Synthesis of fragments of Salmonella Typhi capsular polysaccharide and their zwitterionic analogues

We will report on the synthesis of oligomers of Salmonella enterica serovar Typhi (often called S. Typhi) CPS, and their zwitterionic analogues. S. Typhi is a motile Gram-negative bacterium, whose CPS (often referred to as Vi antigen) is an anionic polymer composed by \u3b1-(1-4)-linked N-acetyl galactosaminuronic acid repeating units predominantly O-acetylated at position 3. We developed a strategy based on versatile intermediates enabling chain elongation either by iterative single monomer attachment or by faster and more flexible approaches using disaccharide donors. All these intermediates were obtained from commercially available D-galactosamine hydrochloride. The non participating azide group was used to mask C-2 amino functionality, which can be converted into the animo group (ZPS) or into the acetamido function (natural Vi) and allows the formation of 1,2-cis glycosidic linkages. Glycosylation reactions were carried out using N-phenyltrifluoroacetimidates as glycosyl donors, yielding stereoselectively the desired \u3b1 product. C-6 oxidation was done with TEMPO/NaClO2. By orthogonally protecting position 3 we were able to obtain both fully 3-O-acetylated and fully 3-O-deactetylated oligomers. Finally, a suitable l inker was installed at C-1 of the reducing end in order to facilitate a subsequent conjugation to protein carrier and/or multivalents caffolds. The immunological properties of the synthetic oligomers will be also investigated in order to correlate the structural features (in particular 3-O-acetylation) with their biological behaviour

Synthesis of fragments of Salmonella Typhi capsular polysaccharide and their zwitterionic analogues

We will report on the synthesis of oligomers of Salmonella enterica serovar Typhi (often called S. Typhi) CPS, and their zwitterionic analogues. S. Typhi is a motile Gram-negative bacterium, whose CPS (often referred to as Vi antigen) is an anionic polymer composed by \u3b1-(1-4)-linked N-acetyl galactosaminuronic acid repeating units predominantly O-acetylated at position 3. We developed a strategy based on versatile intermediates enabling chain elongation either by iterative single monomer attachment or by faster and more flexible approaches using disaccharide donors. All these intermediates were obtained from commercially available D-galactosamine hydrochloride. The non participating azide group was used to mask C-2 amino functionality, which can be converted into the animo group (ZPS) or into the acetamido function (natural Vi) and allows the formation of 1,2-cis glycosidic linkages. Glycosylation reactions were carried out using N-phenyltrifluoroacetimidates as glycosyl donors, yielding stereoselectively the desired \u3b1 product. C-6 oxidation was done with TEMPO/NaClO2. By orthogonally protecting position 3 we were able to obtain both fully 3-O-acetylated and fully 3-O-deactetylated oligomers. Finally, a suitable l inker was installed at C-1 of the reducing end in order to facilitate a subsequent conjugation to protein carrier and/or multivalents caffolds. The immunological properties of the synthetic oligomers will be also investigated in order to correlate the structural features (in particular 3-O-acetylation) with their biological behaviour

Annual Variation Of Sex Ratio In Twin Births And In Singletons In Brazil.

The annual variation of the sex ratio (SR) of 1385 twin births was analyzed and compared to that of 85909 singletons. These births referred not only to live births but also to stillbirths in two southeastern Brazilian maternity hospitals from 1984 to 1993. While the annual variation of the SR of singletons was very small, that of twin births was extremely high, due to the significant heterogeneity of the annual data. It is suggested that the large SR annual variation of the twin birth might be a consequence of the variation of male or female monozygotic twins. The hypothesis that twin births show a lower sex ratio than singletons could be supported by the present data.44163-

Prevalência de nascimentos gemelares em Pelotas, Rio Grande do Sul, Brasil Prevalence of twin births in Pelotas, in the State of Rio Grande do Sul, Brazil

OBJETIVOS: avaliar a prevalência de nascimentos gemelares em Pelotas, RS, em três períodos da última década e a influência de alguns fatores sobre este processo. MÉTODOS: estudo de corte transversal (série temporal), baseado no banco de dados do Programa de Monitorização de Defeitos Congênitos, onde se encontram registrados todos os nascimentos ocorridos nos cinco hospitais da cidade de Pelotas, nos anos de 1993, 1997 e 2003. RESULTADOS: a taxa média de gêmeos por mil nascimentos foi de 8,95&#137; (monozigóticos=2,20&#137; e dizigóticos=6,76&#137; ). A taxa de triplos ficou em 0,07&#137; . A taxa total de nascimentos gemelares, assim como de gêmeos monozigóticos e dizigóticos sofreu elevação no período. A média de idade (27,53 anos) e da ordem gestacional (2,35) das mães de gêmeos foi significativamente mais elevada do que das mães de únicos (26,03 anos e 2,14) respectivamente. Verificaram-se números aproximados de partos gemelares e únicos nos diferentes grupos de renda materna analisados. CONCLUSÕES: as mães com idade maior ou igual a 30 anos foram responsáveis pelo aumento da taxa de gêmeos em Pelotas. A média mais elevada de ordem gestacional em mães de gemelares descartou o uso significativo de técnicas de reprodução assistida.<br>OBJECTIVES: to evaluate the prevalence of twin births in Pelotas, Rio Grande do Sul, Brazil, during three periods, and the influence of a number of factors on this occurrence. METHODS: a cross-cutting (multiple time series) study was carried out, using the database of the Congenital Defect Monitoring Program, which registers all of the births occurring in the five hospitals of the city of Pelotas, for the years 1993, 1997 and 2003. RESULTS: the mean prevalence of twin births per thousand births (&#137; )t was 8.95&#137; (monozygotic=2.20&#137; and dizygotic=6.76&#137; ). The prevalence of triplets was 0.07&#137; . The total prevalence for twin births, in the case of both monozygotic and dizygotic twins rose over the period studied. The mean age of the mother (27.53 years) and the order in the series of gestations (2.35) were significantly higher in cases of twin births than in cases of the birth of a single infant (26.03 years and 2.14 respectively). CONCLUSIONS: mothers aged >30 years were responsible for the increase in the prevalence of twin births in Pelotas. The higher mean position in a sequence of gestations among mothers of twins ruled out the significance of the use of fertility treatment techniques