Annual reproductive cycle of males of the flat-faced fruit-eating bat, Artibeus planirostris (Chiroptera: Phyllostomidae)

Artibeus planirostris is an endemic species of Phyllostomid bat from the Neotropical region. Some studies have indicated that it exhibits seasonal bimodal polyestry; however, others postulate that it may be able to produce young at any time during the year. Thus, the aim of this study was to evaluate the annual variations in testicular and epididymal parameters of this species in southeast Brazil and try to understand how the reproduction of this species is regulated in this environment. Sixty mature male specimens, collected between June 2009 and May 2010, were submitted to morphometric and immunohistochemical analysis. Our study showed that A. planirostris presented a continuously active pattern of spermatogenesis throughout the year, presenting spermatozoa inside its cauda epididymis in all months, but with two pronounced peaks of spermatogenic production, one in September and other in February. We propose that the males developed these two peaks in order to produce sufficient sperm for the reproduction in a harem system and to synchronize with the female reproductive cycle, which had a bimodal polyestric pattern. Control of this variation is directly linked to the expression of the androgen receptor (AR) in Sertoli cells and to serum testosterone levels, which appear to synchronize to establish these two peaks. In the months preceding the two peaks, the testis have a higher expression of the AR, which possibly stimulates the increase in PCNA, and drives a gradual increase in the testicular parameters. Taken together the results suggest that if sperm storage happens in this species, it is of short duration. © 2013 Elsevier Inc.

Lack of protective effects of zinc gluconate against rat colon carcinogenesis

Zinc has been proposed as a promising chemopreventive candidate against colon cancer. However, few studies on the potential beneficial effects of this trace element on cancer chemoprevention are available. The present study was designed to investigate the potential modifying influence of zinc gluconate (ZnGly) on the initiation step of colon carcinogenesis induced by 1,2-dimethylhydrazine (DMH). Male Wistar rats received orally ZnGly (15 mg elemental zinc/kg, 3 times per wk) 2 wk before and during DMH treatment (3 × 40 mg/kg, once a wk). The animals were euthanized at the end of 4th and 16th wk. Colons were analyzed for aberrant crypt foci (ACF) and tumor development. Blood and colon zinc levels, cell proliferation, and apoptosis indexes in colonic crypts were analyzed 24 h after the last DMH administration. Oral treatment with ZnGly did neither alter the number of ACF nor the indexes of cell proliferation and apoptosis in the colonic mucosa. The incidence and multiplicity of colon tumors induced by DMH and their histopathological patterns were not modified by previous treatment with ZnGly. These findings indicate a lack of chemopreventive action of zinc gluconate supplementation on the initiation step of rat colon carcinogenesis induced by DMH. © 2013 Copyright Taylor and Francis Group, LLC.

Caracterização do tratamento medicamentoso com estatinas em unidade básica de saúde

Study Model: Retrospective study. Study Objective: To characterize statin treatment management due to lipid alterations and side effects throughout statin treatment in basic healthcare unit. Methods: Medical reports of women from a basic healthcare unit were analyzed, obtaining: disease presence, regular medication prescription, statin type and dosage, biochemical exams results, musculoskeletal complaints, and statin use cessation, going back the information until the medical consultation of first prescription. Results: Prescribed statins were Simvastatin and Atorvastatin at low doses (10-20 mg). Dose (48,4%) and/or type (25,4%) alterations occurred for lipid profile adequacy. Lipid levels were reduced without creatine kinase elevation. Treatment withdrawn (30,6%) was mainly due to their own decision (74%), which was strongly associated with records of musculoskeletal complaints (Odds Ratio: 6,40[1,53-26,78]). Conclusion: Statin treatment was effective in reducing serum lipid levels and self-reported pain was underestimated, characterizing the major limiting factor for treatment adherence.

A randomized clinical trial of high volume peritoneal dialysis versus extended daily hemodialysis for acute kidney injury patients

Background: Acute kidney injury (AKI) requiring dialysis in critically ill patients is associated with an in-hospital mortality rate of 50-80 %. Extended daily hemodialysis (EHD) and high volume peritoneal dialysis (HVPD) have emerged as alternative modalities. Methods: A double-center, randomized, controlled trial was conducted comparing EHD versus HVPD for the treatment for AKI in the intensive care unit (ICU). Four hundred and seven patients were randomized and 143 patients were analyzed. Principal outcome measure was hospital mortality, and secondary end points were recovery of renal function and metabolic and fluid control. Results: There was no difference between the two groups in relation to median ICU stay [11 (5.7-20) vs. 9 (5.7-19)], recovery of kidney function (26.9 vs. 29.6 %, p = 0.11), need for chronic dialysis (9.7 vs. 6.5 %, p = 0.23), and hospital mortality (63.4 vs. 63.9 %, p = 0.94). The groups were different in metabolic and fluid control. Blood urea nitrogen (BUN), creatinine, and bicarbonate levels were stabilized faster in EHD group than in HVPD group. Delivered Kt/V and ultrafiltration were higher in EHD group. Despite randomization, there were significant differences between the groups in some covariates, including age, pre-dialysis BUN, and creatinine levels, biased in favor of the EHD. Using logistic regression to adjust for the imbalances in group assignment, the odds of death associated with HVPD was 1.4 (95 % CI 0.7-2.4, p = 0.19). A detailed investigation of the randomization process failed to explain the marked differences in patient assignment. Conclusions: Despite faster metabolic control and higher dialysis dose and ultrafiltration with EHD, this study provides no evidence of a survival benefit of EHD compared with HVPD. The limitations of this study were that the results were not presented according to the intention to treat and it did not control other supportive management strategies as nutrition support and timing of dialysis initiation that might influence outcomes in AKI. © 2012 Springer Science+Business Media Dordrecht.

Previous contact with Strongyloides venezuelensis contributed to prevent insulitis in MLD-STZ diabetes

Epidemiological and experimental studies support the idea that helminth infections can induce a protective effect against the development of autoimmune and allergic diseases. In this study we characterized the immune response induced by Strongyloides venezuelensis infection in C57BL/6 mice and then evaluated the effect of a previous contact with this helminth in the outcome of type 1 diabetes. Animals were initially infected with 2000 L3 larvae from S. venezuelensis and euthanized 22. days later. An acute phase, identified by a high amount of eggs per gram of feces, was established between days 7 and 9 post-infection. Recovery from infection was associated with a Th2 polarized response characterized by a significant level of serum IgG1 specific antibodies and also a significant production of IL-5 and IL-10 by spleen cells stimulated with S. venezuelensis soluble antigen. Immunization with soluble S. venezuelensis antigen associated with complete Freund's adjuvant followed by infection with S. venezuelensis protected mice from diabetes development induced by streptozotocin. Protection was characterized by a higher body weight gain, lower glycemic levels, much less severe insulitis and preserved insulin production. Together, these results indicate that S. venezuelensis contributed to protect C57BL/6 mice against experimental diabetes induced by streptozotocin. © 2013 Elsevier Inc.

Effects of active smoking on airway and systemic inflammation profiles in patients with chronic obstructive pulmonary disease

Background: The markers that characterize local and systemic inflammation in chronic obstructive pulmonary disease (COPD) remain unclear, as do their correlations with smoking status and presence of disease. The aim of this study was to assess markers of inflammation in the peripheral blood and airways of current smokers without COPD, of current smokers with COPD and of ex-smokers with COPD. METHODS: In this study, 17 current smokers with COPD (mean age: 58.2 ± 9.6 years; mean forced expiratory volume in 1 second [FEV1]: 56.1 ± 15.9%), 35 ex-smokers with COPD (mean age: 66.3 ± 7.3 years; mean FEV1: 47.9 ± 17.2%) and 20 current smokers without COPD (mean age: 49.1 ± 6.2 years; mean FEV1: 106.5 ± 15.8%) were evaluated. Spirometry findings, body composition and serum/induced sputum concentrations of tumor necrosis factor α (TNF-α), interleukin (IL)-6, IL-8 and IL-10, together with serum C-reactive protein (CRP) levels, were assessed. RESULTS: Serum TNF-α concentration was higher in all current smokers than in ex-smokers with COPD. In current smokers without COPD, serum CRP level was lower than in ex-smokers with COPD and significantly lower than in current smokers with COPD. Sputum TNF-α concentration was higher in current and ex-smokers with COPD than in current smokers without COPD. Multiple regression analyses showed that serum TNF-α was associated with active smoking, and serum CRP and sputum TNF-α were associated with COPD diagnosis. CONCLUSIONS: Smoking is associated with higher systemic inflammation in patients with COPD. Current findings also support the hypothesis that smoking and COPD have different effects on the regulation of airway and systemic inflammatory processes. © 2013 Lippincott Williams and Wilkins.

Does excess weight interfere with bone mass accumulation during adolescence?

Obesity and osteoporosis are important global health problems characterized by increasing prevalence with high impact on morbidity and mortality. The objective of this review was to determine whether excess weight during adolescence interferes with bone mass accumulation. If bone mineral gain can be optimized during puberty, adults are less likely to suffer from the devastating complications of osteoporosis. The increased fracture risk in obese children has also been attributed to a lower bone mass for weight compared to non-obese children. Thus, adiposity present in this age group may not result in the protection of bone mass, in contrast to what has been observed in adults. However, studies involving adolescents have reported both protective and detrimental effects of obesity on bone. The results and mechanisms of these interactions are controversial and have not been fully elucidated, a fact highlighting the extreme relevance of this topic and the need to monitor intervening and interactive variables. © 2013 by the authors; licensee MDPI, Basel, Switzerland.

Inhibitory mechanism of the nucleus of the solitary tract involved in the control of cardiovascular, dipsogenic, hormonal, and renal responses to hyperosmolality

The nucleus of the solitary tract (NTS) is the primary site of visceral afferents to the central nervous system. In the present study, we investigated the effects of lesions in the commissural portion of the NTS (commNTS) on the activity of vasopressinergic neurons in the hypothalamic paraventricular (PVN) and supraoptic (SON) nuclei, plasma vasopressin, arterial pressure, water intake, and sodium excretion in rats with plasma hyperosmolality produced by intragastric 2 M NaCl (2 ml/rat). Male Holtzman rats with 15-20 days of sham or electrolytic lesion (1 mA; 10 s) of the commNTS were used. CommNTS lesions enhanced a 2 M NaCl intragastrically induced increase in the number of vasopressinergic neurons expressing c-Fos in the PVN (28 ± 1, vs. sham: 22 ± 2 c-Fos/AVP cells) and SON (26 ± 4, vs. sham: 11 ± 1 c-Fos/AVP cells), plasma vasopressin levels (21 ± 8, vs. sham: 6.6 ± 1.3 pg/ml), pressor responses (25 ± 7 mmHg, vs. sham: 7 ± 2 mmHg), water intake (17.5 ± 0.8, vs. sham: 11.2 ± 1.8 ml/2 h), and natriuresis (4.9 ± 0.8, vs. sham: 1.4 ± 0.3 meq/1 h). The pretreatment with vasopressin antagonist abolished the pressor response to intragastric 2 M NaCl in commNTS-lesioned rats (8 ± 2.4 mmHg at 10 min), suggesting that this response is dependent on vasopressin secretion. The results suggest that inhibitory mechanisms dependent on commNTS act to limit or counterbalance behavioral, hormonal, cardiovascular, and renal responses to an acute increase in plasma osmolality. © 2013 the American Physiological Society.

Slimmer or Fertile? Pharmacological Mechanisms Involved in Reduced Sperm Quality and Fertility in Rats Exposed to the Anorexigen Sibutramine

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

Insulin concentrations in cerebellum and body balance in diabetic male rats: Aerobic training effects

Brain insulin has had widespread metabolic, neurotrophic, and neuromodulatory functions and has been involved in the central regulation of food intake and body weight, learning and memory, neuronal development, and neuronal apoptosis. Purpose: The present study investigated the role of swimming training on cerebral metabolism on insulin concentrations in cerebellum and the body balance performance of diabetic rats. Methods: Forty Male Wistar rats were divided in four groups: sedentary control (SC), trained control (TC), sedentary diabetic (SD), and trained diabetic (TD). Diabetes was induced by alloxan (32 mg kg b.w.), single dose injection. The mean blood glucose of diabetic groups was 367 ± 40 mg/dl. Training program consisted in swimming 5 days/week, 1 h/day, 8 weeks, supporting a workload corresponding to 90% of maximal lactate steady state (MLSS). For the body balance testing rats were trained to traverse for 5 min daily for 5-7 days. All dependent variables were analyzed by one-way analysis of variance (ANOVA) and a significance level of p < 0.05 was used for all comparisons. Results: The body balance testing scores were different between groups. Insulin concentrations in cerebellum were not different between groups. Conclusion: It was concluded that in diabetic rats, aerobic training does not induce alterations on cerebellum insulin but induces important metabolic, hormonal and behavioral alterations which are associated with an improvement in glucose homeostasis, serum insulin concentrations and body balance. © 2013 Elsevier Inc.

Induction of the 72 kDa heat shock protein by glucose ingestion in black pregnant women

Obese Black women are at increased risk for development of gestational diabetes mellitus and have worse perinatal outcomes than do obese women of other ethnicities. Since hsp72 has been associated with the regulation of obesity-induced insulin resistance, we evaluated associations between glucose ingestion, hsp72 release and insulin production in Black pregnant women. Specifically, the effect of a 50-g glucose challenge test (GCT) on heat shock protein and insulin levels in the circulation 1 h later was evaluated. Hsp27 and hsp60 levels remained unchanged. In contrast, serum levels of hsp72 markedly increased after glucose ingestion (p = 0.0054). Further analysis revealed that this increase was limited to women who were not obese (body mass index <30). Insulin levels pre-GCT were positively correlated with body mass index (p = 0.0189). Median insulin concentrations also increased post GCT in non-obese women but remained almost unchanged in obese women. Post-GCT serum hsp72 concentrations were inversely correlated with post GCT insulin concentrations (p = 0.0111). These observations suggest that glucose intake during gestation in Black women rapidly leads to an elevation in circulating hsp72 only in non-obese Black women. The release of hsp72 may regulate the extent of insulin production in response to a glucose challenge and, thereby, protect the mother and/or fetus from development of hyperglycemia, hyperinsulinemia, and/or immune system alterations. © 2013 Cell Stress Society International.

SFlt-1/PlGF ratio as a prognostic marker of adverse outcomes in women with early-onset preeclampsia

Soluble fms-like tyrosine kinase 1 (sFlt-1) is an anti-angiogenic factor released in higher amounts by preeclamptic placentas and it has been implicated in the endothelial dysfunction observed in the disease. In this study we evaluated if circulating sFlt-1/PlGF ratio is useful to predict adverse outcomes in women with early-onset preeclampsia. This is a cohort study of 88 preeclamptic women with singleton pregnancies at ≤35 weeks of gestation. According to definitions used, adverse outcomes occurred in 46.5% (N = 43) of the patients. The median sFlt1/PlGF ratio (25th-75th centile) for all patients evaluated was of 42.26 (13.1-226.1). The median sFlt-1/PlGF ratio among women who had any adverse outcome (N = 43) versus no adverse outcomes (N = 45) was of 227.6 (80.3-346.1) versus 14.4 (3.35-30.0), (P < 0.0001). According to our analyses a sFlt-1/PlGF ratio cut-point of ≥85 gave a sensitivity of 74.0% and specificity of 97.0%. The positive predictive value and the negative predictive value were 96.0% and 80.0%, respectively. The median sFlt-1/PlGF ratio (25th-75th centile) for patients who delivered within <7 days was 260.0 (127.7-404.7) as compared to 14.4 (3.35-34.97) for those patients who delivered within two weeks or more (P < 0.0001). Our results suggest that sFlt-1/PlGF ratio is a promising marker for adverse outcomes in women with early-onset preeclampsia. © 2013 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.

Time-course of neuroendocrine changes and its correlation with hypertension induced by ethanol consumption

Ethanol (ETOH) consumption has been associated with endocrine and autonomic changes, including the development of hypertension. However, the sequence of pathophysiological events underlying the emergence of this effect is poorly understood. Aims: This study aimed to establish a time-course correlation between neuroendocrine and cardiovascular changes contributing to the development of hypertension following ETOH consumption. Methods: Male adult Wistar rats were subjected to the intake of increasing ETOH concentrations in their drinking water (first week: 5%, second week: 10%, third and fourth weeks: 20% v/v). Results: ETOH consumption decreased plasma and urinary volumes, as well as body weight and fluid intake. Furthermore, plasma osmolality, plasma sodium and urinary osmolality were elevated in the ETOH-treated rats. ETOH intake also induced a progressive increase in the mean arterial pressure (MAP), without affecting heart rate. Initially, this increasein MAP was correlated with increased plasma concentrations of adrenaline and noradrenaline. After the second week of ETOH treatment, plasma catecholamines returned to basal levels, and incremental increases were observed in plasma concentrations of vasopressin (AVP) and angiotensin II (ANG II). Conversely, plasma oxytocin, atrial natriuretic peptide, prolactin and the hypothalamus-pituitary-adrenal axis components were not significantly altered by ETOH. Conclusions: Taken together, these results suggest that increased sympathetic activity may contribute to the early increase in MAP observed inETOHtreated rats. However, the maintenance of this effect may be predominantly regulated by the long-term increase in the secretion of other circulating factors, such as AVP and ANG II, the secretion of both hormones being stimulated by the ETOH-induced dehydration. © The Author 2013. Medical Council on Alcohol and Oxford University Press. All rights reserved.

Pulmonary and hepatic lesions caused by the dehydropyrrolizidine alkaloid-producing plants Crotalaria juncea and Crotalaria retusa in donkeys

The effects and susceptibility of donkeys to Crotalaria juncea and Crotalaria retusa poisoning were determined at high and low doses. Seeds of C. juncea containing 0.074% of dehydropyrrolizidine alkaloids (DHPAs) (isohemijunceines 0.05%, trichodesmine 0.016%, and junceine 0.008%) were administered to three donkeys at 0.3, 0.6 and 1g/kg body weight (g/kg) daily for 365 days. No clinical signs were observed and, on liver and lung biopsies, the only lesion was a mild liver megalocytosis in the donkeys ingesting 0.6 and 1g/kg/day. Two other donkeys that received daily doses of 3 and 5g seed/kg showed initial respiratory signs 70 and 40 days after the start of the administration, respectively. The donkeys were euthanized following severe respiratory signs and the main lung lesions were proliferation of Clara cells and interstitial fibrosis. Three donkeys ingested seeds of C. retusa containing 5.99% of monocrotaline at daily doses of 0.025, 0.05 and 0.1g/kg for 365 days. No clinical signs were observed and, on liver and lung biopsies, the only lesion was moderate liver megalocytosis in each of the three donkeys. One donkey that received a single dose of 5g/kg of C. retusa seeds and another that received 1g/kg daily for 7 days both showed severe clinical signs and died with diffuse centrilobular liver necrosis. No lung lesions were observed. Another donkey that received a single dose of 2.5g/kg of C. retusa seeds showed no clinical signs. The hepatic and pneumotoxic effects observed are consistent with an etiology involving DHPAs. Furthermore, the occurrence of lung or liver lesions correlates with the type of DHPAs contained in the seeds. Similarly as has been reported for horses, the data herein suggest that in donkeys some DHPAs are metabolized in the liver causing liver disease, whereas others are metabolized in the lung by Clara cells causing lung disease. © 2013 Elsevier Ltd.

Glucose homoeostasis in rats exposed to acute intermittent hypoxia

Aim: Chronic exposure to intermittent hypoxia commonly induces the activation of sympathetic tonus and the disruption of glucose homoeostasis. However, the effects of exposure to acute intermittent hypoxia (AIH) on glucose homoeostasis are not yet fully elucidated. Herein, we evaluated parameters related to glucose metabolism in rats exposed to AIH. Methods: Male adult rats were submitted to 10 episodes of hypoxia (6% O2, for 45 s) interspersed with 5-min intervals of normoxia (21%), while the control (CTL) group was kept in normoxia. Results: Acute intermittent hypoxia rats presented higher fasting glycaemia, normal insulinaemia, increased lactataemia and similar serum lipid levels, compared to controls (n = 10, P < 0.05). Additionally, AIH rats exhibited increased glucose tolerance (GT) (n = 10, P < 0.05) and augmented insulin sensitivity (IS) (n = 10, P < 0.05). The p-Akt/Akt protein ratio was increased in the muscle, but not in the liver and adipose tissue of AIH rats (n = 6, P < 0.05). The elevated glycaemia in AIH rats was associated with a reduction in the hepatic glycogen content (n = 10, P < 0.05). Moreover, the AIH-induced increase in blood glucose concentration, as well as reduced hepatic glycogen content, was prevented by prior systemic administration of the β-adrenergic antagonist (P < 0.05). The effects of AIH on glycaemia and Akt phosphorylation were transient and not observed after 60 min. Conclusions: We suggest that AIH induces an increase in blood glucose concentration as a result of hepatic glycogenolysis recruitment through sympathetic activation. The augmentation of GT and IS might be attributed, at least in part, to increased β-adrenergic sympathetic stimulation and Akt protein activation in skeletal muscles, leading to a higher glucose availability and utilization. © 2013 Scandinavian Physiological Society.