Carbetocin vs. oxytocin at elective caesarean delivery: a double-blind, randomised, controlled, non-inferiority trial of low- and high-dose regimens.

Carbetocin or oxytocin are given routinely as first-line uterotonic drugs following delivery of the neonate during caesarean delivery to prevent postpartum haemorrhage. Low doses may be as effective as high doses with a potential reduction in adverse effects. In this double-blind, randomised, controlled, non-inferiority trial, we assigned low-risk patients undergoing elective caesarean delivery under spinal anaesthesia to one of four groups: carbetocin 20 µg; carbetocin 100 µg; oxytocin 0.5 IU bolus + infusion; and oxytocin 5 IU bolus + infusion. The study drug was given intravenously after delivery of the neonate. Uterine tone was assessed by the obstetrician 2, 5 and 10 minutes after study drug administration according to an 11-point verbal numerical rating scale (0 = atonic, 10 = excellent tone). The primary outcome measure was uterine tone 2 min after study drug administration. The pre-specified non-inferiority margin was 1.2 points on the 11-point scale. Secondary outcomes included uterine tone after 5 and 10 minutes, use of additional uterotonics, blood loss and adverse effects. Data were available for 277 patients. Carbetocin 20 µg resulting in uterine tone of (median (IQR [range])) 8 (7-8 [1-10]) was non-inferior to carbetocin 100 µg with tone 8 (7-9 [3-10]), median (95%CI) difference 0 (-0.44-0.44). Similarly, oxytocin 0.5 IU with tone 7 (6-8 [3-10]) was non-inferior to oxytocin 5 IU with tone 8 (6-8 [2-10]), median (95%CI) difference 1 (0.11-1.89). Carbetocin 20 µg was also non-inferior to oxytocin 5 IU, and oxytocin 0.5 IU was non-inferior to carbetocin 100 µg. Uterine tone after 5 and 10 minutes, use of additional uterotonics, blood loss and adverse effects were similar in all groups.

Antifungal and antibiofilm activities of the essential oil of leaves from Lippia gracilis Schauer against phytopathogenic fungi.

AIMS: This study aimed to evaluate the antifungal and antibiofilm effects of essential oil (EO) from leaves of Lippia gracilis and its major constituents, thymol and carvacrol, against phytopathogenic fungi. METHODS AND RESULTS: The leaves of L. gracilis were hydrodistilled to obtain the EO and the chemical composition was determined by GC/MS analysis. The antifungal activity of EO of L. gracilis was evaluated on the vegetative and mycelial growth of Colletotrichum gloeosporioides, Colletotrichum lindemuthianum, Fusarium oxysporum and Fusarium solani. In addition, the ability of the oil to inhibit fungal biofilm formation was assessed by total biomass quantification using crystal violet staining, analysis of metabolic activity, and scanning electron microscopy (SEM). Moreover the antifungal and antibiofilm activities of the monoterpenes, thymol and carvacrol, present in EO of L. gracilis were evaluated against F. oxysporum. The analysis of the chemical composition of EO extracted from L. gracilis, revealed the presence of monoterpenes (94·13%), which included carvacrol (48·57%) and thymol (7·78%), and 4 sesquiterpenes (3·74%). In general, EO showed significant antifungal activity and inhibited the formation of fungal biofilms. Furthermore, thymol and carvacrol showed significant antifungal and antibiofilm activities against F. oxysporum. SEM images showed structural changes in fungal morphology upon treatment with EO of L. gracilis. CONCLUSION: The results presented in this study showed promising antifungal and antibiofilm effects of EO of L. gracilis and its major components, carvacrol and thymol. SIGNIFICANCE AND IMPACT OF THE STUDY: These findings indicate that the EO extracted from L. gracilis, and the monoterpenes, carvacrol and thymol have a great potential as antifungal and antibiofilm agents. Furthermore, this is the first report of the antibiofilm activity of the EO of L. gracilis and its major components against phytopathogenic fungi.

Toxicity of insecticides on Neotropical stingless bees Plebeia emerina (Friese) and Tetragonisca fiebrigi (Schwarz) (Hymenoptera: Apidae: Meliponini).

Use of pesticides in agroecosystems is considered a major cause of bees diversity losses in the Neotropics, where Plebeia emerina (Friese) and Tetragonisca fiebrigi (Schwarz) (Hymenoptera: Apidae: Meliponini) are wild pollinators of native and crop plants. The aim of this study was to know the acute lethal toxicity of acetamiprid, malathion, phosmet and spinosad insecticides on P. emerina and T. fiebrigi. We obtained the mean concentration and mean lethal dose (LC50 and LD50) and the mean survival of workers after oral and topical exposure to insecticides, respectively. The LC50 values (ng a.i./µl of diet) and the decreasing order of toxicity for P. emerina was spinosad (4.96) > malathion (18.75) > phosmet (97.33) > acetamiprid (4204.06), and for T. fiebrigi also was spinosad (5.65) > malathion (8.39) > phosmet (53.91) > acetamiprid (9841.32), when orally exposed. The LD50 values (ng a.i./bee) and the decreasing order of toxicity for P. emerina was spinosad (1.90) > malathion (10.90) > phosmet (19.54) > acetamiprid (6216.55) and for T. fiebrigi was malathion (29.29) ≥ spinosad (29.79) > phosmet (41.95) > acetamiprid (1421.23), when topically exposed. The mean survival (hours) of contaminated bees by malathion, phosmet, and spinosad, was 11.81, 7.20, and 12.32 for P. emerina and 8.55, 7.20, and 13.34 for T. fiebrigi when orally exposed; and was 4.87, 9.87 and 11.17 for P. emerina, and 4.87, 4.76, and 19.05 for T. fiebrigi when topically exposed. Malathion, phosmet, and spinosad were highly toxic, while acetamiprid was moderately toxic. Our results indicated that the insecticides tested, mainly malathion, phosmet, and spinosad may be harmful to P. emerina and T. fiebrigi, making it essential to propose measures to minimize their impact on wild pollinators.

Bioprocess strategies for enhancing the outdoor production of Nannochloropsis gaditana: an evaluation of the effects of pH on culture performance in tubular photobioreactors.

A priority of the industrial applications of microalgae is the reduction of production costs while maximizing algae biomass productivity. The purpose of this study was to carry out a comprehensive evaluation of the effects of pH control on the production of Nannochloropsis gaditana in tubular photobioreactors under external conditions while considering the environmental, biological, and operational parameters of the process. Experiments were carried out in 3.0 m3 tubular photobioreactors under outdoor conditions. The pH values evaluated were 6.0, 7.0, 8.0, 9.0, and 10.0, which were controlled by injecting pure CO2 on-demand. The results have shown that the ideal pH for microalgal growth was 8.0, with higher values of biomass productivity (Pb) (0.16 g L-1 d-1), and CO2 use efficiency ([Formula: see text]) (74.6% w w-1); [Formula: see text]/biomass value obtained at this pH (2.42 [Formula: see text] gbiomass-1) was close to the theoretical value, indicating an adequate CO2 supply. At this pH, the system was more stable and required a lower number of CO2 injections than the other treatments. At pH 6.0, there was a decrease in the Pb and [Formula: see text]; cultures at pH 10.0 exhibited a lower Pb and photosynthetic efficiency as well. These results imply that controlling the pH at an optimum value allows higher CO2 conversions in biomass to be achieved and contributes to the reduction in costs of the microalgae production process.

Tau-dependent suppression of adult neurogenesis in the stressed hippocampus.

Stress, a well-known sculptor of brain plasticity, is shown to suppress hippocampal neurogenesis in the adult brain; yet, the underlying cellular mechanisms are poorly investigated. Previous studies have shown that chronic stress triggers hyperphosphorylation and accumulation of the cytoskeletal protein Tau, a process that may impair the cytoskeleton-regulating role(s) of this protein with impact on neuronal function. Here, we analyzed the role of Tau on stress-driven suppression of neurogenesis in the adult dentate gyrus (DG) using animals lacking Tau (Tau-knockout; Tau-KO) and wild-type (WT) littermates. Unlike WTs, Tau-KO animals exposed to chronic stress did not exhibit reduction in DG proliferating cells, neuroblasts and newborn neurons; however, newborn astrocytes were similarly decreased in both Tau-KO and WT mice. In addition, chronic stress reduced phosphoinositide 3-kinase (PI3K)/mammalian target of rapamycin (mTOR)/glycogen synthase kinase-3ß (GSK3ß)/ß-catenin signaling, known to regulate cell survival and proliferation, in the DG of WT, but not Tau-KO, animals. These data establish Tau as a critical regulator of the cellular cascades underlying stress deficits on hippocampal neurogenesis in the adult brain.

Human visceral leishmaniasis: factors associated with deaths in Belo Horizonte, Minas Gerais state, Brazil from 2006 to 2013.

The aim of this study was to evaluate the distribution of cases and the social determinants associated with death from human visceral leishmaniasis (HVL) and VL-HIV co-infection in Belo Horizonte, Minas Gerais state, Brazil, between 2006 and 2013. Descriptive statistics and analysis of associations were performed using chi-square of the raised variables, such as sex, age, skin colour and schooling of cases of HVL. During the study period, there were 866 cases of HVL with 111 deaths in Belo Horizonte. Morbidity and lethality rates (LR) of HVL in Belo Horizonte remained high over almost all the years evaluated, with an average incidence rate of 4.18 cases/100 000 inhabitants and a LR of 11.16%. With respect to skin colour, it was found that people characterised as black or mulatto had higher morbidity, followed by white. Regarding schooling, LR was more prevalent among individuals with lower education. One of the social risk factors was co-infection with HIV, which was present in many cases of HVL. Furthermore, it was found that older age and the male sex were also risk factors for death from HVL in Belo Horizonte.

ITS2 as a molecular marker for the identification of Diatraea saccharalis and D. flavipennella and possible infection with Cotesia spp.

In Brazil, the species Diatraea flavipennella and D. saccharalis play an important role in the sugar and alcohol agribusiness by causing many damages in sugarcane fields. The egg, larva, pupa, and adult stages are very morphologically similar between these species, and the identification can be confused. The internal transcribed spacer 2 (ITS 2) from ribosomal DNA has important features as evolutionary divergence. It is a good marker for species identification, participates in the rDNA processing, and has been applied in phylogenetic and population studies. This study aimed to make available a molecular marker to assist on the identification method of pests' species of Diatraea and to identify possible traces of Cotesia in the resistant host. The DNA was extracted from the egg, larva, and adult samples. PCR amplicons were purified and sequenced. The sequences were analyzed in MEGA 5.01. The ITS 2 length was 410 bp in D. flavipennella and 448 bp in D. saccharalis. The GC content was similar between the species. Three microsatellite loci were present in D. saccharalis and absent in D. flavipennella, contributing to differences in ITS 2 length in the species. An additional 367-bp band was attributed to Cotesia spp. The differences among ITS 2 from D. flavipennella, D. saccharalis, and Cotesia sp were sufficient to identify them on electrophoresis gel and sequencing. The presence of Cotesia sp traits in adult D. flavipennella showed possible host refractoriness, but further studies are necessary.

Analysis of p53 gene polymorphism (codon 72) in symptomatic patients with atherosclerosis.

Atherosclerosis is a multifactorial pathological disease that alters the morphology and function of arterial walls. The atheroma growth leads to vessel hardening and lumen narrowing, limiting the blood flow. The atheroma plaque can eventually break, expose highly thrombogenic material and lead to platelet activation and subsequent formation of a thrombus that may block blood flow in loco, or even leading to obstruction of other vessels with a smaller diameter. This process is one of the main determinants of the clinical manifestations of atherosclerosis, such as coronary artery disease, ischemic stroke, and peripheral arterial disease. Although the inflammatory theory about atherosclerosis is the most renowned one, observations point to common biological characteristics between cancer and atherosclerosis suggesting a possible association between p53 and atherosclerotic diseases. We collected peripheral blood samples from 200 individuals with clinical manifestations of atherosclerotic disease and 100 individuals without manisfestation of the disease to form the control group. DNA was subjected to molecular analysis (PCR) to identify the polymorphism of the p53 gene. We have not found any relationship between the polymorphism of the p53 gene and atherosclerosis in the population studied (P = 0.36). There was no relationship between atherosclerosis, polymorphism of p53 and the variables accounted: smoking habit (P = 0.72, 0.51 and 0.62 for smokers, non-smokers and former smokers respectively), alcohol consumption (P = 0.17 for individuals with drinking habits and 0.38 for those who do not consume alcohol beverage), systemic arterial hypertension (P = 0.60), diabetes mellitus (P = 0.34), and dyslipidemia (P = 0.89). Our population has a high rate of miscegenation and heterozygotes, and according to studies the arginine variant is more related to plaque formation because it induces apoptosis more frequently when compared to the proline variant. According to our results, there is no association between the polymorphism of the p53 gene, atherosclerosis and its risk factors in the population studied.

GSTM1 polymorphism in patients with clinical manifestations of atherosclerosis.

Atherosclerosis is characterized by lesions, called atheroma or atheromatous plaques, in the inner layer of blood vessels, which block the vascular lumen and weaken the underlying tunica media. Several modifiable and non-modifiable risk factors for the development of atherosclerosis exist. The modifiable risk factors include hypertension, smoking, obesity, high LDL and low HDL cholesterol levels, sedentary lifestyle, and stress; the non-modifiable factors include diabetes mellitus, family history of hypertension and heart disease, thrombophilia, sex, age, and genetic factors. The association of polymorphisms in GST with coronary artery disease has been studied since the polymorphisms can affect enzyme activity and contribute to the onset of atherosclerosis. We analyzed polymorphisms in GSTM1 in individuals diagnosed with atherosclerosis as well as in healthy individuals (control group). The frequency of the GSTM1 present genotype in the atherosclerosis group was 1.2 times higher than that observed in the control group. We found no sex- or alcohol-consumption-dependent differences between the occurrences of the present and null genotypes. However, the GSTM1 present genotype occurred in 52.6% individuals with atherosclerosis who reported smoking 20 or more cigarettes per day and in 60% individuals who smoked 10 to 20 cigarettes per day (P = 0.0035). In addition, the GSTM1 present genotype was more frequent in individuals who reported being former smokers - 45.5% in individuals with atherosclerosis who smoked for more than 20 years and 50% each for individuals in the control group who smoked for less than 10 years or for 10 to 20 years, respectively (P = 0.0240).

Atherosclerosis: analysis of the eNOS (T786C) gene polymorphism.

The coronary arteriosclerotic disease is the most common cardiovascular disease. Atherosclerosis affects large- and medium-sized arteries leading to severe thrombosis or artery stenosis that could evolve to myocardial infarction, ischemic stroke, ischemic injury of kidneys and intestines, and several other life-threatening clinical manifestations. Nitric oxide has been shown to be a promising therapeutic agent against cardiovascular diseases. The eNOS gene assumes several important functions, including regulation of vascular tone and regional blood flow, the suppression of vascular smooth muscle cell proliferation, and modulation of leukocyte-endothelium interactions. The T786C polymorphism is an important point mutation, where thymine is changed to cytosine. T786C significantly reduces the activity of the eNOS promoter gene. Two hundred and ninety-seven peripheral blood samples were collected from patients with the previous diagnosis of atherosclerotic disease based on clinical examination and confirmed by imaging methods. Results were compared using the chi-square test and the G-test. In the present study, the TC genotype was more frequent in both case and control groups with no statistically significant difference. Comparing the relation TC/TT and CC genotypes in the case and control groups, there was no statistically significant difference. No significant difference was found when genotypes were analyzed regarding gender and smoking. Our results suggest a strong tendency of the T allele, in single or double dose, to be associated with atherosclerosis that was not confirmed by the scientific data.

Polymorphism of the gene eNOS G894T (Glu298Asp) in symptomatic patients with aterosclerosis.

Atherosclerotic and its cardiovascular complications are responsible for 17.5 million deaths a year, according to the World Health Organization. There is consensus that atherosclerosis involves multiple pathogenic processes initiated by endothelial dysfunction, with inflammation and vascular proliferation determining alterations in the matrix, with consequent formation of the atheromatous plaque and its clinical implications. Risk factors such as hypertension, diabetes mellitus, dyslipidemia, and smoking are widely known. Currently, genotyping, which is not directly related to these factors, is not accepted to estimate the risk of cardiovascular diseases, but strong evidence indicates several polymorphic genes as factors of risk and progression leading to complications of the disease. Among the genes involved, eNOS (endothelial nitric oxide synthase gene), which is responsible for the production of endothelial nitric oxide (an important arterial vasodilator), when presented in polymorphic variation can determine production, malfunction, and predisposition to atherosclerosis. In the present study, we analyzed the G894T polymorphism of the eNOS gene in groups of individuals diagnosed with atherosclerosis and in a control group. We collected 200 blood samples from patients previously diagnosed with atherosclerosis and 100 samples formed the control group. The genotyping analysis for polymorphism of the eNOS gene was determined by PCR. We considered variables such as gender, smoking, smoking history, and alcohol consumption; statistical differences were found in the distribution of case and control groups (P = 0.0378) and in non-smoking patients (P = 0.0263). In the other associations, no statistically significant difference was found. In the population studied, the frequency of the heterozygous genotype (GT) was much higher than in the other populations (GG and TT) in both groups (case and control). The GG genotype showed greater susceptibility to atherosclerosis. Association of the GG genotype in non-smokers also showed greater susceptibility. Gender, alcohol consumption, smoking, and smoking history did not influence atherosclerosis.

Molecular analysis of the GSTT1 gene polymorphism in patients with clinical manifestation of atherosclerosis.

Atherosclerosis is a chronic inflammatory disease formed by the accumulation of lipids in the innermost layer and large-caliber artery (tunica intima). This accumulation, along with platelet factors, stimulates the proliferation of muscle cells in this region. Over than 400 genes may be related to the pathology since they regulate endothelial function, coagulation, inflammation, metabolism of amino acids, lipids, and carbohydrates. Glutathione S-transferases (GST) are enzymes that catalyze the polymorphic detoxification of metabolites produced by oxidative stress within the cells, which is induced by reactive oxygen species. GSTs are one of the defense mechanisms against oxidative stress damage. Due to genetic, cultural, and environmental factors, the rate of atherosclerosis is higher; however, an early diagnosis is crucial for the prevention and treatment of several complications related to the disease. The present study aimed to analyze the frequency of GSTT1 genotypes regarding the presence or absence of the polymorphism in patients with clinical manifestation of atherosclerosis. We collected 200 samples of peripheral blood of patients with the previous diagnosis of atherosclerosis based on clinical examination and imaging, and 100 samples of peripheral blood to compose the control group of patients without clinical manifestation of atherosclerosis. The polymorphism was assessed by PCR and analyzed on the agarose gel stained with 2.0% ethidium bromide. The frequency of the GSTT1 gene polymorphism was compared using the chi-square test (P < 0.05) and the G-test. In the case group, we detected 85.5% of patients with the GSTT1 genotype present and 14.5% of patients with the null genotype. A significant difference was observed between groups (case vs control) for the presence of the GSTT1 polymorphism. According to the analysis of the variable alcohol consumption, we found that in the case group the presence of the GSTT1 gene was higher in individuals who reported not drinking alcohol. In this study, the presence of the GSTT1 gene polymorphism in male patients with atherosclerosis was 1.5 times higher when compared to female patients. Regarding the variable time of smoking, we found that this genotype was more frequent in smokers for both case and control groups.

Does non-pharmacological therapy for antenatal depression reduce risks for the infant?

Depression during pregnancy has been associated with an increased risk of adverse outcomes for the infant such as preterm birth. These risks are not reduced with pharmacological treatment, but the effect of non-pharmacological therapies is unknown. We performed a systematic review to assess the risk of adverse perinatal outcomes in non-pharmacologically treated depressed women compared to non-depressed women. We found no studies that met our inclusion criteria, highlighting a critical need for research on this topic.

Distribution of Dekkera bruxellensis in a sugarcane-based fuel ethanol fermentation plant.

UNLABELLED: We investigated the presence of the yeast Dekkera bruxellensis in samples collected at three points surrounding the industrial alcoholic fermentation plants of two distilleries where there are often cases of contamination caused by this yeast: this involved sugar cane wash water, feeding sugar cane juice and vinasse from the treatment pond. Total yeast was isolated in WLN medium with bromocresol green and cycloheximide and further selected on the basis of its ability to grow in synthetic medium containing nitrate. Following this, colonies were selected from the distribution on nitrate plates and identified by amplification with species-specific primers and DNA sequencing of the 26S-D1/D2 locus. The results showed that D. bruxellensis is introduced through the feeding substrate, which suggests that its cells originated with the harvested cane. Subsequently, its population circulates as a result of the reuse of water for washing the cane, in a continuous re-inoculation of the plant with yeasts. Furthermore, the yeast population is formed in the vinasse by the addition of wash water into the treatment ponds and then reintroduced to the culture fields by fertigation, so that the process can be renewed in the following season. It is now possible to adopt sanitation procedures that can prevent the entry of the contamination to the fermentation process. SIGNIFICANCE AND IMPACT OF THE STUDY: The presence of the yeast Dekkera bruxellensis is sometimes attributed to a decline in the industrial productivity of ethanol since it has a more limited fermentation capacity than Saccharomyces cerevisiae. Although its adaptability to the industrial environment has been noted, so far, there has been no evidence to determine the source of this contamination. In this study, we provide evidence to show that D. bruxellensis comes from the fields together with the harvested cane and is then accumulated and recirculated. It might be possible to prevent the accumulation of this yeast by carrying out sanitation controls during the harvesting season.

High intracellular trehalase activity prevents the storage of trehalose in the yeast Dekkera bruxellensis.

UNLABELLED: Dekkera bruxellensis hit the spotlight in the past decade mostly due to its rather high ability to adapt to several different fermentation processes. This yeast relies on different genetic and physiological aspects to achieve and preserve its high industrial fitness and some of these traits are shared with Saccharomyces cerevisiae. We have previously described that D. bruxellensis is unable to make use of accumulating trehalose as a strategy for cell adaptation and survival in the industrial scenario, as opposed to S. cerevisiae. Since trehalose is often involved in mechanisms related to cell protection, we aimed to investigate both cause and effect of the absence of this metabolite in the cell adaptive capacity in the industrial environment. Our results indicate that the major cause for the nonaccumulation of trehalose is the high constitutive activity of neutral trehalase. Therefore, the rate of trehalose degradation could be higher than its rate of synthesis, preventing accumulation. Altogether, our data elucidate the mechanisms involved in the lack of trehalose accumulation in D. bruxellensis as well as evaluates the implications of this feature. SIGNIFICANCE AND IMPACT OF THE STUDY: Dekkera bruxellensis can successfully take advantage of its peculiar physiological and genetic traits in order to adapt and survive in fermentation processes. So far, tolerance to stress has been credited to trehalose synthesis. The data presented in this work provided information on the underlying mechanism that prevents trehalose accumulation and corroborated the recent information that trehalose itself is not implicated in yeast stress tolerance. Second, it showed that D. bruxellensis responds differently to Saccharomyces cerevisiae to excess of sugar, which may explain its preference for respiration (oxidative metabolism) over fermentation (reductive metabolism) even at limited oxygen supply. These findings help to understand the drop on ethanol production in processes overtaken by this yeast.

Intestinal microbiota and allergic diseases: A systematic review.

Evidence suggests that possible imbalances in intestinal microbiota composition may be implicated in the occurrence of allergic diseases. Although several studies published until 2006 indicated a correlation between microbiota composition and allergic symptoms, it has not been possible to distinguish protective microorganisms from those associated with increased risk of allergic diseases. Therefore, the objective of this study was to review the studies published since 2007 that address the intestinal microbiota in allergic diseases. Twenty-one studies were identified after excluding those that performed a clinical intervention before stool collection. In the early microbiota of children who later developed allergies, lower bacterial diversity was observed, with a predominance of Firmicutes; a higher count of Bacteroidaceae; a higher prevalence of the anaerobic bacteria Bacteroides fragilis, Escherichia coli, Clostridium difficile, Bifidobacterium catenulatum, Bifidobacterium bifidum, and Bifidobacterium longum; and a lower prevalence of Bifidobacterium adolescentis, B. bifidum, and Lactobacillus. In the microbiota of allergic children whose intestinal microbiota was assessed at the onset of allergic symptoms, there was a higher count of Bacteroides; a lower count of Akkermansia muciniphila, Faecalibacterium prausnitzii, and Clostridium; a higher prevalence of B. adolescentis; a lower prevalence of B. catenulatum and Staphylococcus aureus; and a lower bacterial diversity.

Male idiopathic infertility and the TP53 polymorphism in codon 72.

Many environmental agents affect the development of male germ cells at different stages. Apoptosis is common during normal spermatogenesis; it plays an important role in controlling the number of germ cells and the disposal of defective stem cells to produce functional sperm. The presence of p53 in primary spermatocytes suggests that it plays a role in the prophase of meiosis. p53 is expressed in the testis in both spermatocytes and spermatogonia. This suggests that the p53 gene (TP53) is important for apoptosis regulation during spermatogenesis, and may be associated with male infertility. The main causes of male infertility are genetic, physical, and pathological abnormalities, intense and prolonged exercise, aging, drug use, and long periods of sexual abstinence. Approximately 20% of male infertility is idiopathic. The Trp53 gene is involved in meiosis in male rats and mice suggesting that the p53 plays a critical role in spermatogenesis. We investigated the association between the TP53 polymorphism in codon 72 and idiopathic male infertility in 208 semen samples: 106 showed abnormal semen analysis results and were from infertile men, and 102 were from fertile individuals (the control group). Changes in Trp53 expression are associated with the main phase regulating meiotic progression with a peak in the pachytene stage, and Trp53-deficient mice exhibit degenerative syndrome (giant cells). The genotypic and allelic frequencies were not significantly different among the groups in this study; the results suggest that the TP53 polymorphism in codon 72 is not associated with the pathogenesis of idiopathic male infertility or failure of spermatogenesis.

Serotonin 2C receptor antagonists induce fast-onset antidepressant effects.

Current antidepressants must be administered for several weeks to produce therapeutic effects. We show that selective serotonin 2C (5-HT2C) antagonists exert antidepressant actions with a faster-onset (5 days) than that of current antidepressants (14 days) in mice. Subchronic (5 days) treatment with 5-HT2C antagonists induced antidepressant behavioral effects in the chronic forced swim test (cFST), chronic mild stress (CMS) paradigm and olfactory bulbectomy paradigm. This treatment regimen also induced classical markers of antidepressant action: activation of cAMP response element-binding protein (CREB) and induction of brain-derived neurotrophic factor (BDNF) in the medial prefrontal cortex (mPFC). None of these effects were induced by subchronic treatment with citalopram, a prototypical selective serotonin reuptake inhibitor (SSRI). Local infusion of 5-HT2C antagonists into the ventral tegmental area was sufficient to induce BDNF in the mPFC, and dopamine D1 receptor antagonist treatment blocked the antidepressant behavioral effects of 5-HT2C antagonists. 5-HT2C antagonists also activated mammalian target of rapamycin (mTOR) and eukaryotic elongation factor 2 (eEF2) in the mPFC, effects recently linked to rapid antidepressant action. Furthermore, 5-HT2C antagonists reversed CMS-induced atrophy of mPFC pyramidal neurons. Subchronic SSRI treatment, which does not induce antidepressant behavioral effects, also activated mTOR and eEF2 and reversed CMS-induced neuronal atrophy, indicating that these effects are not sufficient for antidepressant onset. Our findings reveal that 5-HT2C antagonists are putative fast-onset antidepressants, which act through enhancement of mesocortical dopaminergic signaling.

Occult hepatitis B virus infection among blood donors from the Brazilian Amazon: implications for transfusion policy.

BACKGROUND: Brazil requires the performance of both a test for hepatitis B surface antigen (HBsAg) and a test for antibodies to the core of hepatitis B for blood donor screening. Blood centres in regions of high HBV endemicity struggle to maintain adequate stocks in face of the high discard rates due to anti-HBc reactivity. We evaluated the potential infectivity of donations positive for anti-HBc in search of a rational approach for the handling of these collections. STUDY DESIGN AND METHODS: We tested anti-HBc reactive blood donations from the state of Amazonas for the presence of HBV DNA and for titres of anti-HBs. The study population consists of village-based donors from the interior of Amazonas state. RESULTS: Among 3600 donations, 799 were anti-HBc reactive (22·2%). We were able to perform real-time PCR for the HBV S gene on specimens from 291 of these donors. Eight of these samples were negative for HBsAg and positive for HBV DNA and were defined as occult B virus infections (2·7%). Six of those eight specimens had anti-HBs titres above 100 mIU/ml, indicating the concomitant presence of the virus with high antibody titres. CONCLUSION: A small proportion of anti-HBc reactive donors carry HBV DNA and anti-HBs testing is not useful for predicting viremia on them. This finding indicates the possibility of HBV transmission from asymptomatic donors, especially in areas of high HBV prevalence. Sensitive HBV DNA nucleic acid testing may provide another level of safety, allowing eventual use of anti-HBc reactive units in critical situations.

Maturation and antioxidant activity of 'Giombo' and 'Rama Forte' persimmons produced in the Brazilian semiarid.

The objective of this work was characterizing persimmons of the 'Giombo' and 'Rama Forte' cultivars harvested at different ripening stages in the Brazilian semiarid. Fruits were harvested at three ripening stages - green, semi-ripe and ripe - then evaluated for the following characteristics: fruit weight and diameter, skin and pulp color, fruit firmness, pulp pH, soluble solids content, titratable acidity, SSC/TA ratio, total soluble sugars, reducing sugars, astringency index, and the contents of tannin, vitamin C, carotenoid, ß-carotene, and total extractable polyphenols. Also, total antioxidant activity by the DPPH and ABTS methods and pectin methylesterase, and polygalacturonase enzyme activities were evaluated. Two experiments were carried out in a completely randomized design, one for each cultivar, with treatments consisting of different stages of maturation, with five replications of three fruits each. Data were submitted to analysis of variance and the differences between the means were compared using the Tukey test at 5% probability. Fruit firmness and soluble solids content did not vary between maturation stages for any of the cultivars. However, the skin color index increased with advancing maturation for both 'Giombo' and 'Rama Forte'. The astringency index, the content of total extractable polyphenols, soluble tannins and the antioxidant capacity were lower in fruits harvested at the ripe stage, for both cultivars. It can be concluded that persimmons of the 'Giombo' and 'Rama Forte' cultivars present better physicochemical quality characteristics when harvested when ripe, with a totally yellow skin.