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Retrospective analyses of twelve medical ICU patients (out of 120 patients with liver cirrhosis) with histological proven AH.
Proteinuria and urinary NAG excretion were significantly greater in patients with DM with respect to healthy controls. Before PTF administration, baseline parameters were similar in both groups of patients with DM. At the end of the study, urinary protein excretion and NAG-creatinine ratios decreased in the active group from 920 +/- 522 mg/d and 14.3 +/- 16.9 U/g to 803 +/- 523 mg/d (P < 0.001) and 10.5 +/- 9.3 U/g (P < 0.05), respectively. Conversely, proteinuria and urinary NAG excretion did not change in the control group. Regression analysis showed that urinary NAG excretion was significantly associated with duration of DM (r = 0.61; P < 0.001) and proteinuria (r = 0.51; P < 0.001).
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The literature demonstrates inconsistent results amongst investigators who have used pentoxifylline in an effort to enhance skin flap survival. This study employed a standardized skin flap model in the rat and a standard intraperitoneal dose of pentoxifylline (10 mg/kg) delivered in four different temporal regimens. Fluorescein staining and length of flap survival were measured. The only regimen that demonstrated increased flap survival over saline controls included administration of the drug immediately upon raising the flap and every 12 hours for the next 7 days. Three different regimens that included preoperative administration of the drug failed to demonstrate a beneficial effect on skin flap survival. Slight improvement in flap survival was seen in animals receiving fluorescein. These results suggest an inconsistent pentoxifylline effect even within a single controlled study.
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Up-regulation of IFN-γ and IP-10 in the culture medium of macrophages elicited by CSE was inhibited by PTX in a dose-dependent manner. Chronic cigarette smoke exposure led to overexpression of IFN-γ and IP-10 in BALF, upregulation of IP-10 mRNA and increased infiltration of CXCR3(+) cells into lung parenchyma. Administration of PTX decreased the level of IFN-γ from (6.26 ± 1.38) ng/ml to (4.43 ± 0.66) ng/ml by low dose PTX or to (1.74 ± 0.28) ng/ml by high dose PTX. IP-10 was reduced from (10.35 ± 1.49) ng/ml to (8.19 ± 0.79) ng/ml by low dose PTX or to (7.51 ± 0.60) ng/ml by high dose PTX. The expression of IP-10 mRNA was also down-regulated (P < 0.05). But only with a high dose of PTX was the ratio of CXCR3(+) cells decreased; 15.2 ± 7.3 vs. 10.4 ± 1.8 (P < 0.05).
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Pentoxifylline, an anti-tumor necrosis factor-alpha drug, prevented the dorsal root ganglion compartment syndrome caused by topical application of nucleus pulposus. Anti-inflammatory cytokine therapy may become an effective treatment of sciatica due to disc herniation.
It is recommended that the diagnosis of veno-occlusive disease (sinusoidal obstruction syndrome) [VOD (SOS)] be based primarily on established clinical criteria (modified Seattle or Baltimore criteria) (1A). Ultrasound imaging may be helpful in the exclusion of other disorders in patients with suspected VOD (SOS) (1C). It is recommended that liver biopsy be reserved for patients in whom the diagnosis of VOD (SOS) is unclear and there is a need to exclude other diagnoses (1C). It is recommended that liver biopsies are undertaken using the transjugular approach in order to reduce the risks associated with the procedure (1C). It is suggested that the role of plasminogen activator inhibitor 1 levels remains an area for further research but that these levels should not form part of the routine diagnostic work-up for VOD (SOS) at present (2C).
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Rapid tumor growth and metastasis are 2 major problems associated with treatment of malignant melanoma. Therefore, drugs that can intervene these processes are of clinical importance. Pentoxifylline (PTX), a methyl xanthine derivative, has been shown to inhibit B16F10 melanoma tumor growth and metastasis. We hypothesized that suramin when combined with PTX enhances its antineoplastic effects, which we have examined using the B16F10 mouse melanoma model. Suramin in simultaneous or sequential combination potentiated the cytotoxic effects of PTX on B16F10 cells. PTX arrested cells in the G0-G1 phase and suramin augmented the effects. Both the drugs inhibited F10 adhesion to laminin, matrigel and collagen type IV and showed enhanced inhibition in combination The combination also demonstrated significantly higher inhibition in cell motility (p = 0.002) and invasion through matrigel (p = 0.005) as compared to the single agents. Suramin synergized with PTX in its effects on secretion of MMP-9 gelatinase. DBA2/J mice implanted with intradermal B16F10 tumor were used as a model to study tumor growth. Animals were intratumorally treated with 50 mg/kg of PTX, 10 mg/kg of suramin and their combinations. Simultaneous administration of the drugs inhibited tumor growth by 5- to 6-folds. Tumor growth was completely blocked in sequential regimen with regression in some cases. The number and size of metastatic nodules on lung was also reduced significantly by the combination treatment. In conclusion, the novel combination of PTX and suramin has synergistic antitumor and antimetastatic activity in B16F10 melanoma and may be a promising approach in treatment of patients suffering from malignant melanoma.
According to intergroup comparisons, colonic bursting pressure was found to be higher in the treatment groups than in the control group; however, the difference was not statistically significant. Intergroup comparisons regarding tissue hydroxyproline levels showed statistically significant differences between Groups A and B, Groups A and C and Groups B and C.
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Pentoxifylline possesses vasodilator properties, but little information is available on the mechanism of action explaining this vasodilator effect. The present experiments were designed to determine the effects of the compound on vascular smooth muscle, endothelium, and adrenergic nerves in rings of isolated canine blood vessels. Pentoxifylline did not affect basal tension in coronary and femoral arteries or in saphenous and mesenteric veins; it did not alter the rhythmic activity of the latter, but did cause endothelium-independent relaxations of unstimulated basilar arteries. In coronary arteries and saphenous veins, but not femoral arteries contracted with prostaglandin F2 alpha, the compound caused relaxations which were not affected by propranolol or by removal of the endothelium. Pentoxifylline inhibited the endothelium-dependent contractions to the Ca2(+)-ionophore A23187 in the basilar artery. In saphenous veins (with endothelium), pentoxifylline did not inhibit responses to high K+, electrical stimulation of the adrenergic nerves, or exogenous norepinephrine (NE); it reduced contractions evoked by xylazine and hypoxia. In the basilar artery and the saphenous vein, the inhibitory effect of pentoxifylline was prevented by inhibitors of cyclooxygenase and thromboxane synthetase. These experiments suggest that the dilator properties of pentoxifylline in isolated canine blood vessels are primarily at the level of the vascular smooth muscle and may involve decreased production of, or reduced responsiveness to, endogenous thromboxanes.
The short-term effects of pentoxifylline (PTX) on granulomatous lesions during Schistosoma mansoni infection in Swiss mice were evaluated. Drug administration was initiated 42 and 140 days post-infection (DPI) for the acute and chronic infection groups, respectively. Treatment was carried out daily with 200 mg/kg (subcutaneous route) of the drug for five consecutive days. Recovery of parasites and tissues was performed at 49 DPI and 147 DPI, respectively. Liver histological analysis showed a decrease in the inflammatory reaction and fibrous content of the granulomas studied, and a significant reduction (P < 0.001) in their mean diameter was observed in the groups of rodents treated with PTX in acute and chronic infection, when compared to their respective control groups. However, no alteration in the number of S. mansoni recovered from the portal system was observed, and egg-laying kinetics was not notably modified by PTX treatment, and the immature stage distribution of S. mansoni eggs showed minor intrinsic variations with no statistical differences in the parameter second-stage/female/g among untreated mice and treated mice in acute and chronic infections, respectively, when evaluated by intestinal oograms. Data obtained indicate probable immunomodulatory effects of PTX in murine schistosomiasis both in acute and chronic infection.
Vital signs and organ function were determined at diagnosis; daily from day 1 to 7; on days 10, 14, 17, 21, and 24; and 28 days after diagnosis of sepsis. There were no differences in characteristics of patients at diagnosis in the Acute Physiology and Chronic Health Evaluation II (APACHE II) score (mean+/-SEM, 17+/-4 points for the pentoxifylline group and 18+/-5 points for the placebo group), the multiple organ dysfunction score (mean+/-SEM, 11.0+/-0.8 vs 11.8+/-1.0 points), tumor necrosis factor alpha and interleukin 6 bioactivity, serum endotoxin levels, or organ dysfunction. At study entrance, 23 of 27 patients in the pentoxifylline group and 21 of 24 patients in the placebo group experienced septic shock. No adverse effects of pentoxifylline treatment were observed. The 28-day mortality rate was 30% (8/27) in pentoxifylline-treated patients and 33% (8/24) in the placebo group. Hospital mortality was 41% (11/27) in the pentoxifylline group and 54% (13/24) in the placebo group. The multiple organ dysfunction score decreased in patients receiving pentoxifylline 4 days after diagnosis of sepsis compared with placebo-treated patients; a significant difference was reached on day 14 (P<.05; Student t test, Bonferoni correction). The PaO2/FIO2 (fraction of inspired oxygen) ratio was significantly improved in pentoxifylline-treated patients on days 14 and 17 (P<.05), and the pressure-adjusted heart rate was significantly improved on day 6 (P<.05) compared with the placebo group. Serum endotoxin levels, tumor necrosis factor alpha and interleukin 6 bioactivity were not different between the groups during the study.
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All PDE inhibitors induced dose-dependent venodilation. The value of maximum venodilation was the same for amrinone, enoximone and theophylline. The infusion rate needed to induce 50% of maximum venodilation (ED50) was not significantly different for amrinone (geometric mean, 8.8 microg x min(-1)) and enoximone (14.2 microg x min(-1)), whereas the ED50 of theophylline (84.0 microg x min(-1)) was significantly higher than either amrinone or enoximone. The dose necessary to dilate the vein to 50% the maximum dilation (as determined during sodium chloride infusion) was significantly higher for pentoxifylline than for theophylline (409 vs 71 microg x min(-1)).
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Damage of the photoreceptors in the retina affects melatonin secretion and its circadian rhythm.
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Prostanoids, which promote vasodilation and reduce platelet aggregation, have been proposed as candidate therapies for intermittent claudication due to peripheral arterial disease (PAD). However, studies of these medications have yielded inconsistent results. This study tested the hypothesis that iloprost, an oral prostacyclin analogue, would improve walking distance and quality of life in patients with intermittent claudication. The study was a multi-center, randomized, double-blind, placebo-controlled trial comparing three doses of oral iloprost (50 microg, 100 microg, or 150 microg twice daily), pentoxifylline, or placebo in 430 patients with intermittent claudication. The primary outcome measure was improvement in absolute claudication distance (ACD) after 6 months. Secondary outcomes included initial claudication distance and quality of life assessment. Placebo increased ACD by 3.3%, and iloprost increased peak ACD by 7.7%, 8.8% and 11.2% at the 50 microg, 100 microg, and 150 microg twice-daily doses, respectively (all insignificant relative to placebo). Pentoxifylline increased ACD by 13.9% relative to placebo (p = 0.039). Neither iloprost nor pentoxifylline enhanced quality of life. These results indicate that oral iloprost is not effective in improving exercise performance or quality of life in patients with PAD who have intermittent claudication.
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Controlled laboratory investigation on tumor necrosis factor-alpha and nitric oxide production by alveolar macrophages of rats that had acid-induced lung injury.
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Calciphylaxis is a rare syndrome developing predominantly in female patients suffering from end-stage renal disease (ESRD) with secondary hyperparathyroidism. Skin lesions begin as superficial patches that quickly progress to painful necrotic ulcers. Histopathological findings are calcification of small arteries and arterioles and infarction of subcutis and skin. The prognosis of calciphylaxis is poor due to an increased risk of systemic infection.
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Sperm banking should be encouraged at cancer diagnosis regardless of semen quality. Artificial stimulation of sperm motility results in significant improvement in sperm motion characteristics.
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Peripartum cardiomyopathy is a rare condition of unclear etiology that accounts for an important percentage of pregnancy-related deaths. Deaths from peripartum cardiomyopathy can be attributed to profound left ventricular failure, thromboembolic events, or arrhythmia. Prompt recognition of the condition, initiation of appropriate medical management, collaboration with perinatology for delivery management, referral to cardiac transplant centers when necessary, and counseling regarding future pregnancies is required for a successful outcome. Patients should be diagnosed by clinical evaluation and echocardiography. After establishing left ventricular dysfunction, a standard heart failure medical regimen should be instituted. Hospitalization should be considered for patients with class III or greater symptoms, or for those patients not responding to outpatient management. If the diagnosis is made in the antepartum period, delivery should be strongly considered. Endomyocardial biopsy has low yield in this situation and should not be considered standard care, especially because controversy exists over the effectiveness of immunosuppressive therapy for myocarditis. Selenium, pentoxifylline, and immune globulin have all been shown to have a beneficial effect in small series of patients. The addition of these agents to standard therapy, however, should be considered on a case-by-case basis. Anticoagulation should be considered in patients with ejection fractions less than 35%. Transplantation results in survival comparable to women with idiopathic-dilated cardiomyopathy, and should be pursued in the appropriate setting. Future pregnancies should be discouraged, even if the left ventricular function recovers. Significant improvement in ventricular function can be expected in up to 50% of patients.
PTX mediated transformation of pulmonary emphysema into pulmonary fibrosis under chronic cigarette smoke exposure is associated with upregulation of β-catenin and elevation of TGF-β(1), implying that activation of Wnt/β-catenin signaling may be involved in the pathogenesis of pulmonary fibrosis.
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Patients with chronic occlusive arterial disease of lower limbs have an excess mortality due to associated cardiovascular diseases or cancer. They also have an important morbidity with a high prevalence of coronary artery diseases and strokes. In this context, the only benefit of peripheral vasodilators devoid of any effect on morbidity and mortality, could be only on quality of life. Haemodynamic effects of these drugs have been evaluated by several reproducible techniques in order to measure the peripheral blood flow (plethysmography, 133Xe clearance, transcutaneous oxygen-pressure, electromagnetic debimetry). An increase in blood flow has been demonstrated in patients receiving pentoxifylline, naftidrofuryl, or blufomedil in phase II clinical trials using these different methods. No general haemodynamic effect has been observed with these drugs which were better denominated vaso-active drugs. However the most relevant criteria remained to confirm a clinical benefit, particularly on intermittent claudication. Number of positive clinical trials in patients with intermittent claudication have been published, but from a methodological point of view few of them were suitable and demonstrated a statistically significant benefit. Criticisms were mainly related to the type of trial (cross-over is not recommended because of the drug-period effect), the lack of 'intention to treat' analysis, the inhomogeneity of the compared groups (for example different percentages of diabetics and excess of drop-outs). In spite of an established haemodynamic effect and of a demonstrated benefit in claudicants, peripheral vasodilators appear to have a slight interest in the global care of patients with occlusive arterial disease of lower limbs mainly on functional symptoms.
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Previous studies demonstrated a high incidence of local thrombosis in patients in whom external arteriovenous shunts were used for vascular access. This procedure provides, therefore, a useful model for the evaluation of potential antithrombotic agents. The effect of the hemorheologically and hemostasiologically active drug Pentoxifylline on the incidence of thrombosis of arteriovenous shunts (Ramires shunt) was investigated in a long-term, double-blind, placebo-controlled study in 51 patients on chronic hemodialysis. The two treatment groups were comparable in age, sex, concomitant medication, and dialysis program (three times per week for four hours). Drugs known to affect platelet function or coagulation were excluded, with the exception of heparin, during the dialysis procedure. All shunts were placed in the forearm and inserted into the distal part of the radial artery and basilic antebrachial vein. Simultaneously, for medical reasons, in all patients an arteriovenous fistula was performed (proximal part of radial artery and cephalic antebrachial vein). Shunt thrombosis was assumed when the flow in the shunt discontinued under visual and auscultatory control. Thrombi were documented by physical removal from the arterial part of the shunt by use of gentle suction or by complete shunt thrombosis (both arterial and venous part of the shunt). Thereafter, the patients' trial period terminated. The total number of thrombi during the observation period was 44 in the pentoxifylline group (26 patients), compared with 82 in the placebo group (25 patients). The mean number of thrombi per patient was 1.69 +/- 1.29 in the pentoxifylline group, significantly lower than that in the placebo group (3.28 +/- 1.99/p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)