Highlights from the I international symposium of thrombosis and anticoagulation in internal medicine, October 23-25, 2008, Sao Paulo, Brazil

The importance of thrombosis and anticoagulation in clinical practice is rooted firmly in several fundamental constructs that can be applied both broadly and globally. Awareness and the appropriate use of anticoagulant therapy remain the keys to prevention and treatment. However, to assure maximal efficacy and safety, the clinician must, according to the available evidence, choose the right drug, at the right dose, for the right patient, under the right indication, and for the right duration of time. The first International Symposium of Thrombosis and Anticoagulation in Internal Medicine was a scientific program developed by clinicians for clinicians. The primary objective of the meeting was to educate, motivate and inspire internists, cardiologists and hematologists by convening national and international visionaries, thought-leaders and dedicated clinician-scientists in Sao Paulo, Brazil. This article is a focused summary of the symposium proceedings. © Springer Science+Business Media, LLC 2009.

Integração de práticas culturais e redução da dose do bentazon na cultura da soja: I - efeitos sobre o crescimento da cultura

O trabalho foi desenvolvido no município de Jaboticabal, SP, no ano agrícola de 1990/91, onde testou-se a integração de práticas culturais e menor dose de herbicida aplicado em pósemergência na cultura da soja, cultivar Paraná. O delineamento experimental utilizado foi o de blocos ao acaso, com dezesseis tratamentos e quatro repetições, no esquema fatorial 4x2x2, sendo quatro tipos de manejos de plantas daninhas: testemunha infestada, 50% da dose recomendada (360 g ia/ha) do herbicida bentazon, dose recomendada do herbicida bentazon (720 g ia/ha) e testemunha capinada; dois espaçamentos entre-linhas: 30 cm e 60 cm; e duas densidades: normal e reduzida (média de 20 e 10 plantas por metro, respectivamente). Observou-se que a quantidade de matéria seca das plantas daninhas por época da colheita da soja, foi significativamente maior nos tratamentos com espaçamento maior e densidade reduzida. O arranjo proporcionado pela densidade normal (média de 20 plantas /m) e menor espaçamento (30 cm) entre-linhas, proporcionou sombreamento mais precoce do solo e foi a melhor opção de controle cultural das plantas daninhas em todos os tratamentos testados. Não foi observado sintomas de intoxicação e nem efeitos negativos sobre a nodulação das plantas de soja, por parte do herbicida aplicado, em ambas as doses testadas.

Integração de práticas culturais e redução da dose de bentazon na cultura da soja

O trabalho foi desenvolvido no município de Jaboticabal, SP, no ano agrícola de 1990/91, onde testou-se a integração de práticas culturais e menor dosagem de herbicida aplicado em pós-emergência na cultura da soja, cultivar Paraná. O delineamento experimental utilizado foi o de blocos ao acaso, com dezesseis tratamentos e quatro repetições, sendo quatro tipos de manejos de plantas daninhas: testemunha infestada, 50% da dose recomendada (360 g/ha do herbicida bentazon, dose recomendada do herbicida bentazon (720 g/ha) e testemunha capinada; dois espaçamentos entre-linhas: 30 cm e 60 cm; e duas densidades: normal e reduzida (em torno de 20 e 10 plantas por metro linear, respectivamente). Observou-se que a quantidade de matéria seca das plantas daninhas por época da colheita da soja, foi ligeiramente maior no tratamento com 50% do que no tratamento com 100% da dose do herbicida, porém a diferença não foi significativa. A produtividade no tratamento com 50% de redução na dose do herbicida foi 8,7% menor do que no tratamento com 100%. A redução de 50% na dose do herbicida testado, quando se interagiu com espaçamento e densidades adequadas (30 cm entre-linhas e densidade normal), é possível, considerando-se aceitável as perdas menores que 10% de grãos de soja em relação ao tratamento com dose normal e levando-se em conta os benefícios de tal redução da dose do herbicida.

Eficácia e segurança da atorvastatina no tratamento de pacientes com hipercolesterolemia primária

Introduction: Hypercholesterolemia is an important risk factor for cardiovascular disease, the first cause of death and third reason for hospital admissions in Brazil. The reduction of serum cholesterol levels reduces morbidity and mortality from cardiovascular disease. The present study evaluated the efficacy and safety of atorvastatin in the treatment of Brazilian patients with primary hypercholesterolemia (types IIA and IIB dyslipidemias). Patients and methods: After a 4-week wash-out period, 152 patients were treated with atorvastatin at the initial dose of 10 mg/day. According to treatment efficacy within the first 8 weeks this dose could be increased to 20 mg/day. Treatment lasted for a total of 16 weeks, and its efficacy was evaluated by the reduction of serum levels of LDL-cholesterol, total cholesterol, HDL-cholesterol, and triglycerides, as well as by the propotion of patients that achieved the target levels recommended by the National Cholesterol Education Program - Adult Treatment Panel II (NCEP ATP II) Results: The analysis of efficacy was conducted in 145 patients. Atorvastatin led to significant reductions in the levels of LDL-cholesterol after 8 and 16 weeks of treatment (P<0.001 for both comparisons). The relative reduction of such levels was 38% (P<0.001 after 8 and 16 weeks). Atorvastatin also led to significant reductions of total cholesterol and triglycerides. At the end of the study, 81% of patients achieved the target LDL-cholesterol levels recommended by NCEP ATP II. Treatment was well tolerated, and was interrupted due to creatine phosphokinase elevation in only one patient. Conclusion: Atorvastatina is efficacious and safe in the treatment of patients with primary hypercholesteromia. © Copyright Moreira Jr. Editora. Todos os direitos reservados.

Induction pegylated interferon Alfa-2a and high dose ribavirin do not increase SVR in heavy patients with HCV genotype 1 and high viral loads

Background & Aims Patients infected with hepatitis C virus (HCV) genotype 1, body weight <85 kg, and high baseline viral load respond poorly to standard doses of pegylated interferon (peginterferon) and ribavirin. We evaluated intensified therapy with peginterferon alfa-2a plus ribavirin. Methods This double-blind randomized trial included HCV genotype 1-infected outpatients from hepatology clinics with body weight <85 kg and HCV RNA titer <400,000 IU/mL. Patients were randomized to 180 μg/wk peginterferon alfa-2a for 48 weeks plus 1200 mg/day ribavirin (standard of care) (group A, n = 191) or 1400/1600 mg/day ribavirin (group B, n = 189). Additional groups included 360 μg/wk peginterferon alfa-2a for 12 weeks then 180 μg/wk peginterferon alfa-2a for 36 weeks plus 1200 mg/day ribavirin (group C, n = 382) or 1400/1600 mg/day ribavirin (group D, n = 383). Follow-up lasted 24 weeks after treatment. Results Sustained virologic response rates (HCV RNA level <15 IU/mL at end of follow-up) in groups A, B, C, and D were 38%, 43%, 44%, and 41%, respectively. There were no significant differences among the 4 groups or between pooled peginterferon alfa-2a regimens (A + B vs C + D: odds ratio [OR], 1.08; 95% confidence interval [CI], 0.831.39; P = .584) or pooled ribavirin regimens (A + C vs B + D: OR, 1.00; 95% CI, 0.791.28; P = .974). Conclusions In patients infected with HCV genotype 1 who are difficult to treat (high viral load, body weight <85 kg), a 12-week induction regimen of peginterferon alfa-2a and/or higher-dose ribavirin is not more effective than the standard regimen. © 2010 AGA Institute.

Advances in sickle cell disease treatment: From drug discovery until the patient monitoring

Sickle Cell Disease (SCD) is one of the most prevalent hematological diseases in the world. Despite the immense progress in molecular knowledge about SCD in last years few therapeutical sources are currently available. Nowadays the treatment is performed mainly with drugs such as hydroxyurea or other fetal hemoglobin inducers and chelating agents. This review summarizes current knowledge about the treatment and the advancements in drug design in order to discover more effective and safe drugs. Patient monitoring methods in SCD are also discussed. © 2011 Bentham Science Publishers Ltd.

Advances in drug design based on the amino acid approach: Taurine analogues for the treatment of CNS diseases

Amino acids are well known to be an important class of compounds for the maintenance of body homeostasis and their deficit, even for the polar neuroactive aminoacids, can be controlled by supplementation. However, for the amino acid taurine (2-aminoethanesulfonic acid) this is not true. Due its special physicochemical properties, taurine is unable to cross the blood-brain barrier. In addition of injured taurine transport systems under pathological conditions, CNS supplementation of taurine is almost null. Taurine is a potent antioxidant and anti-inflammatory semi-essential amino acid extensively involved in neurological activities, acting as neurotrophic factor, binding to GABA A/glycine receptors and blocking the excitotoxicity glutamate-induced pathway leading to be a neuroprotective effect and neuromodulation. Taurine deficits have been implicated in several CNS diseases, such as Alzheimer's, Parkinson's, epilepsy and in the damage of retinal neurons. This review describes the CNS physiological functions of taurine and the development of new derivatives based on its structure useful in CNS disease treatment.&; 2012 by the authors; licensee MDPI, Basel, Switzerland.

Immunomodulatory effects of low dose chemotherapy and perspectives of its combination with immunotherapy

Given that cancer is one of the main causes of death worldwide, many efforts have been directed toward discovering new treatments and approaches to cure or control this group of diseases. Chemotherapy is the main treatment for cancer; however, a conventional schedule based on maximum tolerated dose (MTD) shows several side effects and frequently allows the development of drug resistance. On the other side, low dose chemotherapy involves antiangiogenic and immunomodulatory processes that help host to fight against tumor cells, with lower grade of side effects. In this review, we present evidence that metronomic chemotherapy, based on the frequent administration of low or intermediate doses of chemotherapeutics, can be better than or as efficient as MTD. Finally, we present some data indicating that noncytotoxic concentrations of antineoplastic agents are able to both up-regulate the immune system and increase the susceptibility of tumor cells to cytotoxic T lymphocytes. Taken together, data from the literature provides us with sufficient evidence that low concentrations of selected chemotherapeutic agents, rather than conventional high doses, should be evaluated in combination with immunotherapy. Copyright © 2012 UICC.

Diazepam, em dose única, inibe a migração celular, a estimulação macrofágica e a atividade de TNF-α na reação inflamatória aguda induzida por LPS em camundongos

Benzodiazepines are one of the most frequently prescribed drugs due to their anxiolytic properties. The aim of this study was to evaluate the effects of diazepam on lipopolysaccharide-induced peritoneal acute inflammatory responses. Swiss mice were treated with diazepam in a single dose of 1 or 10 mg/kg- subcutaneously 1 h before an intraperitoneal injection of lipopolysaccharide or sterile saline solution. The mice were killed 16 h after and the cells were washed from the peritoneal cavity to determine the total number of cells and the mononuclear and polimorfonuclear subpopulations, as well as the TNF-alpha activity and percentage of spread macrophages. Our results showed that the diazepam treatment (1 and 10 mg/kg) induced a significant reduction in the LPS-induced macrophage stimulation and TNF-α activity. Diazepam (10 mg/kg) also reduced the inflammatory cellular migration when compared to the control. It can be concluded that the diazepam treatment in a single dose is able to influence the inflammatory cellular influx, macrophage stimulation and TNF-α activity in the acute inflammatory response in mice, having possible implications on the anti-infectious response efficiency.

Effects of 15d-PGJ(2)-loaded poly(D,L-lactide-co-glycolide) nanocapsules on inflammation

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Adubação fosfatada no meloeiro-amarelo: reflexos na produção e qualidade dos frutos

O melão (Cucumis melo L.) é uma das culturas de grande expressão econômica e social para a região Nordeste do Brasil. Apesar disso e dos baixos níveis de fósforo (P) dos solos tropicais, existem poucas pesquisas sobre adubação com P nesta cultura, embora seja frequentemente mencionado que este nutriente tem papel preponderante na produção e qualidade dos frutos. Neste contexto, objetivou-se com este trabalho avaliar o efeito de doses de P (0; 120; 240; 360 e 480 kg ha-1 de P2O5), na produção e qualidade do melão-amarelo híbrido Goldex F1, nas condições ambientais de Teresina - Piauí. O experimento foi conduzido em um delineamento de blocos ao acaso, com quatro repetições, tendo 40 plantas por parcela. Os frutos foram colhidos aos 75 após o plantio. Foram avaliados os dados médios da produção total, produção de frutos comerciais, massa e número de frutos por planta, comprimento e diâmetro de frutos, espessura da polpa de frutos, sólidos solúveis, acidez titulável e o índice de maturação. A produção total e comercial, assim como a massa e o número de frutos e acidez titulável aumentaram com as doses de P aplicadas até a dose de 278 kg ha-1 de P2O5. Doses acima de 278 kg ha-1 de P2O5 prejudicaram a produtividade de frutos classificados como comerciais. O comprimento, o diâmetro de frutos e a espessura de polpa aumentaram até a dose de 355 kg ha-1 de P2O5, com aumentos pouco expressivos entre 278 e 355 kg ha-1 de P2O5. O teor de sólidos solúveis totais não foi afetado pela adubação fosfatada. Para as condições de fertilidade do solo deste trabalho, recomenda-se uma dose ao redor de 275 kg ha-1 de P2O5.

Uso de la cefalexina en infecciones piogenas de la piel: comparacion de dos esquemas terapeuticos

50 patients with pyogenic infections of the skin were divided into 2 groups and treated with cephalexin. Group A, 26 patients, received 500 mg/12 hours; Group B, 24 patients, 250 mg/6 hours. Clinical diagnosis was substantiated by bacteriologic study of cultures to identify the organism and determination of its susceptibility to the drug. Group A showed 91%, group B 95%; satisfactory results. No side-effects were noted. Either form of dosage was effective in the treatment of pyogenic infections of the skin.

Envolvimento do sistema dopaminérgico na sensibilização comportamental ao femproporex

The effects of repeated administration of fenproporex (FEN) on motor activity of rats were studied. FEN-treated group (5.0 mg/kg, i.p., single dose, 7 consecutive days), showed a marked increase in the motor activity of rats, indicating that the drug induced behavioral sensitization. Repeated coadministration of haloperidol prevented the development of sensitization to repeated administration of FEN. Repeated administration of FEN increased also locomotor activity measured in the open field, ratifying the occurence of sensitization. These findings indicated development of sensitization to repeated FEN administration and that the dopamine system might be involved in the mechanism of sensitization.

Evaluation of cardiac rhythm in dogs treated with levamisole hydrochloride using 24-hour ambulatory electrocardiography

The objective of this study was to evaluate the electrocardiographic alterations in the cardiac rhythm in dogs treated with levamisole hydrochloride over a period of 24 hours. Thirty-six mixed-breed dogs, both male and female, all clinically healthy, were used in the experiment. The dogs were divided into 6 groups with 6 dogs in each group, according to dosage and route of administration. The Holter test was initiated immediately after the treatment, and was maintained for 24 hours. In the group treated with 10 mg/kg by way of subcutaneous injection, one of them showed ventricular premature complexes, sometimes isolated and other times in pairs, and ventricular tachycardia, concentrated mainly in the first hour after administration of the drug. In the group of 6 animals treated subcutaneously with 25mg/kg, four showed isolated ventricular premature complexes, ventricular bigeminy and trigeminy, mainly during the first 2 hours after administration of the drug. All the animals in the other groups showed sinus arrhythmia followed by sinus arrest. The disturbances in the cardiac rhythm observed in clinically healthy animals treated with levamisole hydrochloride, indicate that it is preferable to avoid subcutaneous administration of levamisole hydrochloride and that the oral administration of the drug should be done with caution. © 2003 Elsevier B.V. All rights reserved.