Metabolic Effects of the Ingestion of Different Fructose Sources in Rats

Introduction: Fructose is a simple carbohydrate that should be ingested in a restricted manner. However, current data suggest increased daily consumption of fructose which may lead to an increased incidence of diseases such as obesity, diabetes and co-morbidities associated with excess weight. Thus, the objective of the present study was to assess the effect of the ingestion of different fructose sources on weight gain, glycemia and serum triglyceride levels in rats.Methods: The study was conducted on male Wistar rats divided into 5 groups according to the source and concentration of fructuse (ingested ad libitum in liquid form).Results: Drink intake was increased and chow consumption was reduced in all groups compared to control (p<0.05). The animals of the groups receiving 10 and 20% fructose solutions showed increased triglyceride levels and the 20% group also showed weight gain. The exaggerate consumption of fructose promotes a reduced consumption of chow, an increase in serum triglyceride levels, and weight gain in some animals.

Signal transducer and activator of transcription 3-regulated sarcoendoplasmic reticulurn Ca2+-ATPase 2 expression by prolactin and glucocorticoids is involved in the adaptation of insulin secretory response during the peripartum period

During pregnancy, the maternal endocrine pancreas undergoes, as a consequence of placental lactogens and prolactin (PR,L) action, functional changes that are characterized by increased glucose-induced insulin secretion. After delivery, the maternal endocrine pancreas rapidly returns to nonpregnant state, which is mainly attributed to the increased serum levels of glucocorticoids (GCs). Although GCs are known to decrease insulin secretion and counteract PRL action, the mechanisms for these effects are poorly understood. We have previously demonstrated that signal transducer and activator of transcription 3 (STAT3) is increased in islets treated with PRL. In the present study, we show that STAT3 expression and serine phosphorylation are increased in pancreatic islets at the end of pregnancy (P19). STAT3 serine phosphorylation rapidly returned to basal levels 3 days after delivery (U). The expression of the sarcoendoplasmic reticulum Ca2+-ATPase 2 (SERCA2), a crucial protein involved in the regulation of calcium handling in P-cells, was also increased in P19, returning to basal levels at L3. PRL increased SERCA2 and STAT3 expressions and STAT3 serine phosphorylation in RINm5F cells. The upregulation of SERCA2 by PRL was abolished after STAT3 knockdown. Moreover, PRL-induced STAT3 serine phosphorylation and SERCA2 expression were inhibited by dexamethasone (DEX). Insulin secretion from islets of PI 9 rats pre-incubated with thapsigargin and L3 rats showed a dramatic suppression of first phase of insulin release. The present results indicate that PRL regulates SERCA2 expression by a STAT3-dependent mechanism. PRL effect is counteracted by DEX and might contribute to the adaptation of maternal endocrine pancreas during the peripartum period.

Implantação do Serviço de Avaliação Pré-Anestésica em Hospital Universitário: dificuldades e resultados

JUSTIFICATIVA E OBJETIVOS: A avaliação pré-operatória é a chave principal para um bom preparo pré-operatório e manuseio intra-operatório. Quando realizada em nível ambulatorial permite uma análise melhor, possibilitando investigações adicionais, melhorando a qualidade do preparo e diminuindo os custos hospitalares. O objetivo deste estudo foi analisar a implantação e o desenvolvimento do Serviço de Avaliação Pré-Anestésica (SAPAN) em Hospital Universitário, verificando quais foram as dificuldades e os resultados positivos encontrados. MÉTODO: Foram avaliados os dados relativos aos pacientes atendidos no ambulatório do SAPAN, pelos médicos em especialização com supervisão de um docente, nos primeiros nove meses de instalação. A consulta era feita seguindo uma ficha padronizada. Ao término, os pacientes eram liberados para o procedimento cirúrgico ou encaminhados para consulta com outros especialistas para controle de doenças específicas. Analisou-se o número de pacientes avaliados e o número de procedimentos cirúrgicos eletivos realizados nesse período e as diversas especialidades cirúrgicas, porcentagem de pacientes com intervenção cirúrgica suspensa por necessidade de controle de doenças, e as especialidades clínicas mais solicitadas. RESULTADOS: Realizaram-se 913 consultas ambulatoriais e 5.409 intervenções cirúrgicas eletivas. Várias clínicas não encaminharam seus pacientes para a avaliação. Por necessidade clínica, 11,9% dos pacientes tiveram o procedimento cirúrgico suspenso, e as clínicas envolvidas foram cardiologia (43,08%), pneumologia (25,74%), hematologia (21,65%) e endocrinologia (9,52%). CONCLUSÕES: Embora grande parte dos pacientes não tenha sido encaminhada pelas especialidades cirúrgicas, os dados iniciais do SAPAN permitiram demonstrar os benefícios de um serviço de preparo ambulatorial dos pacientes.

A novel mutation (Q40P) in PAX8 associated with congenital hypothyroidism and thyroid hypoplasia: Evidence for phenotypic variability in mother and child

Congenital hypothyroidism associated with thyroid hypoplasia can be caused by several genetic defects, including mutations in the TSH beta -subunit, the TSH receptor, the G(A)alpha -subunit, and the transcription factor PAX8. Four girls with sporadic congenital hypothyroidism and hypoplastic thyroid glands were analyzed for mutations in PAX8 and TTF2 (FKHL15). Mutations in the coding region of the TSH beta -subunit gene, the TSH receptor gene, and exons 8 and 9 of G(mu)alpha had been excluded previously. Serum TSH concentrations were 150 mU/liter or more, TG levels were within normal limits, and thyroid autoantibodies were absent. Technetium scintigraphies did not reveal the presence of thyroid tissue, but ultrasonography documented hypoplastic, normally located glands.One patient was found to harbor a heterozygous transversion 119A -->C in exon 3 of PAX8 replacing a conserved glutamine by proline in the paired box domain (Q40P). Analysis of her family members revealed that her mother, who has a thyroid gland of normal size and mild, adult-onset autoimmune hypothyroidism, is also heterozygous for this mutation. Functional analyses of the PAX8 Q40P mutation showed impaired binding to a PAX8 response element and absent transactivation of a thyroid peroxidase promoter luciferase reporter gene.These findings confirm the important role of PAX8 in the development of the thyroid, but they indicate that PAX8 gene mutations may have a variable penetrance or expressivity. The absence of mutations in the coding sequences of the analyzed genes in the three other patients supports the concept that the pathogenesis of congenital hypothyroidism associated with thyroid hypoplasia is diverse.

Diet-induced obesity in rats leads to a decrease in sperm motility

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Association between anthropometric indicators of body fat and metabolic risk markers in post-menopausal women

Objective. to evaluate anthropometric indicators of body fat and their association with metabolic risk markers in postmenopausal women.Methods. A cross-sectional study with 80 Brazilian women (40-70 years) was carried out. Body mass index (BMI = weight/height(2)), waist circumference (WC) and waist-to-hip ratio (WHR) were obtained for anthropometric evaluation. Trunk fat mass (TFM) was measured by dual-energy X-ray absorptiometry. The following metabolic variables were evaluated: total cholesterol (TC), HDL, LDL, triglycerides (TG), as well as glycemia and insulin to determine insulin resistance (HOMA-IR).Results. Overweight and obesity were observed in 81% of the women. Values of WC >88 cm were observed in 68.5% of the women. on average, TC, LDL and TG levels were above normal levels in 60, 50 and 42.5% of the women, respectively; and HDL was normal in 82.5%. IR was observed in 37.5% of the women. Positive correlations were found between anthropometric indicators and TFM (P < 0.05). WC was most correlated with TFM (r = 0.92), followed by BMI (r = 0.88) and by WHR (r = 0.48; P < 0.05). All anthropometric indicators and TFM showed significant negative correlations with HDL and significant positive correlations with HOMA-IR (P < 0.05). Only WHR was significantly associated with dysglycemia (R(2) = 12%), hypertriglyceridemia (R(2) = 17%) and decreased HDL (R(2) = 27%). WC was significantly associated with HOMA-IR (R(2) = 34%).Conclusion. WC and WHR are anthropometric measures that showed strong correlation with TFM and with metabolic risk markers in postmenopausal women.

Maternal-Fetal Outcome, Lipid Profile and Oxidative Stress of Diabetic Rats Neonatally Exposed to Streptozotocin

Background: There is no evidence about the integrated issue on glycemia, lipid profile, oxidative stress, and anomaly frequency of pregnant diabetic rats neonatally exposed to streptozotocin.Objective: Evaluating the impact of hyperglycemia in diabetic rats neonatally exposed to streptozotocin on maternal reproductive and fetal outcomes and the relationship with lipid profile and maternal oxidative stress.Material and Methods: Ten 90-day-old female Wistar rats were mated to obtain offspring. Some of these newborns received streptozotocin (70 mg/kg, i.p. - n5-STZ group) and the remainder given only citrate buffer (control group) on their day 5 of life. At adult life, these rats (n =13 animals/group) were mated and, at day 21 of pregnancy, they were killed to obtain a maternal blood samples for biochemical determinations. The gravid uterus was weighed with its contents and fetuses were analyzed.Results: At day 0 of pregnancy, glycemic means of n5-STZ rats were significantly greater compared to those of control rats, but presented fetuses classified as small for pregnancy age. The n5-STZ rats showed increased total cholesterol, triglycerides, MDA concentrations, lower SOD activity and increased frequency fetal visceral anomalies as compared to the control group.Conclusion: This study showed that the experimental model used led to mild hyperglycemia during pregnancy, although it did not lead to increased macrosomic fetus rates. The hyperglycemic maternal environment caused metabolic alterations, including increased triglyceride and total cholesterol concentrations, and elevated oxidative stress, contributing to increase fetal visceral anomalies.

Genetic polymorphisms associated with steroids metabolism and insulin action in polycystic ovary syndrome

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Seasonal variability in the fertilization rate of women undergoing assisted reproduction treatments

The objective of this study was to evaluate whether seasonality affects human-assisted reproduction treatment outcomes. For this, 1932 patients undergoing intracytoplasmic sperm injection (ICSI) were assigned to a season group according to the day of oocyte retrieval: winter (n = 435), spring (n = 444), summer (n = 469) or autumn (n = 584). Analysis of variance was used to compare the ICSI outcomes. The fertilization rate was increased during the spring (winter: 67.9%, spring: 73.5%, summer: 68.7% and autumn: 69.0%; p < 0.01). In fact, a nearly 50% increase in the fertilization rate during the spring was observed (odds ratio 1.45, confidence interval 1.20-1.75; p < 0.01). The oestradiol concentration per number of oocytes was significantly higher during the spring (winter: 235.8 pg/mL, spring: 282.1 pg/mL, summer: 226.1 pg/mL and autumn: 228.7 pg/mL; p = 0.030). This study demonstrates a seasonal variability in fertilization after ICSI, where fertilization is higher during the spring than at any other time.

Genotoxicity and Fetal Abnormality in Streptozotocin-Induced Diabetic Rats Exposed to Cigarette Smoke Prior to and during Pregnancy

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Genotoxicity Evaluation in Severe or Mild Diabetic Pregnancy in Laboratory Animals

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Menstrual irregularity: a possible clinical marker of metabolic dysfunction in women with class III obesity

Purpose. To evaluate whether menstrual irregularity in morbidly obese women is indicative of metabolic dysfunction.Patients and Methods. Fifty-seven women with morbid obesity were evaluated. They were divided into two groups: one comprising women without menstrual dysfunctions or hirsutism (Group 1), and another obese women showing menstrual dysfunction with or without hirsutism (Group 2). The following were evaluated: age, colour, childbirth, marital status, profession, socio-economic level, education, age at menarche, body weight, height, body mass index, presence of hirsutism (Ferriman Gallwey Index), abdominal circumference, hip circumference, waist-to-hip ratio, menstrual cycle, blood pressure, presence of acanthosis nigricans, insulin resistance (IR), fasting glycaemia, total cholesterol, HDL-C, LDL-C, triglycerides, thyroid-stimulating hormone, free T4, luteinising hormone (LH), follicle-stimulating hormone, prolactin, total testosterone, dehydroepiandrosterone sulfate, insulin and the Homeostasis Model Assessment (HOMA test).Results. Clinical and epidemiological aspects did not present statistical differences. Clinical and laboratory parameters did not show statistically significant alterations; however, HOMA test values for Group 2 were significantly higher than those for Group 1.Conclusions. The presence of IR in class III obese women can cause menstrual dysfunctions such as amenorrhoea or oligomenorrhoea even in the absence of hyperandrogenism, suggesting that IR plays an important role in the ovarian mechanisms involved in the menstrual cycle control.

Single-embryo transfer reduces clinical pregnancy rates and live births in fresh IVF and Intracytoplasmic Sperm Injection (ICSI) cycles: a meta-analysis

Background: It has become an accepted procedure to transfer more than one embryo to the patient to achieve acceptable ongoing pregnancy rates. However, transfers of more than a single embryo increase the probability of establishing a multiple gestation. Single-embryo transfer can minimize twin pregnancies but may also lower live birth rates. This meta-analysis aimed to compare current data on single-embryo versus double-embryo transfer in fresh IVF/ICSI cycles with respect to implantation, ongoing pregnancy and live birth rates.Methods: Search strategies included on-line surveys of databases from 1995 to 2008. Data management and analysis were conducted using the Stats Direct statistical software. The fixed-effect model was used for odds ratio (OR). Fixed-effect effectiveness was evaluated by the Mantel Haenszel method. Seven trials fulfilled the inclusion criteria.Results: When pooling results under the fixed-effect model, the implantation rate was not significantly different between double-embryo transfer (34.5%) and single-embryo transfer group (34.7%) (P = 0.96; OR = 0.99, 95% CI 0.78, 1.25). on the other hand, double-embryo transfer produced a statistically significantly higher ongoing clinical pregnancy rate (44.5%) than single-embryo transfer (28.3%) (P < 0.0001; OR: 2.06, 95% CI = 1.64,2.60). At the same time, pooling results presented a significantly higher live birth rate when double-embryo transfer (42.5%) (P < 0.001; OR: 1.87, 95% CI = 1.44,2.42) was compared with single-embryo transfer (28.4%).Conclusion: Meta-analysis with 95% confidence showed that, despite similar implantation rates, fresh double-embryo transfer had a 1.64 to 2.60 times greater ongoing pregnancy rate and 1.44 to 2.42 times greater live birth rate than single-embryo transfer in a population suitable for ART treatment.

Administration of single-dose GnRH agonist in the luteal phase in ICSI cycles: a meta-analysis

Background: The effects of gonadotrophin-releasing hormone agonist (GnRH-a) administered in the luteal phase remains controversial. This meta-analysis aimed to evaluate the effect of the administration of a single-dose of GnRH-a in the luteal phase on ICSI clinical outcomes.Methods: The research strategy included the online search of databases. Only randomized studies were included. The outcomes analyzed were implantation rate, clinical pregnancy rate (CPR) per transfer and ongoing pregnancy rate. The fixed effects model was used for odds ratio. In all trials, a single dose of GnRH-a was administered at day 5/6 after ICSI procedures.Results: All cycles presented statistically significantly higher rates of implantation (P < 0.0001), CPR per transfer (P = 0.006) and ongoing pregnancy (P = 0.02) in the group that received luteal-phase GnRH-a administration than in the control group (without luteal-phase-GnRH-a administration). When meta-analysis was carried out only in trials that had used long GnRH-a ovarian stimulation protocol, CPR per transfer (P = 0.06) and ongoing pregnancy (P = 0.23) rates were not significantly different between the groups, but implantation rate was significant higher (P = 0.02) in the group that received luteal-phase-GnRH-a administration. on the other hand, the results from trials that had used GnRH antagonist multi-dose ovarian stimulation protocol showed statistically significantly higher implantation (P = 0.0002), CPR per transfer (P = 0.04) and ongoing pregnancy rate (P = 0.04) in the luteal-phaseGnRH- a administration group. The majority of the results presented heterogeneity.Conclusions: These findings demonstrate that the luteal-phase single-dose GnRH-a administration can increase implantation rate in all cycles and CPR per transfer and ongoing pregnancy rate in cycles with GnRH antagonist ovarian stimulation protocol. Nevertheless, by considering the heterogeneity between the trials, it seems premature to recommend the use of GnRH-a in the luteal phase. Additional randomized controlled trials are necessary before evidence-based recommendations can be provided.

Effects of recombinant LH supplementation to recombinant FSH during induced ovarian stimulation in the GnRH-agonist protocol: a matched case-control study

Background: Some studies have suggested that the suppression of endogenous LH secretion does not seem to affect the majority of patients who are undergoing assisted reproduction and stimulation with recombinant FSH (r-FSH). Other studies have indicated that a group of normogonadotrophic women down-regulated and stimulated with pure FSH preparations may experience low LH concentrations that compromise the IVF parameters. The present study aimed to compare the efficacy of recombinant LH (r-LH) supplementation for controlled ovarian stimulation in r-FSH and GnRH-agonist (GnRH-a) protocol in ICSI cycles.Methods: A total of 244 patients without ovulatory dysfunction, aged < 40 years and at the first ICSI cycle were divided into two groups matched by age according to an ovarian stimulation scheme: Group I (n = 122): Down-regulation with GnRH-a + r-FSH and Group II (n = 122): Downregulation with GnRH-a + r-FSH and r-LH (beginning simultaneously).Result(s): The number of oocytes collected, the number of oocytes in metaphase II and fertilization rate were significantly lower in the Group I than in Group II (P = 0.036, P = 0.0014 and P = 0.017, respectively). In addition, the mean number of embryos produced per cycle and the mean number of frozen embryos per cycle were statistically lower (P = 0.0092 and P = 0.0008, respectively) in Group I than in Group II. Finally the cumulative implantation rate (fresh+thaw ed embryos) was significantly lower (P = 0.04) in Group I than in Group II. The other clinical and laboratory results analyzed did not show difference between groups.Conclusion: These data support r-LH supplementation in ovarian stimulation protocols with r-FSH and GnRH-a for assisted reproduction treatment.