Lab-on-a-Drone: remote voltammetric analysis of lead in water with real-time data transmission.

The present work describes a laboratory-on-a-drone (Lab-on-a-Drone) developed to perform in situ detection of contaminants in environmental water samples. Toward this goal, the system was mounted on an unmanned aerial vehicle (UAV) (drone) and remotely controlled via Wi-Fi to acquire a water sample, perform the electrochemical detection step, and then send the voltammetry data to a smartphone. This Lab-on-a-Drone system was also able to recharge its battery using a solar cell, greatly increasing the autonomy of the system, even in the absence of a power line. As a proof of concept, the Lab-on-a-Drone was employed for the detection of Pb2+ in environmental waters, using a simple electrochemical cell containing a miniaturized screen-printed boron-doped diamond electrode (SP-BDDE) as a working electrode, an Ag/AgCl as a reference electrode, and a graphite ink as a counter electrode. For quantification purposes, analytical curves were constructed covering a concentration range from 1.0 µg L-1 (4.83 nmol L-1) to 80.0 µg L-1 (386.10 nmol L-1), featuring a detection limit of 0.062 µg L-1 (0.30 nmol L-1). The Lab-on-a-Drone was applied to monitor a water reservoir in the Metropolitan Region of Recife, Brazil. To evaluate its performance regarding accuracy and precision, a reference method based on inductively coupled plasma optical emission spectrometry (ICP-OES) was applied, and the results obtained by both methods showed no statistical differences (t-test at 95% confidence level, n = 3). These results represent the first demonstration of the capabilities of an adapted UAV for the quantification of electroactive environmental contaminant using voltammetry, with real-time data transmission. Thus, the Lab-on-a-Drone makes it possible to reach difficult-to-access environmental reserves and to monitor potentially polluting activity in distant water bodies. Thus, this tool can be used by governments and non-profit organizations to monitor environmental waters using fast, low-cost, process autonomy with accurate and precise data useful to decision making.

Molecular pathology quality control in Southeast Asia: Results of a multiregional quality assurance study from MASTER KEY Asia.

Tissue specimen quality assurance is a major issue of precision medicine for rare cancers. However, the laboratory standards and quality of pathological specimens prepared in Asian hospitals remain unknown. To understand the methods in Southeast Asian oncology hospitals and to clarify how pre-analytics affect the quality of formalin-fixed paraffin-embedded (FFPE) specimens, a questionnaire surveying pre-analytical procedures (Part I) was administered, quality assessment of immunohistochemistry (IHC) staining and DNA/RNA extracted from the representative FFPE specimens from each hospital (Part II) was conducted, and the quality of DNA/RNA extracted from FFPE of rare-cancer patients for genomic sequencing (Part III) was examined. Quality measurements for DNA/RNA included ΔΔCt, DV200, and cDNA yield. Six major cancer hospitals from Malaysia, Philippines, and Vietnam participated. One hospital showed unacceptable quality for the DNA/RNA assessment, but improved by revising laboratory procedures. Only 57% (n = 73) of the 128 rare-cancer patients' specimens met both DNA and RNA quality criteria for next-generation sequencing. Median DV200 was 80.7% and 64.3% for qualified and failed RNA, respectively. Median ΔΔCt was 1.25 for qualified and 4.89 for failed DNA. Longer storage period was significantly associated with poor DNA (fail to qualify ratio = 1579:321 days, p < 0.001) and RNA (fail to qualify ratio = 1070:280 days, p < 0.001). After improvement of pre-analytical factors, the qualification rate increased for hospitals A and E from 41.5% to 70.5% and 62.5% to 86%, respectively. This is the first report to elucidate the pre-analytical laboratory procedures of main Southeast Asian oncology hospitals. An external quality assessment program may improve factors associated with tumor FFPE specimen quality.

The Replacement of Fetal Bovine Serum with Bovine Serum Albumin During Oocyte Maturation and Embryo Culture Does Not Improve Blastocyst Quality After Slow Freezing Cryopreservation.

In the present study, four experimental groups were used: fresh embryos, cultured during in vitro maturation and in vitro culture in media supplemented with bovine serum albumin (BSA) (fresh BSA) or fetal bovine serum (FBS) (fresh FBS); and two groups of cryopreserved and thawed embryos, produced under the same conditions (frozen BSA and frozen FBS). Experiment 1 evaluated the protein source effect on embryo development and response to cryopreservation. At day 7, half of the expanded blastocysts (Bx) from each group were cryopreserved and warmed and the other half were used as controls. After warming, embryos were incubated under the same conditions for 48 hours, and the hatching rate was measured at 24 and 48 hours. The total and the apoptotic cell numbers were measured in a subset of Bx after 24 hours. Experiment 2 used the Bx of experiment 1 to compare the expression of KRT8, PLAC8, FOSL1, HSP1A1, and HSPA5 genes in hatched blastocysts at 24 and 48 hours for all groups. The FBS group showed a higher percentage (p < 0.05) of embryos (42.8% vs. 27.9%) and higher rates of Bx (75.0% vs. 63.8%) on day 7, compared with the BSA group. At 24 hours postwarming, the fresh FBS group showed the highest hatching rate (p < 0.05) in comparison with other treatments. However, at 48 hours, the hatching rate was similar (p > 0.05) among groups: fresh FBS (68.1% ± 23.3%), fresh BSA (70.0% ± 31.0%), frozen FBS (39.2 ± 27.1), and frozen BSA (38.2 ± 23.9). After 24 hours, frozen BSA showed a higher number of cells compared with frozen FBS (p < 0.05). The expression of the PLAC8 gene was higher (p < 0.05) in fresh BSA embryos compared with frozen FBS embryos at 24 hours. In the present study, BSA replacement reduced embryo development, but did not affect the response to cryopreservation. However, upregulation of the PLAC8 gene suggests that embryos cultured in BSA might have better quality to support further development.

Synthesis of phenylpyrimidinones as guanylyl cyclase C inhibitors.

Diarrhea is one of the most important causes of mortality in the developing world, being responsible for 2.5 million deaths each year. Many of these deaths are caused by enterotoxigenic strains of bacteria, like Escherichia coli, that produce enterotoxins that cause acute watery diarrhea, commonly defined as secretory diarrhea. Studies on symptomatic patients indicate a high prevalence of enterotoxigenic E. coli strains producing the heat-stable toxin, STa. STa is a small, cysteine-rich peptide that binds to the extracellular receptor domain of guanylyl cyclase C (GCC), located at the luminal membrane of intestinal epithelial cells. GCC and its endogenous peptide ligands, guanylin and uroguanylin, play a key role in balancing water absorption and hydration of the intestinal lumen, as exemplified by the finding that loss of GCC function causes severe dehydration of the intestinal lumen, culminating in intestinal obstruction. From a mechanistic viewpoint, reduction of GCC activity offers an efficient approach to limit enterotoxigenic E. coli- provoked secretory diarrhea. Inhibition of GCC-mediated cGMP production would not only reduce anion secretion, but would also restore NHE3 activity, resulting in a comprehensive antidiarrheal action. In the present study, two novel phenylpyrimidinone derivatives were simultaneously synthesized and tested for their ability to block STa-induced CFTR activity in T84 cells.

Terminal complement inhibitor eculizumab in atypical hemolytic-uremic syndrome.

BACKGROUND: Atypical hemolytic-uremic syndrome is a genetic, life-threatening, chronic disease of complement-mediated thrombotic microangiopathy. Plasma exchange or infusion may transiently maintain normal levels of hematologic measures but does not treat the underlying systemic disease. METHODS: We conducted two prospective phase 2 trials in which patients with atypical hemolytic-uremic syndrome who were 12 years of age or older received eculizumab for 26 weeks and during long-term extension phases. Patients with low platelet counts and renal damage (in trial 1) and those with renal damage but no decrease in the platelet count of more than 25% for at least 8 weeks during plasma exchange or infusion (in trial 2) were recruited. The primary end points included a change in the platelet count (in trial 1) and thrombotic microangiopathy event-free status (no decrease in the platelet count of >25%, no plasma exchange or infusion, and no initiation of dialysis) (in trial 2). RESULTS: A total of 37 patients (17 in trial 1 and 20 in trial 2) received eculizumab for a median of 64 and 62 weeks, respectively. Eculizumab resulted in increases in the platelet count; in trial 1, the mean increase in the count from baseline to week 26 was 73×10(9) per liter (P<0.001). In trial 2, 80% of the patients had thrombotic microangiopathy event-free status. Eculizumab was associated with significant improvement in all secondary end points, with continuous, time-dependent increases in the estimated glomerular filtration rate (GFR). In trial 1, dialysis was discontinued in 4 of 5 patients. Earlier intervention with eculizumab was associated with significantly greater improvement in the estimated GFR. Eculizumab was also associated with improvement in health-related quality of life. No cumulative toxicity of therapy or serious infection-related adverse events, including meningococcal infections, were observed through the extension period. CONCLUSIONS: Eculizumab inhibited complement-mediated thrombotic microangiopathy and was associated with significant time-dependent improvement in renal function in patients with atypical hemolytic-uremic syndrome. (Funded by Alexion Pharmaceuticals; C08-002 ClinicalTrials.gov numbers, NCT00844545 [adults] and NCT00844844 [adolescents]; C08-003 ClinicalTrials.gov numbers, NCT00838513 [adults] and NCT00844428 [adolescents]).

Cross-sectional validation study of patient-reported outcomes in patients with paroxysmal nocturnal haemoglobinuria.

BACKGROUND: Paroxysmal nocturnal haemoglobinuria (PNH) is a rare, acquired, clonal haemopoietic stem cell disorder that causes chronic intravascular haemolysis, increases the risk of thrombosis and results in significant patient morbidity and mortality. The symptoms of PNH may have a major impact on patient quality of life. AIMS: To assess patient fatigue and health-related quality of life in 29 patients with PNH using the Functional Assessment of Chronic Illness Therapy Fatigue subscale version 4 (FACIT-Fatigue) and the European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire-C30, version 3 (EORTC QLQ-C30). METHODS: Following completion of the questionnaires, patients were interviewed to assess the validity, clarity, relevance and comprehensiveness of the assessments. RESULTS: Overall, patients considered both the FACIT-Fatigue and EORTC QLQ-C30 instruments to be relevant and adequate in assessing the level of PNH-associated fatigue and other quality-of-life measures. The FACIT-Fatigue questionnaire was considered to be clear and to comprehensively cover PNH-related fatigue. The EORTC QLQ-C30 instrument was considered to be easy to understand, but of an overall lower relevance, although some differences between countries were observed. Patients suggested additional questions that could be incorporated into future EORTC QLQ-C30 versions to make it more relevant to PNH. CONCLUSIONS: This study confirms the validity of the FACIT-Fatigue and the EORTC QLQ-C30 questionnaires in this patient population and their routine use should be considered in the management of patients with PNH.

Efeito da administração oral do Saccharamyces cerevisiae na tolerabilidade à terapia de erradicação do Helicobacter pylori e na redução de sintomas indesejáveis / Effect of oral administration of Saccharomyces cerevisiae on Helicobacter pylori eradication therapy tolerability and on undersirable symptoms reduction

Objetivo: a terapia tríplice por sete dias tem sido a mais utilizada na erradicação do Helicobacter pylori. Efeitos gastrointestinais indesejáveis deste tratamento são frequentes. A suplementação de probióticos deverá prevenir ou reduzir tais manifestações. O presente estudo constitui-se na primeira avaliação do Saccharomyces cerevisiae e seu papel na tolerabilidade aos efeitos colaterais da terapia de erradicação do H. pylori, e teve como objetivo avaliar o efeito da administração oral do S. cerevisiae na prevenção ou redução dos sintomas indesejáveis da terapia convencional anti-Helicobacter pylori. Métodos: oitenta e oito voluntários assintomáticos, triados positivamente para infecção por H. pylori, foram randomizados para tratamento de uma semana com lansoprazol 30mg, duas vezes ao dia, amoxicilina 1g, duas vezes ao dia, claritromicina 500mg, duas vezes ao dia, e o probiótico S. cerevisiae, duas vezes ao dia por 14 dias ou o mesmo regime com placebo em substituição ao S. cerevisiae. Os pacientes foram orientados a preencherem um questionário durante a semana do tratamento, e as três semanas seguintes para determinar o tipo e a severidade dos efeitos colaterais e fazer um julgamento geral sobre a sua tolerabilidade. Resultados: alterações de paladar, perda de apetite e vômitos foram significativamente reduzidos no grupo com S. cerevisiae (p=0,001, p=0,02 e p=0,03, respectivamente). Uma avaliação geral da tolerabilidade ao tratamento mostrou uma diferença significativa em favor do grupo com probiótico. Conclusão: a suplementação com o S. cerevisiae mostrou um impacto positivo sobre os efeitos colaterais da terapia de erradicação do H. pylori e uma melhor tolerabilidade ao tratamento.

Background: the one week triple therapy is considered gold standard for Helicobacter pylori eradication. Undesirable gastrointestinal effects during the treatment are frequent. The additional administration of probiotics should prevent or reduce those effects. This essay is the first description of the role of Saccharomyces cerevisiae´s administration on reducing side effects of the H. pylori eradication therapy. Objectives: to evaluate the effects of oral administration of Saccharomyces cerevisiae on reducing or preventing undesirable symptoms during the conventional anti-H. pylori therapy. Patients and Methods: Eighty eight asymptomatic volunteers infected by H. pylori were randomized and treated with lansoprazole 30mg twice a day, amoxicillin 1000mg twice a day, claritromicin 500mg twice a day for one week and Saccharomyces cerevisiae twice a day for two weeks or the same regimen with placebo instead of S. cerevisiae. Patients fulfilled a questionnaire regarding the kind and severity of the symptoms during the week of the treatment and the following three weeks and also made a general judgment of the tolerability of the treatment. Results: taste disorders, loss of appetite and vomits were significantly reduced in the Saccharomyces cerevisiae group (p=0,001, p=0,02 e p=0,03, respectively). A significant difference in favor of the probiotic group was found in the general judgment of treatment tolerability. Conclusion: the additional administration of S. cerevisiae showed a positive impact on side effects of H. pylori eradication therapy and a beter treatment tolerability.

Inhibitory effects of bromelain, a cysteine protease derived from pineapple stem (Ananas comosus), on intestinal motility in mice.

BACKGROUND: Bromelain (BR) is a cysteine protease with inhibitory effects on intestinal secretion and inflammation. However, its effects on intestinal motility are largely unexplored. Thus, we investigated the effect of this plant-derived compound on intestinal contractility and transit in mice. METHODS: Contractility in vitro was evaluated by stimulating the mouse isolated ileum, in an organ bath, with acetylcholine, barium chloride, or electrical field stimulation. Motility in vivo was measured by evaluating the distribution of an orally administered fluorescent marker along the small intestine. Transit was also evaluated in pathophysiologic states induced by the pro-inflammatory compound croton oil or by the diabetogenic agent streptozotocin. KEY RESULTS: Bromelain inhibited the contractions induced by different spasmogenic compounds in the mouse ileum with similar potency. The antispasmodic effect was reduced or counteracted by the proteolytic enzyme inhibitor, gabexate (15 × 10(-6) mol L(-1) ), protease-activated receptor-2 (PAR-2) antagonist, N(1) -3-methylbutyryl-N(4) -6-aminohexanoyl-piperazine (10(-4) mol L(-1) ), phospholipase C (PLC) inhibitor, neomycin (3 × 10(-3) mol L(-1) ), and phosphodiesterase 4 (PDE4) inhibitor, rolipram (10(-6) mol L(-1) ). In vivo, BR preferentially inhibited motility in pathophysiologic states in a PAR-2-antagonist-sensitive manner. CONCLUSIONS & INFERENCES: Our data suggest that BR inhibits intestinal motility - preferentially in pathophysiologic conditions - with a mechanism possibly involving membrane PAR-2 and PLC and PDE4 as intracellular signals. Bromelain could be a lead compound for the development of new drugs, able to normalize the intestinal motility in inflammation and diabetes.

Synthesis and in vitro pharmacological evaluation of a new series of 5-HT1A 5-HT2A and 5-HT2C receptor ligands containing a norbornene nucleus.

A series of 4-substituted piperazine derivatives bearing a norbornene nucleus have been prepared and their affinity for serotonin 5-HT1A, 5-HT2A and 5-HT2C receptors has been evaluated. Compounds showing the highest affinity have been selected and evaluated on dopaminergic (D1 and D2) and adrenergic (alpha1 and alpha2) receptors. The combination of structural elements (heterocyclic nucleus, oxyalkyl chain and 4-substituted piperazine) known to be critical in order to have affinity on serotonin receptors and the proper selection of substituents led to compounds with higher receptor specificity and affinity. In binding studies, several molecules showed affinity in nanomolar range towards 5-HT1A, 5-HT2A and 5-HT2C receptors and moderate to no affinity for other relevant receptors (D1, D2, alpha1 and alpha2). Compound 2q 4-[2-[4-(3,4-dichlorophenyl)piperazin-1-yl]ethoxy]-4-aza-tricyclo[5.2.1.02,6]dec-8-ene-3,5-dione (Ki = 1.13 nM), was the most active and selective derivative for the 5-HT2C receptor with respect to other serotonin, dopaminergic and adrenergic receptors. Moreover, compound 3p showed mixed 5-HT2A/5-HT2C activity with affinity values in nanomolar range.

Folic acid-based intervention in non-ST elevation acute coronary syndromes.

Homocysteinemia is a risk factor for cardiovascular diseases. Folic acid combined with vitamins B(6) and B(12) is effective in lowering homocysteine levels. This randomized placebo-controlled study was designed to determine the effect of a folic acid-based supplement on secondary prevention of clinical events in non-ST-segment elevation acute coronary syndromes. The study comprised 240 patients with either unstable angina or non-ST-elevation myocardial infarction in the previous 2 weeks who were randomized to a folate group (n =116) or a placebo group (n =124). The folate group received 1 mg folic acid, 400 microg vitamin B(12), and 10 mg vitamin B(6) daily. Clinical outcomes within 6 months were assessed. The composite endpoint of death, nonfatal acute coronary syndrome, and serious re-hospitalization was significantly higher in the folate group; serious re-hospitalization alone was significantly higher in this group. Advanced age and diabetes increased susceptibility to the composite outcome. Folic acid-based supplementation is not beneficial and may even be harmful in the secondary prevention of cardiovascular events in patients with unstable angina and non-ST-elevation myocardial infarction. Further studies on the safety of such supplements are suggested. Controlled Clinical Trials Registry no. ISRCTN30249553.

Recent advances in synthesis of PAR ligands as therapeutic strategy for inflammatory diseases.

Several studies have been published on discovering involvement of PARs receptors in a number of disease states, including cancer and inflammation of the cardiovascular, respiratory, musculoskeletal, gastrointestinal and nervous systems. This mini-review will focus on recent advances in the synthesis of PAR ligands highlighting their therapeutic potential in the treatment of various inflammatory diseases.

Microwave assisted synthesis: a new technology in drug discovery.

The interest in the microwave assisted organic synthesis has been growing during the recent years. It results from an increasing knowledge of fundamentals of the dielectric heating theory, availability of an equipment designed especially for the laboratory use as well as the discovery of the special techniques of the microwave syntheses. The efficiency of microwave flash-heating chemistry in dramatically reducing reaction times (reduced from days and hours to minutes and seconds) has recently been proven in several different fields of organic chemistry and this aspect is of great importance in high-speed combinatorial and medicinal chemistry. In this contribution, the current state of the art is summarized providing examples of the most recent applications in the field of microwave assisted synthesis of biologically active compounds both in heterocyclic and in peptide and peptidomimetic optimization.

Homocysteine predicts adverse clinical outcomes in unstable angina and non-ST elevation myocardial infarction: implications from the folate intervention in non-ST elevation myocardial infarction and unstable angina study.

BACKGROUND: Unstable angina and non-ST elevation myocardial infarction (NSTEMI) are common acute coronary events. Homocysteine is a novel risk factor for coronary heart diseases. Together with the conventional risk factors, they may affect the outcome of non-ST coronary events. OBJECTIVE: This study aims to determine the effect of clinical risk factors that are responsible for the occurrence of mortality, and the composite outcome of mortality, nonfatal myocardial infarction and serious rehospitalization within 6 months after the onset of non-ST acute coronary syndromes. METHODS: A total of 124 Filipino patients were interviewed and tested for blood homocysteine levels and lipid profiles. Outcomes were assessed after 6 months. RESULTS: Homocysteinemia (>16 micromol/l) is associated with increased mortality and composite outcomes (mortality, nonfatal reinfarction, and serious rehospitalization), even if adjusted for conventional risk factors. No association was detected for the conventional risk factors. Earlier acute coronary syndrome was found to be positively associated with mortality and the composite outcomes. Early stroke is associated with increased composite outcomes, whereas greater mortality and adverse outcomes were observed in NSTEMI compared with intermediate-risk unstable angina. CONCLUSION: Increased homocysteine level is associated with mortality and serious nonfatal outcomes in patients with unstable angina and NSTEMI.

Milk and fat production of crossbred Holstein-Gir cows (Bos taurus taurus-Bos taurus indicus) in the agreste region of the Brazilian state of Pernambuco

The productive performance of four Holstein-Gir genetic groups (1/2H, 1/4H, 5/8H, 5/8Hinter se) and the effects of non-genetic factors on production traits was evaluated using a data set of 7,951 test-day samples collected between January 1980 and December 1999 from the Arcoverde Experimental Station in the Brazilian state of Pernambuco (Empresa Pernambucana de Pesquisa Agropecuária). The statistical model included the fixed effects of calving year (1980 to 1999) and month (January to December), genetic group of the cow, age at months of calving (33 to 190) and days in milk at each test-day. Random effects were sire, cow and residual with test-days treated as repeated records within each cow within each lactation. For the four genetic groups the milk yield (MY) means were 1/2H = 8.61 kg ± 1.16 kg, 1/4H = 5.34 kg ± 0.46 kg, 5/8H = 7.42 kg ± 0.39 kg and 5/8Hinter se = 5.76 kg ± 0.46 kg; the fat yield (FY) means were 1/2H = 0.375 kg ± 0.052 kg, 1/4H = 0.231 kg ± 0.026 kg, 5/8H = 0.299 kg ± 0.025 kg and 5/8Hinter se = 0.231 kg ± 0.026 kg; and the fat percentage (FP) means were 1/2H = 4.45 kg ± 0.29 percent, 1/4H = 4.08 kg ± 0.12 percent, 5/8H = 3.87 kg ± 0.10 percent and 5/8Hinter se = 3.89 kg ± 0.12 percent. Phenotypic correlations between tests were MY = 0.97, FY = 0.94 and FP = 0.98. The best productive performance was for the 1/2H group, followed by the 5/8H group. The performance of the synthetic group was substantially below the performance of the 5/8H group.

Synthesis of 6beta-D-glucosyl and 6-nitroxy (-)-galanthamine derivatives as acetylcholinesterase inhibitors.

Galanthamine is an alkaloid approved for the treatment of Alzheimer's disease. In this paper the syntheses and the anticholinesterase activities of new glucosyl and nitroxy derivatives substituted on position 6 are reported. Compounds 2, 3 and 5 presented a percentage of inhibition of 35.22%, 47.48% and 67.89% respectively.

[Association between serum markers for celiac and thyroid autoimmune diseases]. / Associação entre marcadores sorológicos de doença celíaca e das doenças autoimunes da tireóide.

Celiac disease (CD) is an autoimmune disease of the small bowel characterized by a strong genetic association with HLA - DQ2 and DQ8. Gluten is the etiological factor and the tissue enzyme transglutaminase (TGase) is its autoantigen. CD is associated with several autoimmune diseases such as type 1 diabetes, systemic lupus erythematous, rheumatoid arthritis, Sjögrens syndrome and autoimmune thyroid diseases. The aim of this study was to investigate the occurrence of serum IgA anti-endomysial and anti-human TGase antibodies in individuals with positive anti-thyroid antibody (ATA). The concordance between these two tests was also evaluated. Anti-endomysial antibodies were positive in 10 out of 456 (2.2%) and anti-human TGase were positive in 14 of 454 (3.1%) individuals with positive ATA. In control subjects they were positive in 1 of 197 (0.5%) and 2 of 198 (1%) for anti-endomysial and anti-human tissue TGase antibodies, respectively. The odds ratio (OR) for the anti-endomysial antibodies was 4.42 and for the anti-human TGase 3.12 in individuals with ATA when compared with controls. An elevated concordance index (k= 0.84) was observed between anti-endomisyal antibodies and anti-human TGase. We conclude that the determination of anti-TGase antibodies is a good test for DC screening.

Associação entre marcadores sorológicos de doença celíaca e das doenças autoimunes da tireóide / Association between serum markers for celiac and thyroid autoimmune diseases

Doença celíaca (DC) é uma doença autoimune do intestino delgado com importante associação com HLA-DQ2 e DQ8. Tem o glúten como fator etiológico e a enzima transglutaminase (TGase) tecidual como autoantígeno. A DC é associada a outras doenças autoimunes como diabetes mellitus tipo 1, lupus eritematoso sistêmico, artrite reumatóide, síndrome de Sjõgren e doenças autoimunes da tireóide. O objetivo deste estudo foi investigar a ocorrência de anticorpos séricos da classe IgA anti-endomísio e anti-TGase tecidual humana em indivíduos com anticorpo anti-tireoidiano (AAT) positivo. Foi também pesquisada a concordância destes dois marcadores. Anticorpos anti-endomísio foram positivos em 10 de 456 (2,2 por cento) e anti-TGase tecidual foi positiva em 14 de 454 (3,1 por cento) dos indivíduos com AAT positivo. No grupo controle, 1 de 197 (0,5 por cento) e 2 de 198 (1 por cento) foram positivos para anticorpo anti-endomísio e anti-TGase tecidual humana, respectivamente. A chance de positividade dos anticorpos anti-endomísio foi de 4,42 e do anti-TGase tecidual humana 3,12 vezes maior nos indivíduos com positividade para AAT que nos controles. Um elevado índice de concordância (k= 0,84) foi obtido entre os testes para anticorpos anti-endomísio e anti-TGase. Os resultados obtidos neste trabalho não justificam uma triagem rotineira de DC em portadores de AAT. Concluímos que a pesquisa de anticorpos anti-TGase mostrou-se um teste útil para rastrear DC.

Prioridades valorativas e individualismo-coletivismo: padrões de convergência / Priorities values, individualism and collectivism patterns of convergence

Este trabalho teve como objetivo principal conhecer a relação dos valores humanos com os construtos individualismo e coletivismo, considerando seus atributos vertical e horizontal. Participaram do estudo 510 estudantes da 5º e da 7º séries do ensino fundamental, do 1º e do 3º anos do ensino médio e de cursos universitários, de ambos os sexos. Estes responderam ao Questionário dos Valores Básicos e à Escala de Individualismo e Coletivismo. Os resultados confirmam as relações teoricamente esperadas (Gouveia, 2000): a pontuações em individualismo, considerado como um fator geral, correlacionaram-se direta e significativamente com os valores pessoais, enquanto que o coletivismo o fez com os valores sociais. Estes achados são discutidos, considerando a possibilidade de um paradigma normativo no estudo destes construtos (Kagitçibasi, 1997)

Probing the shape of a hydrophobic pocket in the active site of delta-opioid antagonists.

The change of selectivity and the induction of antagonism by the insertion of 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (Tic) in the second position of several opioid peptides have led to the interpretation of Tyr-Tic as a specific message domain for delta-opioid antagonists and to the discovery of dipeptides with substantial opioid activity. Selectivity and activity increase enormously when Tyr is substituted by 2',6'-dimethyl tyrosine (Dmt), hinting that the side chain of Dmt fits a hydrophobic cavity of the receptor very tightly and precisely. We have investigated the specificity of this fit by systematic changes of the substituents on the aromatic ring of ryr. Mono- and disubstitutions different from 2',6'- invariably lead to catastrophic decreases of activity. The only substitution compatible with retention of substantial antagonism is 2-methyl. An analysis of the conformational properties of all analogues reveals that substitutions do not affect the global shape of the molecule significantly. Accordingly, it is possible to use the shape of the different side chains to map the hydrophobic cavity of the receptor. The resulting complementary image is funnel shaped.

Synthesis of substituted benzamides as anti-inflammatory agents that inhibit preferentially cyclooxygenase 1 but do not cause gastric damage.

Parsalmide (5-amino-N-butyl-2-(2-propynyloxy) benzamide) (5a), is a non-steroidal anti-inflammatory drug (NSAID), commercialised in Italy until 1985 with the brand name of Synovial(R), that has been widely used to treat arthritic patient. In addition, it was shown to spare gastric mucosa. Here we have synthesised a series of novel substituted benzamides, related to Parsalmide, and have evaluated their activity in vitro on COX-1 and COX-2 as well as in vivo in the carrageenin-induced rat paw edema, a classical in vivo anti-inflammatory assay. Compounds 5b, 11a and 11b, which showed a favourable profile in vitro and in vivo, were screened in comparison with Parsalmide for gastrointestinal (GI) tolerability in vivo in the rat. Results obtained showed that Parsalmide and compound 11b inhibited both COX-1 and COX-2 in vitro as well as they were active in vivo. Both compounds were devoid of gastric effect at the efficacious dose. In addition, both prevented indomethacin-induced gastric damage. Thus, these compounds may guide the definition of a new leading structure with anti-inflammatory activity that may allow designing new safer NSAIDs.