evidenced by significant hyperinsulinemia and hyperglycemia, and PTX administration did not affect this IR. When subjected to experimental angina, IR hearts were less resistant to the ischemia following induction of angina (reflected by the large ST height depression) compared with controls, and PTX completely prevented the excessive ST height depression in IR animals. In addition, left ventricular pressure development was largely attenuated during and after induction of angina in IR animals compared with controls. PTX administration prevented the excessive attenuation in ventricular pressure development in IR animals. IR was associated with elevated levels of the inflammatory cytokine TNFα, whereas PTX treatment elevated the serum level of the anti-inflammatory cytokine adiponectin. PTX alleviates cardiac ischemia and dysfunction following experimental angina in IR directly through inhibition of the low-grade inflammation that accompanies IR.

Pentoxifylline vs. corticosteroid to treat severe alcoholic hepatitis: A randomised, non-inferiority, open trial

Both corticosteroid and pentoxifylline reduce short-term mortality in severe alcoholic hepatitis. However, few studies have directly compared the efficacy of pentoxifylline and corticosteroid in patients with this condition. In this multicentre, open-labelled, randomised non-inferiority trial, we assigned 121 patients with severe alcoholic hepatitis (Maddrey's discriminant function ⩾32) to receive either pentoxifylline (400 mg, 3 times daily, in 62 subjects) or prednisolone (40 mg daily, in 59 subjects). The primary end point was non-inferiority in survival at the 1 month time point for the pentoxifylline treatment compared with prednisolone. The 1-month survival rate of patients receiving pentoxifylline was 75.8% (15 deaths) compared with 88.1% (7 deaths) in those, taking prednisolone, for a treatment difference of 12.3% (95% confidence interval, -4.2% to 28.7%; p = 0.08). The 95% confidence interval for the observed difference exceeded the predefined margin of non-inferiority (Δ15%) and included zero. The 6-month survival rate was not significantly different between the pentoxifylline and prednisolone groups (64.5% vs. 72.9%; p = 0.23). At 7 days, the response to therapy assessed by the Lille model was significantly lower in the prednisolone group (n = 58) than in the pentoxifylline group (n = 5 9): 0.35 vs. 0.50 (p = 0.012). Hepatitis complications, including hepatorenal syndrome and side effects, such as infection and gastrointestinal bleeding, were similar in the two groups. The findings demonstrate that the efficacy of the pentoxifylline is not statistically equivalent to the efficacy of prednisolone, supporting the use of prednisolone as a preferred treatment option in patients with severe alcoholic hepatitis.

Effect of Pentoxifylline on Spinal Fusion

Randomized, double-blinded, animal model. The objective of this study is to evaluate the effect of pentoxifylline (PTX) on spinal fusion in a rabbit model. Previous studies assert that PTX increases new bone formation. Because PTX seems to have these profound effects on bone metabolism, it may be hypothesized that it may enhance spinal fusion. Twenty-four New Zealand white rabbits were randomized and each received single-level posterolateral, inter-transverse process fusion with autologous iliac crest. In group 1, 12 male New Zealand white rabbits were treated with intravenous PTX treatment in 100-mg/kg/day dose after the surgical procedure. In group 2, 12 received no PTX medication and were accepted as the control group. Nine weeks after surgery, the animals were killed. The spines were tested via a manual palpation test, biomechanical testing, plain radiography, computed tomographic scans, and histomorphometric analysis. The fusion rates of manual palpation were 40% in the control group and 80% in the PTX group (P = 0.17). Using a 5-grade radiographical system, the mean fusion grade was 2.4 in the control group and 3.1 in PTX group (P = 0.012). Total displacement of the fused level for the control group under flexion and extension was 0.2515 mm and was lower for the PTX-treated group: 0.1266 mm (P = 0.012). In the control group, the mean bone volume of the fusion mass determined from computed tomographic analysis was 4.0678 cm, whereas in the PTX group it was 4.7802 cm (P = 0.009). The mean trabecular bone area was 14% and 19% for the control and PTX groups, respectively (P = 0.002). The differences between groups was statistically significant in terms of radiological fusion grading, biomechanical testing, volume of the fusion mass, and percentage of trabecular bone area. These results suggest that PTX may have a beneficial effect on spinal fusion. 2.

Vascular Endothelium Derived Endothelin-1 Is Required for Normal Heart Function after Chronic Pressure Overload in Mice

BackgroundEndothelin-1 participates in the pathophysiology of heart failure. The reasons for the lack of beneficial effect of endothelin antagonists in heart failure patients remain however speculative. The anti-apoptotic properties of ET-1 on cardiomyocytes could be a reasonable explanation. We therefore hypothesized that blocking the pro-apoptotic TNF-α pathway using pentoxifylline could prevent the deleterious effect of the lack of ET-1 in a model for heart failure.MethodsWe performed transaortic constriction (TAC) in vascular endothelial cells specific ET-1 deficient (VEETKO) and wild type (WT) mice (n = 5–9) and treated them with pentoxifylline for twelve weeks.ResultsTAC induced a cardiac hypertrophy in VEETKO and WT mice but a reduction of fractional shortening could be detected by echocardiography in VEETKO mice only. Cardiomyocyte diameter was significantly increased by TAC in VEETKO mice only. Pentoxifylline treatment prevented cardiac hypertrophy and reduction of fractional shortening in VEETKO mice but decreased fractional shortening in WT mice. Collagen deposition and number of apoptotic cells remained stable between the groups as did TNF-α, caspase-3 and caspase-8 messenger RNA expression levels. TAC surgery enhanced ANP, BNP and bcl2 expression. Pentoxifylline treatment reduced expression levels of BNP, bcl2 and bax.ConclusionsLack of endothelial ET-1 worsened the impact of TAC-induced pressure overload on cardiac function, indicating the crucial role of ET-1 for normal cardiac function under stress. Moreover, we put in light a TNF-α-independent beneficial effect of pentoxifylline in the VEETKO mice suggesting a therapeutic potential for pentoxifylline in a subpopulation of heart failure patients at higher risk.

Histological study on the possible protective effect of pentoxifylline on pancreatic acini of l-arginine-induced acute pancreatitis in adult male albino rats

ObjectiveThe aim of this study was to determine the histological changes of l-arginine-induced acute pancreatitis and the possible protective effect of pentoxifylline on pancreatic acini in adult male albino rats.BackgroundAcute pancreatitis is a reversible inflammation that is either localized to the pancreas or may spread to adjoining tissues.Materials and methodsForty adult male albino rats weighing 180-200 g each were used in this study. The rats were divided into four equal groups (10 rats each). Group I was the control group. In group II (l-arginine-treated), rats were administered two intraperitoneal injections of l-arginine at a dose of 200 mg/100 g/body weight with 1-h interval. They were randomly subdivided into two equal subgroups: in IIA, rats were killed after 24 h of the last l-arginine injection and in IIB, rats were killed after 1 week of the last l-arginine injection. In group III (l-arginine and pentoxifylline-treated), rats were administered l-arginine and pentoxifylline. l-arginine was given similar to group II and pentoxifylline was given as a single intraperitoneal injection at a dose of 12 mg/kg body weight/day. They were randomly subdivided into two equal subgroups: in IIIA, rats were given a single dose of pentoxifylline then were killed after 24 h and in subgroup IIIB, rats were given pentoxifylline daily for 1 week then were killed. In group IV (pentoxifylline-treated), rats were administered pentoxifylline as a single intraperitoneal injection of 12 mg/kg body weight/day for 1 week then rats were killed.Resultsl-arginine-treated rats for 24 h showed pancreatic edema, degenerative changes of pancreatic acini, and inflammatory cell infiltration. These changes were marked after 1 week; however, pentoxifylline supplementation in group III showed amelioration of the histological picture, which was marked after daily pentoxifylline treatment for a week.ConclusionIt is concluded that pentoxifylline was found to improve the histological changes of pancreatic acini caused by l-arginine.