Márcia A. Carrara

Coexistence of insulin resistance and increased glucose tolerance in pregnant rats: a physiological mechanism for glucose maintenance.

AIM The contribution of insulin resistance (IR) and glucose tolerance to the maintenance of blood glucose levels in non diabetic pregnant Wistar rats (PWR) was investigated. MAIN METHODS PWR were submitted to conventional insulin tolerance test (ITT) and glucose tolerance test (GTT) using blood sample collected 0, 10 and 60 min after intraperitoneal insulin (1 U/kg) or oral (gavage) glucose (1g/kg) administration. Moreover, ITT, GTT and the kinetics of glucose concentration changes in the fed and fasted states were evaluated with a real-time continuous glucose monitoring system (RT-CGMS) technique. Furthermore, the contribution of the liver glucose production was investigated. KEY FINDINGS Conventional ITT and GTT at 0, 7, 14 and 20 days of pregnancy revealed increased IR and glucose tolerance after 20 days of pregnancy. Thus, this period of pregnancy was used to investigate the kinetics of glucose changes with the RT-CGMS technique. PWR (day 20) exhibited a lower (p<0.05) glucose concentration in the fed state. In addition, we observed IR and increased glucose tolerance in the fed state (PWR-day 20 vs. day 0). Furthermore, our data from glycogenolysis and gluconeogenesis suggested that the liver glucose production did not contribute to these changes in insulin sensitivity and/or glucose tolerance during late pregnancy. SIGNIFICANCE In contrast to the general view that IR is a pathological process associated with gestational diabetes, a certain degree of IR may represent an important physiological mechanism for blood glucose maintenance during fasting.

Prevalence of metabolic syndrome among Kaingang native americans in southern Brazil

The aim of this work was to evaluate the prevalence of metabolic syndrome, diabetes mellitus, and obesity among a Brazilian indigenous population. A cross-sectional study was carried out in 2008 among Kaingang native Americans from the central region of the state of Parana, Brazil. Eighty two of the inhabitants aged 15 or older were selected. Height, weight, blood pressure, waistline circumference, and hip circumference were measured. After fasting, the blood was collected for the measurement of glucose, HDL cholesterol, triglyceride, total cholesterol, AI and B apolipoprotein, and hemoglobin. The prevalences found were: fasting hyperglycemia (9.8%), hypercholesterolemia (4.9%), reduced HDL cholesterol (13.4%), hypertriglyceridemia (11%), abdominal obesity (37.8%), generalized obesity (26.8%), arterial hypertension (26.8%), and anemia (46.3%). The prevalence of Metabolic Syndrome among the Kaingang was 11%, all in females 20 to 49 years of age. The results suggested that the changes in the indigenous lifestyle, especially in eating habits and physical activity, have occurred.

Effect of experimental diabetes on the development and maintenance of vulvovaginal candidiasis in female rats.

OBJECTIVE The purpose of this study was to develop an experimental model of diabetes in female rats and verify its influence on vulvovaginal candidiasis. STUDY DESIGN The animals were divided into control and diabetic groups. Diabetes was induced with the use of an intravenous solution of alloxan (42 mg/kg bodyweight). One week after confirmation of hyperglycemia, the inoculation of Candida albicans yeast, previously standardized from a vaginal isolate, in concentrations of about 5 x 10(8), was performed. Infection control was made through vaginal culture, Papanicolaou cytology, and scanning electron microscopy (SCEM). RESULTS The results pointed to different glycemias between the control (74.8 +/- 2.6) and experimental groups (543.1 +/- 12.1) and a significant bodyweight decrease (227.6 +/- 4.77 and 204 +/- 6.39, respectively). The positive infection was shown by culture, Papanicolaou test, and SCEM in the experimental group. CONCLUSION Diabetes mellitus causes hyperglycemia, which was favorable to the vaginal colonization and infection by C albicans.

Design and optimization of self-microemulsifying drug delivery system (SMEDDS) of felodipine for chronotherapeutic application

The objective of this study was to determine the effect of medroxyprogesterone acetate (DMPA) on the development and maintenance of Candida albicans in the vagina of oophorectomized Wistar rats. The animals were divided into negative control groups (NCG), which received injections of sterile saline; positive control groups (PCG), which were given injections of estradiol valerate; and progesterone groups (PG), which were given injections of Depo-Provera®. After one week of hormonal induction, vaginal infection by C. albicans was induced in all the groups and detected by vaginal yeast culture and Papanicolaou smear. In addition, scanning and transmission electron microscopy images were obtained to confirm the vaginal infection by yeast in PG. A difference in progesterone levels in PG was observed between the basal level and after hormonal induction (P<0.0001). In this group, 100% of the rats acquired vaginal infection in the first week, but did not maintain it until the third week. The pharmaceutical brand of DMPA was effective for inducing the metestrus or diestrus phase of the estrous cycle in rats, similar to the use of pure progesterone. In contrast to estrogen treatment, progesterone alone could not support an experimental vaginal infection by C. albicans for any significant period of time.

Participation of the liver gluconeogenesis in the glibenclamide‐induced hypoglycaemia in rats

We previously demonstrated an increased liver gluconeogenesis (LG) during insulin‐induced hypoglycaemia. Thus, an expected effect of sulphonylureas induced hypoglycaemia (SIH) could be the activation of LG. However, sulphonylureas infused directly in to the liver inhibits LG. Considering these opposite effects we investigated herein LG in rats submitted to SIH. For this purpose, 24 h fasted rats that received glibenclamide (10 mg kg−1) were used (SIH group). Control group received oral saline. Glycaemia at 30, 60, 90, 120 and 150 min after oral administration of glibenclamide were evaluated. Since the lowest glycaemia was obtained 120 min after glibenclamide administration, this time was chosen to investigate LG in situ perfused livers. The gluconeogenesis from precursors that enters in this metabolic pathway before the mitochondrial step, i.e. L‐alanine (5 mM), L‐lactate (2 mM), pyruvate (5 mM) and L‐glutamine were decreased (p < 0·05). However, the gluconeogenic activity using glycerol (2 mM), which enters in the gluconeogenesis after the mitochondrial step was maintained. Taken together, the results suggest that the inhibition of LG promoted by SIH overcome the activation of this metabolic pathway promoted by IIH and could be attributed, at least in part, to its effect on mitochondrial function. Copyright

Oxidative stress parameters as biomarkers of risk factor for diabetic foot among the patients with type 2 diabetes

The aim of this study was to determine whether plasma levels of carbonylated proteins, total antioxidant capacity (TAC) and reduced protein thiols could be suitable biomarkers of risk factors for diabetic foot. Individuals with type 2 diabetes with normal protective sensation (normal foot group) vs. loss of protective sensation and/or signs of peripheral arterial disease and/or foot deformities and/or history of ulcers and/or neuropathic fractures and/or amputation (diabetic foot group) were compared. The diabetic foot group showed higher carbonylated protein levels (P = 0.0457) and lower levels of TAC (P = 0.0148) and reduced protein thiols (P = 0.0088), compared with the normal foot group. In general, several other parameters of risk of diabetes complication (blood levels of glycated hemoglobin, glucose and cholesterol, duration of diabetes, body mass index and waist circumference) showed a tendency of higher values in the diabetic foot group. The results suggest that the plasma levels of carbonylated proteins, TAC and reduced protein thiols could furnish information about the risk of diabetic foot, considering that the changes in these biomarkers were associated with the loss of sensitivity and foot ulcerations.

Comparative performance of lab tests and blood testing device to monitor glucose, total cholesterol and triacylglycerol in type 2 diabetic patients

Comparou-se a performance de avaliacao da glicemia atraves de dosagens laboratoriais (DL) ou dispositivo para teste de sangue capilar (DTSC) vs. hemoglobina glicada A1c (A1c). Comparou-se ainda a performance de avaliacao da glicemia, colesterol total (CT) e triacilglicerol (DL vs. DTSC). Avaliou-se estes parametros a partir das mesmas amostras de sangue coletadas em pacientes diabeticos tipo 2 (PDT2) em jejum noturno, sendo as comparacoes realizadas atraves de analise de regressao linear. A A1c correlacionou-se melhor com a glicemia-DL (r = 0,58) em relacao a glicemia-DTSC (r = 0,42). Comparou-se DL vs. DTSC obtendo se r = 0,90, 0,82 e 0,92 para glicemia, CT e triacilglicerol, respectivamente. Concluiu-se que houve melhor performance da glicose-DL em relacao a glicose-DTSC. Alem disso, considerando que o triacilglicerol e TC avaliado atraves de DTSC correlaciona-se melhor com DL em comparacao a DTSC-glicose vs. DL-glicose, a inclusao de DTSC-TC e DTSC-triacilglicerol visando detectar e monitorar hyperlipidemia in PDT2 deve ser considerada.

Ultrastructural Imaging of Candida albicans Adhesion to Rat Genital Epithelium through Scanning and Transmission Electron Microscopy

The adhesion of Candida albicans to the genital epithelium has not been fully investigated in vivo. The objective of this study was to evaluate the ultrastructural aspects of C. albicans adhesion in the lower genital system of female Wistar rats through scanning and transmission electron microscopy. The genital infection persisted until the end of the experiment, and all rats showed the same adhesion aspects. Various associated yeast/hyphae were observed in the lumen and adhered both at the vaginal and endocervical levels where the fungal filamentation process occurred. In the vaginal epithelium, closely adhered yeasts were observed as stretched strands bridging between yeasts and the epithelium surface. Different stages of the adhesion, where yeasts internalized into the epithelial cell inside a cytoplasmic vacuole, resembling endocytosis, and a wide fibrillar-floccular, glycocalyx-like layer on the yeasts were observed. On the endocervix, the adhesion occurred between the cilia. In the uterine body, only a yeast-like form was observed with superficial contact. This study reached the initial goal of demonstrating an experimental model for in vivo studies. Continuation of this line of research is important for studies of vulvovaginal candidiasis.