In a randomized, phase 3 study, superior complete/near-complete response (CR/nCR) rates and extended progressionfree survival were demonstrated with bortezomib-thalidomide-dexamethasone (VTD) versus thalidomide-dexamethasone (TD) as induction therapy before, and consolidation after, double autologous stem cell transplantation for newly diagnosed myeloma patients (intention-totreat analysis; VTD, n ‫؍‬ 236; TD, n ‫؍‬ 238). This per-protocol analysis (VTD, n ‫؍‬ 160; TD, n ‫؍‬ 161) specifically assessed the efficacy and safety of consolidation with VTD or TD. Before starting consolidation, CR/nCR rates were not significantly different in the VTD (63.1%) and TD arms (54.7%). After consolidation, CR (60.6% vs 46.6%) and CR/nCR (73.1% vs 60.9%) rates were significantly higher for VTDtreated versus TD-treated patients. VTD consolidation significantly increased CR and CR/nCR rates, but TD did not (McNemar test). With a median follow-up of 30.4 months from start of consolidation, 3-year progression-free survival was significantly longer for the VTD group (60% vs 48% for TD). Grade 2 or 3 peripheral neuropathy (8.1% vs 2.4%) was more frequent with VTD (grade 3, 0.6%) versus TD consolidation. The superior efficacy of VTD versus TD as induction was retained despite readministration as consolidation therapy after double autologous transplantation. VTD consolidation therapy significantly contributed to improved clinical outcomes observed for patients randomly assigned to the

RESUMO -(Conhecimento popular sobre plantas medicinais em comunidades rurais de Mata Atlântica -Itacaré, BA, Brasil). O presente trabalho teve por objetivo o levantamento etnobotânico sobre o conhecimento e uso de plantas medicinais em duas comunidades rurais (Marambaia e Camboinha), localizadas em uma Área de Proteção Ambiental, na Mata Atlântica do Sul da Bahia, Brasil. Estas comunidades têm usado plantas medicinais como uma importante atividade terapêutica, a qual permite a auto-suficiência da população rural em relação aos cuidados com a saúde. Os dados foram coletados através de entrevistas com 26 famílias (24% do número total). As plantas medicinais coletadas (98 espécies) foram catalogadas, identificadas e depositadas no Herbário Rio Clarense (HRCB). Elas pertencem a 40 famílias, dentre as quais Lamiaceae foi a mais citada. A maioria destas espécies (78%) é cultivada, comumente nos quintais, pelos moradores locais. A folha é a parte da planta mais usada nos preparos medicinais. As espécies com maior número de citações são Chenopodium ambrosioides L. (mastruz) e Lippia alba (Mill) N.E. Br. (erva-cidreira), também associadas ao maior número de usos terapêuticos. Comparam-se no presente trabalho os índices de concordância de uso e de diversidade obtidos com os de outros estudos realizados em Florestas Tropicais no Brasil.Palavras-chave: plantas medicinais, etnobotânica, Mata Atlântica, práticas populares ABSTRACT -(Folk knowledge about medicinal plants within rural communities in Atlantic Forest, Itacaré, Bahia State, Brazil). This study's goal was to caryy out an ethnobotanical survey focusing on the knowledge and use of medicinal plants within two rural communities (Marambaia and Camboinha), which are situated in an Environmental Protection Area in Atlantic Forest of Southern Bahia, Brazil. These communities use medicinal plants as an important therapeutic activity, which permits the rural inhabitants to be selfsufficient regarding health care. Data were collected through interviews with 26 families (24% of the total). The medicinal plants collected (98 species) were catalogued, identified and deposited at the Herbarium Rio Clarense (HRCB). They belong to 40 families so that Lamiaceae was the most cited. The majority of these species (78%) are cultivated, usually in backyards by local inhabitants. The leaf is the most common part of the plant used in medicinal preparations. The species with the greatest number of citations were Chenopodium ambrosioides L. and Lippia alba (Mill) N.E. Br. These species are also associated with the highest number of therapeutic uses. Use agreement and diversity index from this survey were compared to other surveys conducted in Brazilian Tropical Forests.Key words: medicinal plants, ethnobotany, Atlantic Forest, folk knowledge IntroduçãoAs populações humanas que ocupam florestas tropicais convivem com a grande diversidade destes ambientes e desenvolvem, cada qual à sua maneira, formas de explorá-los para sua sobrevivência. De seu repertório cultural, destaca-se o conhecimento ...

RESUMO -(Obtenção e uso das plantas medicinais no distrito de Martim Francisco, Município de Mogi-Mirim, SP, Brasil). O objetivo do presente trabalho foi realizar um inventário das plantas medicinais conhecidas e usadas pela população do distrito de Martim Francisco, Município de Mogi-Mirim, SP, bem como conhecer seus empregos e sua importância na comunidade. Foram amostradas aleatoriamente 50 unidades domiciliares. Apenas um dos adultos responsáveis pela casa (homem ou mulher) foi entrevistado, através de questionários. As plantas citadas foram coletadas e fotografadas paralelamente à aplicação dos questionários. O material botânico foi identificado e depositado no Herbarium Rioclarense (HRCB). Ao todo, foram catalogadas 107 espécies botânicas, predominantemente herbáceas e cultivadas, distribuídas em 40 famílias, sendo as famílias Lamiaceae e Asteraceae as mais representativas. Os índices de diversidade (H' = 4,07; e = 0,87) foram altos, se comparados aos obtidos em outros trabalhos no interior do Estado de São Paulo. Na preparação dos remédios, as folhas foram a parte da planta mais utilizada e a decocção a principal forma de preparo. A via oral foi a mais empregada para a administração dos medicamentos e as doenças mais freqüentemente tratadas por remédios caseiros referem-se aos Sistemas Digestivo e Respiratório. Não existe um rigor na posologia e na duração do tratamento, ficando este a critério do hábito de cada pessoa entrevistada. As plantas que apresentaram índice de importância relativa e concordância de uso acima de 60% foram: boldo (Plectranthus barbatus Andrews), capim-santo (Cymbopogon citratus (DC) Stapf), hortelã (Mentha sp. 2) e poejo (Cunila microcephala Benth.). A questionnaire was applied to a random sample of 50 households; in each, one adult (male or female) was interviewed. Plants cited were collected and photographed in conjunction with the interview; they were then identified and deposited at the Herbarium Rioclarense (HRCB). The 107 species were mainly cultivated herbs belonging to 40 botanical families; Lamiaceae and Asteraceae were the most representative. Diversity indexes (H'= 4.07; e = 0.87) were high when compared to surveys in other localities of São Paulo State. Leaves were the plant parts most utilized and decoction the most common way of preparation. Plant remedies were generally taken orally, and used to treat digestive and respiratory systems ailments. Dosage and treatment duration were rather loosely defined. Plants presenting relative importance and use agreement above 60% were as follows: "boldo" (Plectranthus barbatus Andrews), "capim-santo" (Cymbopogon citrates (DC) Stapf), mint (Mentha sp. 2) and "poejo" (Cunila microcephala Benth.). Palavras-chave: etnobotânica, plantas medicinais, medicina popular ABSTRACT -(Acquisition and use of medicinal plants in Martim

Objective. The current treatment options for systemic-onset juvenile idiopathic arthritis (JIA) are methotrexate, steroids, and biologic agents. This study was undertaken to evaluate the safety of the orally active histone deacetylase inhibitor givinostat (ITF2357) and its ability to affect the disease.Methods. Givinostat was administered orally, for up to 12 weeks at a dosage of 1.5 mg/kg/day, to 17 patients with systemic-onset JIA who had had active disease for >1 month. Disease activity was clinically assessed using the American College of Rheumatology Pediatric 30 (ACR Pedi 30), ACR Pedi 50, or ACR Pedi 70 criteria for improvement and a systemic feature score. The primary goal was safety and the primary efficacy end point was the number of patients completing 12 weeks of treatment who were responders.Results. Givinostat was safe and well tolerated, with adverse events (AEs) being mild or moderate, of short duration, and self-limited. The 17 patients from the intent-to-treat population reported a total of 44 AEs, and the 9 patients in the per-protocol population reported a total of 25. Six AEs in 3 patients (nausea, vomiting, and fatigue) were related to the study drug, but each resolved spontaneously and no patient was withdrawn from the study due to drug-related AEs. In the per-protocol population at week 4, the improvement as measured by the ACR Pedi 30, ACR Pedi 50, and ACR Pedi 70, respectively, was 77.8%, 55.6%, and 22.2%, and this increased further to 77.8%, 77.8%, and 66.7% at week 12. The most consistent finding was the reduction in the number of joints with active disease or with limited range of motion.Conclusion. After 12 weeks, givinostat exhibited significant therapeutic benefit in patients with systemiconset JIA, particularly with regard to the arthritic component of the disease, and showed an excellent safety profile.Histone deacetylases (HDAs) are intracellular enzymes that maintain nucleosome histones in a state of deacetylation so that DNA remains tightly bound and inaccessible to transcription factors. Inhibition of HDAs results in hyperacetylation of histones, which allows for the sufficient unraveling of DNA for binding transcription factors and the synthesis of messenger RNA (1,2). There is increasing evidence that HDA inhibitors may also exhibit antiinflammatory properties (3). ITF2357 (recently named givinostat) is a hydroxamic acid containing an HDA inhibitor, which reduces the production and release of several proinflammatory cytokines (tumor necrosis factor ␣, interleukin-1␤ [⌱L-1␤], interferon-␥, IL-6, and IL-12) from human blood monocytes (4) as well as in models of autoimmune diseases and inflammation, including models of arthritis and synovial cell functions (5,6).Systemic-onset juvenile idiopathic arthritis (JIA) is an example of combined autoinflammatory and autoimmune disease. Reduction of the painful and destructive arthritis component of the disease remains a goal that has still not been achieved even with anticytokine parenteral therapies (7,8). The primary objective of t...

Objectives Chromatin-associated repression is one mechanism that maintains HIV-1 latency. Inhibition of histone deacetylases (HDAC) reverses this repression resulting in viral expression from quiescently infected cells. Clinical studies with the HDAC inhibitor valproic acid (VPA) failed to substantially decrease the latent pool within resting CD4+ cells. Here we compared the efficacy of ITF2357, an orally active and safe HDAC inhibitor, with VPA for HIV-1 expression from latently infected cells in vitro. We also evaluated the effect of ITF2357 on the surface expression of CXCR4 and CCR5. Methods Latently infected cell lines were incubated with either ITF2357 or VPA and p24 levels were measured. Peripheral blood mononuclear cells of un-infected donors were treated with ITF2357 and HIV-1 co-receptors expression was assessed by flow cytometry. Results At clinically relevant concentrations, ITF2357 increased p24 by 15-fold in ACH2 cells and by 9-fold in U1 cells whereas VPA increased expression less than 2-fold. Analogues of ITF2357 primarily targeting HDAC-1 increased p24 up to 30-fold. In CD4+ T-cells treated with ITF2357, CXCR4 expression decreased by 54% (P<0.001). Conclusion ITF2357 is superior to VPA in inducing HIV-1 from latently infected cells. Safely used in humans, ITF2357 is an attractive candidate for HIV-1 clinical purging.

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