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NIH3T3 murine cells transfected with mutant p53 constructs were examined for the influence of pentoxifylline on radiotoxicity to Co(60) gamma-irradiation by colony assay. DNA repair (0-100 Gy) was measured by constant-field gel electrophoresis. Apoptosis was assessed by flow cytometry with the annexin-V-binding assay.
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The ability of pentoxifylline and 2-deoxyadenosine to stimulate sperm motility and motion characteristics was assessed in unprocessed and processed (Percoll-separated) cryopreserved specimens. Specimens from 12 healthy volunteers were obtained, and the motion characteristics were analyzed; half the sample was immediately cryopreserved and the other was washed using the Percoll gradient technique. To study stimulation, samples were thawed and divided into four aliquots: One was used as a control, and the others were incubated with 2.5 mM 2-deoxyadenosine, 2.5 mM pentoxifylline, or 5.0 mM pentoxifylline for 60 min. Sperm characteristics were analyzed on a sperm motion analyzer at 0 and 60 min incubation. In both unprocessed and processed samples, percentage motility improved significantly after stimulation with 2-deoxyadenosine or pentoxifylline (p = .003 or p = .0002, respectively); other characteristics improved to varying extent after 2-deoxyadenosine or pentoxifylline stimulation. Comparison after stimulation revealed that sperm motion characteristics in the unprocessed specimen were similar to sperm motion characteristics in the processed group.
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The effects of pentoxifylline on intermittent claudication were evaluated at a dose of 1200 mg/day in an open-label twelve-week study on geriatric patients with chronic occlusive arterial disease (COAD). Standardized treadmill testing and clinical signs and symptoms of COAD were followed up before and during drug administration. Twenty-four subjects with a mean age of 73.5 years, capable of walking between 20 and 200 meters on the treadmill, were entered into the trial; 22 participated for eight weeks and 19 completed the study in terms of treadmill walking distance measurements at 12 weeks. The mean walking distance for all patients was increased 111% over baseline at week 12. Thirteen subjects were considered drug responders (greater than or equal to 50% increase in treadmill walking distance) and 9 were considered nonresponders (less than 50% increase). Improvements in clinical signs and symptoms of COAD were noted. Decreases in elevated systemic systolic pressures (but not diastolic) were unexpectedly observed in many drug responders. Seven of 19 males reported sexual function improvements while receiving pentoxifylline. Fourteen (58%) of the 24 subjects reported mild side effects of dyspepsia, nausea, vomiting, dizziness, headache, or insomnia; no subjects were withdrawn from the study because of side effects. In summary, pentoxifylline improved function and symptoms in 13 of 22 geriatric patients with intermittent claudication; the drug was safe and well tolerated at the usual dosage in this geriatric patient population.
In patients with an acute destructive pancreatitis the lowering of sulphhydride (SH) groups in proteinic and nonproteinic fraction of the blood plasma, the reduction of the ascorbic acid level and increase of its oxidized forms concentration was noted. After the operation the disordered indexes have restored, moreover, and after the programmed relaparotomy conduction--as after a single operative intervention. Acceleration of the disordered indexes restoration was promoted by application of pentoxifylline and low-intensity laser irradiation as well.
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This report describes the case of a young woman from Mayotte (Comoros Islands) who presented a combination of three cutaneous diseases, i.e. pityriasis versicolor, scabies, and multibacillary leprosy. Symptoms of leprosy were concealed by those of the other two diseases. After multidrug therapy for leprosy, the patient developed erythema nodosum leprosum that was successfully treated using pentoxifylline. Combination of cutaneous diseases can alter usual presentations and lead to misdiagnosis. It is important to take into account possible disease combination to establish proper diagnosis and prescribe effective treatment.
In five of eight patients an improvement of central visual acuity was observed. It changed from perception of hand movement only to 12/20 in three patients. In two of these patients visual acuity had continued to improve after 6-9 months, to 16/20 and 20/20. In one patient visual acuity fell to 6/20 because of progression of ischemic ophthalmopathy. In our patients visual acuity could still be improved even 27 h after arterial occlusion.
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The effects of antithrombotic drugs on random and free flap survival have been investigated in the past, but the experimental and clinical results are not in agreement. A perforator-based critical ischaemia model was used to evaluate the effects of different perioperatively administered pharmaceutical agents on tissue ischaemia and to assess the potential additional haemorheological or vasodilative effects of antithrombotics on flap microcirculation. Combined laser Doppler flowmetry and remission spectroscopy revealed an increase in certain microcirculation parameters in most groups in comparison with saline controls, and these changes correlated with flap survival. Clopidogrel and hirudin significantly improved the amount of viable flap tissue in comparison with controls, while unfractioned heparin had a negative effect on flap survival. Low molecular weight heparin, aspirin, pentoxifylline, and hydroxyethyl starch had no impact on the amount of viable flap tissue. A higher complication rate was observed in all experimental groups, but only clopidogrel had a negative impact on the flap viability. Our results add to the body of evidence supporting the conclusion that perioperative antithrombotic treatment improves flap survival. Clopidogrel and hirudin are effective pharmacological agents that significantly increased the viability of perforator-based skin flaps in rats, but at a higher risk of postoperative bleeding.
Human mononuclear cells were stimulated with LPS (1 microg/mL), in the presence and absence of Pentoxifylline (PTX; 20 mM), a nonspecific phosphodiesterase inhibitor. Western blotting of phosphorylated cytoplasmic I-kBalpha, nuclear factor-kB p65 (NF-kB), and nuclear cAMP-response element binding protein (CREB) was performed. DNA binding of NF-kB and CREB was verified by electrophoretic mobility shift assay. TNF-a levels were determined in the supernatant of stimulated cells in the presence and absence Protein kinase A inhibition by an enzyme-linked immunosorbent assay (ELISA).
Caco-2 human enterocytes were grown as confluent monolayers and incubated under control conditions, or with PTX (2 mM), Cytomix (TNF-alpha, IFN-gamma, IL-1), or Cytomix+PTX for 24 h. Occludin and ZO-1 protein levels were analyzed by Western blot. Confocal microscopy was used to assess the cytoplasmic localization of ZO-1 and occludin.
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Male Sprague-Dawley rats were given continuous infusion of LPS, PTX + LPS combined, or saline (sham) by implantable pumps. Neutrophil CD11b expression, lung histopathology, lung intercellular adhesion molecule-1 (ICAM-1) expression assessed by immune staining, serum TNF-alpha, serum interleukin-6 (IL-6), and bronchoalveolar lavage (BAL) IL-8 were evaluated at different time points. Lung injury was graded in a blinded fashion from 0 (normal) to 4 (severe) for interstitial inflammation, neutrophil infiltration, congestion, and edema. Total lung injury score (TLIS) was calculated by adding listed categories. White cell count in the peripheral blood and in the BAL was also performed.
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This suggests that urodilatin and pentoxifylline might be useful to protect renal function if given before a septic renal insult. Additionally, treatment with urodilatin is capable of restoring renal function in early Gram-negative sepsis-induced ARF even if given after the septic insult.
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Twelve patients, 9 males and 3 females between 22 to 65 years in age having air-borne contact dermatitis (ABCD) for 6 months to 12 years were included in this study. The diagnosis in each patient was confirmed by patch tests. Six of these patients (group I) were treated with pentoxifylline 400 mg three times a day orally in addition to topical clobetasol propionate and oral betamethasone 1.0 to 2.0 mg per day for 5 to 10 weeks. The other 6 patients (group II) were given the same treatment for the same duration but without pentoxifylline. The response to the treatment in both the groups was almost the same. The patients treated with pentoxifylline did not have any added benefit. There were no significant side effects of the therapy in either of the groups.
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Pentoxifylline could reduce the aminotransferase activities and improve the histological parameters in NAFLD patients. Large well-designed, randomized, placebo-controlled studies are needed to confirm these results.
Monocytes and macrophages produce tumor necrosis factor-alpha (TNF alpha) in response to microbial products including endotoxin. TNF alpha is a potent primer of neutrophil (PMN) oxidative activity. Certain xanthine phosphodiesterase (PDE) inhibitors such as pentoxifylline have been shown to inhibit stimulated oxidative activity in PMN. In the present study, the non-xanthine PDE type IV inhibitor rolipram (4-[3'-cyclopentyloxy-4'-methoxyphenyl]-2-pyrrolidone) alone and in combination with adenosine is examined as a potential modulator of TNF alpha-primed PMN oxidative activity. Attainable in vivo concentrations of rolipram and physiological concentrations of adenosine alone and together synergistically decreased rhTNF alpha-primed suspended PMN oxidative activity stimulated by the chemoattractant f-met-leu-phe. The rolipram effect was reversible by washing, and rolipram had a comparable effect if added before or after priming, indicating that its effect was on the primed response rather than on priming per se. In addition, rolipram especially when combined with adenosine, decreased rhTNF alpha-stimulated PMN adherence to a fibrinogen-coated surface, and the oxidative burst of rhTNF alpha-stimulated adherent PMN. The specific adenosine A2a receptor agonists CGS 21680 and WRC-0474 had comparable activity to adenosine in these experiments. Adenosine (or CGS 21680) combined with rolipram synergistically increased f-met-leu-phe-stimulated PMN cAMP content. The effects of both adenosine and rolipram with adenosine could be only partly counteracted by treatment of the PMN with the protein kinase A inhibitor KT 5720, indicating that protein phosphorylation is only partially involved. Rolipram activity was about 1000 x (by molar concentration) greater than pentoxifylline in comparable assays. Thus, rolipram, especially when combined with adenosine, has potent modulating effects on PMN activation and may be useful in decreasing inflammatory tissue damage in patients with sepsis.
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We examined hyperactivation and acrosomal loss in asthenozoospermic patients with a history of failed in-vitro fertilization (IVF). After selection by a Percoll gradient, spermatozoa were incubated with 3.6 mM pentoxifylline (PTX), 3.0 mM 2-deoxyadenosine (2-DXA) or both. Hyperactivation and ionophore A-23187-induced acrosome reaction were assessed immediately after sperm treatment and again after 180 min. In all groups studied, the mean hyperactivation rates were found to be low. No significant differences were noted between assessments immediately after treatment and 180 min later, except after treatment with both PTX and 2-DXA. The mean hyperactivation rates were found not to improve as a result of either PTX or 2-DXA, while the combination of both PTX and 2-DXA revealed a significant enhancement of total hyperactivation. When individual hyperactivation rates between control and treated sperm samples were compared, large differences in response were observed. Some sperm samples showed a marked increase in hyperactivation with one treatment, while another treatment led to a decrease. Acrosome reaction rates assessed immediately after ionophore A-23187 stimulation were found not to be significantly different from those assessed 180 min later. No significant effect could be demonstrated for either treatment, although, here too, marked interindividual variations were noted. It was concluded that an unselective use of PTX, 2-DXA or both compounds together, may restore sperm function in certain of these patients, and perhaps improve fertilization in vitro, but in others it may produce no change or may even be detrimental to sperm function.
To determine whether pentoxifylline treatment altered hematologic, rheologic, electrolyte, or blood gas test results of Thoroughbreds during submaximal treadmill exercise.
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Seventeen boys with DMD, between 4 and 8 years of age, were enrolled at one of five Cooperative International Neuromuscular Research Group (CINRG) centers. Only 9 were able to complete the 12-month PTX treatment phase; the primary reason for discontinuation was adverse events. Intolerable gastrointestinal side effects were experienced by 65% of participants. Two participants had severe leukopenia that resolved with medication withdrawal.
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The question whether progressive sensorineural hearing loss during childhood is the fateful course of a main illness has been discussed controversially over 60 years. No medicamentous therapy with satisfactory results has been described in the literature. The goal of this study was to determine whether an infusion therapy, developed for the treatment of sudden hearing loss in the elderly, can induce recovery after progression in sensorineural hearing loss during childhood.
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Pentoxifylline appeared to reduce the contraceptive effectiveness of the IUDs in this model.
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Data from the preliminary semen analyses and AR to ionophore challenge scores were correlated with the fertilization rates achieved using control and treated sperm preparations. The rates of total fertilization failure and the numbers of clinical pregnancies occurring in each subgroup were also recorded.
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Initially, 21 patients with various surgical, traumatic, or burn wounds and scars were enrolled into this case series. Patients applied a compounded topical anhydrous silicone base containing pracaxi oil with or without additional active ingredients, including pentoxifylline, caffeine, tranilast, and mupirocin. Wound/scar photographs taken before and after application of the compounded pracaxi oil topical formulation (with/without additional ingredients) were reviewed and adjudicated by a blinded dermatology reviewer. Improvements in wound size, coloration, and overall appearance before and after treatment were determined. Patient satisfaction was assessed after application of compounded topical formulation using a self-report questionnaire distributed at the time of dispensing.
Individuals who suffer from severe joint destruction caused by the various arthritidies often undergo total joint arthroplasty. A major limitation of this treatment is the development of aseptic loosening of the prosthesis in as many as 20% of patients. The current paradigm to explain aseptic loosening proposes that wear debris generated from the prosthesis initiates a macrophage-mediated inflammatory response by resident macrophages, leading to osteoclast activation and bone resorption at the implant interface. No therapeutic interventions have been proved to prevent or inhibit aseptic loosening. The development of therapeutic strategies is limited due to the absence of a quantitative surrogate in which drugs can be screened rapidly in large numbers of animals. We have previously described a model in which titanium particles implanted on mouse calvaria induce an inflammatory response with osteolysis similar to that observed in clinical aseptic loosening. Here, we present new methods by which the osteolysis in this model can be quantified. We determined that 6-8-week-old mice in normal health have a sagittal suture area of 50 (+/-6) microm2, which contains approximately five osteoclasts. As a result of the titanium-induced inflammation and osteolysis, the sagittal suture area increases to 197 (+/-27) microm2, with approximately 30 osteoclasts, after 10 days of treatment. The sagittal suture area and the number of osteoclasts in the calvaria of sham-treated mice remained unchanged during the 10 days. We also determined the effects of pentoxifylline, a drug that blocks the responses of tumor necrosis factor-alpha to wear debris, and the osteoclast inhibitor alendronate. We found that both drugs effectively block wear debris-induced osteolysis but not osteoclastogenesis. In conclusion, we found the measurements made with this model to be reproducible and to permit quantitative analysis of agents that are to be screened for their potential to prevent aseptic loosening.
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Sprague-Dawley rats were bled to a mean arterial pressure of 35 mm Hg for 1 hour. Animals were divided into 3 groups: sham (no shock, no resuscitation, n = 7), RL (32 mL/kg, n = 7), and HSPTX (7.5% NaCl 4 mL/kg + PTX 25 mg/kg; n = 7). Shed blood was infused after fluid resuscitation. Blood pressure was monitored until the end of resuscitation. Animals were sacrificed at 24 hour after resuscitation. Bronchoalveolar lavage fluid (BALF) was obtained for white cell count (total and differential) and TNF-alpha and IL-1beta levels were measured by ELISA. Lung and intestinal injury at 24 hour were evaluated by histopathology. Organ damage was graded by a pathologist and a score was created (0 = no injury; 3 = severe). Lung neutrophil infiltration was evaluated by MPO immune staining.
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Autoimmune encephalomyelitis (EAE) in Lewis rats is a classical experimental model of demyelinating inflammatory disease of the central nervous system. EAE is widely accepted for study of immune-inflammatory mechanisms in the CNS related to multiple sclerosis (MS) due to similar clinical evolution.
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In advanced or refractory cases of ORN surgical treatment, including microvascular reconstructive techniques for bone and soft tissue, remains the only option available.
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Motility variables and binding capacity.
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Neither ActoHorm nor pentoxifylline prevented the development of radiation-induced rectal ulcers. The stimulation of mucosal epithelium with ActoHorm might, however, be effective in healing of superficial erosions of the intestinal mucosa.
Twenty-three consecutive patients who received inhaled NO (10 ppm) and PTX (NO-PTX group) at the time of reperfusion were compared retrospectively with (1) 23 consecutive patients transplanted just before the use of NO-PTX (control group 23); (2) 95 patients representing all the patients of the series who did not receive NO-PTX (control group 95), with respect to I/R injury related complications. In particular, the incidence of pulmonary reimplantation edema and early hemodynamic failure, the PaO2/FIO2 ratio as well as the duration of mechanical ventilation and the 2-month mortality rates were compared.
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Most animal models of sepsis induced high mortality or early recovery and do not mimic the long-lasting catabolic state observed in patients. The purpose of this study is to develop a model of sepsis which reproduces these disorders, especially the long-lasting muscle wasting. This report summarizes our observations in a series of seven experiments using this model with rats to study the route of live Escherichia coli administration, dose of bacteria, reproducibility of the model, bacterial count in tissues, comparison of injection of live or dead bacteria, metabolic perturbations linked to infection, and potential role of tumor necrosis factor alpha (TNF-alpha) in muscle wasting. After intravenous infection, animals were anorexic and the catabolic state was long-lasting: body weight loss for 2 to 3 days followed by a chronic wasting state for several days. Liver, spleen, lung protein content, and plasma concentration of alpha2-macroglobulin were increased 2 and 6 days after infection. At 6 days, muscle protein content was substantially (-40%) reduced. The plasma TNF-alpha level measured 1.5 h after infection correlated with body weight loss observed 9 days later. The inhibition of TNF-alpha secretion by administration of pentoxifylline 1 h before infection reduced muscle wasting and activation of proteolysis at day 2 and abolished them at day 6. This septic model mimics in rats the prolonged protein metabolism alterations and muscle atrophy characteristics of infected patients and thus is useful for studying the impact of nutritional support on outcome.