Catecholamine-induced vasoconstriction is sensitive to carbonic anhydrase I activation

We studied the relationship between alpha- and beta-adrenergic agonists and the activity of carbonic anhydrase I and II in erythrocyte, clinical and vessel studies. Kinetic studies were performed. Adrenergic agonists increased erythrocyte carbonic anhydrase as follows: adrenaline by 75%, noradrenaline by 68%, isoprenaline by 55%, and orciprenaline by 62%. The kinetic data indicated a non-competitive mechanism of action. In clinical studies carbonic anhydrase I from erythrocytes increased by 87% after noradrenaline administration, by 71% after orciprenaline and by 82% after isoprenaline. The increase in carbonic anhydrase I paralleled the increase in blood pressure. Similar results were obtained in vessel studies on piglet vascular smooth muscle. We believe that adrenergic agonists may have a dual mechanism of action: the first one consists of a catecholamine action on its receptor with the formation of a stimulus-receptor complex. The second mechanism proposed completes the first one. By this second component of the mechanism, the same stimulus directly acts on the carbonic anhydrase I isozyme (that might be functionally coupled with adrenergic receptors), so that its activation ensures an adequate pH for stimulus-receptor coupling for signal transduction into the cell, resulting in vasoconstriction.

Association between dental-oral health in young adults and salivary glutathione, lipid peroxidation and sialic acid levels and carbonic anhydrase activity

The aim of the present study was to evaluate the relationship between salivary oxidative stress and dental-oral health. Healthy young adults, matched for gender and age, with (N = 21, 10 men, mean age: 20.3 ± 1 years) and without (N = 16, 8 men, mean age: 21.2 ± 1.8 years) caries were included in this study. The World Health Organization (WHO) caries diagnostic criteria were used for determining the decayed, missing, filled teeth (DMFT) index. The oral hygiene and gingival status were assessed using the simplified oral hygiene index and gingival index, respectively. Unstimulated salivary total protein, glutathione (GSH), lipid peroxidation and total sialic acid levels, carbonic anhydrase activity, and salivary buffering capacity were determined by standard methods. Furthermore, salivary pH was measured with pH paper and salivary flow rate was calculated. Simplified oral hygiene index and gingival index were not significantly different between groups but DMFT scores were significant (P < 0.01). Only, GSH values were significantly different (P < 0.05) between groups (2.2 and 1.6 mg/g protein in young adults without caries and with caries, respectively). There was a significant negative correlation between DMFT and GSH (r = -0.391; P < 0.05; Pearson's correlation coefficient). Our results suggest that there is an association between caries history and salivary GSH levels.

The association of genetic markers and malaria infection in the Brazilian Western Amazonian region

Almost all individuals (182) belonging to an Amazonian riverine population (Portuchuelo, RO, Brazil) were investigated for ascertaining data on epidemiological aspects of malaria. Thirteen genetic blood polymorphisms were investigated (ABO, MNSs, Rh, Kell, and Duffy systems, haptoglobins, hemoglobins, and the enzymes glucose-6-phosphate dehydrogenase, glyoxalase, phosphoglucomutase, carbonic anhydrase, red cell acid phosphatase, and esterase D). The results indicated that the Duffy system is associated with susceptibility to malaria, as observed in other endemic areas. Moreover, suggestions also arose indicating that the EsD and Rh loci may be significantly associated with resistance to malaria. If statistical type II errors and sample stratification could be ruled out, hypotheses on the existence of a causal mechanism or an unknown closely linked locus involved in susceptibility to malaria infection may explain the present findings.

Proteomic analysis of the shistosome tegument and its surface membranes

The tegument surface of the adult schistosome, bounded by a normal plasma membrane overlain by a secreted membranocalyx, holds the key to understanding how schistosomes evade host immune responses. Recent advances in mass spectrometry (MS), and the sequencing of the Schistosoma mansoni transcriptome/genome, have facilitated schistosome proteomics. We detached the tegument from the worm body and enriched its surface membranes by differential extraction, before subjecting the preparation to liquid chromatography-based proteomics to identify its constituents. The most exposed proteins on live worms were labelled with impearmeant biotinylation reagents, and we also developed methods to isolate the membranocalyx for analysis. We identified transporters for sugars, amino acids, inorganic ions and water, which confirm the importance of the tegument plasma membrane in nutrient acquisition and solute balance. Enzymes, including phosphohydrolases, esterases and carbonic anhydrase were located with their catalytic domains external to the plasma membrane, while five tetraspanins, annexin and dysferlin were implicated in membrane architecture. In contrast, few parasite proteins could be assigned to the membranocalyx but mouse immune response proteins, including three immunoglobulins and two complement factors, were detected, plus host membrane proteins such as CD44, integrin and a complement regulatory protein, testifying to the acquisitive properties of the secreted bilayer.

Effect of topical dorzolamide on rabbit central corneal thickness

Our objective was to study the effect of dorzolamide on corneal hydration in an 18-week controlled experiment using ultrasonic pachymetry. Twenty-eight male rabbits were divided randomly into four groups. The 7 rabbits in each group received eye drops containing either 2% (w/v) dorzolamide or placebo in their right eye, or in their left eye. The 2% dorzolamide rabbits were treated every 8 h. Fellow eyes are defined as eyes which did not receive either dorzolamide or placebo. The study was blind for both the person who applied the drug and the one who performed the pachymetry. The effect of treatments is reported on the basis of the percentage of pachymetric variation compared to the measurement made before drug application. There was no significant difference (P = 0.061) in pachymetric variation between dorzolamide (-4.42 ± 11.71%) and placebo (2.48 ± 9.63%). However, there was a significant difference (P = 0.0034) in pachymetric variation between the dorzolamide fellow eyes (-7.56 ± 10.50%) and the placebo (-4.42 ± 11.71%). In conclusion, dorzolamide did not increase the corneal thickness in rabbits.

Short-term levosimendan treatment protects rat testes against oxidative stress

The objective of this study was to evaluate the effect of short-term levosimendan exposure on oxidant/antioxidant status and trace element levels in the testes of rats under physiological conditions. Twenty male Wistar albino rats were randomly divided into two groups of 10 animals each. Group 1 was not exposed to levosimendan and served as control. Levosimendan (12 µg/kg) diluted in 10 mL 0.9% NaCl was administered intraperitoneally to group 2. Animals of both groups were sacrificed after 3 days and their testes were harvested for the determination of changes in tissue oxidant/antioxidant status and trace element levels. Tissue malondialdehyde (MDA) was significantly lower in the levosimendan group (P < 0.001) than in the untreated control group and superoxide dismutase and glutathione peroxidase (GSH-Px) levels were significantly higher in the levosimendan group (P < 0.001). Carbonic anhydrase, catalase and GSH levels were not significantly different from controls. Mg and Zn levels of testes were significantly higher (P < 0.001) and Co, Pb, Cd, Mn, and Cu were significantly lower (P < 0.001) in group 2 compared to group 1. Fe levels were similar for the two groups (P = 0.94). These results suggest that 3-day exposure to levosimendan induced a significant decrease in tissue MDA level, which is a lipid peroxidation product and an indicator of oxidative stress, and a significant increase in the activity of an important number of the enzymes that protect against oxidative stress in rat testes.

Specific alterations in plasma proteins during depressed, manic, and euthymic states of bipolar disorder

Bipolar disorder (BD) is a common psychiatric mood disorder affecting more than 1-2% of the general population of different European countries. Unfortunately, there is no objective laboratory-based test to aid BD diagnosis or monitor its progression, and little is known about the molecular basis of BD. Here, we performed a comparative proteomic study to identify differentially expressed plasma proteins in various BD mood states (depressed BD, manic BD, and euthymic BD) relative to healthy controls. A total of 10 euthymic BD, 20 depressed BD, 15 manic BD, and 20 demographically matched healthy control subjects were recruited. Seven high-abundance proteins were immunodepleted in plasma samples from the 4 experimental groups, which were then subjected to proteome-wide expression profiling by two-dimensional electrophoresis and matrix-assisted laser desorption/ionization-time-of-flight/time-of-flight tandem mass spectrometry. Proteomic results were validated by immunoblotting and bioinformatically analyzed using MetaCore. From a total of 32 proteins identified with 1.5-fold changes in expression compared with healthy controls, 16 proteins were perturbed in BD independent of mood state, while 16 proteins were specifically associated with particular BD mood states. Two mood-independent differential proteins, apolipoprotein (Apo) A1 and Apo L1, suggest that BD pathophysiology may be associated with early perturbations in lipid metabolism. Moreover, down-regulation of one mood-dependent protein, carbonic anhydrase 1 (CA-1), suggests it may be involved in the pathophysiology of depressive episodes in BD. Thus, BD pathophysiology may be associated with early perturbations in lipid metabolism that are independent of mood state, while CA-1 may be involved in the pathophysiology of depressive episodes.

Hidropsia endolinfática experimental sob ação de inibidor da óxido nítrico sintase tipo II: avaliação com emissões otoacústicas e eletrococleografia

No modelo experimental de hidropsia endolinfática há redução na amplitude das emissões otoacústicas produtos de distorção (EOAPD) e elevação nos limiares eletrofisiológicos na eletrococleografia. Estudos mostraram que há expressão da óxido nítrico sintase tipo II (ONS II) na cóclea com hidropsia, sugerindo a participação do óxido nítrico (ON) na patogênese desta doença. O objetivo deste trabalho foi avaliar a ação de um inibidor da ONS II nas EOAPD e eletrococleografia em cobaias com hidropisia endolinfática experimental. MATERIAL E MÉTODOS: Foram estudadas 16 cobaias nas quais se induziu hidropsia endolinfática experimental por obliteração do ducto e saco endolinfático na orelha direita durante 16 semanas, divididas em dois grupos: oito cobaias recebendo um inibidor da ONS II, a aminoguanidina, por via oral e um grupo de oito cobaias como controle. Comparamos as amplitudes das EOAPD nas médias geométricas de freqüências de 1062, 2187, 4375 e 7000Hz, os limiares eletrofisiológicos nas freqüências de 1000, 2000, 4000 e 6000Hz e a relação entre os potenciais de somação e de ação (PS/PA) entre os grupos. RESULTADOS: Não houve diferença significante nas EOAPD e na relação PS/PA entre os grupos. O grupo que recebeu a aminoguanidina apresentou menor elevação nos limiares eletrofisiológicos nas freqüências de 2000 (p<0,05) e 6000 Hz (p<0,05) na 12ª semana e nas freqüências de 1000 (p<0,05), 2000 (p<0,001), 4000 (p<0,001) e 6000Hz (p<0,001) na 16ª semana. CONCLUSÕES: O inibidor da ONS II reduziu a elevação dos limiares eletrofisiológicos na eletrococleografia na hidropsia endolinfática experimental.

Processo de adaptação de próteses auditivas em usuários atendidos em uma instituição pública federal: parte II: resultados dos questionários de auto-avaliação

Uma reabilitação eficiente deve reduzir os efeitos da deficiência sobre as habilidades auditivas e comunicativas do indivíduo e aumentar o bem-estar psicossocial. OBJETIVOS:Verificar a viabilidade do uso de questionários de auto-avaliação e comparar os resultados da protetização em usuários de uma instituição pública federal, com e sem queixas relacionadas às características da amplificação. MATERIAL E MÉTODOS:25 indivíduos, de 13 a 77 anos de idade, usuários de próteses auditivas. Foram aplicados os questionários de auto-avaliação HHIE-S/HHIA (Hearing Handicap Inventory for the Elderly Screening Version ou for Adult) e APHAB (Abbreviated Profile of Hearing Aid Benefit), nos indivíduos sem (Grupo 1) e com queixas relacionados às características da amplificação (Grupo 2). RESULTADOS: Diferenças significantes não foram encontradas entre os grupos nos protocolos HHIE-S/HHIA e APHAB, exceto na subescala facilidade de comunicação do APHAB, onde o Grupo 1 obteve melhor benefício. Também evidenciou-se redução significativa da incapacidade auditiva com o uso das próteses em situações favoráveis de comunicação, ambientes reverberantes e na presença de ruído ambiental para ambos os grupos. CONCLUSÃO: Os questionários revelaram ser excelentes preditores das dificuldades enfrentadas pelos usuários, e diferenças significantes foram encontradas em situações favoráveis de comunicação, onde o grupo sem queixas obteve melhor benefício.

Quais carreiras e para qual sociedade? (II)

Na seqüência do artigo, o autor mostra que atualmente, com a diminuição das ofertas de empregos, o desenvolvimento de carreira encontra-se frente a diversos paradoxos. Entre estes pode-se apontar a falta de formação dos estudantes de administração, as dificuldades de mercado, o avanço dos trabalhos temporários. Para que hajam mudanças no cenário futuro é necessário pensar sobre transformações substantivas na ética do trabalho, na formação dos jovens, na preocupação exclusivamente financeira que limita cada vez mais o horizonte profissional. Dando continuidade à primeira parte, o artigo aponta para os paradoxos e desafios a serem enfrentados atualmente pelos que desejam fazer carreira, face à diminuição dos empregos disponíveis.

Modelos quantitativos de apoio as decisões: II

O sucesso da aplicação de técnicas de Análise das Decisões como apoio em problemas com um único objetivo predominante abriu caminho para estudos de problemas mais ambiciosos como os de decisões com multicritérios e decisões e de grupo (estes dois tipos utilizam metodologias muito semelhantes). Como evolução natural da Análise das Decisões, resultou a metodologia MAUT (Multi-Attribute Utility Theory). Seu rigorismo teórico torna as aplicações difíceis para um analista menos preparado. Como conseqüência, surgiu a metodologia AHP (Analytic Hierarchy Process) de utilização extremamente simples. A crítica ao AHP veio da escola européia que criou uma série de métodos conhecidos pela abreviação comum: MCDA (Multicriteria Decision Aid).