Duodenocolic fistula healing by pentadecapeptide BPC 157 in rats. A cytoprotection viewpoint.

Using duodenocolic fistula in rats, this study attempts to highlight the particular cytoprotection aspects of the healing of fistulas and therapy potential of the stable gastric pentadecapeptide BPC 157, a cytoprotection mediator (i.e. upgrading minor vessels to induce healing at both fistula's sides). Upon duodenocolic fistula creation (two 'perforated' lesions put together) (assessed at 3, 6, 9, 12, and 15 min), BPC 157, given locally at the fistula, or intragastrically (10 µg/kg, 10 ng/kg), rapidly induces vessel 'recruitment', 'running' toward the defect, simultaneously at duodenum and colon, providing numerous collaterals and branching. The mRNA expression studies done at that time provided strongly elevated (nitric oxide synthase 2) and decreased (cyclooxygenase-2, vascular endothelial growth factor A, nitric oxide synthase (NOS)-1, NOS-3, nuclear factor-kappa-B-activating protein) gene expression. As therapy, rats with duodenocolic fistulas, received BPC 157 10 µg/kg, 10 ng/kg, per-orally, in drinking water till sacrifice, or alternatively, intraperitoneally, first application at 30 min after surgery, last at 24 h before sacrifice, at day 1, 3, 7, 14, 21, and 28. Controls exhibited both defects persisting, continuous fistula leakage, diarrhea, continuous weight loss, advanced adhesion formation and intestinal obstruction. Contrary, all BPC 157-treated rats have closed both defects, duodenal and colonic, no fistula leakage (finally, maximal instilled volume corresponds to healthy rats), no cachexia, the same weight as before surgery, no diarrhea, markedly less adhesion formation and intestinal passage obstruction. Thus, BPC 157 regimens resolve the duodenal/colon lesions and duodenocolic fistulas in rats, and rapid vessels recovery appears as the essential point in the implementation of the cytoprotection concept in the fistula therapy.

Oxidative stress as a mechanism of combined OTA and CTN toxicity in rat plasma, liver and kidney.

Ochratoxin A (OTA) and citrinin (CTN) commonly coexist in grains. Aiming to evaluate oxidative stress in OTA + CTN toxicity, male Wistar rats were orally treated with two doses of OTA (0.125 and 0.250 mg kg-1 of body weight (b.w.)), CTN (2 mg kg-1 of b.w.) and resveratrol (RSV; 20 mg kg-1 of b.w.) and combined daily during 3 weeks. Protein carbonyl concentrations were measured in kidneys and liver; catalytic activity of glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT) and glutathione (GSH) level in plasma, kidneys and liver, while malondialdehyde (MDA) concentration was measured in plasma, kidneys, liver and urine. Mycotoxin treatment significantly increased MDA concentration in plasma and kidney and decreased SOD activity in the liver. Rats treated with CTN and OTA125 + CTN had lower plasma GPx activity. Concentration of GSH in the kidney and protein carbonyls in the kidney and liver as well as GPx activity in the kidney and liver, SOD activity in the kidney and CAT activity in the liver were not affected. Protective effect of RSV was observed on GSH in the kidney and plasma and MDA in the kidney, plasma and urine. Oxidative stress is involved in OTA + CTN toxicity in vivo because such treatment affects parameters of oxidative stress, particularly in plasma. RSV can reduce but not overcome oxidative stress induced by combined OTA and CTN treatment.

Ischemic preconditioning decreases laparoscopy induced oxidative stress in the liver.

Experimental studies indicate that oxidative stress during and after laparoscopic surgery may cause liver ischemia-reperfusion injury. The aim of the study was to assess the effect of ischemic preconditioning against liver damage during pneumoperitoneum on oxidative stress. Twenty one New Zealand rabbits were divided into three groups of seven animals. Control group (C) rabbits received anesthesia for 60 min alone; 15 mm Hg intra-abdominal pressure with CO2 for 60 min was used in the pneumoperitoneum group animals (PNP); and 15-min insufflation and 10-min desuflation followed by 60-min pneumoperitoneum were used in the ischemic preconditioning group animals (IP). Venous blood samples were obtained at different time points to measure lipid hydroperoxide, glutathione reductase and total antioxidant status as indicators of increased oxidative stress. Aspartate transaminase (AST), alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) levels were evaluated as indicators of hepatocellular injury. The Kruskal-Wallis and Mann-Whitney U tests were used on statistical analysis. Elevated intra-abdominal pressure was found to produce significant increase in lipid hydroperoxide at the end of pneumoperitoneum and 30 min after desuflation in comparison with pre-insufflation period, and with both C and IP groups at the same time points. Total antioxidant status level decreased significantly in the PNP group at 24 h of desuflation. At 24h of desuflation, the AST, ALT and LDH levels were significantly increased in the PNP group in comparison with the levels measured before induction of anesthesia, and with the C and IP groups. Study results demonstrated that ischemic preconditioning prevented hepatocyte injury and oxidative stress during CO2 pneumoperitoneum.

Primary extranodal marginal zone lymphoma of the uvea associated with massive diffuse epibulbar extension and focal infiltration of the optic nerve and meninges, clinically presented as uveitis masquerade syndrome: a case report.

To report a clinical, histopathological and immunohistochemical findings in a case of primary extranodal marginal zone lymphoma of the uvea associated with massive diffuse extraocular episcleral extension and focal infiltration of the optic nerve and meninges, clinically presented as longstanding uveitis masquerade syndrome. Interventional case reports with histopathological correlation. We describe a 80-year-old male patient with a 3-year history of chronic recurrent hypertensive (pan) uveitis associated with ocular pain, unresponsive to topical and systemic anti-inflammatory, immunosuppressive, antibiotic/antiviral and antiglaucomatous therapy. Because the eye was not salvageable with conservative treatment, enucleation of blind and painful eye was performed. Findings from histopathological and immunohistochemistry examination of the enucleated eye showed an extranodal marginal zone lymphoma of the uveal tract with massive epibulbar extension and optic nerve and meningeal penetration. During almost 3 years of clinical course and 6 months after the enucleation, there were no systemic manifestations of lymphoma, and patient has not required subsequent treatment. Primary lymphoproliferative lesions of the uvea, comprising the iris, ciliary body and choroid are very rare, associated with epibulbar extension extremely and with optic nerve and menigeal penetration exceptionally. Despite its rarity, primary lymphoma of the uvea should be included in the differential diagnosis particularly in older patients with longstanding recurrent uveitis.

Human Dirofilaria repens infection in Serbia.

Human infection by Dirofilaria repens in Serbia has been increasing steadily. The first case was reported in 1971, presented in the form of a single subcutaneous nodule on the back of a young boy. As established by a literature search, eight additional cases were reported until mid-2001. The most frequent site of infection was subcutaneous tissue, with the exception of two cases, in which parasites were found in subconjunctiva and epididymis. Our study, conducted from 2001 to 2008, encompasses 19 new cases. Most of them (63.1%) presented as ocular or periocular infections, in which the parasite was typically found under the conjunctiva. In other cases a parasitic nodule was localized in the temporal region of the head, epididymis, testicle, abdomen, breast or arm. The diagnosis was made by morphological and histological analysis of the extracted intact worms and parasite sections from the tissue. Morphology of the filarial worms was well preserved in more than half of the cases (12/19) and there was never more than one parasite found inside the lesions. Adult worms and immature nematodes were observed in nine and seven cases, respectively. Furthermore, in two cases microfilariae were discovered inside the pseudocoelom, sections of the female reproductive tubes filled with clearly visible larval stages. Dirofilaria repens infection was diagnosed by its morphological features (17/19) or by performing polymerase chain reactions (PCR) using paraffin-embedded tissues (2/19) in the cases where the morphology was insufficient for identification and the parasites had been determined initially as Dirofilaria spp. The amplified 246 bp PCR product showed that the worms were D. repens.