OBJECTIVES: Pentoxifylline (PTX) is a methylxanthine derivative that has been implicated in the pathogenesis of peripheral vessel disease and intermittent lameness. The purpose of this study was to investigate the effect of PTX and tocopherol in patients diagnosed with osteoradionecrosis (ORN), bisphosphonate-related osteonecrosis of the jaw (BRONJ), and chronic osteomyelitis using digital panoramic radiographs.MATERIALS AND METHODS: This study was performed in 25 patients who were prescribed PTX and tocopherol for treatment of ORN, BRONJ, and chronic osteomyelitis between January 2014 and May 2018 in Seoul National University Dental Hospital. Radiographic densities of the dental panorama were compared prior to starting PTX and tocopherol, at 3 months, and at 6 months after prescription. Radiographic densities were measured using Adobe Photoshop CS6 (Adobe System Inc., USA). Blood sample tests showing the degree of inflammation at the initial visit were considered the baseline and compared with results after 3 to 6 months. Statistical analysis was performed using the Mann–Whitney test and repeated measurement ANOVA using IBM SPSS 23.0 (IBM Corp., USA).RESULTS: Eight patients were diagnosed with ORN, nine patients with BRONJ, and the other 8 patients with chronic osteomyelitis. Ten of the 25 patients were men, average age was 66.32±14.39 years, and average duration of medication was 151.8±80.65 days (range, 56–315 days). Statistically significant increases were observed in the changes between 3 and 6 months after prescription (P<0.05). There was no significant difference between ORN, BRONJ, and chronic osteomyelitis. Only erythrocyte sedimentation rate (ESR) was statistically significantly lower than before treatment (P<0.05) among the white blood cell (WBC), ESR, and absolute neutrophil count (ANC).CONCLUSION: Long-term use of PTX and tocopherol can be an auxiliary method in the treatment of ORN, BRONJ, or chronic osteomyelitis in jaw.
Bisphosphonate-Associated Osteonecrosis of the Jaw ; Blood Sedimentation ; Humans ; Inflammation ; Jaw ; Leukocytes ; Male ; Methods ; Neutrophils ; Osteomyelitis ; Osteoradionecrosis ; Pentoxifylline ; Prescriptions ; Radiography, Panoramic ; Seoul ; Tocopherols

OBJECTIVE: Hypoxic-ischemic (HI) brain injury in the human perinatal period often leads to significant long-term neurobehavioral dysfunction in the cognitive and sensory-motor domains. Using a neonatal HI injury model (unilateral carotid ligation followed by hypoxia) in postnatal day seven rats, the present study investigated the long-term effects of HI and potential behavioral protective effect of pentoxifylline. METHODS: Seven-day-old rats underwent right carotid ligation, followed by hypoxia (FiO2 = 0.08). Rats received pentoxifylline immediately after and again 2 hours after hypoxia (two doses, 60–100 mg/kg/dose), or serum physiologic. Another set of seven-day-old rats was included to sham group exposed to surgical stress but not ligated. These rats were tested for spatial learning and memory on the simple place task in the Morris water maze from postnatal days 77 to 85. RESULTS: HI rats displayed significant tissue loss in the right hippocampus, as well as severe spatial memory deficits. Low-dose treatment with pentoxifylline resulted in significant protection against both HI-induced hippocampus tissue losses and spatial memory impairments. Beneficial effects are, however, negated if pentoxifylline is administered at high dose. CONCLUSION: These findings indicate that unilateral HI brain injury in a neonatal rodent model is associated with cognitive deficits, and that low dose pentoxifylline treatment is protective against spatial memory impairment.
Animals ; Anoxia ; Brain Injuries ; Brain ; Cognition Disorders ; Hippocampus ; Humans ; Hypoxia-Ischemia, Brain ; Learning ; Ligation ; Memory ; Pentoxifylline ; Rats ; Rodentia ; Spatial Learning ; Spatial Memory ; Water

Introduction: Rising prevalence of non-alcoholic fatty liver disease (NAFLD) suggests its correlation with liver failure worldwide. To date, there is no proven pharmacologic therapy for NAFLD. Pentoxifylline (PTX) with its anti-tumor necrosis factor properties has shown improvement of histological parameters, reductions in transaminase levels and serum cytokines among patients with NAFLD. The main objective is to determine the effectiveness of PTX in the reduction of progression of NAFLD in terms of reducing levels of aspartate transaminase (AST) and alanine transaminase (ALT), improving liver histology parameters and in decreasing TNF-α, IL-6 and IL-8. Methods: A comprehensive literature search showed seven randomized controlled trials (N=222) comparing PTX (1,200mg/day) with placebo. Two reviewers independently selected studies, assessed quality, and extracted and pooled outcomes including AST levels, ALT levels, serum cytokines and liver histology. All selected studies were found to be of low risk of bias based on Cochrane risk of bias assessment tool for randomized trials. Statistical analysis and forrest plot generation were done using the Review Manager Software 5.3. Results: Pooled results showed that PTX significantly reduced the ALT (WMD= -20.08; 95% CI: -40.20, 0.05; p=0.05) and AST (WMD= -11.38; 95% CI: -20.47, -2.29; p=0.01) in NAFLD patients. PTX significantly improved lobular inflammation (WMD= -0.45; 95% CI: -0.89, -0.01; p=0.04), fibrosis (WMD= -0.39; 95% CI: 0.83, 0.05; p=0.08) and NAS score (WMD= -0.52; 95% CI: -1.06, 0.0; p=0.051). Among serum cytokines, greater reduction was demonstrated in TNF-α (WMD= -20.20; 95% CI: -50.46, 10.41; p=0.20). Conclusion Pentoxifylline (PTX) decreases the aminotransferase activities, improves the liver histology and TNF-α of NAFLD patients. Demonstrating effects on serum TNF-α which plays a key role in progression to hepatic steatosis, it may be used as an adjunct to diet and lifestyle modifications in the treatment of NAFLD.
Meta-Analysis ; Non-alcoholic Fatty Liver Disease ; Pentoxifylline

Previous studies report positive effects of pentoxifylline (PTX) alone or in combination with other drugs on some pathologic bone diseases as well as an ability to accelerate osteogensis and fracture healing in both animal models and human patients. The aim of this present study was to evaluate the effects of PTX administration on Hounsfield unit and bone strength at catabolic response (bone resorbing) of a fracture in an experimental rat model of ovariectomy induced osteoporosis (OVX-D). Thirty adult female rats were divided into groups as follows: 1 (OVX, control, no treatment); 2 (OVX, sham: daily distilled water); 3 (OVX, daily alendronate: 3 mg/kg); 4 (OVX, twice daily 100 mg/kg PTX) and 5 (OVX, PTX+alenderonate). OVX was induced by bilateral ovariectomy in all rats. A complete standardized osteotomy of the right femur was made after 3.5 months. PTX and alendronate treatments were performed for eight weeks. Then, rats were euthanized and had its right femur subjected to computerized tomography scanning for measuring Hounsfield unit; eventually, the samples were sent for a three point bending test for evaluation of the bone strength. Administration of PTX with 200 mg/kg and alendronate alone and in combination showed no significant alteration in Hounsfield unit and biomechanical properties of repairing callus of the complete osteotomy compared with the control group. Results showed increased bending stiffness and stress high load mean values of repairing complete osteotomy in PTX-treated rats compared to the control OVX-D.
Adult ; Alendronate ; Animals ; Bone Diseases ; Bony Callus ; Female ; Femur ; Fracture Healing* ; Humans ; Models, Animal* ; Osteoporosis ; Osteotomy ; Ovariectomy ; Pentoxifylline* ; Rats*

PURPOSE: Perinatal hypoxic-ischemic brain damage is a major cause of acute mortality and chronic neurologic morbidity in infants and children. We investigated the effects of pentoxifylline, a methylxanthine derivative and type-4 phosphodiesterase inhibitor, on short-term memory and apoptotic neuronal cell death in the hippocampus following perinatal hypoxic-ischemia in newborn rats. METHODS: We used a step-down avoidance task to evaluate short-term memory and 3ʹ-5ʹ-cyclic adenosine monophosphate (cAMP) assay to detect cAMP levels. We evaluated apoptosis using a terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay for evidence of DNA fragmentation, immunohistochemistry for caspase-3 levels, and western blot for Bcl-2 and Bax. RESULTS: Perinatal hypoxic-ischemic injury increased apoptotic cell death in the hippocampus, resulting in impaired short-term memory with decreased cAMP levels. Pentoxifylline treatment improved short-term memory by suppressing apoptotic cell death in the hippocampus with elevated cAMP levels. CONCLUSIONS: Pentoxifylline ameliorated perinatal hypoxic-ischemia in rat pups. This alleviating effect could be ascribed to the inhibition apoptosis due to increased cAMP production by pentoxifylline.
Adenosine Monophosphate ; Animals ; Apoptosis* ; Blotting, Western ; Brain ; Caspase 3 ; Cell Death ; Child ; Cyclic AMP ; DNA Fragmentation ; Hippocampus* ; Humans ; Immunohistochemistry ; Infant ; Infant, Newborn ; Memory ; Memory, Short-Term* ; Mortality ; Neurons ; Pentoxifylline* ; Rats*

Infection of schistosomiasis japonica may eventually lead to liver fibrosis, and no effective antifibrotic therapies are available but liver transplantation. Hedgehog (HH) signaling pathway has been involved in the process and is a promising target for treating liver fibrosis. This study aimed to explore the effects of pentoxifylline (PTX) on liver fibrosis induced by schistosoma japonicum infection by inhibiting the HH signaling pathway. Phorbol12-myristate13-acetate (PMA) was used to induce human acute mononuclear leukemia cells THP-1 to differentiate into macrophages. The THP-1-derived macrophages were stimulated by soluble egg antigen (SEA), and the culture supernatants were collected for detection of activation of macrophages. Cell Counting Kit-8 (CCK-8) was used to detect the cytotoxicity of the culture supernatant and PTX on the LX-2 cells. The LX-2 cells were administered with activated culture supernatant from macrophages and(or) PTX to detect the transforming growth factor-β gene expression. The mRNA expression of shh and gli-1, key parts in HH signaling pathway, was detected. The mRNA expression of shh and gli-1 was increased in LX-2 cells treated with activated macrophages-derived culture supernatant, suggesting HH signaling pathway may play a key role in the activation process of hepatic stellate cells (HSCs). The expression of these genes decreased in LX-2 cells co-cultured with both activated macrophages-derived culture supernatant and PTX, indicating PTX could suppress the activation process of HSCs. In conclusion, these data provide evidence that PTX prevents liver fibrogenesis in vitro by the suppression of HH signaling pathway.
Animals ; Antigens, Helminth ; isolation & purification ; pharmacology ; Cell Culture Techniques ; Cell Differentiation ; drug effects ; Cell Line ; Culture Media, Conditioned ; chemistry ; pharmacology ; Gene Expression Regulation ; Hedgehog Proteins ; agonists ; antagonists & inhibitors ; genetics ; immunology ; Hepatic Stellate Cells ; cytology ; drug effects ; metabolism ; Humans ; Liver Cirrhosis ; metabolism ; parasitology ; prevention & control ; Macrophage Activation ; drug effects ; Macrophages ; cytology ; drug effects ; immunology ; Models, Biological ; Monocytes ; cytology ; drug effects ; metabolism ; Pentoxifylline ; pharmacology ; Phosphodiesterase Inhibitors ; pharmacology ; RNA, Messenger ; genetics ; immunology ; Schistosoma japonicum ; chemistry ; Signal Transduction ; Tetradecanoylphorbol Acetate ; pharmacology ; Zinc Finger Protein GLI1 ; genetics ; immunology ; Zygote ; chemistry

The effect of pentoxifylline (PTX) administration on histomorphological parameters of streptozotocin (STZ)-induced type 1 diabetes mellitus (DM) in male rat testes were evaluated. We randomly divided 40 male rats into the following four groups: group 1: control or normal glycemic (NG) rats; group 2 or NG rats that received only normal saline (NS), (NG+NS); group 3 or diabetic rats which were not treated by PTX (DM+vehicle solution (NS)); and group 4 which comprised diabetic rats treated with 50 mg/kg of PTX (DM+PTX). Type 1 DM was induced by intraperitoneal injection of STZ (55 mg/kg). Rats were held for 30 days after which the experimental group received PTX twice daily (25 mg/kg) or NS. After 14 days of treatment by PTX or NS, the left testes from all rats were extracted and prpared for histological study. Apoptotic cells, blood vessel density, and spermatogenesis were evaluated. Data were analyzed by ANOVA test. PTX-treated-diabetic rats showed a significant decrease in number of apoptotic cells and decrease in blood vessel density compared to the DM+NS rats. A significant increase in spermatogenesis was observed in the PTX-treated diabetic group, compared to the DM+NS groups. It was concluded that PTX administration to STZ-induced type 1 DM rats affected apoptotic cell number positively. Moreover, blood vessel density significantly decreased and improvements were observed in spermatogenesis.
Animals ; Blood Cells ; Blood Vessels ; Cell Count ; Diabetes Mellitus ; Diabetes Mellitus, Type 1 ; Humans ; Injections, Intraperitoneal ; Male ; Pentoxifylline* ; Rats* ; Spermatogenesis ; Streptozocin ; Testis*

Alcoholic hepatitis (AH) is defined as an acute hepatic manifestation resulting from heavy alcohol intake. Histologically, alcoholic steatohepatitis (ASH) is characterized by hepatocellular steatosis, inflammation, and fibrosis. Alcohol abstinence is the sine qua non of therapy for AH and, in the milder forms, is prerequisite to clinical recovery. Severe ASH may lead to multi-organ failure such as acute kidney injury and infection, which has a major impact on survival and thus should be closely monitored. Patients with severe ASH have a drastic short-term mortality of up to 40-50%. Specific therapies should be considered for patients with severe ASH at risk of early death. Corticosteroids are the standard of care for patients with severe ASH. When corticosteroids are contraindicated, pentoxifylline may be an alternative option. Steroid responsiveness should be evaluated on the basis of Lille score. Tactically, we should explore novel therapeutic targets to suppress inflammation based on cytokine profiles, promote hepatic regeneration, limit innate immune responses, and restore altered gut mucosal integrity in severe ASH.
Adrenal Cortex Hormones/therapeutic use ; Free Radical Scavengers/therapeutic use ; Hepatitis, Alcoholic/*diagnosis/drug therapy/pathology ; Humans ; Liver Transplantation ; Pentoxifylline/therapeutic use ; Prognosis ; Severity of Illness Index

Pigmented purpuric dermatosis (PPD) represents a group of cutaneous lesions exhibiting petechiae, pigmentation, and occasionally telangiectasia in the absence of an associated venous insufficiency or hematological disorder. PPD may resolve spontaneously but tends to persist for months to years. Various treatment modalities such as oral griseofulvin, pentoxifylline, cyclosporine, ascorbic acid, topical corticosteroids, and PUVA therapy have been used with unsatisfactory results. Recently, some studies reported that PPD showed a dramatic response to narrowband ultraviolet B (UVB) phototherapy. In these studies, narrowband UVB phototherapy was an effective treatment method with few side effects. Here, we present the case of a 7-year-old boy with generalized PPD that improved rapidly following narrowband UVB phototherapy.
Adrenal Cortex Hormones ; Ascorbic Acid ; Child* ; Cyclosporine ; Griseofulvin ; Humans ; Male ; Pentoxifylline ; Phototherapy* ; Pigmentation ; Purpura ; PUVA Therapy ; Skin Diseases* ; Telangiectasis ; Venous Insufficiency

OBJECTIVE: Artificial 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. METHODS: The 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). RESULTS: The 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. CONCLUSION: We 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.
Calcium ; Calcium Signaling ; Embryonic Structures ; Fertilization ; Fertilization in Vitro* ; Hospitals, General ; Humans ; Infertility ; Male ; Oocytes* ; Pentoxifylline ; Pregnancy Rate ; Sperm Injections, Intracytoplasmic* ; Sperm Motility ; Spermatozoa*