Prenatal LPS induces sickness behaviour and decreases maternal and predatory behaviours after an LPS challenge.

Purpose: The influence of a challenge dose of lipopolysaccharide (LPS) on the behavioural selection between maternal (MB) and predatory behaviours (PB) of female rats prenatally treated with the same endotoxin or saline solution (F1 generation) were studied.Material and methods: Thus, in adult age, these female rats were mated and, at lactation days 5 or 6, the following groups were formed: (1) LPS + LPS group-female rats prenatally treated with LPS and received an LPS challenge dose; (2) S + LPS group-female rats prenatally treated with saline solution and received a challenge LPS dose (3) S + S group-females rats prenatally treated with saline which received a saline injection. MB, PB to cockroaches, exploratory behaviour, periaqueductal grey (PAG) expression of the astrocytic biomarker glial fibrillary acidic protein (GFAP), and corticosterone and TNF-alpha serum levels were evaluated.Results: Showed that: (1) relative to the S + S group, the LPS + S group showed decreased MB and slightly increased PB, without inducing sickness behaviour; (2) the LPS + LPS group showed decreased MB but few effects on PB; (3) there was increased sickness behaviour associated with increased TNF-alpha serum levels in the LPS + LPS group; (4) a significant increase in GFAP expression was observed in both LPS groups, which was greater in the LPS + LPS group and (5) no differences in the corticosterone of all groups.Conclusions: Prenatal LPS impaired the switch from MB to PB in female rats of the LPS + LPS group by increased sickness behaviour as well as an increase in plasmatic TNF-alpha levels inducing PAG astrogliosis.

Histopathological Findings in the Viscera of Malformed Neotropical Viperids.

Congenital malformations (CMs) or developmental abnormalities are pathological processes defined as morphological defects that originate during embryonic stages. A wide variety of CMs is observed in reptiles, most of which are incompatible with normal life. Characterization of CMs and their pathogenesis are of great importance for the conservation of reptiles, including neotropical viperids (NVs). External CMs are often reported in these species, but little is known about concomitant microscopical findings in the viscera of malformed individuals. In order to partially fill in this gap in knowledge, we aimed to investigate and characterize histopathological findings in the viscera of malformed NVs, jararacas (Bothrops jararaca) and South American rattlesnakes (Crotalus durissus), correlating these findings with features of external CMs. From 78 malformed snakes analysed, 100% (19/19) of rattlesnakes and 98.3% (58/59) of jararacas had histopathological changes in the viscera. Liver and/or kidney fatty degeneration was the most common finding in malformed and control animals. Renal glomerulocystic and tubular disease was significantly correlated with brachygnathia (P < 0.05) in jararacas. These results add to the body of knowledge of snake pathology and demonstrate some associations between external CMs and visceral histopathological findings, some of which could have implications for individual survival.

Histopathological findings in the viscera of malformed neotropical viperids

Congenital malformations (CMs) or developmental abnormalities are pathological processes defined as morphological defects that originate during embryonic stages. A wide variety of CMs is observed in reptiles, most of which are incompatible with normal life. Characterization of CMs and their pathogenesis are of great importance for the conservation of reptiles, including neotropical viperids (NVs). External CMs are often reported in these species, but little is known about concomitant microscopical findings in the viscera of malformed individuals. In order to partially fill in this gap in knowledge, we aimed to investigate and characterize histopathological findings in the viscera of malformed NVs, jararacas (Bothrops jararaca) and South American rattlesnakes (Crotalus durissus), correlating these findings with features of external CMs. From 78 malformed snakes analysed, 100% (19/19) of rattlesnakes and 98.3% (58/59) of jararacas had histopathological changes in the viscera. Liver and/or kidney fatty degeneration was the most common finding in malformed and control animals. Renal glomerulocystic and tubular disease was significantly correlated with brachygnathia (P < 0.05) in jararacas. These results add to the body of knowledge of snake pathology and demonstrate some associations between external CMs and visceral histopathological findings, some of which could have implications for individual survival.

Histopathological findings in the viscera of malformed neotropical viperids

Congenital malformations (CMs) or developmental abnormalities are pathological processes defined as morphological defects that originate during embryonic stages. A wide variety of CMs is observed in reptiles, most of which are incompatible with normal life. Characterization of CMs and their pathogenesis are of great importance for the conservation of reptiles, including neotropical viperids (NVs). External CMs are often reported in these species, but little is known about concomitant microscopical findings in the viscera of malformed individuals. In order to partially fill in this gap in knowledge, we aimed to investigate and characterize histopathological findings in the viscera of malformed NVs, jararacas (Bothrops jararaca) and South American rattlesnakes (Crotalus durissus), correlating these findings with features of external CMs. From 78 malformed snakes analysed, 100% (19/19) of rattlesnakes and 98.3% (58/59) of jararacas had histopathological changes in the viscera. Liver and/or kidney fatty degeneration was the most common finding in malformed and control animals. Renal glomerulocystic and tubular disease was significantly correlated with brachygnathia (P < 0.05) in jararacas. These results add to the body of knowledge of snake pathology and demonstrate some associations between external CMs and visceral histopathological findings, some of which could have implications for individual survival.

Topical Osmoprotectant for the Management of Postrefractive Surgery-Induced Dry Eye Symptoms: A Randomised Controlled Double-Blind Trial.

BACKGROUND: Dry eye disease (DED) is one of the most common complications following refractive surgery. PURPOSE: Evaluate the efficacy of an osmoprotective eye drop (Optive®) for the management of induced DED in refractive surgery patients. DESIGN: Double-masked randomised controlled trial. METHODS: Twenty-two refractive surgery patients oriented to apply FreshTears (FT; n = 13) or Optive (Op; n = 9), topically, QID, for 3 months. Eye exams were performed before surgery (T0) and 1-month (T1) and 3-month (T3) follow-up and consisted of tear film osmolarity, Schirmer 1 test, tear film breakup time (TBUT), fluorescein staining, and ocular surface disease index (OSDI) and patient symptoms questionnaires. MAIN OUTCOME MEASURES: Pain and osmolarity. RESULTS: Pain increased significantly for FT at T3 (p < 0.05). A reduction in osmolarity was observed at T1 and T3 for Op group (p < 0.01) and at T3 for FT group (p < 0.05). TBUT showed a decrease between T0 and T1 for FT (p < 0.05). Schirmer 1 values increased significantly for Op in T1. CONCLUSIONS: Op was superior to FT in regard to pain, osmolarity, TBUT, and Schirmer 1. Osmoprotectant solutes, such as L-carnitine, could attenuate inflammation and secondary DED. Osmoprotective lubricants can be effectively applied for the prevention of refractive surgery-related dry eye symptoms and signs.

The use of reduced glutathione (GSH) as antioxidant for cryopreserved sperm in dogs / O uso da glutationa reduzida (GSH) como antioxidante na criopreservação seminal em cães

The aim of this study was to evaluate the effect of supplementation with different concentrations of reduced glutathione GSH (0; 5; 7.5; 10mM) in the extender for cryopreservation in dogs with evaluations performed after glycerolization (chilled) and thawing (thawed). For this purpose, we used 8 dogs and two semen collections were performed in a weekly interval, totaling 16 semen samples. The sperm were analyzed by automatic sperm motility (CASA) and flow cytometry analysis of mitochondrial potential (JC1 dye) and membrane/acrosome integrity (FITC-PI dyes). We evaluated subjectively the membrane and acrosome integrity, mitochondrial activity and DNA integrity. Seminal plasma was evaluated for lipid peroxidation (TBARS concentration). Chilled and thawed samples supplemented with 7.5 and 10mM of GSH had lower percentage of sperm with high (DAB - Class I) and medium (DAB - Class II) mitochondrial activity. And 10mM of GSH had higher percentage of low mitochondrial activity (DAB - Class III). Moreover, thawed samples of 10mM of GSH had high DNA fragmentation rates. Probably by a reductive stress effect on mitochondria which lead to an increase in reactive oxygen species, and a mitochondrial malfunction.(AU)

O objetivo deste estudo foi avaliar o efeito da suplementação com diferentes concentrações de glutationa reduzida (GSH - 0; 5; 7,5; 10mM) para criopreservação em cães com avaliações realizadas após glicerolização (refrigeração) e descongelação. Para tal, foram utilizados oito cães e foram realizadas duas coletas de sêmen em intervalo semanal, totalizando 16 amostras de sêmen. Foram avaliadas a motilidade espermática computadorizada (CASA) e a análise de citometria de fluxo do potencial mitocondrial (sonda JC-1) e integridade da membrana/acrossomal (sonda FITC-PI). Subjetivamente foi avaliada a integridade da membrana plasmática e do acrossomal, atividade mitocondrial e integridade do DNA. O plasma seminal foi avaliado quanto à peroxidação lipídica (concentração de TBARS). As amostras refrigeradas e descongeladas suplementadas com 7,5 e 10mM de GSH apresentaram menor porcentagem de espermatozoides com alta atividade mitocondrial (DAB - Classe I) e média (DAB - Classe II). Na concentração de 10mM de GSH, apresentaram maior porcentagem de baixa atividade mitocondrial (DAB - Classe III). Além disso, amostras descongeladas de 10mM de GSH apresentaram taxas de fragmentação de DNA elevadas, provavelmente por efeito de estresse redutivo sobre as mitocôndrias que elevam as espécies reativas de oxigênio e disfunção mitocondrial.(AU)

Hypercaloric diet prevents sexual impairment induced by maternal food restriction.

Prenatal undernutrition impairs copulatory behavior and increases the tendency to become obese/overweight, which also reduces sexual behavior. Re-feeding rats prenatally undernourished with a normocaloric diet can restore their physiological conditions and copulatory behavior. Thus, the present study investigated whether a hypercaloric diet that is administered in rats during the juvenile period prevents sexual impairments that are caused by maternal food restriction and the tendency to become overweight/obese. Female rats were prenatally fed a 40% restricted diet from gestational day 2 to 18. The pups received a hypercaloric diet from postnatal day (PND) 23 to PND65 (food restricted hypercaloric [FRH] group) or laboratory chow (food restricted control [FRC] group). Pups from non-food-restricted dams received laboratory chow during the entire experiment (non-food-restricted [NFR] group). During the juvenile period and adulthood, body weight gain was evaluated weekly. The day of balanopreputial separation, sexual behavior, sexual organ weight, hypodermal adiposity, striatal dopamine and serotonin, serum testosterone, and tumor necrosis factor α (TNF-α) were evaluated. The FRH group exhibited an increase in body weight on PND58 and PND65. The FRC group exhibited an increase in the latency to the first mount and intromission and an increase in serum TNF-α levels but a reduction of dopaminergic activity. The hypercaloric diet reversed all of these effects but increased adiposity. We concluded that the hypercaloric diet administered during the juvenile period attenuated reproductive impairments that were induced by maternal food restriction through increases in the energy expenditure but not the tendency to become overweight/obese.

Disruption of prion protein-HOP engagement impairs glioblastoma growth and cognitive decline and improves overall survival.

Glioblastomas (GBMs) are resistant to current therapy protocols and identification of molecules that target these tumors is crucial. Interaction of secreted heat-shock protein 70 (Hsp70)-Hsp90-organizing protein (HOP) with cellular prion protein (PrP(C)) triggers a large number of trophic effects in the nervous system. We found that both PrP(C) and HOP are highly expressed in human GBM samples relative to non-tumoral tissue or astrocytoma grades I-III. High levels of PrP(C) and HOP were associated with greater GBM proliferation and lower patient survival. HOP-PrP(C) binding increased GBM proliferation in vitro via phosphatidylinositide 3-kinase and extracellular-signal-regulated kinase pathways, and a HOP peptide mimicking the PrP(C) binding site (HOP230-245) abrogates this effect. PrP(C) knockdown impaired tumor growth and increased survival of mice with tumors. In mice, intratumor delivery of HOP230-245 peptide impaired proliferation and promoted apoptosis of GBM cells. In addition, treatment with HOP230-245 peptide inhibited tumor growth, maintained cognitive performance and improved survival. Thus, together, the present results indicate that interfering with PrP(C)-HOP engagement is a promising approach for GBM therapy.