Design, synthesis and the effect of 1,2,3-triazole sialylmimetic neoglycoconjugates on Trypanosoma cruzi and its cell surface trans-sialidase

This work describes the synthesis of a series of sialylmimetic neoglycoconjugates represented by 1,4-disubstituted 1,2,3-triazole-sialic acid derivatives containing galactose modified at either C-1 or C-6 positions, glucose or gulose at C-3 position, and by the amino acid derivative 1,2,3-triazole fused threonine-3-O-galactose as potential TcTS inhibitors and anti-trypanosomal agents. This series was obtained by Cu(I)-catalysed azide-alkyne cycloaddition reaction ('click chemistry') between the azido-functionalized sugars 1-N(3)-Gal (commercial), 6-N(3)-Gal, 3-N(3)-Glc and 3-N(3)-Gul with the corresponding alkyne-based 2-propynyl-sialic acid, as well as by click chemistry reaction between the amino acid N(3)-ThrOBn with 3-O-propynyl-GalOMe. The 1,2,3-triazole linked sialic acid-6-O-galactose and the sialic acid-galactopyranoside showed high Trypanosoma cruzi trans-sialidase (TcTS) inhibitory activity at 1.0 mM (approx. 90%), whilst only the former displayed relevant trypanocidal activity (IC(50) 260 mu M). These results highlight the 1,2,3-triazole linked sialic acid-6-O-galactose as a prototype for further design of new neoglycoconjugates against Chagas' disease. (C) 2011 Elsevier Ltd. All rights reserved.

The chemiluminescent peroxyoxalate system: state of the art almost 50 years from its discovery

Almost fifty years after the discovery of the peroxyoxalate reaction by E. A. Chandross in the early nineteen sixties, this review article intends to give a general overview on mechanistic aspects of this system and to describe the principles of its analytical application. After a short general introduction on the principles of chemiluminescence and the history of peroxyoxalate discovery, mechanistic aspects of high-energy intermediate formation, its structure and its reaction with an activator in the peroxyoxalate system are discussed. Finally, analytical applications of peroxyoxalate chemiluminescence are exemplified using representative recent examples, including oxalic acid detection in biological samples.

Digestible lysine levels in diets for pigs from 24 to 50 kg under sanitary segregation

This study evaluated the relationship between digestible lysine and metabolizable energy for barrow and gilts from 24 to 50 kg. Performance, digestibility and blood profile were studied. The experimental design was of randomized blocks, with five treatments, eight replicates and two animals per experimental unit in the performance assay and four replicates and one animal per experimental unit in the digestibility assay. The blood profile was chosen at 20 random animals of each sex, with four replicates per treatment and the animal as experimental unit. The treatments were 0.80, 0.90, 1.00, 1.10 and 1.20% digestible lysine. There was a linear effect of lysine levels on weight gain and feed conversion in females and crude protein in both sexes, gross energy excreted in the urine (kcal) and digestible energy (kcal). A quadratic effect of the amino acid studied in the daily consumption of crude protein (g) in both sexes, weight gain and feed conversion of barrows, as well as the nitrogen excreted in the urine (g) and nitrogen retained, and absorbed and retained. The relationship between neutrophils and lymphocytes had quadratic responses with increasing levels of lysine. The maximum performance for the studied genotype was obtained with 0.88 and 0.91% of digestible lysine or 2.60 and 2.67 g of digestible lysine/Mcal of metabolizable energy for females and barrows, respectively, corrected for digestibility trial.

Structure of the N=50 As, Ge, Ga nuclei

The level structures of the N = 50 As-83, Ge-82, and Ga-81 isotones have been investigated by means of multi-nucleon transfer reactions. A first experiment was performed with the CLARA PRISMA setup to identify these nuclei. A second experiment was carried out with the GASP array in order to deduce the gamma-ray coincidence information. The results obtained on the high-spin states of such nuclei are used to test the stability of the N = 50 shell closure in the region of Ni-78 (Z = 28). The comparison of the experimental level schemes with the shell-model calculations yields an N = 50 energy gap value of 4.7(3) MeV at Z = 28. This value, in a good agreement with the prediction of the finite-range liquid-drop model as well as with the recent large-scale shell model calculations, does not support a weakening of the N = 50 shell gap down to Z = 28. (c) 2012 Elsevier B.V. All rights reserved.

Antenatal depression strongly predicts postnatal depression in primary health care

Objective: To estimate the association between antenatal and postnatal depression and to examine the role of socioeconomic conditions in the risk of postnatal depression. Methods: A prospective cohort study, conducted between May 2005 and January 2006, with 831 pregnant women recruited from primary care clinics in the public sector in the city of Sao Paulo, Brazil. The presence of antenatal and postnatal depression was measured with the Self Report Questionnaire (SRQ-20). Sociodemographic and socioeconomic characteristics and obstetric information were obtained through a questionnaire. Crude and adjusted risk ratios (RR), with 95% CI, were calculated using a Poisson regression. Results: The prevalence of postnatal depressive symptoms was 31.2% (95% CI: 27.8-34.8%). Among the 219 mothers who had depressive symptoms, nearly 50% had already shown depressive symptoms during pregnancy. Women who had antenatal depression were 2.4 times more likely to present with postnatal depression than were women who did not have such symptoms during pregnancy. In the multivariate analysis, higher scores for assets (RR: 0.76, 95% CI 0.61-0.96), higher education (RR: 0.75 95% CI 0.59-0.96), daily contact with neighbors (RR: 0.68, 95% CI 0.51-0.90) and antenatal depression (RR: 2.44, 95% CI 1.93-3.08) remained independently associated with postnatal depression. Conclusions: Antenatal and postnatal depression are highly prevalent in the primary care setting.

Solid Dispersion of Ursolic Acid in Gelucire 50/13: a Strategy to Enhance Drug Release and Trypanocidal Activity

Solid dispersions (SDs) are an approach to increasing the water solubility and bioavailability of lipophilic drugs such as ursolic acid (UA), a triterpenoid with trypanocidal activity. In this work, Gelucire 50/13, a surfactant compound with permeability-enhancing properties, and silicon dioxide, a drying adjuvant, were employed to produce SDs with UA. SDs and physical mixtures (PMs) in different drug/carrier ratios were characterized and compared using differential scanning calorimetry, hot stage microscopy, Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), particle size, water solubility values, and dissolution profiles. Moreover, LLC-MK2 fibroblast cytotoxicity and trypanocidal activity evaluation were performed to determine the potential of SD as a strategy to improve UA efficacy against Chagas disease. The results demonstrated the conversion of UA from the crystalline to the amorphous state through XRD. FTIR experiments provided evidence of intermolecular interactions among the drug and carriers through carbonyl peak broadening in the SDs. These findings helped explain the enhancement of water solubility from 75.98 mu g/mL in PMs to 293.43 mu g/mL in SDs and the faster drug release into aqueous media compared with pure UA or PMs, which was maintained after 6 months at room temperature. Importantly, improved SD dissolution was accompanied by higher UA activity against trypomastigote forms of Trypanosoma cruzi, but not against mammalian fibroblasts, enhancing the potential of UA for Chagas disease treatment.

Safety and efficacy of sitaxsentan 50 and 100 mg in patients with pulmonary arterial hypertension

Objective: To assess safety and efficacy of sitaxsentan 50 and 100 mg in patients with pulmonary arterial hypertension (PAH). Background: Sitaxsentan is a highly selective endothelin-A receptor antagonist that was recently withdrawn by the manufacturer because of a pattern of idiosyncratic liver injury. Methods: Before sitaxsentan withdrawal, this 18-week double-blind, placebo-controlled study randomized patients with PAH to receive placebo or sitaxsentan 50 or 100 mg once daily. The primary efficacy endpoint was change from baseline in 6-min walk distance (6MWD) at week 18. Changes in World Health Organization (WHO) functional class and time to clinical worsening (TTCW) were secondary endpoints. The primary efficacy analysis was powered for sitaxsentan 100 mg versus placebo. Results: Of 98 randomized patients, 61% were WHO functional class II at baseline. Improvement from baseline to week 18 in 6MWD occurred with sitaxsentan 100 but not 50 mg; a strong placebo effect was observed. At week 18, WHO functional class was improved or maintained in more patients receiving sitaxsentan 100 mg than placebo (P = 0.038); 0% versus 12% of patients deteriorated, respectively. TTCW was not significantly different for 100-mg sitaxsentan patients than placebo (P = 0.090). Adverse events (AEs) occurring more frequently with sitaxsentan (50 or 100 mg) included headache, peripheral edema, dizziness, nausea, extremity pain, and fatigue; most AEs were of mild or moderate severity. Conclusion: Sitaxsentan 100 mg improved functional class but not 6MWD in PAH patients who were mostly WHO functional class II at baseline. No patient receiving sitaxsentan 100 mg experienced clinical worsening; sitaxsentan was well tolerated. (C) 2011 Elsevier Ltd. All rights reserved.

The impact of medical education and networking on the outcome of leukemia treatment in developing countries. The experience of International Consortium on Acute Promyelocytic Leukemia (IC-APL)

Objectives: Several clinical trials conducted in Europe and US reported favorable outcomes of patients with APL treated with the combination of all trans retinoic acid (ATRA) and anthracyclines. Nevertheless, the results observed in developing countries with the same regimen was poorer, mainly due to high early mortality mainly due bleeding. The International Consortium on Acute Promyelocytic Leukemia (IC-APL) is an initiative of the International Members Committee of the ASH and the project aims to reduce this gap through the establishment of international network, which was launched in Brazil, Mexico and Uruguay. Methods: The IC-APL treatment protocol is similar to the PETHEMA 2005, but changing idarubicin to daunorubicin. All patients with a suspected diagnosis of APL were immediately started on ATRA, while bone marrow samples were shipped to a national central lab where genetic verification of the diagnosis was performed. The immunofluorescence using an anti-PML antibody allowed a rapid confirmation of the diagnosis and, the importance of supportive measures was reinforced. Results: The interim analysis of 97 patients enrolled in the IC-APL protocol showed that complete remission (CR) rate was 83% and the 2-year overall survival and disease-free survival were 80% and 90%, respectively. Of note, the early mortality rate was reduced to 7.5%. Discussion: The results of IC-APL demonstrate the impact of educational programs and networking on the improvement of the leukemia treatment outcome in developing countries.

Sulcus anatomy and diameter in pseudophakic eyes and correlation with biometric data: Evaluation with a 50 MHz ultrasound biomicroscope

PURPOSE: To evaluate the sulcus anatomy and possible correlations between sulcus diameter and white-to-white (WTW) diameter in pseudophakic eyes, data that may be important in the stability of add-on intraocular lenses (IOLs). SETTING: University Eye Hospital, Tuebingen, Germany. DESIGN: Case series. METHODS: In pseudophakic eyes, the axial length (AL) and horizontal WTW were measured by the IOLMaster device. Cross-sectional images were obtained with a 50 MHz ultrasound biomicroscope on the 4 meridians: vertical, horizontal (180 degrees), temporal oblique, and nasal oblique. Sulcus-to-sulcus (STS), angle-to-angle (ATA), and sclera-to-sclera (ScTSc) diameters were measured. The IOL optic diameter (6.0 mm) served as a control. To test reliability, optic measurements were repeated 5 times in a subset of eyes. RESULTS: The vertical ATA and STS diameters were statistically significantly larger than the horizontal diameter (P=.0328 and P=.0216, respectively). There was no statistically significant difference in ScTSc diameters. A weak correlation was found between WTW and horizontal ATA (r = 0.5766, P<.0001) and between WTW and horizontal STS (r = 0.5040, P=.0002). No correlation was found between WTW and horizontal ScTSc (r = 0.2217, P=.1217). CONCLUSIONS: The sulcus anatomy had a vertical oval shape with the vertical meridian being the largest, but it also had variation in the direction of the largest meridian. The WTW measurements showed a weak correlation with STS. In pseudophakic eyes, Soemmerring ring or a bulky haptic may affect the ciliary sulcus anatomy.

Fatigue Reliability of 3 Single-Unit Implant-Abutment Designs

Objectives: Because the mechanical behavior of the implant-abutment system is critical for the longevity of implant-supported reconstructions, this study evaluated the fatigue reliability of different implant-abutment systems used as single-unit crowns and their failure modes. Methods and Materials: Sixty-three Ti-6Al-4V implants were divided in 3 groups: Replace Select (RS); IC-IMP Osseotite; and Unitite were restored with their respective abutments. Anatomically correct central incisor metal crowns were cemented and subjected to separate single load to failure tests and step-stress accelerated life testing (n = 18). A master Weibull curve and reliability for a mission of 50,000 cycles at 200 N were calculated. Polarized-light and scanning electron microscopes were used for failure analyses. Results: The load at failure mean values during step-stress accelerated life testing were 348.14 N for RS, 324.07 N for Osseotite, and 321.29 N for the Unitite systems. No differences in reliability levels were detected between systems, and only the RS system mechanical failures were shown to be accelerated by damage accumulation. Failure modes differed between systems. Conclusions: The 3 evaluated systems did not present significantly different reliability; however, failure modes were different. (Implant Dent 2012;21:67-71)

Uso da monitorização hemodinâmica contínua não invasiva na insuficiência cardíaca descompensada

FUNDAMENTO: A avaliação clínico-hemodinâmica à beira do leito e o uso do cateter de artéria pulmonar para a estimativa de dados hemodinâmicos têm sido utilizados na insuficiência cardíaca descompensada. Entretanto, não existem dados com o uso da monitorização hemodinâmica contínua não invasiva. OBJETIVO: Comparar as medidas obtidas com a monitorização hemodinâmica não invasiva com as invasivas em pacientes com insuficiência cardíaca descompensada e refratária ao tratamento. MÉTODOS: As medidas hemodinâmicas não invasivas foram obtidas através da monitorização contínua da pressão arterial sistêmica pelo modelo de ondas de pulso (modelflow) e foram comparadas com as medidas obtidas pela passagem do cateter de artéria pulmonar, simultaneamente. RESULTADOS: Foram realizadas 56 medidas em 14 pacientes estudados em dias e horários diferentes. O índice de correlação entre as medidas da pressão arterial sistólica foi de r = 0,26 (IC 95% = 0,00 a 0,49, p = 0,0492) e da diastólica de r = 0,50 (IC 95% = 0,27 a 0,67, p < 0,0001). A correlação foi de r = 0,55 (IC 95% = 0,34 a 0,71, p 0,0001) para o índice cardíaco e de r = 0,32 (IC 95% = 0,06 a 0,53, p = 0,0178) para a resistência vascular sistêmica. CONCLUSÃO: Houve correlação entre as medidas hemodinâmicas não invasivas quando comparadas às medidas do cateter de artéria pulmonar. A monitorização hemodinâmica contínua não invasiva pode ser útil para pacientes internados com insuficiência cardíaca descompensada.

Adaptação cultural cruzada e validação da versão do Índice Funcional de Espondilite Anquilosante de Bath (BASFI) para o português do Brasil

OBJETIVO: Conduzir uma adaptação cultural cruzada do Índice Funcional de Espondilite Anquilosante de Bath (BASFI, Bath Ankylosing Spondylitis Functional Index) para o português do Brasil e avaliar suas propriedades de medição. MéTODOS: O BASFI foi traduzido por quatro reumatologistas e três professores de língua inglesa. O questionário traduzido foi aplicado a pacientes com espondilite anquilosante por observadores treinados e autoaplicado em três momentos, dias 1, 2 e 14. A validade foi estimada analisando-se a associação do BASFI e as medidas de capacidade funcional (rotação cervical, distância intermaleolar, teste de Schober e distância occipito-parede). A consistência interna foi testada pelo coeficiente α de Cronbach, e a confiabilidade pelo teste-reteste (coeficiente de correlação intraclasse [CCI]). RESULTADOS: Foram incluídos 60 pacientes com espondilite anquilosante: 85% do gênero masculino, com idade média de 47 ± 12 anos e duração média da doença de 20 ± 11 anos. A confiabilidade intraobservador no teste-reteste (intervalo de duas semanas) revelou alto ICC (0,999; 95% IC: 0,997-0,999), além de alta consistência interna (coeficiente α de Cronbach: 0,86; 95% IC: 0,80-0,90). Considerando-se a validade, os índices do BASFI foram correlacionados com a rotação cervical (0,53; P < 0,001) e a distância intermaleolar (0,50; P < 0,001). CONCLUSÃO: A versão do BASFI para o português do Brasil é confiável e válida para avaliação de pacientes com espondilite anquilosante.

Audição e linguagem em crianças deficientes auditivas implantadas inseridas em ambiente bilíngue: um estudo de casos

O implante coclear (IC) tem sido indicado para crianças deficientes auditivas de grau severo e/ou profundo que não tem benefício com o aparelho de amplificação sonora individual (AASI), e que apresentem família adequada e motivada para o uso do dispositivo, bem como condições adequadas de reabilitação na cidade de origem. Atualmente, a procura pelo IC também ocorre por pais surdos, fluentes na Língua Brasileira de Sinais (LIBRAS), que recorrem a este tratamento para oferecer outra realidade para seus filhos. O ambiente destas crianças é bilíngue, dado pela LIBRAS dos pais e pela linguagem oral dos familiares próximos, do fonoaudiólogo e da escola. Neste sentido, o presente estudo visou acompanhar quatro crianças deficientes auditivas implantadas, sendo duas crianças filhas de pais deficientes auditivos fluentes na LIBRAS (expostas a ambiente bilíngue) e duas crianças filhas de pais sem alterações auditivas (expostas a ambiente oral). Para tanto, as habilidades de audição e de aquisição da linguagem oral foram comparadas nas quatro crianças implantadas. Foi possível observar que as quatro crianças apresentaram habilidades auditivas e de linguagem semelhantes ao longo do primeiro ano de uso do IC. Contudo, a partir disto, as crianças inseridas em ambiente bilíngue apresentaram melhor desempenho auditivo e linguístico, comparado ao desenvolvimento das outras crianças. As crianças inseridas em ambiente bilíngue podem se beneficiar do IC, desenvolvendo habilidades auditivas e de linguagem similares às das crianças inseridas em ambiente oral. Ressalta-se que os benefícios do dispositivo são obtidos a partir de aspectos multifatoriais, e estudos mais aprofundados são necessários.