Acute, but not repeated, cocaine exposure alters allopregnanolone levels in the midbrain of male and female rats.

RATIONALE: Multiple psychiatric disorders are associated with altered brain and serum levels of neuroactive steroids, including the endogenous GABAergic steroid, allopregnanolone. Clinically, chronic cocaine use was correlated with decreased levels of pregnenolone. Preclinically, the effect of acute cocaine on allopregnanolone levels in rodents has had mixed results, showing an increase or no change in allopregnanolone levels in some brain regions. OBJECTIVE: We hypothesized that cocaine acutely increases allopregnanolone levels, but repeated cocaine exposure decreases allopregnanolone levels compared to controls. METHODS: We performed two separate studies to determine how systemic administration of 15 mg/kg cocaine (1) acutely or (2) chronically alters brain (olfactory bulb, frontal cortex, dorsal striatum, and midbrain) and serum allopregnanolone levels in adult male and female Sprague-Dawley rats. RESULTS: Cocaine acutely increased allopregnanolone levels in the midbrain, but not in olfactory bulb, frontal cortex, or dorsal striatum. Repeated cocaine did not persistently (24 h later) alter allopregnanolone levels in any region in either sex. However, allopregnanolone levels varied by sex across brain regions. In the acute study, we found that females had significantly higher allopregnanolone levels in serum and olfactory bulb relative to males. In the repeated cocaine study, females had significantly higher allopregnanolone levels in olfactory bulb, frontal cortex, and serum. Finally, acute cocaine increased allopregnanolone levels in the frontal cortex of females in proestrus, relative to non-proestrus stages. CONCLUSION: Collectively these results suggest that allopregnanolone levels vary across brain regions and by sex, which may play a part in differential responses to cocaine by sex.

A Single Dose of Ginkgo biloba Extract Induces Gene Expression of Hypothalamic Anorexigenic Effectors in Male Rats.

Previous studies have shown that Ginkgo biloba extract (GbE) reduces food intake and body mass gain and regulates proteins related to lipid metabolism in obese rats. In ovariectomized rats, GbE restored the hippocampal and hypothalamic serotonergic system activity, favoring the spontaneous feeding decrement. Considering the promising hypophagic effect of GbE, this study aimed to investigate the effect of a single acute dose on hypothalamic pathways that regulate feeding behavior in male rats. Four-month-old Wistar male rats received either a single acute oral GbE dose (500 mg/kg) or vehicle. Food intake and body mass were measured after 1, 4, 12, and 24 h. Rats were euthanized, and hypothalami were removed for mRNA quantification of anorexigenic (POMC/CART) and orexigenic (AgRP/NPY) neuropeptides, leptin/serotonin receptors (5HT1A, 5HT1B, 5HT2C), and serotonin transporters. We also investigated POMC, 5-HT1B, and 5-HT2C protein levels. A single acute GbE dose induced the hypothalamic POMC, CART, and 5-HT2C gene expression but failed to modify orexigenic effectors. No alterations in food intake, body mass, and hypothalamic protein levels were observed. In summary, the present findings demonstrate the rapid stimulation of pivotal hypothalamic anorexigenic pathways in response to a single GbE administration, reinforcing the GbE hypophagic activity. However, more studies are necessary to evaluate its potential as an appetite modulator.

Ginkgo biloba Extract Modulates the Retroperitoneal Fat Depot Proteome and Reduces Oxidative Stress in Diet-Induced Obese Rats.

The rapid increase in the number of individuals with obesity, over the past four decades, is triggered by a number of complex interactions among factors. Despite the plethora of treatments available, side effects are commonly observed and, in this context, herbal medicines have been employed as an alternative form of therapy. Ginkgo biloba extract (GbE) has been described as a promising new pharmacological approach to treat obesity. In order to better comprehend the mechanisms involved with this potential effect, the present study evaluated the effects of GbE treatment on diet-induced obese rats, focusing on the proteome and the oxidative stress defense system of visceral adipose tissue. After 14 days treatment, GbE significantly modulated 25 proteins. Retroperitoneal adipose tissue of treated animals exhibited higher amounts of proteins associated with adipogenesis (decorin), carbon metabolism and mitochondrial function (citrate synthase), and a concomitant reduction in adipocyte hypertrophy. In parallel, GbE down-regulated proteins involved in oxidative stress (peroxiredoxin) and the inflammatory response (complement C3, mast cell protease 1, and Ig gamma-2B chain C region). Moreover, also related to oxidative stress defense, GbE stimulated catalase activity, reduced malondialdehyde levels (lipid peroxidation indicator), and increased lactoylglutathione lyase levels. It was concluded that GbE acts as an antioxidant agent, and improved the proteome profile and oxidative stress response in the adipose tissue of diet-induced obese rats.

Potential Anti-obesogenic Effects of Ginkgo biloba Observed in Epididymal White Adipose Tissue of Obese Rats.

Exacerbated expansion of adipose tissue seen in diet-induced obesity leads to endocrine dysfunction and disturbance in adipokine secretion, with such abnormal profile positively associated with type 2 diabetes and other mild chronic inflammatory conditions. Ginkgo biloba extract (GbE), a mixture of polyphenols with antioxidant properties, has been recently investigated in a variety of experimental models of endocrine dysfunction, with several potentially beneficial effects identified, including improvement in insulin sensitivity in obese rats, and reduction of weight gain in ovariectomy-induced obesity and diet-induced obesity. The aim of this study was to investigate in high fat diet-induced obese male rats the effects of GbE supplementation for 2 weeks on adipocyte volume and adipose tissue lipid accumulation. GbE supplementation was effective in reducing energy intake in obese rats compared to the saline-treated placebo group. Epididymal adipocyte volume was reduced in GbE-supplemented rats, as were epididymal [1-14C]-acetate incorporation into fatty acids, perilipin (Plin 1) and fatty acid synthase (Fasn) mRNA, and FAS protein levels. Adipocyte hypertrophy in obesity is associated with insulin resistance, and in the present study we observed a reduction in the adipocyte volume of GbE-supplemented obese rats to dimensions equivalent to adipocytes from non-obese rats. GbE supplementation significantly reduced acetate accumulation and tended to reduce [3H]-oleate incorporation, into epididymal adipose tissue, suggesting a potentially anti-obesogenic effect in longer term therapies. Further studies that investigate the effects of GbE supplementation in other experimental models are required to fully elucidate its suggested beneficial effects on mild chronic inflammatory conditions.

Agomelatine's effect on circadian locomotor rhythm alteration and depressive-like behavior in 6-OHDA lesioned rats.

Parkinson's disease (PD) patients often suffer from circadian locomotor rhythms impairment and depression, important non-motor symptoms. It is known that toxin-based animal models of PD can reproduce these features. In a 6-hydroxydopamine (6-OHDA) intranigral model, we first investigated the possible disturbances on circadian rhythms of locomotor activity. The rats were divided into 6-OHDA and Sham groups. After a partial dopaminergic lesion, the 6-OHDA group showed slight alterations in different circadian locomotor rhythms parameters. In a second experiment, we hypothesized agomelatine, an melatoninergic antidepressant with potential to resynchronize disturbed rhythms, could prevent neuronal damage and rhythm alterations in the same 6-OHDA model. The animals were divided into four groups: 6-OHDA+vehicle, 6-OHDA+ago, Sham+vehicle and 6-OHDA+ago. However, the treated animals (agomelatine 50 mg/kg for 22 days) showed an impaired rhythm robustness, and agomelatine did not induce significant changes in the other circadian parameters nor neuroprotection. Finally, in a third experiment, we examined the effects of agomelatine in the 6-OHDA model regarding depressive-like behavior, evaluated by sucrose preference test. The animals were also divided into four groups: 6-OHDA+vehicle, 6-OHDA+ago, Sham+vehicle and 6-OHDA+ago. The toxin infused animals showed a decrease in sucrose preference in comparison with the vehicle infused animals, however, agomelatine did not prevent this decrease. Our findings indicate that agomelatine worsened circadian locomotor rhythm and was not able to reverse the depressive-like behavior of rats in the 6-OHDA PD model.

Decrease in Adult Neurogenesis and Neuroinflammation Are Involved in Spatial Memory Impairment in the Streptozotocin-Induced Model of Sporadic Alzheimer's Disease in Rats.

Early impairments in cerebral glucose metabolism and insulin signaling pathways may participate in the pathogenesis of the sporadic form of Alzheimer's disease (sAD). Intracerebroventricular (ICV) injections of low doses of streptozotocin (STZ) are used to mimic sAD and study these alterations in rodents. Streptozotocin causes impairments in insulin signaling and has been reported to trigger several alterations in the brain, such as oxidative stress, neuroinflammation, and dysfunctions in adult neurogenesis, which may be involved in cognitive decline and are features of human AD. The aim of the present study was to assess the influence of neuroinflammation on the process of adult neurogenesis and consequent cognitive deficits in the STZ-ICV model of sAD in Wistar rats. Streptozotocin caused an acute and persistent neuroinflammatory response, reflected by reactive microgliosis and astrogliosis in periventricular areas and the dorsal hippocampus, accompanied by a marked reduction of the proliferation of neural stem cells in the dentate gyrus of the hippocampus and subventricular zone. Streptozotocin also reduced the survival, differentiation, and maturation of newborn neurons, resulting in impairments in short-term and long-term spatial memory. These results support the hypothesis that neuroinflammation has a detrimental effect on neurogenesis, and both neuroinflammation and impairments in neurogenesis contribute to cognitive deficits in the STZ-ICV model of sAD.

Haemonchus contortus protease inhibition by n-alkyl ferulates from Maprounea guianensis.

This report describes the inhibition of the proteolytic activity of Haemonchus contortus lysate by a mixture of n-alkyl ferulates isolated from Maprounea guianensis. These compounds were evaluated in vitro for the ability to inhibit the H. contortus proteases using SDS-PAGE copolymerized with gelatine (zymography) and by assaying the hemoglobinolytic activity of these enzymes in solution. The ferulates abrogated the proteolysis compared to E-64, suggesting the activity is the result of a cysteine protease.

Redox profile in liver of Leporinus macrocephalus exposed to different dissolved oxygen levels.

Aquatic organisms are continuously exposed to environmental variations, which can lead to physiological and biochemical alterations. Leporinus macrocephalus, known as piavuçu, is a migratory species that may be exposed to variations in dissolved oxygen levels. Studies evaluating oxidative changes undergone by this species in these conditions are scarce. Therefore, this investigation aimed at evaluating oxidative alterations in L. macrocephalus exposed to different oxygen levels for 96 h: 6.12 ± 0.18, 3.99 ± 0.17, 3.22 ± 0.17, 2.47 ± 0.30 and 0.710 ± 0.07 mg L(-1). At the end of the experimental period, fish were euthanized and livers used to determine lipid hydroperoxides, thiobarbituric acid reactive substances, catalase, glutathione-S-transferase, superoxide dismutase and thiol groups, which are an indirect measure of reduced glutathione. Results indicated a decrease in the studied parameters in hypoxic situations, suggesting a possible metabolic depression.

Crescimento, produção de fitomassa e teor de óleo essencial de melissa (Melissa officinalis L. ) sob diferentes níveis de sombreamento / Growth, biomass production and essential oil content of lemon balm (Melissa officinalis L. ) under different shading levels

O objetivo foi avaliar a variação no teor de óleo essencial, crescimento e produção de fitomassa de Melissa officinalis L. cultivada sob diferentes níveis de sombreamento. O delineamento experimental foi inteiramente ao acaso (DIC) com quatro níveis de radiação fotossinteticamente ativa (RFA), luz plena (testemunha) e sombreamento progressivo com tela tipo sombrite (sombreamento de 75, 50 e 25%) e seis repetições. Foram avaliados: diâmetro do caule, altura da planta, massa fresca e seca da parte aérea, teor do óleo essencial, rendimento de óleo e área foliar. Os dados foram submetidos à análise de variância e análise de regressão a 1 e 5% de probabilidade de erro. As características, diâmetro do caule e altura da planta, não apresentaram diferenças significativas entre os tratamentos. A produção de massa fresca, massa seca e o teor de óleo essencial, foram similares entre todos os tratamentos diferenciando apenas do tratamento em pleno sol, onde (MF): 25%=50%, 91, 33 g e 68, 66 g; (MS): 25%=0%=50%, 11,35, 11,66, 10,66 g e 4,33 g e TO: 25%=50%, 0,48 e 0,40% respectivamente. O tratamento que resultou em menor produtividade foi o sombreado a 75%. Assim, nas condições norte-mineiras, de fevereiro a junho, o cultivo da melissa pode ser conduzido em condições de até 50% de sombreamento, favorecendo a produção de massa seca, massa fresca e teor de óleo essencial; sendo estas variáveis de interesse comercial pelos produtores de plantas medicinais e aromáticas.

The aim of this study was to evaluate the variation in essential oil content, growth and biomass production of Melissa officinalis L. cultivated under different shading levels. Experimental design was completely randomized (CRD) with four levels of photosynthetically active radiation (PAR), full light (control) and progressive shading with shade net (shading of 75, 50 and 25%) and six replicates. The following parameters were assessed: stem diameter, plant height, fresh mass and dry mass of shoot, essential oil content, essential oil yield and leaf area. Data were subjected to analysis of variance and regression analysis at 1 and 5% error probability. The characteristics stem diameter and plant height did not show significant differences among treatments. Production of fresh weight, dry mass and essential oil content was similar among all treatments, except for full light, where (FW): 25%=50%, 91.33 g and 68.66 g; (DW): 25%=0%=50%, 11.35, 11.66, 10.66 g and 4.33 g and OC: 25%=50%, 0.48 and 0.40% respectively. The treatment that resulted in the lowest productivity was 75% shading. Thus, in the north of Minas Gerais State, Brazil, from February to June, lemon balm can be cultivated under conditions of up to 50% shading, favoring the production of dry mass, fresh mass and essential oil content; these variables are of commercial interest for producers of medicinal and aromatic plants.

Atelectasis observed by computerized tomography after Caesarean section.

BACKGROUND: Atelectasis after either vaginal or Caesarean delivery has not been adequately quantified. This study addresses the hypothesis that atelectasis may be worse in women who undergo Caesarean section when compared with vaginal delivery under regional anaesthesia. METHODS: Twenty healthy non-smoking women submitted to a chest computed tomography (CT) 2 h after delivery in a University Hospital, who had experienced vaginal delivery (n=10) under combined spinal-epidural analgesia or a Caesarean section (n=10) under spinal anaesthesia, were evaluated. The percentage cross-sectional area of atelectasis in dependent lung regions were measured from the CT images obtained at cross-section of the xiphoid process and the top of the diaphragm. RESULTS: The percentage cross-sectional area of atelectasis was 3.95% in the vaginal delivery group and 14.1% in the Caesarean group (P<0.001, Mann-Whitney rank sum test). CONCLUSIONS: These results suggested that pulmonary atelectasis is greater after Caesarean section delivery under spinal anaesthesia than after vaginal delivery with combined spinal-epidural analgesia.

Inhibition by transmembrane peptides of chimeric insulin receptors.

Receptor tyrosine kinases play essential roles in cell proliferation and differentiation. We have recently shown that peptides corresponding to the transmembrane domains of the epidermal growth factor (EGF) and ErbB2 receptors inhibit their corresponding receptor activation in cancer cell lines. We extend this observation to cells transfected with chimeric insulin receptors where the transmembrane domain has been replaced by that of the EGF receptor or a mutated Erb2 domain. Peptides corresponding to the transmembrane domains of the EGF receptor and ErbB2 are able to inhibit specifically the autophosphorylation of insulin receptors with the corresponding domain. This inhibitory effect is correlated with the propensity of the different transmembrane domains to self-associate in a genetic reporter assay. Thus, our data strengthen the notion that transmembrane domains are involved in erbB receptor activation, and that these receptors can be modulated by inhibiting protein-protein interactions within the membrane.

Análise de pontos críticos de controle em certas preparações servidas em quiosques de praia / Control critics points analysis in certain preparations served in beach bars

O Ministério da Saúde define Enfermidade Transmitidas por Alimentos (ETAs) como “doenças causadas pela ingestão de alimento contaminado por um agente infeccioso específico ou pela toxina por ele produzida por meio da transmissão desse agente, ou de seu produto tóxico”. Uma das formas de controlar a ocorrência de tais enfermidades é utilizar o sistema APPCC, um método que analisa e aponta os pontos críticos de controle dos processos onde o perigo microbiológico pode aparecer. O presente estudo teve como objetivo analisar os pontos críticos de controle das preparações mais consumidas em quiosques de praia e avaliar as condições higiênicas, ambiental e de manipuladores, assim como a estrutura física dos estabelecimentos visitados. Para isso foi aplicado o sistema APPCC em três quiosques de praia na cidade de Peruíbe (SP), avaliando os pontos críticos de controle, desde o recebimento da matéria prima até o produto final. Foram escolhidos os critérios de tempo e temperatura como parâmetros por serem os mais relevantes na prevenção de toxinfecções das preparações mais consumidas. Os resultados revelaram que isca de peixe e camarão frito são as preparações mais consumidas nos quiosques visitados. O transporte e o armazenamento foram os principais pontos críticos onde os critérios de tempo e temperatura não foram atingidos, representando um risco de ocorrência de ETAs. A avaliação da higiene de manipuladores revelou a falta do uso de uniformes. Quanto à área física, observou-se que as construções mais recentes estão mais adequadas à legislação vigente, embora tenha sido constatada a ausência de lavatórios para as mãos. Conclui-se que a aplicação do sistema APPCC é uma forma viável de reduzir os riscos de ETAs em quiosques de praia.

Comparison of the activity spectra against pathogens of bacterial strains producing a mutacin or a lantibiotic.

The increase of drug resistance among bacterial pathogens is currently a major threat in hospital settings. New and more efficient antibiotic compounds have to be developed to fight infectious diseases. In the present work, a deferred antagonism test was used to determine the activity of different bacterial strains producing either a mutacin or a lantibiotic against bacterial pathogens. The mutacins A, B, C, D, I, K, L, M, and nisins A and Z were active against all enterococci tested. Mutacins A and B, and nisins A and Z inhibited all the staphylococci tested. Except for the strains producing mutacins P, Q, and X, all the other producing strains inhibited the streptococci tested. Mutacins A, B, I, J, T, nisins A and Z, and epidermin inhibited the two antibiotic-resistant strains of Neisseria gonorrhoeae tested. Mutacins A, B, C, D, and nisins A and Z inhibited Campylobacter jejuni and Helicobacter pylori. Thus, the wide activity spectra of nisin A and Z are confirmed. These results also indicate that many of the mutacins, especially those of groups A, B, C, D, I, J, K, L, M, and T, could be candidates for further development as useful antibiotics.

MICs of mutacin B-Ny266, nisin A, vancomycin, and oxacillin against bacterial pathogens.

Peptide antibiotics, particularly lantibiotics, are good candidates for replacing antibiotics to which bacteria have become resistant. In order to compare two such lantibiotics with two antibiotics, the MICs of nisin A, mutacin B-Ny266, vancomycin, and oxacillin against various bacterial pathogens were determined. The results indicate that nisin A and mutacin B-Ny266 are as active as vancomycin and oxacillin against most of the strains tested. Furthermore, mutacin B-Ny266 remains active against strains that are resistant to nisin A, oxacillin, or vancomycin. The wide spectrum of activity of mutacin B-Ny266, its low MICs against bacterial pathogens, and its activity against bacteria resistant to other inhibitors support the development of this substance for therapeutic use.

Purification and structure of mutacin B-Ny266: a new lantibiotic produced by Streptococcus mutans.

Mutacins are bactericidal substances of proteinaceous nature produced by Streptococcus mutans. Lantibiotics are antibacterial substances containing post-translationally modified amino acids such as lanthionine. Mutacin B-Ny266 was purified from the cell pellet of S. mutans strain Ny266 by ethanol extraction at pH 2.0 followed by reversed-phase chromatography (Sep-Pak cartridge) and by HPLC on a C18 column. The mean purification factor was 3240 +/- 81 and the mean yield was 1.0 +/- 0.1%. Molecular mass of mutacin B-Ny266 as determined by mass spectroscopy is 2270.29 +/- 0.21 Da. The amino acid sequence of the purified active fraction was obtained by Edman degradation after treatment with alkaline ethanethiol. Twenty-one amino acids were detected in this analysis. Mutacin B-Ny266 belongs to the type A lantibiotics. The proposed sequence is: F-K-A-W-U-F-A-Abu-P-G-A-A-K-O-G-A-F-N-U-Y-A. The molecule differs from that of epidermin/staphylococcin 1580 and gallidermin at positions 1, 2, 4, 5 and 6.