Withanolides and related steroids

Since the isolation of the first withanolides in the mid-1960s, over 600 new members of this group of compounds have been described, with most from genera of the plant family Solanaceae. The basic structure of withaferin A, a C28 ergostane with a modified side chain forming a δ-lactone between carbons 22 and 26, was considered for many years the basic template for the withanolides. Nowadays, a considerable number of related structures are also considered part of the withanolide class; among them are those containing γ-lactones in the side chain that have come to be at least as common as the δ-lactones. The reduced versions (γ and δ-lactols) are also known. Further structural variations include modified skeletons (including C27 compounds), aromatic rings and additional rings, which may coexist in a single plant species. Seasonal and geographical variations have also been described in the concentration levels and types of withanolides that may occur, especially in the Jaborosa and Salpichroa genera, and biogenetic relationships among those withanolides may be inferred from the structural variations detected. Withania is the parent genus of the withanolides and a special section is devoted to the new structures isolated from species in this genus. Following this, all other new structures are grouped by structural types. Many withanolides have shown a variety of interesting biological activities ranging from antitumor, cytotoxic and potential cancer chemopreventive effects, to feeding deterrence for several insects as well as selective phytotoxicity towards monocotyledoneous and dicotyledoneous species. Trypanocidal, leishmanicidal, antibacterial, and antifungal activities have also been reported. A comprehensive description of the different activities and their significance has been included in this chapter. The final section is devoted to chemotaxonomic implications of withanolide distribution within the Solanaceae. Overall, this chapter covers the advances in the chemistry and biology of withanolides over the last 16 years.Fil: Misico, Rosana Isabel. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Orgánica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad de Microanálisis y Métodos Físicos Aplicados a la Química Orgánica (i); ArgentinaFil: Nicotra, V.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Instituto Multidisciplinario de Biología Vegetal (p); Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Química Orgánica; ArgentinaFil: Oberti, Juan Carlos María. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Instituto Multidisciplinario de Biología Vegetal (p); Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Química Orgánica; ArgentinaFil: Barboza, Gloria Estela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Instituto Multidisciplinario de Biología Vegetal (p); Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Farmacia; ArgentinaFil: Gil, Roberto Ricardo. University Of Carnegie Mellon; Estados UnidosFil: Burton, Gerardo. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Orgánica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad de Microanálisis y Métodos Físicos Aplicados a la Química Orgánica (i); Argentin

Italian guidelines for primary headaches: 2012 revised version

The first edition of the Italian diagnostic and therapeutic guidelines for primary headaches in adults was published in J Headache Pain 2(Suppl. 1):105–190 (2001). Ten years later, the guideline committee of the Italian Society for the Study of Headaches (SISC) decided it was time to update therapeutic guidelines. A literature search was carried out on Medline database, and all articles on primary headache treatments in English, German, French and Italian published from February 2001 to December 2011 were taken into account. Only randomized controlled trials (RCT) and meta-analyses were analysed for each drug. If RCT were lacking, open studies and case series were also examined. According to the previous edition, four levels of recommendation were defined on the basis of levels of evidence, scientific strength of evidence and clinical effectiveness. Recommendations for symptomatic and prophylactic treatment of migraine and cluster headache were therefore revised with respect to previous 2001 guidelines and a section was dedicated to non-pharmacological treatment. This article reports a summary of the revised version published in extenso in an Italian version

Characteristics of eating disorder patients without a drive for thinness.

OBJECTIVE: The aim of this study was to investigate two samples of patients affected by anorexia nervosa (AN) or bulimia nervosa (BN), respectively, with and without the diagnostic feature of drive for thinness (DT). METHOD: The samples comprised 70 consecutive eating disorder (ED) outpatients at the Department of Psychiatry (University of Pisa) and 106 AN patients admitted to a day hospital in Toronto, Canada. Subjects were assessed on clinical and psychometric parameters. RESULTS: In both countries, 17% of the subjects had low DT as measured by the Eating Disorder Inventory (EDI). They comprised the atypical group and appeared to have less severe psychopathology. DISCUSSION: Weight phobia should not be viewed as critical to the diagnosis of ED and DT could be a culture-bound dimension. Considering the differences between the two groups, the characterization of patients as typical and atypical may be clinically useful

Carcinoma diferenciado da tireóide: a validade da complementação da tireoidectomia

OBJETIVO: Analisar a invasão tumoral do lobo contralateral da glândula tireóide no carcinoma diferenciado, correlacionando o risco/benefício com as complicações decorrentes de uma segunda intervenção. MÉTODO: De outubro/93 a dezembro/96 foram operados 20 pacientes com carcinomas diferenciados da glândula tireóide. Os parâmetros analisados foram sexo, idade, tipo de operação, tipo de complicações, histopatológico da peça cirúrgica e invasão do lobo contralateral. Eram dois pacientes do sexo masculino (10%) e 18 do feminino (90%); as idades variaram de 17 a 89 anos; o tipo histológico mais freqüente foi o carcinoma papilífero (13 casos), seguido do folicular (seis casos) e carcinoma de células de Hürthle (um caso). Como primeiro procedimento cirúrgico houve 11 lobectomias + istmectomias, quatro lobectomias subtotais e uma istmectomia. Cinco pacientes não realizaram a totalização (um por fibrose, três por perda de seguimento e um por ser microcarcinoma). RESULTADOS: Na análise do lobo contralateral realizada em 15 pacientes, 11 resultaram negativas e outras quatro positivas (26,6%). As complicações apresentadas foram rouquidão (dois casos revertidos com tratamento fonoterápico), hipoparatireoidismo (dois casos, um transitório e um permanente). CONCLUSÃO: A totalização da tireoidectomia é um procedimento importante no tratamento do tumor maligno da tireóide pela alta porcentagem de metástase contralateral (26,6%). Além disso, é um procedimento com mortalidade nula e pequena incidência de complicações

Sample Size Estimation for Non-Inferiority Trials: Frequentist Approach versus Decision Theory Approach

<div><p>Background</p><p>Non-inferiority trials are performed when the main therapeutic effect of the new therapy is expected to be not unacceptably worse than that of the standard therapy, and the new therapy is expected to have advantages over the standard therapy in costs or other (health) consequences. These advantages however are not included in the classic frequentist approach of sample size calculation for non-inferiority trials. In contrast, the decision theory approach of sample size calculation does include these factors. The objective of this study is to compare the conceptual and practical aspects of the frequentist approach and decision theory approach of sample size calculation for non-inferiority trials, thereby demonstrating that the decision theory approach is more appropriate for sample size calculation of non-inferiority trials.</p><p>Methods</p><p>The frequentist approach and decision theory approach of sample size calculation for non-inferiority trials are compared and applied to a case of a non-inferiority trial on individually tailored duration of elastic compression stocking therapy compared to two years elastic compression stocking therapy for the prevention of post thrombotic syndrome after deep vein thrombosis.</p><p>Results</p><p>The two approaches differ substantially in conceptual background, analytical approach, and input requirements. The sample size calculated according to the frequentist approach yielded 788 patients, using a power of 80% and a one-sided significance level of 5%. The decision theory approach indicated that the optimal sample size was 500 patients, with a net value of €92 million.</p><p>Conclusions</p><p>This study demonstrates and explains the differences between the classic frequentist approach and the decision theory approach of sample size calculation for non-inferiority trials. We argue that the decision theory approach of sample size estimation is most suitable for sample size calculation of non-inferiority trials.</p></div