Is the use of Pentoxifylline and Tocopherol effective in the treatment of Osteoradionecrosis of the jaws or for the treatment of medicationosteonecrosis of the jaw? An overview.

PURPOSE: The aim of the present study was to determine the methodological quality of systematic reviews that evaluated the effectiveness of pentoxifylline and tocopherol (PENTO) in the treatment of osteoradionecrosis of the jaw (ORNJ) and medication-related osteonecrosis of the jaw (MRONJ). METHODS: Searches were performed in Databases including PubMed, Scopus, LILACS, DARE, Cochrane Library, and SIGLE through OpenGrey until March 2024, were evaluated by two independent reviewers to answer the following question: Is the use of PENTO protocol effective in the treatment of ORNJ or for the treatment of MRONJ? RESULTS: A total of 256 articles were initially identified; however, following the use of appropriate inclusion and exclusion criteria, five systematic reviews were identified for detailed analysis. The final study sample comprised 588 patients: 397 patients with ORN and 197 patients with MRONJ who were treated with PENTO. The total recovery of individuals who used the PENTO protocol was 62,2 % for ORN and 100 % for MRONJ, with a follow-up period of 1 month to 10 years. The methodological quality of the studies was assessed using the AMSTAR 2 tool, in which four were of low quality and 1 moderate quality. CONCLUSION: The treatment of ORN and MRONJ with pentoxifylline and tocopherol has shown good results in the studies presented, with a partial or total reduction in bone exposure. However, the low quality of the relevant reports highlights the need for primary and secondary studies with better methodological rigor to reduce bias and provide reassurance for this treatment option.

Evaluation of antifibrotic and antifungal combined therapies in experimental pulmonary paracoccidioidomycosis.

Paracoccidioidomycosis (PCM) is a systemic mycosis caused by the Paracoccidioides genus. Most of the patients with chronic form present sequelae, like pulmonary fibrosis, with no effective treatment, leading to impaired lung functions. In the present study, we aimed to investigate the antifibrotic activity of three compounds: pentoxifylline (PTX), azithromycin (AZT), and thalidomide (Thal) in a murine model of pulmonary PCM treated with itraconazole (ITC) or cotrimoxazole (CMX). BALB/c mice were inoculated with P. brasiliensis (Pb) by the intratracheal route and after 8 weeks, they were submitted to one of the following six treatments: PTX/ITC, PTX/CMX, AZT/ITC, AZT/CMX, Thal/ITC, and Thal/CMX. After 8 weeks of treatment, the lungs were collected for determination of fungal burden, production of OH-proline, deposition of reticulin fibers, and pulmonary concentrations of cytokines and growth factors. Pb-infected mice treated with PTX/ITC presented a reduction in the pulmonary concentrations of OH-proline, associated with lower concentrations of interleukin (IL)-6, IL-17, and transforming growth factor (TGF)-ß1 and higher concentrations of IL-10 compared to the controls. The Pb-infected mice treated with AZT/CMX exhibited decreased pulmonary concentrations of OH-proline associated with lower levels of TGF-ß1, and higher levels of IL-10 compared controls. The mice treated with ITC/Thal and CMX/Thal showed intense weight loss, increased deposition of reticulin fibers, high pulmonary concentrations of CCL3, IFN-γ and VEGF, and decreased concentrations of IL-6, IL-1ß, IL-17, and TGF-ß1. In conclusion, our findings reinforce the antifibrotic role of PTX only when associated with ITC, and AZT only when associated with CMX, but Thal did not show any action upon addition.

Safety and efficacy of miltefosine monotherapy and pentoxifylline associated with pentavalent antimony in treating mucosal leishmaniasis.

INTRODUCTION: Mucosal Leishmaniasis (ML) is a difficult to treat and severe form of Leishmaniasis. In general, more than 40% of subjects with ML have therapeutic failure upon the use of pentavalent antimony (Sbv) at 20mg/kg/day during 30 days. Additionally, Sbv is a toxic drug that requires parenteral administration, and many patients will need several courses to be cured. In cases that cannot be treated or cured by Sbv, the alternative is amphotericin B, another toxic and parenteral drug. As a consequence, many ML patients will be cured only after years of disease and may present several morbidities due to the aggressiveness of the disease or toxicity related to the treatment. Areas covered: We aimed to review clinical trials with Miltefosine or Sbv associated with pentoxifylline in the treatment of ML. Expert commentary: There are few studies to define more effective and safer therapy in mucosal disease caused by Leishmania, with an urgent need to supporting and funding well designed trials. Miltefosine monotherapy, as well as pentoxifylline combined with Sbv are promising therapeutic approaches to increase the cure rate of this neglected disease.

Is pentoxifylline effective in alcoholic hepatitis? –First update. / ¿Es efectiva la pentoxifilina en hepatitis alcohólica? - Primera actualización.

ABOUT THE UPDATE: This article updates the June 2014 Living FRISBEE (Living FRISBEE: Living FRIendly Summary of the Body of Evidence using Epistemonikos). It incorporates a new systematic review identifying one study not included in previous reviews. The new evidence leads to substantial changes in the existing evidence. ASBTRACT: Pentoxifylline is an inhibitor of tumor necrosis factor, and has been proposed as treatment for alcoholic hepatitis. However, it is not clear if it is effective, or if it adds benefit to the treatment with corticosteroids. Searching in Epistemonikos database, which is maintained by screening 30 databases, we identified three systematic reviews including eight randomized controlled trials addressing the question of this article. We combined the evidence using meta-analysis and generated a summary of findings following the GRADE approach. We concluded pentoxifylline probably leads to little or no difference in mortality in alcoholic hepatitis.

ACERCA DE LA ACTUALIZACIÓN: Este resumen Epistemonikos (Living FRISBEE: Living FRIendly Summary of the Body of Evidence using Epistemonikos) es una actualización del resumen publicado en Junio de 2014. Incorpora una nueva revisión sistemática que identificó un estudio no incluido en las revisiones previas. La incorporación de esta nueva evidencia lleva a cambios sustantivos en la evidencia existente. RESUMEN: La pentoxifilina, un inhibidor del factor de necrosis tumoral oral, se ha planteado como un posible tratamiento para la hepatitis alcohólica. Sin embargo, no está claro si es efectiva o si su adición al tratamiento con corticoides agrega beneficios. Utilizando la base de datos Epistemonikos, la cual es mantenida mediante búsquedas en 30 bases de datos, identificamos tres revisiones sistemáticas que en conjunto incluyen ocho estudios aleatorizados. Realizamos un metanálisis y tablas de resumen de los resultados utilizando el método GRADE. Concluimos que la pentoxifilina probablemente no disminuye la mortalidad en pacientes con hepatitis alcohólica.

Direct intraperitoneal resuscitation with lidocaine, methylene blue and pentoxiphylline combination does not decreases inflammation after intestinal ischemia-reperfusion injury in rats.

PURPOSE: To evaluate the effects of an intraperitoneal solution of methylene blue (MB), lidocaine and pentoxyphylline (PTX) on intestinal ischemic and reperfusion injury. METHODS: Superior mesenteric artery was isolated and clamped in 36 adult male Sprague Dawley rats. After 60 minutes, clamp was removed and a group received intraperitoneally UNITO solution (PTX 25mg/kg + lidocaine 5mg/kg + MB 2mg/kg), while the other group was treated with warm 0.9% NaCl solution. Rats were euthanized 45 min after drug administration. Lung and bowel were collected for histological evaluation (using Park's score) and determination of myeloperoxidase (MPO) and malondialdehyde (MDA) levels. RESULTS: Control samples showed lymphoplasmocytic infiltrate and crypt necrosis of villi. MPO and MDA measurements shown no differences between treated and control groups. CONCLUSION: The combination of lidocaine, methylene blue and pentoxyphylline administered intraperitoneally at the studied dose, did not decreased histological lesion scores and biochemical markers levels in intestinal ischemia/reperfusion injury.

Direct intraperitoneal resuscitation with lidocaine, methylene blue and pentoxiphylline combination does not decreases inflammation after intestinal ischemia-reperfusion injury in rats

ABSTRACT PURPOSE: To evaluate the effects of an intraperitoneal solution of methylene blue (MB), lidocaine and pentoxyphylline (PTX) on intestinal ischemic and reperfusion injury METHODS: Superior mesenteric artery was isolated and clamped in 36 adult male Sprague Dawley rats. After 60 minutes, clamp was removed and a group received intraperitoneally UNITO solution (PTX 25mg/kg + lidocaine 5mg/kg + MB 2mg/kg), while the other group was treated with warm 0.9% NaCl solution. Rats were euthanized 45 min after drug administration. Lung and bowel were collected for histological evaluation (using Park's score) and determination of myeloperoxidase (MPO) and malondialdehyde (MDA) levels. RESULTS: Control samples showed lymphoplasmocytic infiltrate and crypt necrosis of villi. MPO and MDA measurements shown no differences between treated and control groups. CONCLUSION: The combination of lidocaine, methylene blue and pentoxyphylline administered intraperitoneally at the studied dose, did not decreased histological lesion scores and biochemical markers levels in intestinal ischemia/reperfusion injury.

Metadoxine improves the three- and six-month survival rates in patients with severe alcoholic hepatitis.

AIM: To evaluate the impact of metadoxine (MTD) on the 3- and 6-mo survival of patients with severe alcoholic hepatitis (AH). METHODS: This study was an open-label clinical trial, performed at the "Hospital General de México, Dr. Eduardo Liceaga". We randomized 135 patients who met the criteria for severe AH into the following groups: 35 patients received prednisone (PDN) 40 mg/d, 35 patients received PDN+MTD 500 mg three times daily, 33 patients received pentoxifylline (PTX) 400 mg three times daily, and 32 patients received PTX+MTD 500 mg three times daily. The duration of the treatment for all of the groups was 30 d. RESULTS: In the groups treated with the MTD, the survival rate was higher at 3 mo (PTX+MTD 59.4% vs PTX 33.3%, P = 0.04; PDN+MTD 68.6% vs PDN 20%, P = 0.0001) and at 6 mo (PTX+MTD 50% vs PTX 18.2%, P = 0.01; PDN+MTD 48.6% vs PDN 20%, P = 0.003) than in the groups not treated with MTD. A relapse in alcohol intake was the primary independent factor predicting mortality at 6 mo. The patients receiving MTD maintained greater abstinence than those who did not receive it (74.5% vs 59.4%, P = 0.02). CONCLUSION: MTD improves the 3- and 6-mo survival rates in patients with severe AH. Alcohol abstinence is a key factor for survival in these patients. The patients who received the combination therapy with MTD were more likely to maintain abstinence than those who received monotherapy with either PDN or PTX.

Nebulized pentoxifylline for reducing the duration of oxygen supplementation in extremely preterm neonates.

OBJECTIVE: To evaluate the efficacy and safety of nebulized pentoxifylline for reducing the duration of oxygen supplementation in extremely preterm neonates at high risk of bronchopulmonary dysplasia (BPD). STUDY DESIGN: Single-center, randomized, double-blind, placebo-controlled trial was conducted. Infants of 23(0) to 27(6) weeks' gestational age requiring mechanical ventilation or ≥30% supplemental oxygen on continuous positive airway pressure at 72-168 hours were randomized to receive 20 mg/kg (1 mL/kg) nebulized pentoxifylline or an equal volume of normal saline placebo every 6 hours for 10 consecutive days via a vibrating mesh nebulizer. The primary outcome was the duration of oxygen supplementation at 40 weeks' postmenstrual age. We used Cox proportional hazards regression modeling to analyze outcomes. RESULTS: All infants had adequate data for analysis of the primary outcome. Intention-to-treat analysis revealed no differences in duration of oxygen supplementation at 40 weeks' postmenstrual age between pentoxifylline (n=41) and placebo (n=40) groups (median 2262 vs 2160 hours, adjusted hazard ratio: 1.14, 95% CI 0.72-1.80, P=.63). There was no difference in mortality and further secondary outcomes. No adverse effects were noted. CONCLUSIONS: Nebulized pentoxifylline is safe but did not reduce the duration of oxygen supplementation in extremely preterm infants at high risk of BPD. Dose-ranging studies and large, well-designed clinical trials are required to determine whether the use of nebulized or systemic pentoxifylline as a prophylactic therapy offers small but relevant benefits for prevention of BPD. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry: ACTRN12611000145909.

The effects of vardenafil and pentoxifylline administration in an animal model of ischemic colitis.

OBJECTIVES: Vardenafil enhances dilatation of vascular smooth muscle and inhibits platelet aggregation. The purpose of this study was to evaluate the clinical effects of vardenafil and pentoxifylline administration in an experimental model of ischemic colitis. METHODS: Forty female Wistar albino rats weighing 250-300 g were randomized into five experimental groups (each with n = 8) as follows:1) a sham group subjected to a sham surgical procedure and administered only tap water; 2) a control group subjected to a standardized surgical procedure to induce ischemic colitis and administered only tap water; 3) and 4) treatment groups subjected to surgical induction of ischemic colitis followed by the postoperative administration of 5 mg/kg or 10 mg/kg vardenafil, respectively; and 5) a treatment group subjected to surgical induction of ischemic colitis followed by postoperative administration of pentoxifylline at 50 mg/kg/day per day as a single dose for a 3-day period. All animals were sacrificed at 72 h post-surgery and subjected to relaparotomy. We scored the macroscopically visible damage, measured the ischemic area and scored histopathology to determine the severity of ischemia. Tissue malondialdehyde levels were also quantified. RESULTS: The mean Gomella ischemic areas were 63.3 mm2 in the control group; 3.4 and 9.6 mm2 in the vardenafil 5 and vardenafil 10 groups, respectively; and 3.4 mm2 in the pentoxifylline group (p = 0.0001). The mean malondialdehyde values were 63.7 nmol/g in the control group; 25.3 and 25.6 nmol/g in the vardenafil 5 and vardenafil 10 groups, respectively; and 22.8 nmol/g in the pentoxifylline group (p = 0.0001). CONCLUSION: Our findings indicate that vardenafil and pentoxifylline are effective treatment options in an animal model of ischemic colitis. The positive clinical effects produced by these drugs are likely due to their influence on the hemodynamics associated with vascular smooth muscle and platelet functions.

The effects of vardenafil and pentoxifylline administration in an animal model of ischemic colitis

OBJECTIVES: Vardenafil enhances dilatation of vascular smooth muscle and inhibits platelet aggregation. The purpose of this study was to evaluate the clinical effects of vardenafil and pentoxifylline administration in an experimental model of ischemic colitis. METHODS: Forty female Wistar albino rats weighing 250-300 g were randomized into five experimental groups (each with n = 8) as follows:1) a sham group subjected to a sham surgical procedure and administered only tap water; 2) a control group subjected to a standardized surgical procedure to induce ischemic colitis and administered only tap water; 3) and 4) treatment groups subjected to surgical induction of ischemic colitis followed by the postoperative administration of 5 mg/kg or 10 mg/kg vardenafil, respectively; and 5) a treatment group subjected to surgical induction of ischemic colitis followed by postoperative administration of pentoxifylline at 50 mg/kg/day per day as a single dose for a 3-day period. All animals were sacrificed at 72 h post-surgery and subjected to relaparotomy. We scored the macroscopically visible damage, measured the ischemic area and scored histopathology to determine the severity of ischemia. Tissue malondialdehyde levels were also quantified. RESULTS: The mean Gomella ischemic areas were 63.3 mm2 in the control group; 3.4 and 9.6 mm2 in the vardenafil 5 and vardenafil 10 groups, respectively; and 3.4 mm2 in the pentoxifylline group (p = 0.0001). The mean malondialdehyde values were 63.7 nmol/g in the control group; 25.3 and 25.6 nmol/g in the vardenafil 5 and vardenafil 10 groups, respectively; and 22.8 nmol/g in the pentoxifylline group (p = 0.0001). CONCLUSION: Our findings indicate that vardenafil and pentoxifylline are effective treatment options in an animal model of ischemic colitis. The positive clinical effects produced by these drugs are likely due to their influence on the hemodynamics associated ...

Effectiveness of miltefosine-pentoxifylline compared to miltefosine in the treatment of cutaneous leishmaniasis in C57Bl/6 mice.

INTRODUCTION: The treatment of leishmaniasis ischallenging, given the difficulties in drug administration and resistance. Therefore, we chose to test the efficacy of miltefosine combined with pentoxifylline. METHODS: Twenty-seven isogenic C57Bl/6 mice were infected with Leishmania (Leishmania) amazonensis, and equally divided into three groups: miltefosine (200mg/kg/day), miltefosine (200mg/kg/day) with pentoxifylline (8mg/kg/day), and untreated. Response to treatment was evaluated using paw diameter and parasitological criteria. RESULTS: The number of viable Leishmania reduced significantly within the miltefosine-pentoxifylline group (p < 0.05). CONCLUSIONS: There is hope that a viable treatment exists for Leishmania infection.

Unilateral livedoid vasculopathy associated with involutional phase of cutaneous infantile hemangioma: the connection to coagulation disorders.

Livedoid vasculopathy is a bilateral painful and recurrent cutaneous ulcerative disorder of the legs that leads to atrophie blanche, atrophic white-porcelain scars, and is associated with disorders of fibrinolysis and/or coagulation. We present a young boy with an association between livedoid vasculopathy in the area of a previous involuted cutaneous hemangioma. We found 4 uncommon abnormalities associated with thrombo-occlusive events: heterozygous 20210 A→G genotype of prothrombin, reduced activity of anticoagulation proteins C and S, and elevated lipoprotein (a).

Preventive and therapeutic anti-TNF-α therapy with pentoxifylline decreases arthritis and the associated periodontal co-morbidity in mice.

AIMS: The association between rheumatoid arthritis (RA) and periodontal disease (PD) has long been studied and some reports suggest that treating RA may improve the associated PD, and vice versa. This study aimed to evaluate the effects of an anti-tumor necrosis factor (TNF)-α therapy with pentoxifylline (PTX) in an experimental model of RA-associated PD. MAIN METHODS: Male C57BL/6 mice were subjected to chronic antigen-induced arthritis (AIA) and daily treated with PTX (50mg/kg, i.p.) using preventive (Pre-PTX) or therapeutic (The-PTX) strategies. Fourteen days after the antigen challenge, mice were euthanized and knee joints, maxillae and serum were collected for microscopic and/or immunoenzymatic analysis. KEY FINDINGS: AIA triggered significant leukocyte recruitment to the synovial cavity, tissue damage and proteoglycan loss in the knee joint. Pre-PTX and The-PTX regimens decreased these signs of joint inflammation. The increased levels of TNF-α and IL-17 in periarticular tissues of AIA mice were also reduced by both PTX treatments. Serum levels of C-reactive protein, which were augmented after AIA, were reduced by the PTX regimens. Concomitantly to AIA, mice presented alveolar bone loss, and recruitment of osteoclasts and neutrophils to periodontal tissues. Pre-PTX and The-PTX prevented and treated these signs of PD. PTX treatment also decreased TNF-α and increased IL-10 expression in the maxillae of AIA mice, although it did not affect the expression of IFN-γ and IL-17. SIGNIFICANCE: The current study shows the anti-inflammatory and bone protective effects of preventive and therapeutic PTX treatments, which decreased the joint damage triggered by AIA and the associated periodontal co-morbidity.

Efeitos da pentoxifilina sobre a qualidade espermática e hemodinâmica uterina em equinos / Effects of Pentoxifylline on sperm quality and uterine hemodinamics in equine

A resposta inflamatória uterina pós-cobertura ocorre para remoção de espermatozoides e contaminantes; todavia, o atraso em debelar este processo têm sido identificado, em equinos, como a principal causa de endometrite persistente pós-cobertura. A pentoxifilina atua como um inibidor da fosfodiesterase e aumenta as características de motilidade espermática, ainda tem sido relatada sua participação como agente reológico, aumentando o fluxo sanguíneo de tecidos comprometidos, e como agente imunomodulador. O propósito deste estudo foi examinar os efeitos da pentoxifilina adicionada ao diluidor seminal pós-descongelação, sobre a motilidade espermática, membranas plasmática, acrossomal e mitocondrial e integridade de cromatina, bem como sobre a resposta inflamatória uterina após a inseminação artificial de éguas. Dez partidas de sêmen de um único garanhão foram criopreservadas (100x106 espermatozoides/palheta 0,5 mL) em sistema automatizado (TK 3000) e mantidas em botijão criogênico, sendo posteriormente utilizadas para análises laboratoriais e inseminação artificial. [...] A adição de pentoxifilina não exerceu efeito sobre a motilidade progressiva, porém, a pentoxifilina aumentou velocidade de trajeto, velocidade progressiva e velocidade curvilinear quando comparada ao controle. Não houve diferença significativa na porcentagem de células apresentando membrana plasmática intacta, acrossoma intacto e alto potencial mitocondrial (PIAIC). Nenhuma diferença estatística foi encontrada no fluxo sanguíneo uterino de éguas após os tratamentos. Porém, a citologia endometrial demonstrou maior resposta inflamatória em grupos contendo pentoxifilina quando comparado aos controles. Concluiu-se que a pentoxifilina exerce efeito positivo sobre parâmetros de velocidade, mas não influencia as membranas celulares e a cromatina. No entanto, quando as éguas são inseminadas com sêmen contendo pentoxifilina, uma resposta inflamatória mais intensa é observada

The post breeding uterine inflammatory response occurs due to remove spermatozoa and contaminants; however, delayed uterine clearance has been identified, in equines, as the underlying cause of persistent post breeding endometritis. Pentoxifylline acts as a phosphodiesterase inhibitor and increases sperm motion characteristics, and it has been reported to participate as a rheologic agent, improving blood flow to compromised tissues, and as an immunomodulatory agent. The purpose of this study was to examine the effects of pentoxifylline added to the seminal extender after thawing, on sperm motion, plasmatic, acrosomal and mitochondrial membranes and chromatin integrities, as well as the uterine inflammatory response on mares after artificial insemination. Ten batches of a unique stallion were cryopreserved (100x106 spermatozoa/0.5 mL straws), in an automated system (TK 3000) and storaged in cryogenic cylinder for posterior use for laboratory analysis and artificial insemination. [...] Pentoxifylline addition did not exert effect on progressive motility, however, pentoxifylline increased path velocity, progressive velocity and curvilinear velocity when compared to controls. There were no significant differences on the percentage of cells presenting intact plasma membrane, intact acrosome and high mitochondrial membrane potential (IPIAH). No statistical difference was found on uterine blood flow of mares after treatments. However, endometrial cytology showed a major inflammatory response on groups containing Pentoxifylline when compared to controls. In conclusion, pentoxifylline exerted a positive effect on velocity parameters, but do not influence cellular membranes and chromatin. Furthermore, when mares were inseminated with semen containing pentoxifylline, an intense inflammatory response was observed

Recurrent cutaneous leishmaniasis.

We present a case of an 18-year-old male patient who, after two years of inappropriate treatment for cutaneous leishmaniasis, began to show nodules arising at the edges of the former healing scar. He was immune competent and denied any trauma. The diagnosis of recurrent cutaneous leishmaniasis was made following positive culture of aspirate samples. The patient was treated with N-methylglucamine associated with pentoxifylline for 30 days. Similar cases require special attention mainly because of the challenges imposed by treatment.

Recurrent cutaneous leishmaniasis / Leishmaniose recidiva cútis

We present a case of an 18-year-old male patient who, after two years of inappropriate treatment for cutaneous leishmaniasis, began to show nodules arising at the edges of the former healing scar. He was immune competent and denied any trauma. The diagnosis of recurrent cutaneous leishmaniasis was made following positive culture of aspirate samples. The patient was treated with N-methylglucamine associated with pentoxifylline for 30 days. Similar cases require special attention mainly because of the challenges imposed by treatment.

Paciente do sexo masculino, 18 anos. Dois anos após tratamento insuficiente para leishmaniose tegumentar americana, apresentou, na mesma localização, lesão formada por cicatriz atrófica central e nódulos verrucosos na periferia. Era imunocompetente, hígido e negava qualquer trauma local. O diagnóstico de leishmaniose recidiva cutis foi feito através de cultura do aspirado da lesão. Realizou tratamento com N-metilglucamina (20mgSbV/kg/dia) associado à pentoxifilina (1200mg/dia) durante 30 dias alcançando cura clínica. Os casos semelhantes requerem atenção diferenciada pela dificuldade ao tratamento.

Valproic acid: an anticonvulsant drug with potent antinociceptive and anti-inflammatory properties.

Valproic acid (VA) is a major antiepileptic drug, used for several therapeutic indications. It has a wide activity spectrum, reflecting on mechanisms of action that are not fully understood. The objectives of this work were to study the effects of VA on acute models of nociception and inflammation in rodents. VA (0.5, 1, 10, 25, and 50 mg/kg, p.o.) effects were evaluated on the carrageenan-induced paw edema, carrageenan-induced peritonitis, and plantar tests in rats, as well as by the formalin test in mice. The HE staining and immunohistochemistry assay for TNF-α in carrageenan-induced edema, from paws of untreated and VA-treated rats, were also carried out. VA decreased paw edema after carrageenan, and maximum effects were seen with doses equal to or higher than 10 mg/kg. VA also preserved the tissue architecture as assessed by the HE staining. Immunohistochemical studies revealed that VA significantly reduced TNF-α immunostaining in carrageenan-inflamed rat paws. In addition, the anti-inflammatory action of VA was potentiated by pentoxifylline (a phosphodiesterase inhibitor, known to inhibit TNF-α production), but not by sodium butyrate or by suberoylanilide hydroxamic acid (SAHA), nonspecific and specific inhibitors, respectively, of histone deacetylase. However, the decrease in the number of positive TNF-α cells in the rat paw was drastically potentiated in the VA + SAHA associated group. VA also reduced leukocytes and myeloperoxidase (MPO) releases to the peritoneal exudate, in the carrageenan-induced peritonitis. Although in the formalin test, VA inhibited both phases, the inhibition was mainly on the second phase. Furthermore, VA significantly increased the reaction time to thermal stimuli, as assessed by the plantar test. VA is a multi-target drug, presenting potent antinociceptive and anti-inflammatory properties at a lower dose range. These effects are partly dependent upon its inhibitory action on TNF-α-related pathways. However, the participation of the HDAC inhibition with the VA anti-inflammatory action cannot be ruled out. Inflammatory processes are associated with free radical damage and oxidative stress, and their blockade by VA could also explain the present results.

Effects of intravenous administration of pentoxifylline in pancreatic ischaemia-reperfusion injury.

BACKGROUND: Therapeutic strategies to reduce the occurrence of pancreatic ischaemia-reperfusion (I-R) injury might improve outcomes in human pancreas and kidney transplantation. In addition to its haemorrheologic effects, pentoxifylline has an anti-inflammatory effect by inhibiting NF-κB activation. This group has previously demonstrated that pentoxifylline induces an anti-inflammatory response in acute pancreatitis and liver I-R models. This led to the hypothesis that pentoxifylline might reduce pancreatic and renal lesions and the systemic inflammatory response in pancreatic I-R injury. The aim of this experimental study was to evaluate the effect of pentoxifylline administration in a rat model of pancreatic I-R injury. METHODS: Pancreatic I-R was performed in Wistar rats over 1 h by clamping the splenic vessels. The animals submitted to I-R were divided into two groups: Group 1 (n = 20, control) rats received saline solution administered i.v. at 45 min after ischaemia, and Group 2 (n = 20) rats received pentoxifylline (25 mg/kg) administered i.v. at 45 min after ischaemia. Blood samples were collected to enable the determination of amylase, creatinine, tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6) and IL-10. Pancreatic malondialdehyde (MDA) content, pancreas histology and pulmonary myeloperoxidase (MPO) were also assessed. RESULTS: Significant reductions in serum TNF-α, IL-6 and IL-10 were observed in Group 2 compared with Group 1 (P < 0.05). No differences in pancreatic MDA content or serum amylase levels were observed between the two groups. The histologic score was significantly lower in pentoxifylline-treated animals, denoting less severe pancreatic histologic damage. CONCLUSIONS: Pentoxifylline administration reduced the systemic inflammatory response, the pancreatic histological lesion and renal dysfunction in pancreatic I-R injury and may be a useful tool in pancreas and kidney transplantation.

Current applications of oogram methodology in experimental schistosomiasis; fecundity of female Schistosoma mansoni and egg release in the intestine of AKR/J mice following immunomodulatory treatment with pentoxifylline.

Oogram methodology permitted a direct assessment of the fecundity of Schistosoma mansoni and the passage of parasite eggs from mesenteric vessels into the intestinal lumen in AKR/J mice that had been infected via the intraperitoneal route with 60 cercariae of the trematode and later subjected to short-term subcutaneous treatments with pentoxifylline (PTX). The administration of PTX did not change oviposition kinetics, the individual fecundity of female parasites (as determined by the study of the ratio of second-stage S. mansoni eggs per g intestine/number of female parasites recovered from the portal system), nor the number of mature and dead eggs retained in the host tissue, though the drug has known immunomodulatory effects, as shown previously in experimental schistosomiasis. A better appraisal was also carried out, including the study of statistical parameters, concerning the utilization of the ratios of each stage of immature eggs (first to fourth) per g intestine/number of female worms from the portal system. The second-stage eggs had the lowest variability, confirming that the utilization of this stage as an indicator of the individual fecundity of parasite females is indeed viable. In the light of our findings, current uses of oogram methodology are discussed. Moreover, additional consideration is given to data obtained in the present study concerning intraperitoneal infection with S. mansoni cercariae in both untreated and treated mice of the AKR/J strain, such as the recovery of mature worms, eggs and free granulomas from the peritoneal cavity of these rodents.