1.Alteration in bulbar conjunctiva microcirculation and interventional effect of Pentoxifylline after high-voltage electrical burn in rabbits.
Qing-fu ZHANG ; Bao-yong YAN ; Hui-min ZHOU ; Che-jiang WANG
Chinese Journal of Burns 2010;26(3):185-191
OBJECTIVETo study the changes in bulbar conjunctiva microcirculation (BCM) and the therapeutic effect of Pentoxifylline on BCM disturbance after high-voltage electrical burn (HEB) in rabbits.
METHODSForty-five rabbits were divided into control group (C), electrical burn group (EB), and Pentoxifylline treatment group (PT) according to random number table, with 15 rabbits in each group. Model of HEB was reproduced in rabbits from EB and PT groups with voltage regulator and experimental transformer. Rabbits in C group were sham injured with the same devices without electrification. Changes in BCM were observed with microcirculation microscope at 15 minutes before HEB and 5 minutes, 1, 2, 4, 8 hour(s) post HEB (PHM or PHH), including: (1) morphology of microvessels, such as the discernible, diameters of arterioles, venules, and capillaries, the unevenness in caliber, and ischemic area; (2) dynamic changes in microvascular blood flow, such as blood flow speed in arterioles, venules, and capillaries, erythrocyte aggregation, and microthrombi formation; (3) condition of tissues surrounding microvessel, such as bleeding and exudation. Measurement data were processed with t test; enumeration data were processed with Fisher's exact test.
RESULTS(1) Morphology of microvessel: discernible of microvessels in EB and PT groups was decreased, but that of PT group was better than that of EB group. At PHM 5, diameter of arterioles, venules and capillaries was respectively (7.3+/-2.5), (12.3+/-2.4), (3.5+/-0.7) microm in EB group, all narrower than those of the control group [(14.6+/-3.1), (27.2+/-3.5), (9.0+/-1.4) microm, with t value respectively 5.23, 13.66, 14.04, P values all below 0.05]. Diameters of the microvessels in PT group [(10.2+/-3.8), (21.5+/-3.1), (7.1+/-1.2) microm] were larger than those in EB group (with t value respectively 2.21, 8.99, 10.18, P values all below 0.05). Diameters of arterioles, venules and capillaries in EB and PT groups recovered to the before HEB size at PHH 1. From PHH 2 to 8, arterioles and capillaries decreased gradually in caliber, venules dilated gradually in EB and PT groups, but the changes in PT group were not obvious. Thickness of microvessel was observed uneven in EB group at PHM 5, which lasted until PHH 8. Ischemia of the tissue was observed in EB group at PHM 5, which improved at PHH 2. Situation in PT group was better. (2) Dynamic changes in microvascular blood flow: at PHM 5, blood flow speed in arterioles, venules and capillaries was respectively (202+/-53), (198+/-44), (46+/-12) microm/s in EB group, all slower than those of the control group [(544+/-37), (359+/-32), (220+/-19) microm/s, with t value respectively 20.47, 11.51, 30.02, P values all below 0.05], and those of PT group [(335+/-42), (260+/-35), (119+/-23) microm/s] were faster than those of EB group (with t value respectively 7.55, 4.26, 14.85, P values all below 0.05). Blood flow speed in EB and PT groups recovered to the before HEB level at PHH 1. From PHH 2 to 8, blood flow speed decreased gradually in EB and PT groups, but that of PT group was faster than that of EB group. Erythrocyte aggregation in venules and capillaries was observed in EB group at PHM 5, which eased up at PHH 1, but aggregated at PHH 2, lasting until PHH 8. Obvious microthrombi were observed in EB group at PHH 2, which increased gradually. These changes were less obvious in PT group. (3) Condition of surrounding tissues of microvessel: in EB group, exudation was observed around microvessels at PHH 1, bleeding at PHH 2, with a worsening tendency. Changes in those in PT group were less obvious.
CONCLUSIONSHEB causes disturbance in BCM, but it can be ameliorated by Pentoxifylline.
Animals ; Burns, Electric ; drug therapy ; pathology ; Conjunctiva ; blood supply ; Microcirculation ; Microvessels ; pathology ; Pentoxifylline ; therapeutic use ; Rabbits
2.Diagnostic and Therapeutic Strategies for Severe Alcoholic Hepatitis.
The Korean Journal of Gastroenterology 2015;65(1):4-11
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
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Free Radical Scavengers/therapeutic use
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Hepatitis, Alcoholic/*diagnosis/drug therapy/pathology
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Humans
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Liver Transplantation
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Pentoxifylline/therapeutic use
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Prognosis
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Severity of Illness Index
4.Managing alcoholic liver disease.
Clinical and Molecular Hepatology 2015;21(3):212-219
Alcoholic liver disease continues to be a significant cause of liver-related morbidity and mortality throughout the world. A number of diagnostic and prognostic models have been developed in the management of this condition, although specific roles for liver biopsy still remain particularly in the setting of alcoholic hepatitis. Despite a large number of recent treatment trials, the ideal pharmacotherapy approach remains undefined. Most essential is the supportive care and focus on abstinence and nutrition. Owing in part to a great deal of attention from governmental funding sources, a number of new treatment approaches are undergoing rigorous evaluation, hopefully providing future treatment options in this very severe condition.
Adrenal Cortex Hormones/therapeutic use
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Biomarkers/analysis
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Humans
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Interleukins/metabolism
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Liver Diseases, Alcoholic/diagnosis/*therapy
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Liver Transplantation
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Pentoxifylline/therapeutic use
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Prognosis
5.Non-surgical therapy of Peyronie's disease.
Frederick L TAYLOR ; Laurence A LEVINE
Asian Journal of Andrology 2008;10(1):79-87
The present paper provides a review of the available non-surgical treatments for Peyronie's disease (PD). A review of published literature on oral, intralesional, external energy and iontophoresis therapies for PD was performed, and the published results of available treatment options reviewed. The authors recommendations for appropriate non-surgical management of PD are provided. Although there are many published reports that show the efficacy of non-surgical therapies for PD, there is a lack of large scale, multicenter controlled clinical trials, which makes treatment recommendations difficult. Careful review of the literature does suggest that there are treatment options that make scientific sense and appear to stabilize the disease process, reduce deformity, and improve function. Offering no treatment at all will encourage our patients to pursue alternative treatments, which might do harm, and misses the opportunity to do some good. Clearly further work is necessary to develop safe and effective non-surgical treatments for PD.
Animals
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Arginine
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therapeutic use
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Carnitine
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therapeutic use
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Collagenases
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therapeutic use
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Combined Modality Therapy
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Electric Stimulation Therapy
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Humans
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Male
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Penile Induration
;
therapy
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Pentoxifylline
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therapeutic use
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Randomized Controlled Trials as Topic
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Traction
6.The Hematologic Response to Anti-apoptotic Cytokine Therapy: Results of Pentoxifylline, Ciprofloxacin, and Dexamethasone Treatment for Patients with Myelodysplastic Syndrome.
Min Kyoung KIM ; Jae Lyun LEE ; Hee Soon CHO ; Sung Hwa BAE ; Hun Mo RYOO ; Kyung Hee LEE ; Myung Soo HYUN
Journal of Korean Medical Science 2006;21(1):40-45
TNF-alpha mediated apoptosis of the hematopoietic cells has been thought to contribute to the ineffective hematopoiesis observed in myelodysplastic syndrome (MDS). The combination of pentoxifylline (P) and ciprofloxacin (C) has been shown to reduce the serum levels of TNF-alpha, and an earlier trial of P and C with dexamethasone (D) provided good palliation for patients with MDS. The purpose of this study is to assess the hematologic response to PCD therapy for patients suffering with MDS. 21 of 25 patients who completed at least of 12 weeks of treatment were evaluable for the treatment efficacy. At baseline, the patient's median age was 60 yr (range: 18-75 yr). The diagnoses according to WHO classification included: RA (n=5), RCMD (n=10), RARS (n=1), RCMD/RS (n=1), RAEB (3), and CMML (n=1). 11 patients (52%) had at least single lineage response. 3 patients (11%) showed improvement of triple lineage cytopenia. There were no differences in the response rates between the FAB subtypes. The median time to response was 4 weeks (range: 2-12 weeks), and it is interesting that 9 of 11 patients who had a response remained without relapse for a median of 177 days (range: 78-634 days). These preliminary results indicate that anti-cytokine therapy with PCD is an effective and well tolerated palliative treatment for patients with MDS.
Adolescent
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Adult
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Aged
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Anti-Infective Agents/adverse effects/therapeutic use
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Anti-Inflammatory Agents/adverse effects/therapeutic use
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Apoptosis/*drug effects
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Ciprofloxacin/adverse effects/therapeutic use
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Comparative Study
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Dexamethasone/adverse effects/therapeutic use
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Drug Therapy, Combination
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Erythrocyte Count
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Female
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Hematologic Agents/adverse effects/therapeutic use
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Humans
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Male
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Middle Aged
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Myelodysplastic Syndromes/*blood/drug therapy
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Nausea/chemically induced
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Pentoxifylline/adverse effects/therapeutic use
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Platelet Count
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Time Factors
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Treatment Outcome
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Tumor Necrosis Factor-alpha/*metabolism
7.Functional protection of pentoxifylline against spinal cord ischemia/reperfusion injury in rabbits: necrosis and apoptosis effects.
Dan-jie ZHU ; Bing XIA ; Qing BI ; Shui-jun ZHANG ; Bin-song QIU ; Chen ZHAO
Chinese Medical Journal 2008;121(23):2444-2449
BACKGROUNDLittle is known about neuronal death mechanisms following spinal cord ischemia. The present study aimed to investigate the protective effect of pentoxifylline (PTX) against spinal cord ischemia/reperfusion (I/R) injury.
METHODSRabbits sustained spinal cord ischemia following 45 minutes cross-clamping of the infrarenal aorta. Experimental groups were as follows: the first group of animals (sham, n = 8) underwent laparotomy alone and served as the sham group; the second group (I/R, n = 20) received carrier (3 ml saline solution) and served as the control group; the third group (PTX-A, n = 20) received PTX intravenously 10 minutes prior to ischemia; and the fourth group (PTX-B, n = 20) received PTX intravenously at the onset of reperfusion. Rabbits were evaluated for hind-limb motor function with the Tarlov scoring system at 48 hours. Serum was assayed with enzyme-linked immunosorbent assay for tumor necrosis factor alpha (TNF-alpha) and spinal cords were harvested for myeloperoxidase (MPO) activity, histopathological analysis, terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling staining, platelet/endothelial cell adhesion molecule-1 (PECAM-1) and caspase-3 immunohistochemistry, and the number of necrotic and apoptotic neuron were counted and data analyzed at 12, 24, 48 and 72 hours of reperfusion. Spinal cords were studied by electron microscopy.
RESULTSImproved Tarlov scores were seen in PTX-treated rabbits as compared with ischemic control rabbits at 48 hours. A significant reduction was found in TNF-alpha in serum, activity of MPO and immunoreactivity of the PECAM-1 and caspase-3 in PTX-treated rabbits. There were fewer apoptotic neurons than necrotic neurons (P < 0.05). A significant decrease in both necrotic and apoptotic neurons was observed in the PTX-treated groups (PTX-A and PTX-B) compared with the I/R group (P < 0.05). Both necrotic and apoptotic neurons were found with the electron microscope.
CONCLUSIONSPTX may induce protection against ischemia injury in the spinal cord, thereby preventing both necrosis and apoptosis. A major mode of cell death in spinal cord ischemia/reperfusion injury is necrosis while apoptosis is not dominant.
Animals ; Apoptosis ; drug effects ; Caspase 3 ; metabolism ; Immunohistochemistry ; In Situ Nick-End Labeling ; Microscopy, Electron, Transmission ; Necrosis ; Pentoxifylline ; pharmacology ; therapeutic use ; Rabbits ; Reperfusion Injury ; prevention & control ; Spinal Cord ; blood supply ; pathology ; ultrastructure ; Spinal Cord Ischemia ; prevention & control ; Vasodilator Agents ; pharmacology ; therapeutic use
8.Pentoxifylline attenuates cigarette smoke-induced overexpression of CXCR3 and IP-10 in mice.
Zheng WANG ; Yan-Wei CHEN ; Jin-Nong ZHANG ; Xiao-Fei HU ; Mei-Jun PENG
Chinese Medical Journal 2012;125(11):1980-1985
BACKGROUNDCigarette smoke-induced emphysema is associated with overexpression of the chemokine receptor CXCR3 and its ligands. Previously, we have demonstrated that pentoxifylline (PTX) alleviated cigarette smoke-induced emphysema. The aim of this study was to determine if the overexpression of CXCR3 and its ligand interferon-inducible protein-10 (IP-10) that was elicited by smoke exposure were attenuated by PTX.
METHODS(1) The study in vitro: a given number of RAW264.7 macrophages with decreasing concentrations of PTX in the culture medium were challenged with cigarette smoke extract (CSE); (2) The study in vivo: male BALB/c mice were randomized into four groups, i.e., sham-smoke, smoke only, smoke with 2 mg/kg PTX, and smoke with 10 mg/kg PTX. The smoke exposure time was 90 minutes once a day, 6 days a week for 16 weeks. PTX was given intraperitoneally before each episode of smoke exposure. Interferon (IFN)-γ and IP-10 in broncho-alveolar lavage fluid (BALF) and in culture medium were measured by enzyme-linked immunosorbent assay (ELISA). IP-10 mRNA in lung tissue was assessed by RT-PCR. CXCR3 positive cells in lung sections were visualized by immunochemistry staining.
RESULTSUp-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).
CONCLUSIONPTX attenuates cigarette smoke-induced overexpression of chemokine receptor CXCR3 and its ligand IP-10, which is relevant to its inhibitory effect on pulmonary emphysema.
Animals ; Cell Line ; Chemokine CXCL10 ; genetics ; metabolism ; Gene Expression ; drug effects ; Immunohistochemistry ; Male ; Mice ; Mice, Inbred BALB C ; Pentoxifylline ; pharmacology ; therapeutic use ; Pulmonary Emphysema ; drug therapy ; genetics ; metabolism ; Random Allocation ; Receptors, CXCR3 ; genetics ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Smoking ; adverse effects