Lupeol and its esters: NMR, powder XRD data and in vitro evaluation of cancer cell growth

ABSTRACT The triterpene lupeol (1) and some of its esters are secondary metabolites produced by species of Celastraceae family, which have being associated with cytotoxic activity. We report herein the isolation of 1, the semi-synthesis of eight lupeol esters and the evaluation of their in vitro activity against nine strains of cancer cells. The reaction of carboxylic acids with 1 and DIC/DMAP was used to obtain lupeol stearate (2), lupeol palmitate (3) lupeol miristate (4), and the new esters lupeol laurate (5), lupeol caprate (6), lupeol caprilate (7), lupeol caproate (8) and lupeol 3',4'-dimethoxybenzoate (9), with high yields. Compounds 1-9 were identified using FT-IR, 1H, 13C-NMR, CHN analysis and XRD data and were tested in vitro for proliferation of human cancer cell activity. In these assays, lupeol was inactive (GI50> 250µg/mL) while lupeol esters 2 -4 and 7 - 9 showed a cytostatic effect. The XRD method was a suitable tool to determine the structure of lupeol and its esters in solid state. Compound 3 showed a selective growth inhibition effect on erythromyeloblastoid leukemia (K-562) cells in a concentration-dependent way. Lupeol esters 4 and 9 showed a selective cytostatic effect with low GI50 values representing promising prototypes for the development of new anticancer drugs.

Representação social da violência sexual e sua relação com a adesão ao protocolo de quimioprofilaxia do HIV em mulheres jovens e adolescentes / Social representation of sexual violence and its relationship with the adherence to the chemoprophylaxis protocol of HIV in young women and adolescents

O objetivo deste estudo foi conhecer as representações sociais da violência sexual e sua relação com a adesão do protocolo da quimioprofilaxia do HIV em mulheres jovens e adolescentes. Realizou-se uma pesquisa qualitativa, orientada pela teoria das representações sociais, através de entrevista gravada com 13 mulheres, com idades entre 12 e 23 anos. No grupo, observou-se que as representações sociais construídas acerca da violência sexual exerceram uma considerável influência na adesão ao tratamento quimioprofilático. As pesquisadas elaboraram imagens nas quais as preocupações geradas à família, desconfortos causados pelos efeitos dos fármacos, a mudança de rotina, o medo de adoecer, de ser estigmatizada, ansiedade e raiva, apareceram como elementos constantes, podendo acarretar o abandono do tratamento. Considerando a influência dessas representações no tratamento, verifica-se a necessidade de uma maior atenção dos serviços de saúde com relação a estas possibilidades, dispondo de recursos para planejar sua assistência com base nestas diferentes necessidades. É preciso que, além do investimento em pesquisas com novos fármacos, exista um investimento em pesquisas qualitativas, que forneçam subsídios para um acompanhamento mais apropriado das pacientes.

The scope of this study was to understand the social representations of sexual violence and its relationship with adherence to the chemoprophylaxis protocol of HIV in young women and adolescents. Qualitative research was conducted based on the theory of social representations through recorded interviews with 13 female subjects aged between 12 and 23. It was observed that the social representations about sexual violence exerted a considerable influence on adherence to chemoprophylaxis treatment in the group. The individuals surveyed elaborated images in which the concern caused to the family, discomfort caused by the effects of drugs, change of routine, fear of getting sick, being stigmatized, anxiety and anger, appeared as constant elements, which can lead to the abandonment of treatment. Considering the influence of these representations on treatment, there is a need for greater attention of the health services in relation to these possibilities, and for resources to ensure care based on these different needs. In addition to investing in research into new drugs, it is necessary to invest in qualitative research, providing input for more appropriate care for patients.

Venous thromboembolism risk & prophylaxis in the acute hospital care setting (ENDORSE), a multinational cross-sectional study: Results from the Indian subset data.

Background & objectives: Venous thromboembolism (VTE) is a major health problem with substantial morbidity and mortality. It is often underdiagnosed due to lack of information on VTE risk and prophylaxis. The ENDORSE (Epidemiologic International Day for the Evaluation of Patients at Risk for Venous Thromboembolism in the Acute Hospital Care Setting) study aimed to assess the prevalence of VTE risk in acute hospital care setting and proportion of at-risk patients receiving effective prophylaxis. We present here the risk factor profile and prophylaxis pattern of hospitalized patients who participated in ENDORSE study in India. Methods: In this cross-sectional study in India, all patients (surgical >18 yr, medical >40 yr) from 10 hospitals were retrospectively studied. Demographics, VTE risk factors and prophylaxis patterns were assessed according to the 2004 American College of Chest Physicians (ACCP) evidence-based consensus guidelines. Results: We recruited 2058 patients (1110 surgical, 948 medical) from 10 randomly selected hospitals in India between August 2006 and January 2007. According to the ACCP criteria, 1104 (53.6%) patients [surgical 680 (61.3%), medical 424 (44.7%)] were at-risk for VTE. Chronic pulmonary disease/heart failure and complete immobilization were the most common risk factors before and during hospitalization, respectively. In India, 16.3 per cent surgical and 19.1 per cent medical at-risk patients received ACCP-recommended thromboprophylaxis. Interpretation & conclusions: Despite a similar proportion of at-risk hospitalized patients in India and other participating countries, there was major underutilization of prophylaxis in India. It necessitates increasing awareness about VTE risk and ensuring appropriate thromboprophylaxis.

Adherence to and outcome of isoniazid chemoprophylaxis among household contact children of adults having pulmonary tuberculosis in Alexandria, Egypt

Background: Current international guidelines recommend 6-9 months of isoniazid [INH] preventive chemotherapy to prevent the development of active tuberculosis [TB] in susceptible children exposed to Mycobacterium tuberculosis. However, this is dependent on good adherence, as shown by previous studies

Objectives: This study was conducted to describe the outcome of screening of contact children aged 5 years or less with household exposure to an adult pulmonary TB index case to determine the prevalence and possible risk factors of infection among contact children and to determine the extent and outcome of adherence of contact children to unsupervised INH chemoprophylaxis for 6 months

Methods: A descriptive facility-based cross-sectional study was conducted from March 2009 to August 2010. Research settings were three of the National TB control program chest dispensaries [primary care facilities] in Alexandria, Egypt. Facility-based TB treatment registers of the previous 3 months were used to identify all new adult pulmonary TB cases. All children aged 5 years or less living in the same house as the index cases were identified and screened for TB. The contact children were given unsupervised INH preventive chemotherapy once active TB was excluded. Adherence to and outcome of preventive chemotherapy were followed up. Preventive chemotherapy consisted of unsupervised INH monotherapy for 6 months with monthly collection of tablets from the clinic. Adherence was documented after completion of the 6-month preventive treatment period. Adherence was considered reasonable if tablets were collected for more than 4 months, poor if collected for 2-4 months, and very poor if collected for less than 2 months

Outcome measures: [a] Prevalence of infection and disease and the possible risk factors among contacts. [b] The extent and outcome of adherence to unsupervised INH chemoprophylaxis among contact children. [c] Factors behind poor adherence

Results: In total, 197 adult TB index cases from 187 households were identified. In all, 297 children aged 5 years or less experienced household exposure, of whom 252 [84.9%] were fully evaluated. Tuberculin test was positive in 136 of the 252 child contacts [54.0%], of whom 130 were contacts of sputum-positive patients and six were contacts of sputum-negative patients. The important risk factors for transmission of TB infection were younger age, male sex, severe malnutrition, absence of BCG vaccination, contact with a sputum-positive adult who was a source case, household overcrowding, and exposure to environmental tobacco smoke. Thirty-three children were diagnosed and treated for TB at the baseline screening and 217 received preventive INH chemotherapy. Of the children who received preventive chemotherapy, only 36 [16.6%] completed at least 4 months of unsupervised INH monotherapy. During the subsequent follow-up period, eight children developed TB [secondary attack rate for TB disease was 3.7%], of whom four received no preventive chemotherapy and four were poorly adherent

Conclusion: The prevalence of TB infection and clinical disease among children in household contact with adult patients is high, and risk is significantly increased because of child contact, index patients and environmental factors. Adherence to 6 months of unsupervised INH chemoprophylaxis was very poor