Background. Taurine, which is the major intracellular free β‐amino acid, is known to be an endogenous antioxidant and a membrane‐stabilizing agent. In this study, we wished to know whether taurine altered the concentration of gentamicin in kidney tissue and could protect against gentamicin‐induced acute proximal tubular injury. Methods. Wistar albino rats of both sexes were assigned to three groups, which all received one of the following daily intraperitoneal injections for 8 days: (i) 0.9% sodium chloride (NaCl) alone at the same volume as gentamicin treated rats (group C; n=8); (ii) 100 mg/kg/day gentamicin alone (group G; n=8, four male, four female); or (iii) 100 mg/kg/day gentamicin plus 7.5 ml/kg/day taurine (group G+T; n=9, five male, four female). Urine was collected for 24 h for the determination of urine volume and creatinine. Intracardiac blood was collected for blood urea nitrogen (BUN) and serum creatinine determination. The kidneys were removed, weighed, and the left kidneys were subjected to biochemical analysis for the determination of thiobarbituric acid‐reactive substance (TBARS) and lactate levels, and glutathione peroxidase (Gpx) and superoxide dismutase (SOD) activities. The right kidneys were divided vertically in half. The upper halves were used for histopathological examination, by light and electron microscopy. The lower halves were used to detect the gentamicin concentration within the kidney tissue, by high‐performance liquid chromatography (HPLC). Changes in body weight and normalized kidney weight were recorded. Results. Taurine treatment reduced gentamicin‐induced increases in serum creatinine, 24 h urine volume, BUN and tissue lactate and TBARS levels (0.57±0.02 vs 1.06±0.08 mg/dl, P<0.001; 9.00±1.46 vs 20.9±2.73 ml, P<0.001; 25.3±1.87 vs 54.1±6.99 mg/dl, P<0.001; 2.56±0.10 vs 3.44±0.08 μmol/g wet tissue, P0.05, respectively). Taurine reduced the accumulation of gentamicin within the kidney tissue (233±29 vs 494±93 μg/g wet tissue, P<0.05). Taurine treatment also prevented body weight loss due to gentamicin administration (17.8±1.64 vs −10.0±7.08 g, P<0.01) and normalized reduced Gpx and SOD activities (3.46±0.16 vs 2.37±0.15 U/g wet tissue, P<0.01; and 15577±377 vs 12662±577 U/g wet tissue, P<0.01, respectively). Light microscopic examination of the renal tissues from gentamicin‐treated rats revealed severe histopathological changes, whereas specimens obtained from taurine‐treated rats revealed only mild changes. This finding was supported by electron microscopic examination. Conclusions. Our observations suggest that taurine treatment attenuates the accumulation of gentamicin within kidney tissue and counteracts the deleterious effect of gentamicin on renal tubular function. They may have potentially important clinical implications.

Cervical carcinoma, the second leading cause of cancer deaths in women worldwide, is associated with human papillomavirus (HPV). HPV-infected individuals are at high risk for developing cervical carcinoma; however, the molecular mechanisms that lead to the progression of cervical cancer have not been established. We hypothesized that in a multistep carcinogenesis model, HPV provides the initial hit and activation of canonical Wnt pathway may serve as the second hit. To test this hypothesis, we evaluated the canonical Wnt pathway as a promoting factor of HPV-induced human keratinocyte transformation. In this in vitro experimental cervical carcinoma model, primary human keratinocytes immortalized by HPV were transformed by SV40 small-t (smt) antigen. We show that smt-transformed cells have high cytoplasmic β-catenin levels, a hallmark of activated canonical Wnt pathway, and that activation of this pathway by smt is mediated through its interaction with protein phosphatase-2A. Furthermore, inhibition of downstream signaling from β-catenin inhibited the smt-induced transformed phenotype. Wnt pathway activation transformed HPV-immortalized primary human keratinocytes even in the absence of smt. However, activation of the Wnt pathway in the absence of HPV was not sufficient to induce transformation. We also detected increased cytoplasmic and nuclear staining of β-catenin in invasive cervical carcinoma samples from 48 patients. We detected weak cytoplasmic and no nuclear staining of β-catenin in 18 cases of cervical dysplasia. Our results suggest that the transformation of HPV expressing human keratinocytes requires activation of the Wnt pathway and that this activation may serve as a screening tool in HPV-positive populations to detect malignant progression.

Objective: To correlate the histopathology of adenomyosis particularly the depth and spread of adenomyosis and symptomatology. Study Design: Medical records of 94 patients who had undergone a hysterectomy and who were found to have adenomyosis on histopathologic examination were reviewed and histopathologic slides were reexamined. The symptoms were correlated with the presence of adenomyosis, the depth of penetration, and the spread of adenomyosis foci. Results: Specimens were stratified according to the degree of adenomyosis penetration into 4 groups: group A consisted of specimens with adenomyosis penetration into the myometrium of up to 25%; group B, 26–50%; group C, 51–75%, and group D, >75%. There was a significant correlation between the depth of penetration and the number of adenomyosis foci (r = 0.3446; p = 0.0001). Hemosiderin deposition was found mainly in the specimens with penetration of >75%. The symptoms did not correlate with the degree of penetration (r = 0.088; p NS). However, the spread of adenomyosis correlated significantly with pelvic pain (r = 0.80, p = 0.02), and with dysmenorrhea (r = 0.81, p = 0.01), but not with menorrhagia or dyspareunia. Conclusions: Hemosiderin deposition and adenomyosis foci are found predominantly in specimens with deep adenomyosis penetration. It suggests that the deeper the penetration, the more extensive the adenomyosis. Symptoms of adenomyosis do not correlate with the depth of penetration, but there is a correlation between the spread of adenomyosis and pelvic pain, and dysmenorrhea.

Salman MC, et al. J Gynecol Oncol. 2010 Jun;21(2):97-101. http://dx.doi.org/10.3802/jgo.2010.21.2.97