Specificity and sensitivity of differentiation antigens in superficial soft tissue tumors: comparison of SMA, calponin, H-caldesmon, C-kit, PLAP and HPL.

We examined the expression pattern of smooth muscle actin (SMA), h-caldesmon (HCD), calponin (CALP), placental alkaline phosphatase (PLAP) and human placental lactogen (HPL) in benign and malignant spindle cell superficial soft tissue tumors in order to determine the role of these markers in differential diagnosis. Archival tissue from 38 patients with superficial smooth muscle cell and so-called fibrohistiocytic tumors (8 benign fibrous histiocytomas (BFHs), 6 dermatofibrosarcoma protuberans (DFPT), 9 malignant fibrous histiocytomas (MFHs), 9 leiomyomas (LMs) and 6 leiomyosarcomas (LMSs)) were immunostained with antibodies against SMA, HCD, CALP, PLAP and HPL. smooth muscle cell (SMC) tumors showed significantly high immunopositivity for HCD than that of so-called fibrohistiocytic tumors (p is less than or equal to 0.05) but 1/3 of DFPT and MFH cases and half of BFH cases also showed HCD immunopositivity; thus, this difference is debatable and not highly discriminative as expected. All tumor groups showed 100% immunopositivity for CALP. SMC tumors displayed significantly stronger and more widespread immunostaining pattern for PLAP than so-called fibrohistiocytic tumors (p < 0.05). Superficial soft tissue tumors did not express c-kit. In conclusion, HCD and PLAP can be used as ancillary immunomarkers in differential diagnosis of SMC tumors (Tab. 2, Fig. 7, Ref. 37).

Central nervous system complications of diabetes in streptozotocin-induced diabetic rats: a histopathological and immunohistochemical examination.

Diabetes mellitus is a common, potentially serious metabolic disorder. Over the long term, diabetes leads to serious consequences in a number of tissues, especially those that are insulin insensitive (retina, neurons, kidneys). It also causes a variety of functional and structural disorders in the central and peripheral nervous systems. We investigated whether neurodegenerative changes were observable in the hippocampus, cortex, and cerebellum after 4 weeks of streptozotocin (STZ)-induced diabetes in rats and the effect(s) of melatonin. Male Wistar rats (n = 32) were divided into four groups (n = 8 each): untreated controls, melatonin-treated controls, untreated diabetics, and melatonin-treated diabetics. Experimental diabetes was induced by a single dose of STZ (60 mg/kg, intraperitoneal (ip)). For 3 days before the administration of STZ, melatonin (200 microg/kg/day, ip) was injected and continued for 4 weeks. Sections of hippocampus, cortex, and cerebellum were stained with hematoxylin and eosin and examined using light microscopy. In addition, brain tissues were examined immunohistochemically for the expression of glial and neuronal markers, including glial fibrillary acidic protein (GFAP), neuron-specific enolase (NSE), and heat shock protein-70 (HSP-70). No neurodegenerative changes were observed in the hippocampus, cortex, or cerebellum of the untreated diabetic group after 4 weeks compared with the other groups. We did not observe any change in GFAP, NSE, or HSP-70 immunostaining in the brain tissues of STZ-induced diabetic rats. In summary, after 4 weeks of STZ-induced diabetes in rats, no degenerative or immunohistochemical changes were detected in the hippocampus, cortex, or cerebellum.

Early glutamine-enriched enteral feeding facilitates colonic anastomosis healing: light microscopic and immunohistochemical evaluation.

Problems related to colonic anastomosis healing constitute the major morbidity in colorectal surgery. Patients without appropriate nutritional support are at higher risk of postsurgical complications, mainly due to reduced wound healing. Therefore, we investigated the effect of early and late postoperative total enteral nutrition (TEN) and glutamine addition on colon anastomosis healing using light microscopy and immunohistochemistry (IGF-I immunolabelling). In this study, 40 Wistar-albino rats underwent distal left colonic transection and anastomosis. The rats were then divided into four groups given different diets: delayed total enteral nutrition (dTEN; beginning 3 days postoperatively), delayed TEN with added glutamine (dTEN+Glutamine), early TEN (eTEN; beginning within 6h postoperatively), and early TEN with added glutamine (eTEN+Glutamine). Colon segments, including the anastomosis, were excised 7 days postoperatively and evaluated histopathologically for inflammation, mucosal healing, submucosal-muscular layer repair, the amounts of necrosis and vascularisation and immunohistochemically for IGF-I labelling. The inflammation and necrosis scores in the dTEN and dTEN+Glutamine groups were significantly greater than in the eTEN and eTEN+Glutamine groups. The IGF-I immunoreactivity increased in the eTEN, eTEN+Glutamine, and dTEN+Glutamine groups compared to dTEN (p<0.05). We concluded that early TEN and glutamine enrichment in the postoperative period improve anastomosis healing via IGF-I.

Melatonin protects against epirubicin-induced cardiotoxicity.

We investigated the cytoprotective effect of melatonin in epirubicin-induced cardiotoxicity using four experimental groups of male Wistar rats: untreated control rats, epirubicin-treated rats, epirubicin+melatonin-treated rats, and melatonin-treated rats. We examined the histopathological and biochemical effects of melatonin on the epirubicin-induced changes and measured the levels of the lipid peroxidation end-product (malondialdehyde, MDA), an indicator of nitric oxide (NO) synthesis (nitrite/nitrate production), and reduced glutathione (GSH) in the heart. We also studied the extracellular matrix components (fibronectin, laminin) in the heart. Vacuole formation, mitochondrial deformation and degeneration, and disordered myofibrillary structures were detected ultrastructurally in the epirubicin-treated group. The degeneration was reduced in the heart tissues of the epirubicin+melatonin group. Epirubicin increased the nitrite/nitrate production, but did not change the MDA and GSH levels significantly. Melatonin treatment lowered the nitrite/nitrate concentrations, while increasing the GSH levels, which exceeded the levels in epirubicin+melatonin-treated rats. We conclude that the epirubicin increased the nitrozative stress, not the oxidative stress, in heart tissue, and the cardioprotective effect of melatonin was partially attributed to the suppression of epirubicin-induced nitrozative stress. These results suggest that melatonin partially protects against epirubicin-induced cardiotoxicity.

Effects of melatonin on streptozotocin-induced diabetic liver injury in rats.

This study investigated the possible protective effects of melatonin as an antioxidant against streptozotocin (STZ)-induced diabetic liver injury in rats. Wistar rats were divided into four groups: untreated control (UC), melatonin-treated control (MC), untreated diabetic (UD), and melatonin-treated diabetic (MD). Experimental diabetes was induced by a single-dose (60 mg/kg, intraperitoneally (ip)) STZ injection, and melatonin was injected (200 microg/kg/day, ip) for 4 weeks. Upon light and electron microscopic examination, we observed that melatonin improved the morphological and histopathological changes of the liver caused by diabetes. Malondialdehyde levels in the liver homogenates of UD rats were higher than those of controls and were markedly reduced after melatonin treatment. Although no significant difference was observed with respect to antioxidant status, the superoxide dismutase activity tended to be higher in the UD rats than in the treated rats. Our findings showed that melatonin administration partially reduced liver injury in STZ-induced diabetic rats.

Protective effect of melatonin on beta-cell damage in streptozotocin-induced diabetes in rats.

The aim of the present study was the evaluation of possible protective effects of melatonin against beta-cell damage in streptozotocin-induced diabetes in rats. Malondialdehyde levels and glutathione peroxidase activity were measured in pancreatic homogenates. Pancreatic beta-cells were examined by immunohistochemical methods. Streptozotocin was injected intraperitoneally at a single dose of 60 mg/kg for induction of diabetes. Melatonin (200 microg/kg/day, ip) was injected for 3 days prior to administration of streptozotocin; these injections were continued until the end of the study (4 weeks). Streptozotocin induced a significant increase in malondialdehyde levels (p < 0.01) and a significant decrease in glutathione peroxidase activity (p < 0.05) in pancreatic tissue. Degeneration of islet cells and weak immunohistochemical staining of insulin was observed in diabetic rats. Treatment of diabetic rats with melatonin markedly reduced malondialdehyde production (p < 0.05) and increased glutathione peroxidase activity (p < 0.01) without affecting hyperglycemia. Increased staining of insulin and preservation of islet cells were apparent in the melatonin-treated diabetic rats. These data suggest that melatonin treatment has a therapeutic effect in diabetes by reduction of oxidative stress and preservation of pancreatic beta-cell integrity.

Protective effects of chronic melatonin treatment against renal injury in streptozotocin-induced diabetic rats.

The aim of this study was to investigate the effects of melatonin as an antioxidant, on prevention and treatment of streptozotocin (STZ)-induced diabetic renal injury in rats. Male Wistar rats were divided into four groups: (1) untreated, (2) melatonin-treated, (3) untreated diabetic (UD), (4) melatonin-treated diabetic (MD). Experimental diabetes was induced by single dose (60 mg/kg, i.p.) STZ injection. For 3 days prior to administration of STZ, melatonin was injected (200 microg/kg/day, i.p.); these injections were continued until the end of the study (4 weeks). Malondialdehyde (MDA) levels as a marker of lipid peroxidation were significantly increased in the renal homogenates of UD animals and decreased after melatonin administration. The activity of the antioxidative enzyme glutathione peroxidase (GSH-Px) was significantly reduced in UD rats. Melatonin treatment reversed STZ-induced reduction of GSH-Px activity without having an effect on blood glucose. Upon histopathological examination, it was observed that the melatonin treatment prevented the renal morphological damage caused by diabetes. Upon immunohistochemical investigation, glomerular anti-laminin beta1 staining decreased in MD rats. Additionally, no tubular anti-IGF-1 staining was observed in melatonin-treated rats. In conclusion, chronically administered melatonin reduced renal injury in STZ-induced diabetic rats and thus it may provide a useful therapeutic option in humans to reduce oxidative stress and the associated renal injury in patients with diabetes mellitus.

A new mutation of the fukutin gene in a non-Japanese patient.

Fukuyama-type congenital muscular dystrophy (FCMD), Walker-Warburg syndrome, and muscle-eye-brain disease are clinically similar autosomal recessive disorders characterized by congenital muscular dystrophy, cobblestone lissencephaly, and eye anomalies. FCMD is frequent in Japan, but no FCMD patient with confirmed fukutin gene mutations has been identified in a non-Japanese population. Here, we describe a Turkish CMD patient with severe brain and eye anomalies. Sequence analysis of the patient's DNA identified a homozygous 1bp insertion mutation in exon 5 of the fukutin gene. To our knowledge, this is the first case worldwide in which a fukutin mutation has been found outside the Japanese population. This report emphasizes the importance of considering fukutin mutations for diagnostic purposes outside of Japan.