Moxidectin interference on sexual behavior, penile erection and hypothalamic GABA levels of male rats

The moxidectin (MXD) is an antiparasitic drug used in domestic animals. The mechanism of action, in mammals, involves GABA, a neurotransmitter with an important role in the sexual behavior control. Presently, the effects of 0.2 mg/kg therapeutic dose were studied on sexual behavior, sexual motivation, penile erection and central GABA levels. Sexual behavior results showed increased latencies to the first mount and intromission as well as in inter-intromission interval; a reduction in total mounts was detected on the drug post-treatment. No difference was observed between sexual motivation of control and experimental animals. MXD treatment reduced penile erection and hypothalamic GABA levels. The results suggest that MXD reduced sexual behavior and penile erection by an action on the hypothalamic GABA system. Probably, the lack of effects in the motivational test and the increased mount and intromission latencies as well as decreased total mounts could be explained as a consequence of reduced male rat erection process. (C) 2007 Elsevier Ltd. All rights reserved.

In Vitro and In Vivo Antiplasmodial Activities of Risedronate and Its Interference with Protein Prenylation in Plasmodium falciparum

The increasing resistance of malarial parasites to almost all available drugs calls for the identification of new compounds and the detection of novel targets. Here, we establish the antimalarial activities of risedronate, one of the most potent bisphosphonates clinically used to treat bone resorption diseases, against blood stages of Plasmodium falciparum (50% inhibitory concentration [IC(50)] of 20.3 +/- 1.0 mu M). We also suggest a mechanism of action for risedronate against the intraerythrocytic stage of P. falciparum and show that protein prenylation seems to be modulated directly by this drug. Risedronate inhibits the transfer of the farnesyl pyrophosphate group to parasite proteins, an effect not observed for the transfer of geranylgeranyl pyrophosphate. Our in vivo experiments further demonstrate that risedronate leads to an 88.9% inhibition of the rodent parasite Plasmodium berghei in mice on the seventh day of treatment; however, risedronate treatment did not result in a general increase of survival rates.

Nd:YAG laser irradiation effect on apical intracanal dentin - a microleakage and SEM evaluation

The purpose of this in vitro study was to evaluate the effect of neodymium:yttrium-aluminum-garnet (Nd:YAG) laser irradiation on intracanal dentin surface by SEM analysis and its interference in the apical seal of filled canals. After endodontic treatment procedures, 34 maxillary human incisors were randomly assigned to 2 groups. In the negative control group (n=17), no additional treatment was performed and teeth were filled with vertically condensed gutta-percha; in the laser-treated group (n=17), the root canals were irradiated with Nd:YAG laser (1.5 W, 100 mJ, 15 Hz) before filling as described for the control group. Two specimens of each group were prepared for SEM analysis to evaluate the presence and extent of morphological changes and removal of debris; the other specimens were immersed in 0.5% methylene blue dye (pH 7.2) for 24 h for evaluation of the linear dye leakage at the apical third. SEM analysis of the laser-treated group showed dentin fusion and resolidification without smear layer or debris. The Student’s t-test showed that the laser-treated group had significantly less leakage in apical third than the control group. Within the limitations of this study, it may be concluded that the morphological changes on the apical intraradicular dentin surface caused by Nd:YAG laser resulted in less linear dye apical leakage.

Timing and sequence of primary tooth eruption in children with cleft lip and palate

OBJECTIVE: To determine the timing and sequence of eruption of primary teeth in children with complete bilateral cleft lip and palate. MATERIAL AND METHODS: This cross-sectional study was conducted at the Hospital for Rehabilitation of Craniofacial Anomalies of the University of São Paulo, Bauru, SP, Brazil, with a sample of 395 children (128 girls and 267 boys) aged 0 to 48 months, with complete bilateral cleft lip and palate. RESULTS: Children with complete bilateral clefts presented a higher mean age of eruption of all primary teeth for both arches and both genders, compared to children without clefts. This difference was statistically signifcant for all teeth, except for the maxillary first molar. Mean age of eruption of most teeth was lower for girls compared to boys. The greatest delay was found for the maxillary lateral incisor, which was the eighth tooth of children with clefts of both genders. Analyzing by gender, the maxillary lateral incisor was the eighth tooth to erupt in girls and the last in boys. CONCLUSION: The results suggest an interference of the cleft on the timing and sequence of eruption of primary teeth.

Benign focal seizures of adolescence and neuropsychological findings in patients from community

RATIONALE: Benign focal seizures of adolescence (BFSA) described by Loiseau et al in 1972, is considered a rare entity, but maybe underdiagnosed. Although mild neuropsychological deficits have been reported in patients with benign epilepsies of childhood, these evaluations have not so far been described in BFSA. The aim of this study is to evaluate neuropsychological functions in BFSA with new onset seizures (<12 months). METHODS: Eight patients with BFSA (according to Loiseau et al, 1972, focal or secondarily tonic clonic generalized seizures between the ages of 10-18 yrs., normal neurologic examination, normal EEG or with mild focal abnormalities) initiated in the last 12 months were studied between July 2008 to May 2009. They were referred from the Pediatric Emergency Section of the Hospital Universitário of the University of Sao Paulo, a secondary care regionalized facility located in a district of middle-low income in Sao Paulo city, Brazil. The study was approved by the Ethics Committee of the Institution. All patients performed neurological, EEG, brain CT and neuropsychological evaluation which consisted of Raven's Special Progressive Matrices - General and Special Scale (according to different ages), Wechsler Children Intelligence Scale-WISC III with ACID Profile, Trail Making Test A/B, Stroop Test, Bender Visuo-Motor Test, Rey Complex Figure, Rey Auditory Verbal Learning Test-RAVLT, Boston Naming Test, Fluency Verbal for phonological and also conceptual patterns - FAS/Animals and Hooper Visual Organization Test. For academic achievement, we used a Brazilian test for named "Teste do Desempenho Escolar", which evaluates abilities to read, write and calculate according to school grade. RESULTS: There were 2 boys and 6 girls, with ages ranging from 10 yrs. 9 m to 14 yrs. 3 m. Most (7/8) of the patients presented one to two seizures and only three of them received antiepileptic drugs (AEDs). Six had mild EEG focal abnormalities and all had normal brain CT. All were literate, attended regular public schools and scored in a median range for IQ, and seven showed discrete higher scores for the verbal subtests. There were low scores for attention in different modalities in six patients, mainly in alternated attention as well as inhibitory subtests (Stroop test and Trail Making Test part B). Four of the latter cases who showed impairment both in alternated and inhibitory attention were not taking AEDs. Visual memory was impaired in five patients (Rey Complex Figure). Executive functions analysis showed deficits in working memory in five, mostly observed in Digits Indirect Order and Arithmetic tests (WISC III). Reading and writing skills were below the expected average for school grade in six patients according to the achievement scholar performance test utilized. One patient of this series who had the best scores in all tests was taking phenobarbital. CONCLUSIONS: Neuropsychological imbalance between normal IQ and mild dysfunctions such as in attention domain and in some executive abilities like working memory and planning, as well as difficulties in visual memory and in reading and writing, were described in this group of patients with BFSA from community. This may reflect mild higher level neurological dysfunctions in adolescence idiopathic focal seizures probably caused by an underlying dysmaturative epileptogenic process. Although academic problems often have multiple causes, a specific educational approach may be necessary in these adolescents, in order to improve their scholastic achievements, helping in this way, to decrease the stigma associated to epileptic seizures in the community.

Memória de reconhecimento social em ratos

O paradigma intruso-residente vem sendo intensamente empregado em estudos para avaliar a memória de reconhecimento social em roedores. Tipicamente, ratos adultos (residentes) são expostos a dois encontros de 5 minutos cada com um mesmo intruso juvenil ou com juvenis diferentes; o intervalo entre encontros é usualmente 30 minutos. A quantidade de comportamentos sociais do residente, no segundo encontro, em relação a um intruso familiar é substancialmente menor do que o observado no primeiro encontro, o que não ocorre quando o segundo encontro envolve um juvenil novo; esse resultado caracteriza memória de reconhecimento social. Neste estudo discutimos achados recentes sobre os tipos de comportamentos usualmente incluídos nas categorias social e não-social, a influência da fase temporal, a interferência de rotinas laboratoriais na memória de reconhecimento social, modalidades sensoriais usualmente empregadas por roedores no processamento de informações na memória social e alternativas adicionais para o estudo da socialidade em roedores.

5-HT1A autoreceptor modulation of locomotor activity induced by nitric oxide in the rat dorsal raphe nucleus

The dorsal raphe nucleus (DRN) is the origin of ascending serotonergic projections and is considered to be an important component of the brain circuit that mediates anxiety- and depression-related behaviors. A large fraction of DRN serotonin-positive neurons contain nitric oxide (NO). Disruption of NO-mediated neurotransmission in the DRN by NO synthase inhibitors produces anxiolytic- and antidepressant-like effects in rats and also induces nonspecific interference with locomotor activity. We investigated the involvement of the 5-HT1A autoreceptor in the locomotor effects induced by NO in the DRN of male Wistar rats (280-310 g, N = 9-10 per group). The NO donor 3-morpholinosylnomine hydrochloride (SIN-1, 150, and 300 nmol) and the NO scavenger S-3-carboxy-4-hydroxyphenylglycine (carboxy-PTIO, 0.1-3.0 nmol) were injected into the DRN of rats immediately before they were exposed to the open field for 10 min. To evaluate the involvement of the 5-HT1A receptor and the N-methyl-D-aspartate (NMDA) glutamate receptor in the locomotor effects of NO, animals were pretreated with the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT, 8 nmol), the 5-HT1A receptor antagonist N-(2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl)-N-2-pyridinyl-cyclohexanecarboxamide maleate (WAY-100635, 0.37 nmol), and the NMDA receptor antagonist DL-2-amino-7-phosphonoheptanoic acid (AP7, 1 nmol), followed by microinjection of SIN-1 into the DRN. SIN-1 increased the distance traveled (mean ± SEM) in the open-field test (4431 ± 306.1 cm; F7,63 = 2.44, P = 0.028) and this effect was blocked by previous 8-OH-DPAT (2885 ± 490.4 cm) or AP7 (3335 ± 283.5 cm) administration (P < 0.05, Duncan test). These results indicate that 5-HT1A receptor activation and/or facilitation of glutamate neurotransmission can modulate the locomotor effects induced by NO in the DRN.

Biological activity of metal-edds (ethylenediaminedisuccinate) complexes in K562 and PBMC cells

The effect of S,S-ethylenediaminedisuccinic acid (edds) on the quenching of metal-catalyzed (metal = Mn, Fe, Co, Ni, Cu, Zn) oxidation of ascorbic acid was tested in vitro via oxidation of the fluorescent probe 1,2,3-dihydrorhodamine dihydrochloride. The pro-oxidant activity of iron was not fully suppressed, even at a four-fold molar excess of the ligand. The effect of serum on the toxicity to peripheral blood mononuclear cells (PBMC) and K562 cells was investigated. The cytotoxic effect of Fe-edds was abrogated in the presence of Trolox or serum proteins. The probable pathways of cell toxicity were investigated through blocking of the monocarboxylate transporters (MCT) in association with cell cycle studies by flow cytometry. Cells treated with metal complexes and alpha-cyano-4-hydroxycinnamic acid, a known MCT inhibitor, showed recovery of viability, suggesting that MCT proteins may be involved in the internalization of metal-edds complexes. The free acid induced cell cycle arrest in G0/G1 (PBMC) and S (K562) phases, suggesting direct DNA damage or interference in DNA replication.

Determination of paracetamol at a graphite-polyurethane composite electrode as an amperometric flow detector

A bare graphite-polyurethane composite was evaluated as an amperometric flow injection detector in the determination of paracetamol (APAP) in pharmaceutical formulations. A linear analytical curve was observed in the 5.00 x 10-5 to 5.00 x 10-3 mol L-1 range with a minimum detectable net concentration of 18.9 µmol L-1 and 180 determinations h-1, after optimization of parameters such as the detection potential, sample loop volume, and carrier solution flow rate. Interference of ascorbic acid was observed, however, it was possible overcome the interference, reaching results that agreed with HPLC within 95% confidence level. These results showed that the graphite-polyurethane composite can be used as an amperometric detector for flow analysis in the determination of APAP.

Determinação de ácido acéttico em amostra de vinagre adulterada com ácido clorídrico - um experimento integrado de titulação potenciométrica e condutométrica

The determination of acetic acid in vinegar adulterated sample using simultaneous potentiometric and condutometric titrations was used as an example of integrated experiment in instrumental analysis. An Excel® spreadsheet, which allows the entry of simultaneous data and the construction of the superimposed experimental curves (condutometric, potentiometric, first and second derivative potentiometric curve and, distribution diagrama of the acetic species as function of pH), was used as powerful tool to discuss the fundamental concepts involved in each technique and choose the best of them to quantify, without mutual interference, H3CCOOH and HCl in vinegar adulterated sample.

Development and validation of a simple and rapid capillary zone electrophoresis method for determination of nnrti nevirapine in pharmaceutical formulations

A simple and fast capillary zone electrophoresis (CZE) method has been developed and validated for quantification of a non-nucleoside reverse transcriptase inhibitor (NNRTI) nevirapine, in pharmaceuticals. The analysis was optimized using 10 mmol L-1 sodium phosphate buffer pH 2.5, +25 kV applied voltage, hydrodynamic injection 0.5 psi for 5 s and direct UV detection at 200 µm. Diazepam (50.0 µg mL-1) was used as internal standard. Under these conditions, nevirapine was analyzed in approximately less than 2.5 min. The analytical curve presented a coefficient of correlation of 0.9994. Limits of detection and quantification were 1.4 µg mL-1 and 4.3 µg mL-1, respectively. Intra- and inter-day precision expressed as relative standard deviations were 1.4% and 1.3%, respectively and the mean recovery was 100.81%. The active pharmaceutical ingredient was subjected to hydrolysis (acid, basic and neutral) and oxidative stress conditions. No interference of degradation products and tablet excipients were observed. This method showed to be rapid, simple, precise, accurate and economical for determination of nevirapine in pharmaceuticals and it is suitable for routine quality control analysis since CE offers benefits in terms of quicker method development and significantly reduced operating costs.

Determinação espectrofotométrica do bromidrato de fenoterol em preparações farmacêuticas

Um método espectrofotométrico simples foi desenvolvido para a determinação do bromidrato de fenoterol (BF) em comprimidos, gotas e xarope, como princípio ativo único e associado ao ibuprofeno. O método se baseia na reação de acoplamento oxidativo do BF com o 3-metil-2-benzotiazolinona hidrazona (MBTH), na presença de sulfato cérico, como agente oxidante. A mistura de BF, MBTH e sulfato cérico, em meio ácido, produz um composto colorido (vermelho castanho) com máximo de absorção a 475 nm. A curva de calibração foi linear num intervalo de concentração de 3,0 a 12,0 µg/mL, com coeficiente de correlação linear de 0,9998. Os parâmetros experimentais que afetam o desenvolvimento e a estabilidade do produto colorido foram cuidadosamente estudados e otimizados. O método foi aplicado em amostras comerciais e simuladas, obtendo-se coeficientes de variação entre 0,25 % a 0,82 % e médias de recuperação do padrão que variaram de 98 % a 102 %. O método proposto mostrou-se exato, preciso, linear e não é passível de interferência de excipientes, para as formas farmacêuticas comprimidos e gotas. Não houve interferência do ibuprofeno que consta de uma das formulações analisadas, associado ao BF. Quanto ao xarope, houve interferência do veículo sugerindo reações de seus componentes com o MBTH.

Efeito de medicamentos indicados para a prevenção da mastite bovina no período seco sobre a função fagocítica in vitro de leucócitos do leite de caprinos

O uso de medicamentos antimamíticos específicos para vacas no período seco é indicado para prevenção de infecções na lactação seguinte. Não obstante, a ação das células envolvidas no período de secagem tem fundamental importância para a involução da glândula mamária e seu restabelecimento para a lactação subseqüente. A indisponibilidade de tais medicamentos para uso em cabras tem resultado na extrapolação do uso de produtos recomendados para vacas sem que se considerem as particularidades e diferenças anátomo-fisiológicas entre as espécies bovina e caprina. O presente estudo teve por objetivo avaliar a influência de cinco antimamíticos específicos para vacas secas sobre a função dos fagócitos provenientes de leite caprino. Para tal, fez-se o isolamento de células somáticas de 20 amostras de leite provenientes de 10 cabras lactantes, sem antecedentes de tratamento de mamite nos últimos 30 dias, sob condições higiênico-sanitárias de colheita e com resultados negativos ao cultivo microbiológico do leite. As células aderidas a lamínulas de vidro foram confrontadas com formulações contendo princípios ativos disponíveis no mercado como Gentamicina (M1), Cefalônio Anidro (M2), Ampicilina (M3), Cloxacilina Benzatínica (M4) e Cefapirina Benzatínica (M5). Avaliou-se, por microscopia, a fagocitose de partículas de Zymosan. As médias dos índices de fagocitose das células submetidas ao tratamento com M2 (15,12% ± 16,22), M3 (6,02% ± 7,96), M4 (4,54% ± 5,45) e M5 (2,47% ± 4,64) foram menores (p<0,001) que a média dos índices de fagocitose do grupo controle (40,67% ± 19,68). A média dos índices de fagocitose das células submetidas ao tratamento com M2 foi maior (p<0,05) que as médias dos tratamentos com M3, M4 e M5 enquanto estas foram estatisticamente iguais entre si. As amostras celulares submetidas ao medicamento M1 exibiram adesão insuficiente ou ausente às lamínulas, inviabilizando a avaliação da fagocitose por meio da técnica utilizada. Os resultados obtidos permitem concluir que os medicamentos estudados exerceram influência negativa sobre os fagócitos do leite, porém, esta interferência sobre as funções das células somáticas não pode por si só determinar o insucesso da terapia proposta para o período seco, pois deve ser considerada, outrossim, a eficácia do princípio ativo sobre o patógeno causador do processo infeccioso.

Digestible lysine and organic zinc for male broiler from 1 to 11 days of age: performance and body composition

This study evaluated levels of digestible lysine and organic zinc for male Ross strain broilers from 1 to 11 days of age. It was used 1,050 chicks distributed in randomized block design, in 5 × 2 factorial scheme, with seven repetitions of 15 birds per experimental unit. The dietary concentrations of digestible lysine were 0.90; 1.00; 1.10; 1.20; and 1.40% combined with 43 and 253 ppm zinc chelate. The diets contained 2,965 ± 18 kcal/kg of apparent metabolizable energy (AME) and 21.48 ± 0.18% of CP. It was determined chemical composition, protein, lipid, mineral and water depositions on carcass and empty body. There was no interaction among the factors digestible lysine and organic zinc. Effect of zinc concentration increase was observed on greatest deposition of body fat, indicating that there is interference in lipid metabolism of the birds in the studied phase. The most pronounced effects resulted from the dietary inclusion of lysine. There was a linear effect on reconstituted body weight as a response to the increase of dietary lysine, which suggests equal or superior requirement to the greatest studied level. However, the deposition of water and protein on the carcass had a quadratic increase, characterizing higher muscle mass accumulation up to the levels 1.25 and 1.27 of this amino acid in the diet. Considering the studied strain, broiler chickens from the first to the 11th days of age require 1.28 ± 0.01% of digestible lysine, according to the deposition of muscle mass.

Interferências do ruído do tráfego urbano na qualidade de vida: zona residencial de Brasília, DF

Objetivo: avaliar o ruído de trânsito e seus possíveis efeitos na qualidade de vida e na saúde em área residencial de Brasília. Métodos: foram feitas medições de ruído em vários andares dos prédios, com janela aberta e fechada. Aplicou-se um questionário para identificar a sensibilidade e os efeitos relacionados à exposição ao ruído. Resultados: entre os resultados identificaram-se: a área de estudo é afetada pela poluição sonora; o nível de ruído incomoda as pessoas que moram na área e interfere na realização de atividades diárias, sendo que pessoas do sexo feminino e os mais jovens se mostraram mais sensíveis ao ruído e declararam sentir, com maior intensidade, seus efeitos negativos.