O-GlcNAcylation reduces proximal tubule protein reabsorption and promotes proteinuria in spontaneously hypertensive rats.

Hypertensive individuals are at greater risk for developing chronic kidney disease (CKD). Reducing proteinuria has been suggested as a possible therapeutic approach to treat CKD. However, the mechanisms underlying the development of proteinuria in hypertensive conditions are incompletely understood. Cardiac and vascular dysfunction is associated with changes in the O-GlcNAcylation pathway in hypertensive models. We hypothesized that O-GlcNAcylation is also involved in renal damage, especially development of proteinuria, associated with hypertension. Using the spontaneously hypertensive rat (SHR) model, we observed higher renal cortex O-GlcNAcylation, glutamine-fructose aminotransferase (GFAT), and O-GlcNAc transferase (OGT) protein expression, which positively correlated with proteinuria. Interestingly, this was observed in hypertensive, but not pre-hypertensive, rats. Pharmacological inhibition of GFAT decreased renal cortex O-GlcNAcylation, proteinuria, and albuminuria in SHR. Using a proximal tubule cell line, we observed that increased O-GlcNAcylation reduced megalin surface expression and albumin endocytosis in vitro, and the effects were correlated in vivo Moreover, megalin is O-GlcNAcylated both in vitro and in vivo In conclusion, our results demonstrate a new mechanism involved in hypertension-associated proteinuria.

High Doses of Essential Oil of Croton Zehntneri Induces Renal Tubular Damage.

The essential oil of Croton zehntneri (EOCZ) and its major compounds are known to have several biological activities. However, some evidence shows potential toxic effects of high doses of EOCZ (>300 mg/kg) in amphibian and human kidneys. The aim of the present work was to investigate the effects on renal function of EOCZ at 300 mg/kg/day in healthy Swiss mice and a subclinical acute kidney injury (subAKI) animal model, which presents tubule-interstitial injury (TII). Four experimental groups were generated: (1) CONT group (control); (2) EOCZ, mice treated with EOCZ; (3) subAKI; (4) subAKI+EOCZ, subAKI treated simultaneously with EOCZ. EOCZ treatment induced TII measured by increases in (1) proteinuria; (2) cortical tubule-interstitial space; (3) macrophage infiltration; (4) collagen deposition. A decrease in tubular sodium reabsorption was also observed. These results were similar and nonadditive to those observed in the subAKI group. These data suggest that treatment with EOCZ at higher concentrations induces TII in mice, which could be mediated by protein overload in the proximal tubule.

A retrospective analysis of clinicopathological and prognostic characteristics of ovarian tumors in the State of Espírito Santo, Brazil.

BACKGROUND: Ovarian cancer is sixth most common cancer among women and the leading cause of death in women with gynecological malignancies. Despite the great impact ovarian cancer has on women's health and its great impact in public economy, Brazil still lacks valuable information concerning epidemiological aspects of this disease METHODS: We've compiled clinical data of all ovarian tumors registered at the two public hospitals of reference (1997 - 2007), such as: patients' age at diagnosis, tumor histological type, tumor stage, chemotherapy regimens, chemotherapy responsiveness, disease-free survival, and overall survival. RESULTS: Women's mean age at diagnosis was 54.67 ± 13.84 for ovarian cancer, 46.15 ± 11.15 for borderline tumors, and 42.01 ± 15.06 for adenomas. Among epithelial ovarian cancer cases, 30.1% were of serous, 13.7% were of mucinous, and 13.7% were of endometrioid type; exceptionally serous carcinoma was diagnosed in women younger than 30 years old. Endometrioid cancer had lower disease-free survival than others (p < 0.05). Cases were predominantly diagnosed as poor prognosis disease (FIGO III and IV, 56.2%). Regarding responsiveness to platinum-based therapy, 17.1% of patients were resistant, whereas 24.6%, susceptible. From these, we found equally responsiveness to platinum alone or its association with paclitaxel or cyclophosphamide. DISCUSSION: Our data agreed with other studies regarding mean patients' age at diagnosis, histological type frequency, FIGO stages distribution, and chemotherapy regimens. However, the histological type distribution, with equal contribution of mucinous and endometrioid types seems to be a unique characteristic of the studied highly miscegenated population. CONCLUSION: We have enlighten the profile of the studied ovarian cancer population, which might enable the development of more efficient political strategies to control this malignancy that is the fifth leading cause of cancer-related deaths among women.