Fábio Teixeira Kuhn

Influence of trans fat and omega-3 on the preference of psychostimulant drugs in the first generation of young rats

The current Western diet often provides considerable amounts of saturated and trans fatty acids (TFA), whose incorporation into neuronal membranes has been implicated in changes of brain neurochemical functions. Such influence has caused concerns due to precipitation of neuropsychiatric disorders, whose data are still unclear. Here we evaluated the influence of different fats on preference parameters for amphetamine (AMPH): adolescent rats were orally supplemented with soybean oil (SO, rich in n-6 FA, which was considered an isocaloric control group), fish oil (FO, rich in n-3 FA) and hydrogenated vegetable fat (HVF, rich in saturated and trans FA) from weaning, which were born of dams supplemented with the same fat from pregnancy and lactation. AMPH preference, anxiety-like symptoms and locomotor index were evaluated in conditioned place preference (CPP), elevated plus maze (EPM) and open-field (OF), respectively, while brain oxidative status was determined in cortex, striatum and hippocampus. HVF increased AMPH-CPP and was associated with withdrawal signs, as observed by increased anxiety-like symptoms. Moreover, SO and FO were not associated with AMPH preference, but only FO-supplemented rats did not show any anxiety-like symptoms or increased locomotion. FO supplementation was related to lower oxidative damages to proteins and increased CAT activity in striatum and hippocampus, as well as increased GSH levels in blood, while HVF was related to increased oxidative status. In conclusion, our study showed the harmful influence of TFA on AMPH-CPP and drug craving symptoms, which can be related to dopaminergic neurotransmission.

Cross-generational trans fat intake modifies BDNF mRNA in the hippocampus: Impact on memory loss in a mania animal model.

Recently, we have described the influence of dietary fatty acids (FA) on mania‐like behavior of first generation animals. Here, two sequential generations of female rats were supplemented with soybean oil (SO, rich in n‐6 FA, control group), fish oil (FO, rich in n‐3 FA) and hydrogenated vegetable fat (HVF, rich in trans FA) from pregnancy and during lactation. In adulthood, half of each group was exposed to an amphetamine (AMPH)‐induced mania animal model for behavioral, biochemical and molecular assessments. FO supplementation was associated with lower reactive species (RS) generation and protein carbonyl (PC) levels and increased dopamine transporter (DAT) levels, while HVF increased RS and PC levels, thus decreasing catalase (CAT) activity and DAT levels in hippocampus after AMPH treatment. AMPH impaired short‐ (1 h) and long‐ (24 h) term memory in the HVF group. AMPH exposure was able to reduce hippocampal BDNF‐ mRNA expression, which was increased in FO. While HVF was related to higher trans FA (TFA) incorporation in hippocampus, FO was associated with increased percentage of n‐3 polyunsaturated FA (PUFA) together with lower n‐6/n‐3 PUFA ratio. Interestingly, our data showed a positive correlation between brain‐derived neurotrophic factor (BDNF) mRNA and short‐ and long‐term memory (r2 = 0.53; P = 0.000/r2 = 0.32; P = 0.011, respectively), as well as a negative correlation between PC and DAT levels (r2 = 0.23; P = 0.015). Our findings confirm that provision of n‐3 or TFA during development over two generations is able to change the neuronal membrane lipid composition, protecting or impairing the hippocampus, respectively, thus affecting neurothrophic factor expression such as BDNF mRNA. In this context, chronic consumption of trans fats over two generations can facilitate the development of mania‐like behavior, so leading to memory impairment and emotionality, which are related to neuropsychiatric conditions.

Toxicological aspects of trans fat consumption over two sequential generations of rats: Oxidative damage and preference for amphetamine

Chronic consumption of processed food causes structural changes in membrane phospholipids, affecting brain neurotransmission. Here we evaluated noxious influences of dietary fats over two generations of rats on amphetamine (AMPH)-conditioned place preference (CPP). Female rats received soybean oil (SO, rich in n-6 fatty acids (FA)), fish oil (FO, rich in n-3 FA) and hydrogenated vegetable fat (HVF, rich in trans fatty acids (TFA)) for two successive generations. Male pups from the 2nd generation were maintained on the same supplementation until 41 days of age, when they were conditioned with AMPH in CPP. While the FO group showed higher incorporation of n-3 polyunsaturated-FA (PUFA) in cortex/hippocampus, the HVF group showed TFA incorporation in these same brain areas. The SO and HVF groups showed AMPH-preference and anxiety-like symptoms during abstinence. Higher levels of protein carbonyl (PC) and lower levels of non-protein thiols (NPSH) were observed in cortex/hippocampus of the HVF group, indicating antioxidant defense system impairment. In contrast, the FO group showed no drug-preference and lower PC levels in cortex. Cortical PC was positively correlated with n-6/n-3 PUFA ratio, locomotion and anxiety-like behavior, and hippocampal PC was positively correlated with AMPH-preference, reinforcing connections between oxidative damage and AMPH-induced preference/abstinence behaviors. As brain incorporation of trans and n-6 PUFA modifies its physiological functions, it may facilitate drug addiction.

In vitro evaluation of triazenes: DNA cleavage, antibacterial activity and cytotoxicity against acute myeloid leukemia cells

). The observation of intermolecular hydrogen bonding in the solid state of compound 3, based on the structural analysis by X-ray crystallography, as well as the results of IR and UV-Vis spectroscopic analyses of compounds 1, 2 and 3 are discussed in the present work.

Cross-Generational trans Fat Consumption Favors Self-Administration of Amphetamine and Changes Molecular Expressions of BDNF, DAT, and D1/D2 Receptors in the Cortex and Hippocampus of Rats.

Amphetamine (AMPH) is an addictive psychostimulant drug whose use has been related to neurotoxicity. Experimentally, AMPH increases anxiety-like symptoms, showing addictive properties. In the last decades, the growing consumption of processed foods has provided an excess of saturated and trans fats in detriment of essential fatty acids, which may modify the lipid profile of brain membranes, thus modifying its permeability and dopaminergic neurotransmission. Here, we assessed the influence of brain incorporation of different fatty acids (FA) on AMPH self-administration. Three groups of young male rats were orally supplemented from weaning with a mixture of soybean oil (SO, rich in n-6 FA) and fish oil (FO, rich in n-3 FA), hydrogenated vegetable fat (HVF, rich in trans fatty acids—TFA), or water (control group). These animals were born from dams that were supplemented with the same fat from pregnancy to lactation. Anxiety-like symptoms and locomotor index were assessed in elevated plus maze and open-field (OF), respectively, while brain molecular expressions of dopaminergic receptors, dopamine transporter (DAT), and BDNF were determined in the cortex and hippocampus. HVF increased the frequency of AMPH self-administration and was associated with reinforcement and withdrawal signs as observed by increased anxiety-like symptoms. Contrarily, SO/FO decreased these parameters. Increased BDNF protein together with decreased DAT expression was observed in the hippocampus of HVF group. Based on these findings, our study points to a harmful influence of trans fats on drug addiction and craving symptoms, whose mechanism may be related to changes in the dopaminergic neurotransmission.

Influence of neonatal tactile stimulation on amphetamine preference in young rats: parameters of addiction and oxidative stress.

This study investigated the influence of neonatal handling on amphetamine-induced conditioned place preference (CPP), as well as the consequent anxiety-like symptoms and oxidative status related to drug abstinence in young rats. Male pups were exposed to tactile stimulation (TS) or neonatal isolation (NI) for 10 min every day from postnatal day one (PND1) to PND21. After being weaned (PND22), pups were separated by handling type until PND40, when treatment with amphetamine (AMPH-4 mg/kg/mL ip, for 8 days) or vehicle (NaCl 0.9% ip, 1 mL/Kg) in CPP started. AMPH-conditioning evoked drug-preference (in 24h and 96 h) and abstinence symptoms in unhandled (UH) animals, followed by oxidative damage in the cortex, hippocampus and striatum. TS showed beneficial influence, as observed by the decreased drug-preference (24 and 96 h) in relation to UH and NI, showing no abstinence symptoms in this last period, as observed by the reduced anxiety-like symptoms. The oxidative status indicated a protective influence of TS on brain tissues: lower lipid peroxidation (LP) and reduced protein carbonylation (PC) in the cortex, hippocampus and striatum. Furthermore, TS also increased antioxidant defenses in brain tissues and blood: i) increased plasma levels of vitamin C; ii) increased activity of catalase (CAT) and iii) higher levels of glutathione (GSH) in red blood cells (RBC). Moreover, there were positive correlations of AMPH-CPP with PC and LP levels in all the brain areas assessed. In summary, TS modifies AMPH-preference in the CPP paradigm, reducing drug abstinence behaviors, and stimulating the antioxidant defense system, thus protecting the brain areas closely related to addiction in young rats. Studies about TS and addiction in animal models should be extended to the molecular level.

Tactile stimulation and neonatal isolation affect behavior and oxidative status linked to cocaine administration in young rats

We investigated the influence of neonatal handling on cocaine-induced conditioned place preference (CPP), anxiety-like symptoms and oxidative status related to drug abstinence in young rats. Pups were submitted to tactile stimulation (TS) or neonatal isolation (NI10 or NI60) after birth, and then were submitted to CPP performed with cocaine. TS group did not show place preference, while unhandled (UH), NI10 and NI60 rats did. Handling was related to anxiety-like symptoms per se in UH and NI60 groups and this behavior was also observed in the cocaine-conditioned rats exposed to the same handlings. Both TS and NI10 pups treated or not with cocaine showed less anxiety-like behavior than animals submitted to other handlings. TS reduced protein carbonyl (PC) in cortex and NI60 increased PC in both striatum and hippocampus of cocaine-treated rats. Among cocaine-treated rats, both times of NI increased plasma lipoperoxidation levels, which was reduced by TS in erythrocytes. TS increased the catalase activity in brain areas, while other handlings did not change this. Both TS and NI10 increased plasma vitamin C levels. These findings indicate that neonatal handling can modify anxiety-like symptoms related to cocaine preference and abstinence, and its protective influence, especially TS, on the antioxidant system.

PREVALÊNCIA E PERFIL DE SENSIBILIDADE DE Staphylococcus aureus ISOLADOS EM UM HOSPITAL ESCOLA NA CIDADE DE SANTA MARIA, BRASIL

Objetivou-se caracterizar a prevalencia e o perfil de suscetibilidade de Staphylococcus aureus isolados no Hospital Universitario de Santa Maria (HUSM), atraves de levantamento de dados junto ao Laboratorio de Analises Clinicas, durante o periodo de abril a junho de 2009. Foram solicitadas 3270 culturas, sendo que 1123 (34%) resultaram positivas. A prevalencia de S. aureus em relacao as culturas positivas foi de 89 (7,93%). Verificou-se que 33% das cepas foram resistentes a oxacilina e que 34,45% apresentaram resistencia relacionada ao gene erm. Elevada sensibilidade ao sulfametoxazol-trimetoprima (72/80%) foi evidenciada pela automacao e nenhuma cepa mostrou-se resistente a vancomicina. Portanto, a prevalencia de S. aureus no HUSM e a resistencia a oxacilina foram inferiores ao observado em outros hospitais terciarios brasileiros. The objective ofthis study was to characterize the prevalence and susceptibility prof ile ofStaphylococcus aureus isolates at University Hospital ofSantaMaria, through data collection at the Laboratory ofClinicalAnalysis, duringApril to June 2009. Were requested 3270 cultures and 1123 (34%) were positive. The prevalence of S. aureus in relation to positive cultures was 89 (7,93%). It was f ound that these strains, 33% were resistant to oxacillin and 34.45% showed resistance related erm gene. High sensitivity to trimethoprim-sulf amethoxazole (72/80%) was detected f or the automation and no strain showed resistance to vancomycin. Theref ore, the prevalence of S. aureus and oxacillin resistance at HUSM were lower than observed in other tertiary hospitals in Brazil. Descritors: Prevalence; Staphylococcus aureus; Bacterial inf ection, Oxacillin.

Influence of Trans Fat on Skin Damage in First-Generation Rats Exposed to UV Radiation

The influence of trans fatty acids (TFA) on lipid profile, oxidative damage and mitochondrial function in the skin of rats exposed to ultraviolet radiation (UVR) was assessed. The first‐generation offspring of female Wistar rats supplemented from pregnancy with either soybean oil (C‐SO, rich in n–6 FA; control group) or hydrogenated vegetable fat (HVF, rich in TFA) were continued with the same supplements until adulthood, when half of each group was exposed to UVR for 12 weeks. The HVF group showed higher TFA cutaneous incorporation, increased protein carbonyl (PC) levels, decreased functionality of mitochondrial enzymes and antioxidant defenses of the skin. After UVR, the HVF group showed increased skin thickness and reactive species (RS) generation, with decreased skin antioxidant defenses. RS generation was positively correlated with skin thickness, wrinkles and PC levels. Once incorporated to skin, TFA make it more susceptible to developing UVR‐induced disorders.

Contaminação bacteriana em concentrados plaquetários: identificação, perfil de sensibilidade aos antimicrobianos e sepse associada à transfusão

INTRODUCTION Bacterial sepsis associated with the transfusion of platelet concentrates (PCs) results in serious clinical implications for patients. Given these implications, certain procedures have been integrated into the preparation and quality control of blood components to reduce the risk of bacterial contamination. This article describes the prevalence of bacterial contamination on transfused PCs, the bacterial spectrum detected and their antimicrobial susceptibility profile and transfusion reactions in receptors. METHODS A total of 292 PCs (278 random and 14 per apheresis) from the Blood Center of the State of Rio Grande do Sul (HEMORGS), located in the city of Santa Maria, were tested. Quantities of 100 μL and 200 μL were collected from platelet bag tubing and seeded using two methodologies. RESULTS Using the qualitative methodology, bacteria were isolated in five units (1.7%; 5/292), while only one was isolated using the quantitative methodology. Staphylococcus epidermidis was the microorganism identified in all samples. Two patients died of transfusion-related sepsis. CONCLUSIONS Bacterial contamination due to PC transfusion is considered a major public health problem due to its association with high rates of morbidity and mortality. In this study only gram-positive microorganisms were isolated and none of the samples obtained by apheresis presented contamination.