Kinetics of venom and antivenom serum levels, clinical evaluation and therapeutic effectiveness in dogs inoculated with Crotalus durissus terrificus venom

This work evaluated the clinical and therapeutic aspects as well as serum levels of venom and antivenom IgG by enzyme-linked immunosorbent assay (ELISA) in experimental envenomation of dogs with Crotalus durissus terrificus venom. Twenty-eight mixed breed adult dogs were divided into four groups of seven animals each, Group I: only venom; Group II, venom + 50 ml of anti-bothropic-crotalic serum (50mg) + fluid therapy; Group III, venom + 50 ml of anti-bothropic-crotalic serum + fluid therapy + urine alkalination; Group IV, 50 ml of anti-bothropic-crotalic serum. The lyophilized venom of Crotalus durissus terrificus was reconstituted in saline solution and subcutaneously inoculated at the dose of 1mg/kg body weight. The dogs presented clinical signs of local pain, weakness, mandibular ptosis, mydriasis, emesis and salivation. The venom levels detected by ELISA ranged from 0 to 90ng/ml, according to the severity of the clinical signs. Serum antivenom ranged from 0 to 3ug/ml and was detected for up to 138h after treatment. ELISA results showed the effectiveness of the serum therapy for the venom neutralization.

Construction of ethics in clinical research - Clinical trials registration

Scientific development that has been achieved through decades finds in clinical research a great possibility of translating findings to human health application. Evidence given by clinical trials allows everyone to have access to the best health services. However, the millionaire world of pharmaceutical industries has stained clinical research with doubt and improbability. Study results (fruits of controlled clinical trials) and scientific publications (selective, manipulated and with wrong conclusions) led to an inappropriate clinical practice, favoring the involved economic aspect. In 2005, the International Committee of Medical Journal Editors (ICMJE), supported by the World Association of Medical Editors, started demanding as a requisite for publication that all clinical trials be registered at the database ClinicalTrials.gov. In 2006, the World Health Organization (WHO) created the International Clinical Trial Registry Platform (ICTRP), which gathers several registry centers from all over the world, and required that all researchers and pharmaceutical industries register clinical trials. Such obligatory registration has progressed and will extend to all scientific journals indexed in all worldwide databases. Registration of clinical trials means another step of clinical research towards transparency, ethics and impartiality, resulting in real evidence to the forthcoming changes in clinical practice as well as in the health situation.

Systematic review of randomized controlled trials of new anticoagulants for venous thromboembolism prophylaxis in major orthopedic surgeries, compared with enoxaparin

Background: In the past 10 years, new anticoagulants (NACs) have been studied for venous thromboembolism (VTE) prophylaxis. Objective: To evaluate the risk/benefit profile of NACs versus enoxaparin for VTE prophylaxis in major orthopedic surgery. Methods: A systematic review of double-blind randomized phase III studies was performed. The search strategy was run from 2000 to 2011 in the main medical electronic databases in any language. Independent extraction of articles was performed by 2 authors using predefined data fields, including study quality indicators. Results: Fifteen published clinical trials evaluating fondaparinux, rivaroxaban, dabigatran, and apixaban were included. Primary efficacy (any deep vein thrombosis [DVT], nonfatal pulmonary embolism, or all-cause mortality) favored fondaparinux (relative risk [RR] 0.50; 95% CI, 0.39, 0.63) and rivaroxaban (RR, 0.50; 95% CI, 0.34, 0.73) over enoxaparin, although significant heterogeneity was observed in both series. The primary efficacy of dabigatran at 220 mg, apixaban, and bemiparin were similar, with RRs of 1.02 (95% CI, 0.86, 1.20), 0.63 (95% CI, 0.39, 1.01), and 0.87 (95% CI, 0.65, 1.17), respectively. The primary efficacy of dabigatran at 150 mg (RR, 1.20; 95% CI, 1.03, 1.41), was inferior to enoxaparin. The incidence of proximal DVT favored apixaban (RR, 0.45; 95% CI, 0.27, 0.75) only. Rivaroxaban (RR, 0.45; 95% CI, 0.27, 0,77) and apixaban (RR, 0.38; 95% CI, 0.16, 0.90) produced significantly lower frequencies of symptomatic DVT. The incidence of major VTE favored rivaroxaban (RR, 0.44; 95% CI, 0.25, 0.81), only. Bleeding risk was similar for all NACs, except fondaparinux (RR, 1.27; 95% CI, 1.04, 1.55), which exhibited a significantly higher any-bleeding risk compared with enoxaparin, and apixaban (RR, 0.88; 95% CI, 0.79, 0.99), which was associated with a reduced risk of any bleeding. Alanine amino transferase was significantly lower with 220 mg of dabigatran, (RR, 0.67; 95% CI, 0.79, 0.99) than with enoxaparin. Conclusions: NACs can be considered alternatives to conventional thromboprophylaxis regimens in patients undergoing elective major orthopedic surgery, depending on clinical characteristics and cost-effectiveness. The knowledge of some differences concerning efficacy or safety profile, pointed out in this systematic review, along with the respective limitations, may be useful in clinical practice. © 2013 Elsevier Inc. All rights reserved.

A success in Toxinology translational research in Brazil: Bridging the gap

Basic research is fundamental for discovering potential diagnostic and therapeutic tools, including drugs, vaccines and new diagnostic techniques. On this basis, diagnosis and treatment methods for many diseases have been developed. Presently, discovering new candidate molecules and testing them in animals are relatively easy tasks that require modest resources and responsibility. However, crossing the animal-to-human barrier is still a great challenge that most researchers tend to avoid. Thus, bridging this current gap between clinical and basic research must be encouraged and elucidated in training programmes for health professionals. This project clearly shows the challenges faced by a group of Brazilian researchers who, after discovering a new fibrin sealant through 20 years of painstaking basic work, insisted on having the product applied clinically. The Brazilian government has recently become aware of this challenge and has accordingly defined the product as strategic to the public health of the country. Thus, in addition to financing research and development laboratories, resources were invested in clinical trials and in the development of a virtual platform termed the Virtual System to Support Clinical Research (SAVPC); this platform imparts speed, reliability and visibility to advances in product development, fostering interactions among sponsors, physicians, students and, ultimately, the research subjects themselves. This pioneering project may become a future model for other public institutions in Brazil, principally in overcoming neglected diseases, which unfortunately continue to afflict this tropical country. © 2013 Elsevier Ltd.

Estudo de dose adequada da droga RO42-1611 (Arteflene) no tratamento da malária por Plasmodium falciparum

A resistência crescente do P. falciparum aos antimaláricos habitualmente empregados, torna urgente a avaliação de novas drogas. O Ro 42-1611 é um antimalárico derivado da planta chinesa Arlabotrys uncinatus. Usado apenas na África em três trabalhos no tratamento da malária por P. falciparum, tem sua ação desconhecida em sul-americanos com esta doença. Apesar do efeito antimalárico ter sido comprovado, ainda não se encontrou a dose adequada para o tratamento supressivo do P. falciparum. Avaliar a tolerância, a toxicidade e a eficácia de três diferentes doses do Ro 42-1611 no tratamento da malária por P. falciparum é o que objetiva este trabalho. O estudo foi realizado em Marabá-Pará, caracterizando-se por ser aberto, prospectivo e randomizado; incluiu pacientes voluntário s, adultos, masculinos, de peso corporal até 80 kg; febris ou com outros sintomas constitucionais de malária e com gota espessa positiva para P. falciparum ( ≥ 200 e ≤ 50.000 parasitas/mm³ de sangue). Grupos de estudo: I -1.500 mg de 12/12 horas por 1 dia; II -1.500 mg de 12/12 horas por2 dias e III -1.500 mg de 12/12 horas por 3 dias. Todos os pacientes foram tratados em regime hospitalar, sendo avaliados no pré-tratamento através de: dados pessoais e biométricos, sinais e sintomas, uso de medicação concomitante, temperatura axilar, freqüência respiratória, pressão arterial, eletrocardiograma, parasitemia, exames hematológicos e bioquímicos. A partir do início da terapêutica, a avaliação destes parâmetros foi feita seguindo protocolo próprio, incluindo a anotação de efeitos colaterais. A análise de variância de Friedman foi usada para avaliar os valores obtidos nos exames hematológicos e bioquímicos. Foram selecionados 16 pacientes, sendo 5 alocados no grupo I, 6 no II e 5 no III. Idade variou de 17 a 41 anos (média: 26,6), peso corporal de 44 a 72 kg (média: 54,9), parasitemia assexuada inicial de 200 a 40.000 formas/mm³ de sangue, sendo os grupos homogêneos quanto a estas variáveis. A febre desapareceu no mínimo com 9 e no máximo com 48 horas a partir do início da terapêutica. A avaliação do traçado eletrocardiográfico e da pressão arterial não mostrou alterações significativas. O desaparecimento da parasitemia assexuada ocorreu em média com 53,6 horas, não se evidenciando diferenças estatísticas i significantes entre os grupos (p=0,7264). Houve uma diminuição significativa entre o pré-tratamento (D0) e o terceiro (D2) e oitavo (D7) dias de acompanhamento quanto os níveis de hematócrito (p=0,0046), um aumento no número de leucócitos entre D2 e D7 (p=0,0171) e plaquetas entre D0 e D7, assim como entre D2 e D7 (p< 0,0001). Entre D0 e D7 detectou-se diminuição nos níveis de bilirrubina total (p=0,0024), fosfatase alcalina (p=0,0195) e uréia (p=0,0168). Efeitos colaterais foram em geral leves ou moderados e de curta duração. Do total de pacientes, 87,5% obtiveram desaparecimento da parasitemia assexuada, porém apenas 2 (12,5%) curaram, ambos incluídos no grupo III. Nenhum dos esquemas posológicos usados foi adequado para a cura desta doença. Talvez em estudos posteriores usando a droga em maior dose ou por maior número de dias ou ainda associando-a a outros antimaláricos, possa obter-se eficácia adequada.

Leprosy: a review of laboratory and therapeutic aspects - Part 2

Leprosy is a chronic infectious condition caused by Mycobacterium leprae(M. leprae). It is endemic in many regions of the world and a public health problem in Brazil. Additionally, it presents a wide spectrum of clinical manifestations, which are dependent on the interaction between M. leprae and host, and are related to the degree of immunity to the bacillus. The diagnosis of this disease is a clinical one. However, in some situations laboratory exams are necessary to confirm the diagnosis of leprosy or classify its clinical form. This article aims to update dermatologists on leprosy, through a review of complementary laboratory techniques that can be employed for the diagnosis of leprosy, including Mitsuda intradermal reaction, skin smear microscopy, histopathology, serology, immunohistochemistry, polymerase chain reaction, imaging tests, electromyography, and blood tests. It also aims to explain standard multidrug therapy regimens, the treatment of reactions and resistant cases, immunotherapy with bacillus Calmette-Guérin (BCG) vaccine and chemoprophylaxis.

Genetic and biochemical markers of hydroxyurea therapeutic response in sickle cell anemia

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Incentive spirometry for prevention of postoperative pulmonary complications in upper abdominal surgery

BackgroundThis is an update of a Cochrane Review first published in The Cochrane Library 2008, Issue 3.Upper abdominal surgical procedures are associated with a high risk of postoperative pulmonary complications. The risk and severity of postoperative pulmonary complications can be reduced by the judicious use of therapeutic manoeuvres that increase lung volume. Our objective was to assess the effect of incentive spirometry compared to no therapy or physiotherapy, including coughing and deep breathing, on all-cause postoperative pulmonary complications andmortality in adult patients admitted to hospital for upper abdominal surgery.ObjectivesOur primary objective was to assess the effect of incentive spirometry (IS), compared to no such therapy or other therapy, on postoperative pulmonary complications and mortality in adults undergoing upper abdominal surgery.Our secondary objectives were to evaluate the effects of IS, compared to no therapy or other therapy, on other postoperative complications, adverse events, and spirometric parameters.Search methodsWe searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2013, Issue 8), MEDLINE, EMBASE, and LILACS (from inception to August 2013). There were no language restrictions. The date of the most recent search was 12 August 2013. The original search was performed in June 2006.Selection criteriaWe included randomized controlled trials (RCTs) of IS in adult patients admitted for any type of upper abdominal surgery, including patients undergoing laparoscopic procedures.Data collection and analysisTwo authors independently assessed trial quality and extracted data.Main resultsWe included 12 studies with a total of 1834 participants in this updated review. The methodological quality of the included studies was difficult to assess as it was poorly reported, so the predominant classification of bias was 'unclear'; the studies did not report on compliance with the prescribed therapy. We were able to include data from only 1160 patients in the meta-analysis. Four trials (152 patients) compared the effects of IS with no respiratory treatment. We found no statistically significant difference between the participants receiving IS and those who had no respiratory treatment for clinical complications (relative risk (RR) 0.59, 95% confidence interval (CI) 0.30 to 1.18). Two trials (194 patients) IS compared incentive spirometry with deep breathing exercises (DBE). We found no statistically significant differences between the participants receiving IS and those receiving DBE in the meta-analysis for respiratory failure (RR 0.67, 95% CI 0.04 to 10.50). Two trials (946 patients) compared IS with other chest physiotherapy. We found no statistically significant differences between the participants receiving IS compared to those receiving physiotherapy in the risk of developing a pulmonary condition or the type of complication. There was no evidence that IS is effective in the prevention of pulmonary complications.Authors' conclusionsThere is low quality evidence regarding the lack of effectiveness of incentive spirometry for prevention of postoperative pulmonary complications in patients after upper abdominal surgery. This review underlines the urgent need to conduct well-designed trials in this field. There is a case for large RCTs with high methodological rigour in order to define any benefit from the use of incentive spirometry regarding mortality.

Therapeutic interventions to reduce the risk of progression from prediabetes to type 2 diabetes mellitus

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Historic of therapeutic efficacy of albendazol sulphoxide administered in different routes, dosages and treatment schemes, against Taenia saginata in cattle experimentally infected

The present study aimed to notify the history of albendazole sulphoxide (ALB-SO) and albendazole (ALBZ) efficacy against Taenia saginata cysticercus (Cysticercus bovis) parasitizing experimentally infected bovines. A total of 11 efficacy trials were performed between the years of 2002 and 2010. In order to perform these trials, animals were individually inoculated with 2 x 104 eggs of T. saginata in each study's day zero (DO). For every trial, a positive control group (untreated infected animals) and a negative control group (animals that were neither infected nor treated) were used. ALB-SO or ALB were administered in the different dosages, in different days of treatments. In a last study with this formulation, this active principle was administered orally, mixed with the mineral supplement, on the 60th DPI, in a dosage of 30 mg/kg. In all trials, on the 100th DPI, all animals were euthanized and submitted to the sequenced slicing of 26 anatomical segments (fragments of approximately five millimeters) for the survey of T. saginata cysticercus. With the obtained results it is possible to verify that in the first trials, conducted in 2002, ALB-SO reached, independently of dosage and treatment scheme, efficacies superior to 98% (arithmetic means). The trials conducted in 2005 (2.5 mg/kg on the 30th, 60th, and 90th DPI) obtained values of efficacy all inferior to 60%. In 2008, the trials with 2.5 and 7.7 mg/kg demonstrated efficacy values inferior to 40%, for both dosages and treatment schemes (30th/60th/90th DPI and 60th DPI). When this formulation was administered orally on the dosage of 30 mg/kg on the 60th DPI, the efficacy against T. saginata cysticercus reached 88.28%. ALB administered orally showed efficacy values of 0.0%, 29.88% and 28.64% in the dosages of 5, 10 and 15 mg/kg, respectively, using the treatment schemes described above for each dosage. Based on the results of these trials, conducted in an eight year period (2002-2010) using the sequenced slicing method for evaluating the efficacy of the aforementioned formulations against T. saginata cysticercus, it is possible to observe that, amongst the few molecules used in the chemotherapic treatment against T. saginata larvae, ALB-SO, administered in varied routes, dosages and treatment schemes, the studies conducted in 2008, 2009, and 2010, have a low therapeutic efficacy against C bovis in Brazil, while ALBZ had insignificant efficacy values against T. saginata larvae parasitizing experimentally infected bovines. However, future studies using molecular biology will be necessary to assess whether the difference on the efficacy of the ALB-SO can be related to strain or another specific factor. (C) 2013 Elsevier Inc. All rights reserved.

Effects of therapeutic approach on the neonatal evolution of very low birth weight infants with patent ductus arteriosus

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

Therapeutic Delivery of miR-200c Enhances Radiosensitivity in Lung Cancer

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

In vitro antibacterial and chemical properties of essential oils including native plants from Brazil against pathogenic and resistant bacteria

The antimicrobials products from plants have increased in importance due to the therapeutic potential in the treatment of infectious diseases. Therefore, we aimed to examine the chemical characterisation (GC-MS) of essential oils (EO) from seven plants and measure antibacterial activities against bacterial strains isolated from clinical human specimens (methicillin-resistant Staphylococcus aureus (MRSA) and sensitive (MSSA), Escherichia coli, Pseudomonas aeruginosa, Salmonella Typhimurium) and foods (Salmonella Enteritidis). Assays were performed using the minimal inhibitory concentration (MIC and MIC90%) (mg/mL) by agar dilution and time kill curve methods (log CFU/mL) to aiming synergism between EO. EO chemical analysis showed a predominance of terpenes and its derivatives. The highest antibacterial activities were with Cinnamomun zeylanicum (0.25 mg/mL on almost bacteria tested) and Caryophyllus aronzaticus EO (2.40 mg/mL on Salmonella Enteritidis), and the lowest activity was with Eugenia uniflora (from 50.80 mg/mL against MSSA to 92.40 mg/mL against both Salmonella sources and P aeruginosa) EO. The time kill curve assays revealed the occurrence of bactericide synergism in combinations of C. aromaticus and C. zeylanicum with Rosmarinus. officinalis. Thus, the antibacterial activities of the EO were large and this can also be explained by complex chemical composition of the oils tested in this study and the synergistic effect of these EO, yet requires further investigation because these interactions between the various chemical compounds can increase or reduce (antagonism effect) the inhibitory effect of essential oils against bacterial strains.

Therapeutic potential of mesenchymal stem cells to treat Achilles tendon injuries

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Effects of neuromuscular electrical stimulation on the masticatory muscles and physiologic sleep variables in adults with cerebral palsy: a novel therapeutic approach

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)