Resveratrol attenuates inflammation and stricture formation in experimental caustic esophageal burns.

The purpose of medical treatment in the caustic esophageal burns (CEB) is to decrease inflammatory reaction and to prevent stricture formation. Resveratrol has anti-inflammatory and antifibrotic properties. The aim of this study is to investigate potential therapeutic effects of resveratrol in experimental CEB. We divided 42 male Wistar albino rats into five groups: a control group, caustic groups 4 and 28 (esophageal burns were created), and resveratrol groups 4 and 28 (esophageal burns were created and resveratrol was administered). We used 25% NaOH to form CEB following the method of Gehanno and Guedon as modified by Liu and Richardson. Animals were killed on the 4th and 28th days for biochemical and histopathological examinations. We found that the mean malondialdehyde and nitric oxide assays of the caustic groups were significantly higher than that of the resveratrol groups (P < 0.05). On the other hand, glutathione assay of the resveratrol groups was significantly higher than that of the caustic groups (P < 0.05). Histologically, edema, inflammation and necrosis were found to be significantly lower in the resveratrol 4 group compared with the caustic 4 group (P < 0.05). Submucosal and muscular collagen accumulation were found significantly lower in the resveratrol 28 group compared with the caustic 28 group (P < 0.05). We conclude that resveratrol decreased both the inflammatory reaction and the stricture formation in experimental CEB.

Effects of resveratrol in inflammatory arthritis.

UNLABELLED: Nuclear factor kappa B (NF-kappaB), is a pivotal transcription factor involved in the activation of the TNF-alpha and IL-1beta genes. Activation of NF-kappaB in synovial cells is a feature seen in arthritis patients. Resveratrol, a polyphenolic, natural phytoalexin found with particularly high levels in grape skin and red wine is potent and specific inhibitor of TNF-alpha and IL-1beta induced NF-kappaB activation. We aimed to determine the in vivo effects of intra-articular injections of resveratrol on cartilage and synovium in an experimental rabbit inflammatory arthritis model. MATERIALS AND METHODS: Arthritis was induced by intra-articular injection of three times of 50 mug lipopolysaccharide (LPS) at day 0, 4 and 8 at 4-day intervals into the knee joints of rabbits. To the test group, 10 muMol/kg resveratrol in the DMSO was injected in the knees at day 0 and then it was continued once daily for 2 weeks. To the control group the same time and amount of DMSO was injected the knees of rabbits. All rabbits were killed 1 week after the last injection and cartilage tissue and synovium were evaluated with semiquantitative scoring histologically. RESULTS: According to control group in the resveratrol group, significantly decreased cartilage destruction was determined by H&E staining (p = 0.04). Loss of matrix proteoglycan content in the cartilage was much lower, as determined by safranin O staining (p = 0.03). We also observed marked synovial inflammation after intra-articular injection to control knees, but not in the resveratrol treated group knees (p = 0.01). CONCLUSION: This study suggests that intra-articular injection of resveratrol may protect cartilage against the development of experimentally induced IA.

Clinical significance of N-acetyl-L-aspartate resonance in ovarian mucinous cystadenoma.

Magnetic resonance spectroscopy (MRS) provides a noninvasive measurement of the biochemistry of living tissue. We report spectroscopy analysis of a 26-year-old woman affected by right ovarian lesion diagnosed as mucinous cystadenoma. MRS was performed by the point-resolved spectroscopy technique with a long echo time (TE) (136 msec). MRS measurements were performed on the two distinct component of the right ovarian tumor. The classification of metabolite peaks area in this study was performed according to the technique described by Okada et al. The features of proton MRS studies are discussed. As well as strongly elevated lactate and N-acetyl-L-aspartate signals, the tumor spectrum showed lipid resonances. Proton MRS imaging may be helpful for the investigation of the underlying pathophysiology of ovarian mucinous cystadenomas.

Resveratrol may reduce apoptosis of rat testicular germ cells after experimental testicular torsion.

The aim of the study is to evaluate the effects of resveratrol on apoptosis of testicular germ cells after experimental testicular torsion. Thirty Wistar albino rats were divided into 3 groups. Torsions were created by rotating the right testis 720 degrees in a clockwise direction for 4 h in all groups except the control group (group 1). They were then repaired by counter-rotation and replaced into the scrotum. In group 2, saline was infused 30 min before detorsion. In group 3, 30 mg/kg resveratrol was infused 30 min before detorsion. In groups 2 and 3, the bilateral testes were removed to determine germ cell apoptosis after 20 h of detorsion. The number of apoptotic cells was evaluated using the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling (TUNEL) technique and caspase 3. Mean apoptotic score of ipsilateral testes in group 3 was lower than that of group 2 (p < 0.05). Mean apoptotic score of the contralateral testes in group 3 was not different from that of group 2 (p > 0.05). The present study demonstrates that intraperitoneal administration of resveratrol in rats may decrease germ cell apoptosis in the ipsilateral testes.

Effect of resveratrol in experimental osteoarthritis in rabbits.

OBJECTIVE: Resveratrol (trans-3,4',5-trihydroxystilbene) is a phytoalexin found in high concentration in the skins of grapes and red wines which has been shown to have antiinflammatory, anticancerogen and antioxidant properties. Resveratrol is a potent and specific inhibitor of nuclear factor kappa B (NF-kappaB). Resveratrol also inhibits COX-2 gene expression and enzyme activity. We aimed to determine the in vivo effects of intra-articular injections of resveratrol on cartilage and synovium in an experimental osteoarthritis (OA) model in rabbits. METHODS: As OA model, rabbits underwent unilateral anterior cruciate ligament transection (ACLT). Five weeks after test group was injected with 10 microMol/kg resveratrol in dimethylsulphoxide (DMSO) in the knees once daily for two weeks and as the control group at the same time DMSO was injected into the knees. All rabbits were killed one week after the last injection. Cartilage tissue and synovium were evaluated with a histological scoring system. RESULTS: Histological evaluation of cartilage tissue by H&E staining revealed a significantly reduced average cartilage tissue destruction score of 1.7 in the resveratrol group versus 2.8 in the control group (p = 0.016). Loss of matrix proteoglycan content in cartilage was also much lower, as determined by safranin O staining. Scores of synovial inflammation didn't show difference between groups (1.3 vs 2.2; p = 0.057). CONCLUSION: A characteristic parameter in arthritis is the progressive loss of articular cartilage. This study suggests that intraarticular injections of resveratrol starting at the onset of disease may protect cartilage against the development of experimentally induced OA.

Effects of pentoxifylline and vitamin E on the bilateral ovary after experimental ovarian ischemia.

Pentoxifylline (PTX) and vitamin E inhibit the release of superoxide and hydroxyl radicals, and PTX improves capillary flow and tissue oxygenation. This experimental study was designed to determine the effects of PTX and vitamin E in the ovary after unilateral ovarian ischemia reperfusion (I-R) in albino Wistar rats. A vascular clamp was placed on the left ovary for 4 hours in all groups except for the control group. Following this, in the ischemia (I) group bilateral ovariectomy was performed. Saline, PTX, vitamin E, and PTX plus vitamin E were infused 30 min before reperfusion in the reperfusion (R), pentoxifylline (P), vitamin E (E), and pentoxifylline plus vitamin E (PE) groups, respectively. After 4 hours of reperfusion, the ovaries were removed for biochemical and histologic examination. MDA levels of bilateral ovaries in the PE group were significantly lower than in the E group (p < 0.0033). NO levels of bilateral ovaries in the PE group were significantly lower than in the P and E groups (p < 0.0033). Massive hemorrhage was determined in the ipsilateral ovaries of the R group. Hemorrhage was minimal or moderate in the ipsilateral ovaries of other groups. The contralateral ovaries showed congestion in different degrees. The contralateral ovaries of the group PE and the bilateral ovaries of the control group showed no pathological changes. PTX and vitamin E given together seems to be more effective in reducing I-R injury in ovarian tissue compared to administration of PTX, or vitamin E alone. However, further studies are required to evaluate the effective dose and duration of PTX and vitamin E on bilateral ovaries.

Resveratrol reduces ischemia reperfusion injury after experimental testicular torsion.

The aim of the study was to evaluate the effects of resveratrol on testicular ischemia reperfusion injury. Forty Wistar albino rats were divided into 4 groups. Torsions (ischemia) were created by rotating the right testis 720 degrees in a clockwise direction for 4 hours in all groups except the control group. In the torsion group after 4 hours' ischemia bilateral orchiectomy was performed. In the detorsion group, saline was injected by an intraperitoneal route, 30 min before detorsion (reperfusion). In the resveratrol group, 30 mg/kg resveratrol was injected by an intraperitoneal route, 30 min before detorsion. In the detorsion and resveratrol groups, the bilateral testes were removed after 20 hours of detorsion. In all groups, the tissue levels of malondialdehyde (MDA) and glutathione (GSH) and histological changes were determined. In rats treated with resveratrol, MDA levels (138 +/- 25 nmol/mg protein) were significantly decreased compared with torsion (426 +/- 178 nmol/mg protein) and detorsion (370 +/- 76 nmol/mg protein) groups (p < 0.05). GSH levels (6.54 +/- 0.8 micromol/g wet tissue) were significantly increased compared with torsion (4.61 +/- 0.4 micromol/g wet tissue) and detorsion groups (5.24 +/- 0.9 micromol/g wet tissue) (p < 0.05). The mean testicular tissue injury score in the resveratrol group was significantly lower than in torsion and detorsion groups (p < 0.05). The present study demonstrates that intraperitoneal administration of resveratrol in rats may protect testis against injury associated with reperfusion.

Protective effect of caffeic acid phenethyl ester (CAPE) on myocardial ischemia-reperfusion-induced apoptotic cell death.

Occlusion of coronary artery causes cardiomyocyte dysfunction. Reperfusion relieves ischemia by providing cells with metabolites and oxygen, thereby preventing extensive tissue damage. Although reperfusion salvages the myocardium, it also initiates a series of events including myocardial apoptosis and necrosis. The common inducers of apoptosis include reactive oxygen species (ROS). Caffeic acid phenethyl ester (CAPE) is known as an antioxidative, anti-inflammatory effects, may protect myocardial ischemia-reperfusion (MI/R)-induced apoptosis. We have previously reported that CAPE reduced MI/R-induced necrosis. Therefore, this study was focused to investigate protective effect of CAPE on the distinct form of cell death; apoptosis in an in vivo rat model. To produce MI/R, a branch of the descending left coronary artery was occluded for 30 min followed by 2 h reperfusion. ECG changes, blood pressure (BP), and heart rate (HR) were measured before occlusion and continued both occlusion and reperfusion. CAPE (50 micromol/kg) was given 10 min before ischemia via jugular vein. Extensive formation of DNA strand breaks, the typical biochemical feature of apoptosis, was detected with the use of the terminal deoxynucleotidyl transferase (TdT)-mediated d UTP-biotin nick and labeling (TUNEL) method. Also, cysteine aspartate specific proteinase (caspase)-3 and caspase-9 activities a universal effector of apoptosis, were determined. Trunk blood was extracted to determine the serum contents related to oxidant-antioxidant status. In hemodynamic parameters, there was no significant difference in HR or BP values among any group. CAPE administration had no a significant effect on hemodynamic parameters during ischemia or reperfusion. Control group revealed extensive TUNEL-positive cardiomyocytes especially in free wall of left ventricule, interventiculare septum and nearly apex zone. Intensity of TUNEL-positive cardiomyocytes reduced as a result of CAPE treatment compared to control group in the same sections. Result of the caspase activities was found to correlate with TUNEL evaluation. CAPE also, ameliorated antioxidant status. We propose that CAPE acts in the heart as a potent scavenger of free radicals to prevent the apoptotic effect of I/R. Further studies are needed to elucidate the mechanisms of apoptotic death machinery.

The effect of sustained and local administration of epidermal growth factor on improving bilateral testicular tissue after torsion.

Epidermal growth factor (EGF) modulates Leydig cell proliferation, steroidogenesis, spermiogenesis, and Sertoli cell activity. It plays an important role in repairing ischemia-reperfusion injury in different tissues. The aim of this study was to evaluate the effects of sustained and local administration of EGF on improving bilateral testicular tissue after torsion. A total of 57 Wistar albino rats were used. For the EGF transport system, 1x2 cm gelatin films containing 2 microg EGF were used. Torsion was created by rotating the right testis 720 degrees in a clockwise direction for 4 h in all groups except the control group. Then, in the torsion group, bilateral orchiectomy was performed. After returning the torsioned ipsilateral testes to their normal state, the bilateral testes were wrapped by 1x2 cm unloaded gelatin films in the gelatin (G7 and G21) groups and, by 2 microg EGF loaded gelatin films in the EGF 7 and EGF 21 groups. The testes were removed on the seventh and 21st days, respectively, for biochemical and histological examination. Histologically, Johnsen's spermatogenesis criteria and mean seminiferous tubule diameter (MSTD) measurements were used. The EGF7 group did not show significant loss of Sertoli cells, while in the G7 group the number of these cells decreased. The ipsilateral ischemic testis of the EGF21 group showed Leydig cell hyperplasia, and the contralateral non-ischemic testes in this group were similar to the control group. In the G21 group, the bilateral testes showed Sertoli cell only syndrome in some sections, and most of the cells were undergoing apoptosis. The mean spermatogenesis scores and MSTD in the EGF7 and EGF21 groups were higher than in the G7 and G21 groups ( P<0.05). Malondialdehyde levels were significantly lower in the EGF groups than in the G groups ( P<0.05). Glutathione peroxidase (GSH-Px) levels in the G21 group were significantly higher than in the EGF21 group. Our study shows that local and sustained EGF release after testicular torsion improves bilateral testicular injury. EGF administration may be a new treatment choice for bilaterally injured testis after detorsion without removing the twisted testis.

Synchronous primary malignant neoplasms of colon and bladder.

Extracolonic and synchronous malignancies are rare in colorectal carcinomas. We report a 68-year-old man with complaints of rectal bleeding and hematuria. Endoscopic biopsies revealed synchronous adenocarcinoma of the colon and transitional cell carcinoma of the bladder. The patient was started on chemotherapy, and is alive (with disease) nine months later.

Case report. Rhinocerebral zygomycosis.

A case of rhinocerebral zygomycosis treated with liposomal amphotericin B is described.

GnRH agonist decreases endothelial nitric oxide synthase (eNOS) expression in leiomyoma.

UNLABELLED: OBJECTIVES To define the effect of GnRH agonist (GnRHa) treatment on endothelial nitric oxide synthase (eNOS) expression in leiomyoma. As eNOS expression is more pronounced in leiomyoma compared to parental myometrium, we hypothesized that the mechanism(s) of tumor shrinkage by GnRHa may be due to decreased nitric oxide (NO) production in leiomyoma. METHODS: Eleven patients with leiomyoma were operated for myoma enucleation by laparatomy. Six of them were treated with GnRHa every 28 days, three times before the operation. The remaining five patients who had no treatment prior to operation formed the control group. Blood was drawn from the patients before treatment and on the day of operation for the assay of serum estradiol (E(2)). Immunohistochemical localization of eNOS expression in leiomyoma and myometrium in treated patients, and in leiomyoma in the control group, was performed using monoclonal antibodies specific to eNOS. RESULTS: All treated subjects showed a significant reduction of fibroid volume at the end of therapy. eNOS-positive cells were localized primarily within the vascular endothelium and smooth muscle cells, but had weak expression in fibroid and myometrial muscle cells in the treated group. The immunoreactivity was similar for both the leiomyoma and myometrium (P > 0.05). In contrast to this, the control group had shown strong expression in leiomyoma muscle cells (P < 0.005) in addition to the vascular endothelium and smooth muscle cells. CONCLUSION: GnRHa-induced tumor shrinkage should be due to diminished eNOS expression, most probably by lowering estrogen secretion.

Potential salvage therapy for accidental intrathecal vincristine administration: a preliminary experimental study.

BACKGROUND: Accidental intrathecal vincristine (VCR) administration results in severe neurotoxicity, usually fatal in outcome. No specific therapy for initrathecal VCR toxicity has been reported so far. In our recent report, complete in vitro degradation of VCR by hypochlorous acid (HOCl) was demonstrated. METHODS: In this comparative study, we examined the in vivo effectiveness of HOCl in the cerebrospinal fluid of 24 New Zealand rabbits following intracisternal VCR administration. RESULTS: There were no significant clinical or histopathologic abnormalities in the control and HOCl groups; however, multiple necrotic foci on histopathological examination of brain sections in the VCR group were determined. There were significantly lower numbers of necrotic foci in brain sections of rabbits which received HOCl administration than those without therapy. CONCLUSION: Our results indicate that HOCl may reduce VCR neurotoxicity.

The crowned dens syndrome: a rare form of calcium pyrophosphate deposition disease.

The crowned dens syndrome has been termed as acute neck pain ascribed to CPPD deposits associated with a tomographic appearance of calcification surrounding the odontoid process. This rare entity resulting in cervical cord compression is generally seen in older female patients. We present a 26-year-old woman with cervical cord compression due to massive calcification in the periodontoid area and discuss the X-ray and CT findings of the disease.

Melatonin administration prevents the nephrotoxicity induced by gentamicin.

OBJECTIVE: To investigate the effect of melatonin on the antioxidant enzyme activity and renal tubular necrosis induced by gentamicin. MATERIALS AND METHODS: Twenty-four adult male Sprague-Dawley rats were divided into three equal groups. In group 1, the rats were injected with vehicle (controls), in group 2 they were injected with gentamicin for 5 days and in group 3 injected with gentamicin plus melatonin for 5 days. At 24 h after the last injection, rats were killed and the renal cortex separated from the medulla. Most of the cortex was homogenized but a small sample was fixed in formaldehyde solution for histological examination by light microscopy. Blood samples were also taken to assess the serum levels of urea, creatinine, Na+, K+ and gamma-glutamyl transpeptidase (gamma-GT); before death, urine samples were analysed for protein content. Crude extracts of the cortex were used to determine lipoperoxides, reduced glutathione (GSH-Px), catalase and superoxide dismutase (SOD). The results were compared using the Mann-Whitney U-test. RESULTS: Compared with the controls rats, gentamicin caused hyperproteinuria, an increase in the level of gamma-GT in serum, a marked increase in lipoperoxides and a significant decrease of GSH-Px, catalase and SOD activity in the kidney. In the rats in group 3 there was a marked restoration in lipid peroxidation, GSH-Px, catalase, SOD activity and proteinuria, and in gamma-GT in serum. In rats in group 2 there was widespread tubular necrosis (grade 2-4) but in rats in group 3 there was a marked reduction in the extent of tubular damage. There was no significant difference in serum levels of Na+, K+, blood urea nitrogen and creatinine. CONCLUSION: These results indicate that melatonin prevents the tubular necrosis induced by gentamicin in rats, presumably because it is a potent antioxidant and restores antioxidant enzyme activity in the rat kidney.

Follicular thyroid cancer presenting initially with soft tissue metastasis.

Follicular thyroid cancer rarely manifests itself as a distant metastatic lesion. We report a case of an otherwise asymptomatic 58-year-old woman with follicular thyroid cancer who initially presented with a soft tissue mass on the right scapular region. An incisional biopsy specimen of soft tissue metastasis showed thyroid follicular neoplasm. Upon this diagnosis, the thyroid gland was re-evaluated by ultrasound, which demonstrated a solitary, hypoechoic nodule in the right lobe. Ultrasonography guided fine-needle aspiration biopsy of the thyroid nodule confirmed follicular neoplasm and the diagnosis of metastatic follicular thyroid cancer was established. The patient refused any type of treatment and left hospital against medical advice. 2.5 years later the patient was admitted to the hospital with giant, sarcoma-like multiple soft tissue masses. On this admission, the serum thyroglobulin level was extremely elevated (3500 ng/ml) and she only accepted to receive chemotherapy. Epirubicin and cyclophosphamide were administered. She received three courses of chemotherapy and is alive with a stable disease after 3 months of follow-up. This case of follicular thyroid cancer is reported because of its uncommon initial presentation with soft tissue metastasis which spread to multiple areas as giant soft tissue masses during follow-up.

Endothelial nitric oxide synthase expression in leiomyoma and parental myometrium.

The aim of this study was to determine the expression of endothelial nitric oxide synthase (eNOS) in leiomyomatous tissue as a possible mediator of the growth process. Nine patients had myoma enucleation during the follicular phase. The myomata and adjacent myometrial tissues were fixed in formol until study. Immunohistochemical localization of leiomyomatous and myometrial tissue eNOS expression was performed using specific monoclonal antibodies to eNOS. Statistical comparisons were made using the Mann-Whitney Wilcoxon rank-sum test for the expression of eNOS. The test was considered significant when p values were <0.05. Immunostaining for eNOS was seen in the cytoplasm of myometrial endothelial and smooth muscle cells in both tissue sections. eNOS expression was significantly higher in the smooth muscle cells of leiomyomata, compared to parental myometrium (p < 0.0005). The expression of eNOS in vascular endothelial cells was not different in the leiomyoma and myometrium (p > 0.05). To our knowledge, this is the first study to document marked expression of eNOS in leiomyomatous tissue, compared to parental myometrium. We also conclude that the mechanism(s) of the growth-promoting effect of estrogen on leiomyomata is mediated by more synthesis of NO.