Osteopenia-osteoporosis discrimination in postmenopausal women by 1H NMR-based metabonomics.

This is a report on how 1H NMR-based metabonomics was employed to discriminate osteopenia from osteoporosis in postmenopausal women, identifying the main metabolites associated to the separation between the groups. The Assays were performed using seventy-eight samples, being twenty-eight healthy volunteers, twenty-six osteopenia patients and twenty-four osteoporosis patients. PCA, LDA, PLS-DA and OPLS-DA formalisms were used. PCA discriminated the samples from healthy volunteers from diseased patient samples. Osteopenia-osteoporosis discrimination was only obtained using Analysis Discriminants formalisms, as LDA, PLS-DA and OPLS-DA. The metabonomics model using LDA formalism presented 88.0% accuracy, 88.5% specificity and 88.0% sensitivity. Cross-Validation, however, presented some problems as the accuracy of modeling decreased. LOOCV resulted in 78.0% accuracy. The OPLS-DA based model was better: R2Y and Q2 values equal to 0.871 (p<0.001) and 0.415 (p<0.001). LDA and OPLS-DA indicated the important spectral regions for discrimination, making possible to assign the metabolites involved in the skeletal system homeostasis, as follows: VLDL, LDL, leucine, isoleucine, allantoin, taurine and unsaturated lipids. These results indicate that 1H NMR-based metabonomics can be used as a diagnosis tool to discriminate osteoporosis from osteopenia using a single serum sample.

Polymorphisms in key bone modulator cytokines genes influence bisphosphonates therapy in postmenopausal women.

Osteoporosis is a multifactorial and debilitating disease resulting from decreased bone mineral density (BMD) and loss of tissue microarchitecture. Ineffective therapies may lead to bone fractures and subsequent death. Single nucleotide polymorphisms (SNPs) in key immune regulator genes have been associated with therapeutic response to bisphosphonates, which are the first therapeutic line of choice for osteoporosis. However, cytokine pathways and their relation with therapeutic adhesion remain to be fully elucidated. Aimed at better understanding these processes, we investigated the response to bisphosphonate therapy in postmenopausal women and four SNPs in key proinflammatory cytokines genes: IL23R +2284 (C>A) (rs10889677), IL17A +672 (G>A) (rs7747909), IL12B +1188 (T>G) (rs3212227) and INF-γ -1616 (G>A) (rs2069705). A total of 69 patients treated with bisphosphonate were followed for a period of 1 up to 4 years, genotyped and compared according to their changes in bone mineral density (BMD) and level of biochemical markers during their treatment. The INF-γ -1616 G/G associated with increased BMD values in femoral neck (GG/AA, p = 0.016) and decreased BMD values in total hip (GG/GA, p = 0.019; GG/AA, p = 0.011). In relation to biochemical markers, INF-γ -1616 SNP associated with increased alkaline phosphatase (GG/AA; p < 0.0001) and parathyroid hormone levels (AA/GA; p = 0.017). Vitamin D values changes were related to IL17A +672 (GG/GA, p = 0.034) and to IL12B +1188 (TT/TG, p = 0.046) SNPs. Besides, significant differences in changes of calcium levels correlated with IL23R +2284 (CC/CA, p = 0.016) genotypes. Altogether, we suggest that these polymorphisms may play an important role for therapeutic decisions in osteoporosis treatment.

Distribuição espacial de acidentes escorpiônicos em Belo Horizonte, Minas Gerais, 2005 a 2009 / Spatial distribution of scorpion sting accidents in Belo Horizonte, Minas Gerais, 2005 to 2009

Acidentes por escorpião constituem problema de saúde pública em Belo Horizonte. Realizou-se um estudo epidemiológico observacional retrospectivo para analisar a frequência e distribuição espacial dos acidentes escorpiônicos em Belo Horizonte, entre 2005 e 2009, e associá-las às categorias de risco classificadas pelo Índice de Vulnerabilidade à Saúde (IVS), um índice socioeconômico regional composto. Foram utilizados dados de notificação do Sistema Nacional de Agravos de Notificação (SINAN) e Sistema de Vigilância Epidemiológica (SISVE), referentes aos anos de 2008 e 2009. Para o período de 2005 a 2007, foi necessário o resgate de dados das fichas clínicas do Hospital João XXIII (HPSJXXIII) correspondentes às variáveis encontradas no SINAN e SISVE, uma vez que os mesmos não estavam digitalizados nos referidos sistemas de informação. Para georreferenciamento e análise espacial, foi utilizada a base geográfica EndGeo, o aplicativo de mapeamento MapInfo versão 10.0 e os programas Hotspot Detective e SatScan. Entre 2005 e 2009, ocorreram em Belo Horizonte 2.769 casos de acidentes por escorpião, o que representa uma incidência média de 22,4 casos por 100.000 habitantes. Do total de casos, 1.924 (69,5 porcento) foram georreferenciados e houve predomínio de incidência em dois Distritos Sanitários (DS), com grande concentração de casos nas regiões de cemitérios do município. Foram detectados dois "clusters" no período, sendo um em 2005, nos DS Noroeste e Oeste, e outro entre 2006 e 2007, nos DS Noroeste e Nordeste. Não houve associação entre as áreas de maior incidência de escorpionismo e as áreas de maior risco à saúde classificadas pelo IVS. Com base nos resultados, conclui-se que há necessidade de melhorias no processo de notificação do agravo e que o mapeamento dos casos é uma ferramenta relevante capaz de embasar o direcionamento das ações educativas de controle para as áreas prioritárias de Belo Horizonte...

Scorpion sting accidents are a public health problem in Belo Horizonte and veterinarians play an important role in its control program when based on capture, mapping of cases and educational actions with the population. A retrospective epidemiological study was done to analyze the frequency and spatial distribution of scorpion sting cases in Belo Horizonte, between 2005 and 2009, and to associate them with the Health Vulnerability Index (IVS), a regional and composed socio-economic index. Notification data of scorpion sting accidents were used from the National System of Notifiable Diseases (SINAN) and Epidemiological Surveillance System (SISVE) for years 2008 and 2009. For the period between 2005 and 2007 it was necessary to retrieve data from the clinical records of João XXIII Hospital (HPSJ XXIII) which were not digitalized in the referred information systems. For georeference and spatial analysis, geographic base EndGeo and features of the programs MapInfo version 10.0, Hotspot Detective and SatScan were used. Between 2005 and 2009 2769 cases of scorpionism, occurred in Belo Horizonte which represents an average incidence of 22.4 cases per 100,000 inhabitants. Among 1924 (69.5 percent) georeferenced cases, the highest incidence was observed in two Sanitary District (DS). A large concentration of cases was also observed in the areas of the city cemeteries. Two clusters were detected during this period, one in 2005, located in the Northwest and West DS, and another between 2006 and 2007 in the Northwest and Northeast DS. There was no association between higher incidence areas of scorpionism in Belo Horizonte and the areas of higher health risk classified by IVS. It is necessary to improve the reporting process regarding scorpion sting accidents. Another conclusion is that the mapping of cases is a relevant tool to base the targeting of educative actions to the priority areas of Belo Horizonte...

Distribuição espacial e temporal da raiva canina e felina em Minas Gerais, 2000 a 2006 / Spatial and temporal distribution of canine and feline rabies in Minas Gerais, Brazil, from 2000 to 2006

Estudou-se a epidemiologia da raiva em cães e gatos, em Minas Gerais, e realizou-se um estudo descritivo de seu comportamento, de 2000 a 2006. Utilizaram-se, como fonte de dados, os relatórios mensais dos laboratórios do Centro de Controle de Zoonoses de Belo Horizonte e do Instituto Mineiro de Agropecuária. Os resultados demonstraram positividade de 1,5 por cento para raiva canina e 0,7 por cento para raiva felina. Houve tendência ao decréscimo do número de casos positivos de raiva canina (y = -3,2143x + 19,714) e também para a raiva felina, com apenas dois casos, ambos em 2000. As regiões com diagnóstico positivo coincidiram com as de menor desenvolvimento sócioeconômico.

In order to know the epidemiology of rabies in dogs and cats, in Minas Gerais State, a descriptive study of its behavior was carried out from 2000 to 2006. Data of monthly reports colleted at the laboratories of "Centro de Controle de Zoonoses (CCZ)" from Belo Horizonte" and "Instituto Mineiro de Agropecuária (IMA)" were used. Positivity of 1.50 percent for canine rabies and 0.70 percent for feline rabies were observed. A tendency to the decrease of canine rabies positive cases was found (y= -3.2143x + 19.714) and the same was observed for cats, since only two cases occurred, both in 2000. The regions that present positive diagnostics also showed the lowest social economic development.

Distribuição espaço-temporal da raiva bovina em Minas Gerais, 1998 a 2006 / Space and time distribution of bovine rabies in Minas Gerais, 1998 to 2006

Estudou-se a situação epidemiológica da raiva bovina em Minas Gerais de 1998 a 2006. Foram avaliadas 6873 fichas de diagnóstico de raiva por imunofluorescência direta. Para análise da distribuição temporal da raiva, foram construídas tabelas e gráficos no software Excel 2003 e o mapeamento dos diagnósticos foi feito no aplicativo Tabwin 1.4. Verificou-se tendência anual decrescente do número de exames e dos diagnósticos positivos (Y= -41,133x+544,89). Os meses de maio, junho e julho apresentaram o maior percentual de diagnósticos positivos. O número de municípios com raiva bovina variou ao longo do período estudado e manteve tendência decrescente (Y= -7,0833x+166,64), com expansão da doença para os municípios da região do Triângulo Mineiro.

Epidemiological data of bovine rabies were evaluated after analyzing 6,873 files collected in Minas Gerais state, from 1998 to 2006. Direct Immunofluorescence was performed to diagnosis the disease. The temporal distribution of the disease was analyzed after tables and graphics were made using the software Excel 2003. A mapping diagnosis was built using the applicatory Tabwin 1.4. It was observed an annual decreasing tendency in the number positive diagnosis (Y= -41.133x+544.89). A higher percentage of positive diagnosis for rabies was observed from May to July. There was a variation in the number of counties in which bovine rabies was diagnosed during the studied period and it maintained a decreasing trend (Y= -7.0833x+166.64), with expansion of the disease in direction of "Triângulo Mineiro" counties.

Influence of neurosteroids on the development of rapid tolerance to ethanol in mice.

Our recent study demonstrated that neurosteroids might either facilitate or block chronic tolerance to the incoordinating effects of ethanol. The present study investigated the effects of neurosteroids on the development of rapid tolerance to ethanol-induced motor impairment using the N-methyl-D-aspartate (NMDA) receptor antagonist dizocilpine [(+)-MK-801] or the gamma-aminobutyric acid (GABA) type A (GABA(A)) receptor agonist muscimol. Male Swiss mice were pretreated with pregnenolone sulfate (0.03 to 0.15 mg/kg) or dehydroepiandrosterone sulfate (0.05 to 0.20 mg/kg) before administration of ethanol (1.9 or 2.25 g/kg) and tested with the rota-rod apparatus. Twenty-four hours later, all animals were re-tested with the rota-rod after receiving the same dose of ethanol. Pretreatment with pregnenolone sulfate or with dehydroepiandrosterone sulfate significantly facilitated the acquisition of tolerance. However, the administration of (+)-MK-801 reversed the stimulatory action of pregnenolone sulfate but did not affect the actions of dehydroepiandrosterone sulfate on ethanol tolerance. Pretreatment with pregnenolone sulfate or dehydroepiandrosterone sulfate prevented the inhibitory action of muscimol on tolerance development. Taken together, our results suggest that neurosteroids may stimulate the development of rapid tolerance to ethanol and that GABA(A) and NMDA receptor systems may be involved in these actions.

Cellulose acetate as solid phase in ELISA for plague.

Antigen from Yersinia pestis was adsorbed on cellulose acetate discs (0.5 cm of diameter) which were obtained from dialysis membrane by using a paper punch. ELISA for human plague diagnosis was carried out employing this matrix and was capable to detect amount of 1.3 microg of antigen, 3,200 times diluted positive serum using human anti-IgG conjugate diluted 1:4,000. No relevant antigen lixiviation from the cellulose acetate was observed even after washing the discs 15 times. The discs were impregnated by the coloured products from the ELISA development allowing its use in dot-ELISA. Furthermore, cellulose acetate showed a better performance than the conventional PVC plates.

Cellulose acetate as solid phase in ELISA for plague

Antigen from Yersinia pestis was adsorbed on cellulose acetate discs (0.5 cm of diameter) which were obtained from dialysis membrane by using a paper punch. ELISA for human plague diagnosis was carried out employing this matrix and was capable to detect amount of 1.3 µg of antigen, 3,200 times diluted positive serum using human anti-IgG conjugate diluted 1:4,000. No relevant antigen lixiviation from the cellulose acetate was observed even after washing the discs 15 times. The discs were impregnated by the coloured products from the ELISA development allowing its use in dot-ELISA. Furthermore, cellulose acetate showed a better performance than the conventional PVC plates.

Effect of epipregnanolone and pregnenolone sulfate on chronic tolerance to ethanol.

The aim of the present study was to investigate the influence of neurosteroids on the development of tolerance to ethanol. Male Swiss mice were injected daily with the positive allosteric modulator of the gamma amino butyric acid-A (GABA(A)) receptor epipregnanolone (5beta-pregnan-3beta-ol-20-one; 0.15 mg/kg i.p.) or pregnenolone sulfate (5-pregnen-3beta-ol-20-one sulfate sodium; 0.08 mg/kg i.p.) - considered a negative allosteric modulator of this receptor and/or positive allosteric modulator of the N-methyl-D-aspartate (NMDA) receptor - 30 min before ethanol (2.5 g/kg i.p.). They were tested on the rota-rod apparatus, under continuous acceleration (1rpm/s), at 30, 60 and 90 min after ethanol injections for 5 days. The results showed that tolerance to the motor incoordinating effect of ethanol occurred on the fifth day of treatment when this effect was blocked by pretreatment with epipregnanolone. On the other hand, ethanol tolerance was enhanced by pretreatment with pregnenolone sulfate from the second to the fifth days of treatment. Taken together, our results suggest that neurosteroids can either stimulate or block the development of chronic tolerance to ethanol. Moreover, since neurosteroids can interact with GABA(A) or NMDA receptor systems, our results suggest the involvement of these systems in the actions of neurosteroids upon ethanol tolerance.

[Appendicitis in the premature newborn] / Apendicite em recém-nascido prematuro.

OBJECTIVE: To present a case of acute appendicitis in a premature infant. METHODS: Retrospective review of the literature using Medline and Lilacs databases, as well as the necropsy report. CLINICAL REPORT: A white male preterm infant born at 34 weeks of gestation weighing 1,750g to a primiparous mother. The Apgar score was 4 and 8 at 1st and 5th minutes, respectively. The physical exam was normal until the 9th day of life when the child developed clinical features suggestive of acute abdomen, possibly due to necrotizing enterocolitis with perforation. He was submitted to exploratory laparotomy, which leaded to the diagnostic of acute appendicitis. CONCLUSION: Acute appendicitis must be discarded on the differential diagnostic when there is a suspicion of necrotizing enterocolitis with perforation, and risk factors are not present.

[Effect of malnutrition and chronic use of nicotine during pregnancy on lung phospholipid concentration in neonate rats] / Efeito da desnutrição e do uso crônico de nicotina durante a gestação sobre a concentração de fosfolipídios pulmonares em ratos recém-nascidos.

OBJECTIVE: The aim of the present study was to determine whether lung phospholipid concentration is affected in neonate rats "Wistar EPM-1" following a continuous 21-day gestational exposure to nicotine. METHODS: Eighty rats "Wistar EPM-1" were randomly divided in four control (diet free and water "ad libitum") groups (10 rats each): 1 - Control, 2 - Physiologic Solution (infused with 0.15ml of NaCl 0.9%), 3 - Nicotine 1 (infused with 900 micro g/kg/day of nicotine bitartrate 95%), and 4 - Nicotine 2 (infused with 2.700 micro g/kg/day of nicotine bitartrate 95%), and four undernourished (diet 13g/day and water ad libitum) groups (10 rats each), that received the same kind of treatment as the control groups. The infusion of nicotine was subcutaneous. The offspring were divided in eight groups according to their origin. RESULTS: A significant high lung phospholipid concentration was observed in the non-undernourished nicotized group which was injected with a high dose of nicotine. In the other groups, there was no alteration in that concentration. CONCLUSION: We conclude that gestational exposure to nicotine increases lung phospholipid concentration in neonate rats, and that the nutritional state also influences this lung phospholipid concentration.

[Tissue weight and histologic alterations in pregnant rats submitted to malnutrition and chronic nicotine distress, and in their neonates]. / Alterações de peso tecidual e histológicas em ratas gestantes submetidas à desnutrição e ao estresse crônico de nicotina, e em seus recém-nascidos.

The effects of a gestational exposure of 80 rats Wistar EPM-1 to nicotine and undernutrition was examined. The weight and histological alterations on the liver and lungs was evaluated on the rats and their offspring. A significantly lower weight gain, including liver and lung weight, was observed in nicotine exposed groups. There was no alteration of the placental weight. Decidual necrosis and hepatic congestion was frequent in the rats. Lung emphysema was found in the neonates.