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We have previously found that pentoxifylline (Ptx) inhibited cytokine induced HLA-DR expression and glycosaminoglycan (GAG) synthesis by retroorbital fibroblasts. We have now tested the clinical efficacy of Ptx in treating TAO. Ten patients with moderately severe ophthalmopathy were selected for study. All patients were euthyroid before and during the 12 weeks of the Ptx therapy. Serum GAG, TNF-alpha, anti-TSH-receptor, anti-eye muscle, anti-thyroglobulin and anti-thyroid peroxidase antibodies were determined sequentially. At the end of 12 weeks eight of the ten patients showed improvement in soft tissue but not in proptosis or extraocular muscle involvement. At baseline the levels of GAG (5.2+/-0.92 mg/dl v.s. 0.7+/-0.14 mg/dl, p<0.001) and TNF-alpha (33.6+/-6.6 pg/ml v.s. 5.4+/-1.3 pg/ml, p<0.001) were increased in patients compared to controls. They gradually decreased in the eight patients who responded to Ptx: after 4, 8 and 12 weeks of therapy serum GAG was 3.4+/-0.42 mg/dl, 2.5+/-0.77 mg/dl (p<0.01) and 1.1+/-0.2 mg/dl (p<0.001), respectively and serum TNF-alpha was 20.9+/-4.8 pg/ml, 14.9+/-2.2 pg/ml (p<0.05) and 9.7+/-1.8 pg/ml (p<0.01), respectively. Serum GAG and TNF alpha did not fall in the two patients who did not respond. The titre of anti-eye muscle antibodies but not anti-thyroid antibodies were lower at 12 weeks. Ptx has a beneficial effect on inflammatory symptoms of TAO and associated laboratory parameters in the majority of patients.
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The therapeutic methods used in this trial provided significant symptom relief. Patients experienced relapses of the lesions; however, this occurred after withdrawal of their medication during the follow-up period.
In a randomized, prospective, double-blind study involving 72 patients, the therapeutic efficacy of ginkgo extract EGb 761 (n = 37) was compared to that of pentoxifylline (n = 35) for the treatment of sudden deafness. The two therapeutic schedules were equally well tolerated and showed a statistically significant equivalence in improvement or in return to normal of the auditory thresholds in the two patient groups. Furthermore, no differences were found between the treatment groups with regard to the criteria for a return to normal of speech discrimination and reduction of the tinnitus which arose at the same time as the sudden hearing loss. The patient's subjective assessment of the treatment with regard to improvement in hearing and reduction in tinnitus suggested that Ginkgo biloba extract was more beneficial than pentoxifylline. In summary, it was shown that treatment of sudden deafness with ginkgo special extract EGb 761 was as effective as treatment with pentoxifylline.
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After stem-cell transplantation, early diagnosis of GvHD is especially important due to possible irreversible sclerodermatous changes and other organ manifestations. Also for this reason, strict clinical follow-up is especially important with respect to compliance and efficacy of the immunosuppression.
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The primary aim of this study was to compare the effects of pentoxifylline (PTX) versus placebo on the histological features of nonalcoholic steatohepatitis (NASH). In all, 55 adults with biopsy-confirmed NASH were randomized to receive PTX at a dose of 400 mg three times a day (n = 26) or placebo (n = 29) over 1 year. The primary efficacy endpoint was defined as improvement in histological features of NASH through reduction in steatosis, lobular inflammation, and/or hepatocellular ballooning as reflected by a decrease of ≥ 2 points in the nonalcoholic fatty liver disease (NAFLD) activity score (NAS). After 1 year, intention-to-treat analysis showed a decrease of ≥ 2 points in the NAS in 38.5% of patients on PTX versus 13.8% of those on placebo (P = 0.036). Per protocol analysis, a decrease of ≥ 2 points in the NAS from baseline was observed in 50% of the patients on PTX versus 15.4% of those on placebo (P = 0.01). The mean change in NAS score from baseline was -1.6 in the PTX group, versus -0.1 in the placebo group (P < 0.001). PTX significantly improved steatosis (mean change in score -0.9 versus -0.04 with placebo, P < 0.001) and lobular inflammation (median change -1 versus 0 with placebo, P = 0.02). No significant effects in hepatocellular ballooning were observed. PTX also improved liver fibrosis (mean change in fibrosis score was -0.2 among those on PTX versus +0.4 among those on placebo, P = 0.038). Although not statistically significant (P = 0.17), improvement in fibrosis was observed in a greater proportion (35%) of patients in the PTX group compared to placebo (15%). Adverse effects were similar in both groups.
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The study was designed to investigate the effects of pentoxifylline on the acrosome reaction of human spermatozoa in vitro, and to determine whether the reaction is differently modulated after sperm selection by multiple tube swim-up and Percoll buoyant density centrifugation. The acrosome reaction was induced in vitro by using calcium ionophore (A23187) and was detected by measuring the fluorescence of FITC-conjugated goat anti-mouse immunoglobulin bound to CD46 antibody (which binds to the CD46 receptor site on the inner acrosomal membrane) by flow cytometry. Spermatozoa separated on Percoll displayed significantly lower spontaneous acrosome reactions (P = 0.002) than did those separated by the swim-up technique. Pentoxifylline did not, by itself, induce acrosome reaction, but after induction with ionophore, it significantly increased the reaction (P = 0.003) and this increase was seen to be greater when Percoll separation was used as compared to the swim-up technique (P = 0.0002). We therefore conclude that Percoll selection of motile spermatozoa together with pentoxifylline treatment may be of value in assisted reproductive techniques, as an increased ARIC score arose after both treatments, and that flow cytometry allows a precise and rapid quantification of the acrosome reaction.
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Clinical investigation on a surgical intensive care unit of a university hospital.
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These motility stimulants that affect adenosine 3':5' monophosphate in human sperm stimulate cyclic hyperactivation.
Cultures of osteoblast-like cells were established from calvariae of Sprague-Dawley rats. Pentoxifylline increased cAMP levels and calcium uptake in these cultures. However, calcium uptake increased at lower levels than required to increase cAMP levels. Thus, it is likely that cAMP unrelated mechanisms are also involved in these phenomena.
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Lobar arterial perfusion pressure, systemic pressure, and left atrial pressure were continuously monitored, electronically averaged, and permanently recorded. Under increased tone conditions in the isolated left lower lobe vascular bed of the cat, NG-L-nitro-L-arginine methyl ester significantly reduced the vasodilator responses to pentoxifylline and to acetylcholine, whereas NG-L-nitro-L-arginine methyl ester had no significant effect on the vasodilator responses to isoproterenol. Vasodilator responses to pentoxifylline and acetylcholine were not significantly changed in the presence of meclofenamate, whereas meclofenamate markedly reduced the vasopressor effects of arachidonic acid.
The lipid peroxidation levels and flap necrosis were significantly higher in the cigarette-smoking group skin flaps. There was also a decrease of MPO activity in this group compared with the non-smoking group. Heparin-treated rats had significantly lower MDA levels and showed the most viable percent area among smoking rats.
The mean hemizona indexes with medium or pentoxifylline treatment were 23% +/- 2.1% (mean +/- SE) and 41% +/- 3.4%, respectively. Taking into consideration a significant change of the hemizona index on rising above the intra-assay coefficient of variation (+/- 8%) after pentoxifylline treatment, 73.1% of specimens improved, 19.5% deteriorated, and 7.4% remained unchanged. Using a threshold hemizona index of 23% as a discriminator between fertile and infertile specimens, 43.5% of the "pentoxifylline-improved" samples ascended to the fertile zone (> 23%). No correlations were found between sperm variables in the raw semen and the effect of pentoxifylline on sperm binding capacity.
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Diabetes was induced by streptozotocin (STZ) in rats. Treatment groups were divided as follows: healthy (H), diabetic without treatment (STZ), PTX treated group (STZ+PTX), and vitamin E supplemented (STZ+E) group. At 8 weeks, kidneys were removed; one was homogenized to quantify lipoperoxide levels (LPOS), and the other was used to study the morphological changes by electron microscopy (EM). Additionally, plasma total antioxidant activity (TAA) was quantified.
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Pentoxifylline has been used to treat nonalcoholic fatty liver diseases (NAFLDs) due to its anti-tumor necrosis factor-α effects. We conducted a meta-analysis of randomized, double-blinded, placebo-controlled trials to investigate the effect of pentoxifylline on the biochemical and histological parameters of NAFLD patients.
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Overall a fertilization rate of 8.8% was achieved with no significant differences between treatment and control groups. Cleavage rate was 81.5% and was not different between groups.
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Overproduction of collagen (I) by activated hepatic stellate cells is a critical step in the development of liver fibrosis. It has been established that these cells express interleukin (IL)-6 and respond to this cytokine with an increase in alpha(I) collagen. Pentoxifylline, a methylxanthine derivate, has been reported to have antifibrotic properties, but the mechanism responsible for this effect is unknown. The aim of this study was to determine the effect of pentoxifylline on acetaldehyde-induced collagen production in a rat hepatic stellate cell line (CFSC-2G cells). Cells were treated with 100 microM acetaldehyde and 200 microM pentoxifyline for 3 h. IL-6 and alpha(I) collagen messenger RNA (mRNA) were determined by reverse transcriptase polymerase chain reaction (RT-PCR) assay. NFkappaB activation was determined by electrophoretic mobility shift assay. To corroborate NFkappaB participation in pentoxifylline effect, cells were pretreated with 10 microM TPCK, a NFkappaB inhibitor. IkappaBalpha was determined by Western blot. IL-6 expression decreased significantly in acetaldehyde-pentoxifylline-treated cells. Acetaldehyde-treated cells pretreated with an anti-IL-6 monoclonal antibody did not show any increase in alpha (I) collagen expression. Acetaldehyde-treated cells increased 1.48 times NFkappaB activation, whereas acetaldehyde-pentoxifylline-treated cells decreased NFkappaB activation to control values. TPCK pretreated acetaldehyde cells did not present NFkappaB activation. To corroborate NFkappaB participation in pentoxifylline effect, IkappaBalpha was determined. IkappaBalpha protein level decreased 50% in acetaldehyde-treated cells, while acetaldehyde-pentoxifylline-treated cells showed IkappaBalpha control cells value. The data suggest that acetaldehyde induced alpha(I) collagen and IL-6 expression via NFkappaB activation. Pentoxifylline prevents acetaldehyde-induced alpha(I) collagen and IL-6 expression by a mechanism dependent on IkappaBalpha degradation, which in turn blocks NFkappaB activation.
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The present investigation sought to evaluate the effects of pentoxifylline and its major hydroxyhexyl metabolite on red blood cell (RBC) deformability using the technique of ektacytometry. Red blood cells were harvested from normal volunteers (normal RBCs) and patients with sickle cell disease (abnormal RBCs) and incubated with varying concentrations of pentoxifylline and its major metabolite for varying time periods. The deformability of both treated and untreated RBCs from both patient groups was assessed by ektacytometric analysis. In contrast to the in vitro effects of pentoxifylline on whole-blood filterability, the present results demonstrated no effect of pentoxifylline or metabolite on RBC deformability at any concentration or incubation time period. Pentoxifylline does not enhance RBC deformability following acute in vitro incubation, and this suggests the need for further evaluation of the mechanism of action of this drug.
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The breaking strength of colonic anastomoses declines after operation to a minimum at days 3-4, with a subsequent risk of anastomotic dehiscence. The mechanism is thought to be collagen degradation by matrix metalloproteinases (MMPs). This study examined the pathogenic role of MMPs on the mechanical strength of colonic anastomoses by giving the synthetic broad-spectrum MMP inhibitor BB-1101 systemically.
The included studies in this review were small and from single centres. Neither study was completely clear about it's method of treatment allocation. One study described the use of pentoxifylline tablets (three 600 mg tablets daily) and the other the use of enhanced external counterpulsation (EECP) combined with haemodilution. Both studies indicated improved retinal perfusion in the non-control group but neither showed an improvement in vision. Large, well-designed RCTs are still required to establish the most effective treatment for acute CRAO. These studies should be looking at factors important to the patient i.e. improved vision with acceptable risk/side-effects.
The aim of this study was to investigate the effect of low-pressure pneumoperitoneum and pentoxifylline, a methylxanthine derivative, in the prevention of injury caused by free oxygen radicals generated during CO(2 )pneumoperitoneum.
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To investigate whether delayed auditory brainstem responses (ABRs) induced by DM improve following pentoxifylline treatment in rats.