Consenso em reumatologia pediátrica: parte II - definição de melhora clínica para o lúpus eritematoso sistêmico e dermatomiosite juvenil

OBJETIVO: avaliar as medidas de atividade e critérios de melhora clínica para o lúpus eritematoso sistêmico juvenil (LESJ) e dermatomiosite juvenil (DMJ), desenvolvidos por meio de consenso entre especialistas. MÉTODOS E RESULTADOS: para o LESJ, as medidas essenciais em cinco domínios e as respectivas variáveis foram: 1) avaliação global pelo médico por escala analógica visual de 0-10 cm; 2) avaliação da qualidade de vida relacionada à saúde (índice Físico - CHQ-PF50); 3) avaliação da atividade pelos pais/paciente por escala analógica visual de 0-10 cm; 4) avaliação renal (proteinúria 24 h); e 5) avaliação global da atividade por instrumento específico (SLEDAI ou ECLAM). A definição preliminar de melhora clínica para o JSLE foi: melhora > 50% em pelo menos 2 das 5 variáveis e não mais que uma com piora > 30%, a qual não pode ser a proteinúria de 24h em casos com envolvimento renal. Os seis domínios e as respectivas variáveis selecionadas para a atividade na DMJ foram: 1) avaliação global pelo médico por escala analógica visual de 0-10 cm; 2) avaliação da força muscular proximal por meio de teste específico - CMAS-Childhood Myositis Assessment Scale 0-52; 3) avaliação da capacidade funcional (CHAQ); 4) avaliação da atividade pelos pais/paciente por escala analógica visual de 0-10 cm; 5) avaliação da qualidade de vida relacionada à saúde (Índice Físico - CHQ-PF50); 6) avaliação global da atividade por meio de instrumento específico (DAS - Disease Activity Score). A definição preliminar de melhora clínica para a DMJ foi: pelo menos 3 de quaisquer das 6 variáveis com melhora > 20% e não mais que uma com piora > 30%, a qual não pode ser o CMAS. CONCLUSÕES: estas variáveis foram testadas em uma casuística representativa e mostraram propriedades estatísticas adequadas de responsividade e validade discriminativa, podendo ser estudadas em ensaios terapêuticos.

Evaluation of the antimutagenic and anticarcinogenic effects of inulin in vivo

The incidence of colorectal cancer is growing worldwide. The characterization of compounds present in the human diet that can prevent the occurrence of colorectal tumors is vital. The oligosaccharide inulin is such a compound. The aim of this study was to evaluate the antigenotoxic, antimutagenic and anticarcinogenic effects of inulin in vivo. Our study is based on 3 assays that are widely used to evaluate chemoprevention (comet assay, micronucleus assay, and aberrant crypt focus assay) and tests 4 protocols of treatment with inulin (pre-treatment, simultaneous, post-treatment, and pre + continuous). Experiments were carried out in Swiss male mice of reproductive age. In order to induce DNA damage, we used the pro-carcinogenic agent 1,2-dimethylhydrazine. Inulin was administered orally at a concentration of 50 mg/kg body weight following the protocols mentioned above. Inulin was not administered to the control groups. Our data from the micronucleus assay reveal antimutagenic effects of inulin in all protocols. The percentage of inulin-induced damage reduction ranged from 47.25 to 141.75% across protocols. These data suggest that inulin could act through desmutagenic and bio-antimutagenic mechanisms. The anticarcinogenic activity (aberrant crypt focus assay) of inulin was observed in all protocols and the percentages of damage reduction ranged from 55.78 to 87.56% across protocols. Further tests, including human trials, will be necessary before this functional food can be proven to be effective in the prevention and treatment of colon cancer. © FUNPEC-RP.

Failures in the rehabilitation treatment with removable partial dentures

Background. Despite being functional and having aesthetic benefits, the acceptance of patients regarding the use of removable partial dentures (RPDs) has been low. In part, this is due to the deleterious effects that causes discomfort to the patient. Success depends not only on the care expended by the patient, including daily care and oral hygiene, but also on common goals set by their professional and clinical staff, aiming beyond aesthetics, to incorporate issues of functionality and the well-being of patients. Methods and results. For rehabilitation treatment with RPDs to reach the desired level of success without damaging the support structure, all the steps (diagnose, cavity preparation, adaptation of the metal structures, functional of distal extension and posterior follow-up) in the rehabilitative treatment should be carefully developed. A literature review was carried out, searching through MEDLINE (PubMed) articles published between 1965 and December 2012 including clinical trials and reviews about the use of RPDs. Conclusions. This study describes factors that lead to failures and complications in oral rehabilitation through the use of RPDs and suggests possible solutions.

Antimicrobial activity of natural products against Helicobacter pylori: a review

Throughout the genetic and physiological evolution of microorganisms, the microbiological sciences have been expanding the introduction of new therapeutic trials against microbial diseases. Special attention has been paid to the bacterium Helicobacter pylori, which induces gastric infections capable of causing damage, ranging from acute and chronic gastritis to the development of gastric cancer and death. The use of compounds with natural origins has gained popularity in scientific research focused on drug innovation against H. pylori because of their broad flexibility and low toxicity. The aim of this study was to describe the use of natural products against H. pylori in order to clarify important parameters for related fields. The study demonstrated the vast therapeutic possibilities for compounds originating from natural sources and revealed the need for innovations from future investigations to expand the therapeutic arsenal in the fight against H. pylori infection.

Syngonanthus nitens (Bong.) Ruhland: caracterização biológica e prospecção terapêutica do extrato metanólico incorporado ou não em sistema nanoestruturado para aplicação no tratamento da candidíase vulvovaginal

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Evaluation of pH effects on genomic integrity in adipose-derived mesenchymal stem cells using the comet assay

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Serum protein concentrations, including acute phase proteins, in calves with hepatogenous photosensitization

Foram examinados 100 bezerros da raça Nelore com 6 a 12 meses de idade, distribuídos em: grupo controle (G1; 50 bezerros sadios) e grupo fotossensibilização (G2; n= 50). As amostras de sangue foram coletadas 12 a 24 horas após o início da dermatite (M1) e 15 a 30 dias após (M2), época da cura das lesões cutâneas. O proteinograma sérico foi obtido por eletroforese em gel de acrilamida. em todos os bezerros foram identificadas 18 proteínas com pesos moleculares (PM) entre 16.000 a 189.000 dáltons (Da). em M1 e M2, as concentrações séricas das proteínas de PM 115.000Da (ceruloplasmina), 61.000Da (1-antitripsina), 45.000Da (haptoglobina) e 40.000Da (glicoproteína ácida) foram significativamente maiores em bezerros com fotossensibilização hepatógena em comparação com aquelas dos animais do grupo-controle. A determinação dos teores séricos de proteínas de fase aguda pode ser útil no monitoramento da progressão da fotossensibilização hepatógena em bovinos, inclusive orientando possíveis alterações em procedimentos terapêuticos.

Tigecycline: A Review of Properties, Applications, and Analytical Methods

Tigecycline is a new glycylcycline with an expanded broad-spectrum antibiotic, including inhibition of Gram-positive, Gram-negative, atypical, anaerobic, and antibiotic-resistant organisms. Trials have demonstrated that tigecycline is noninferior to the comparators for the treatment of complicated skin and skin structure infections as well as complicated intra-abdominal infections. Tigecycline is only available as an intravenous preparation and analytical methods to its quantitation in pharmaceutical products has not been published to date. This review examined tigecycline characteristics, the spectrum and mechanism of action, pharmacokinetics, applications, and, mainly, the instrumental conditions of published chromatographic methods used to measure tigecycline, its metabolites, and some analogs in clinical and biologic research.

Factors predictive of inappropriateness in requests for parenteral antimicrobials for therapeutic purposes: A study in a small teaching hospital in Brazil

Background: The identification of patterns of inappropriate antimicrobial prescriptions in hospitals contributes to the improvement of antimicrobial stewardship programs (ASP). Methods: We conducted a cross-sectional study to identify predictors of inappropriateness in requests for parenteral antimicrobials (RPAs) in a teaching hospital with 285 beds. We reviewed 25% of RPAs for therapeutic purposes from y 2005. Appropriateness was evaluated according to current guidelines for antimicrobial therapy. We assessed predictors of inappropriateness through univariate and multivariate models. RPAs classified as 'appropriate' or 'probably appropriate' were selected as controls. Case groups comprised inappropriate RPAs, either in general or for specific errors. Results: Nine hundred and sixty-three RPAs were evaluated, 34.6% of which were considered inappropriate. In the multivariate analysis, general predictors of inappropriateness were: prescription on week-ends/holidays (odds ratio (OR) 1.67, 95% confidence interval (CI) 1.20-2.28, p = 0.002), patient in the intensive care unit (OR 1.57, 95% CI 1.11-2.23, p = 0.01), peritoneal infection (OR 2.15, 95% CI 1.27-3.65, p = 0.004), urinary tract infection (OR 1.89, 95% CI 1.25 -2.87, p = 0.01), combination therapy with 2 or more antimicrobials (OR 1.72, 95% CI 1.15-2.57, p = 0.008) and prescriptions including penicillins (OR 2.12, 95% CI 1.39-3.25, p = 0.001) or 1(st) generation cephalosporins (OR 1.74, 95% CI 1.01-3.00, p = 0.048). Previous consultation with an infectious diseases (ID) specialist had a protective effect against inappropriate prescription (OR 0.34, 95% CI 0.24-0.50, p < 0.001). Factors independently associated with specific prescription errors varied. However, consultation with an ID specialist was protective against both unnecessary antimicrobial use (OR 0.04, 95% CI 0.01-0.26, p = 0.001) and requests for agents with an insufficient antimicrobial spectrum (OR 0.14, 95% CI 0.03-0.30, p = 0.01). Conclusions: Our results demonstrate the importance of previous consultation with an ID specialist in assuring the quality of prescriptions. Also, they highlight prescription patterns that should be approached by ASP policies.

Snake venom phospholipase A(2) inhibitors: Medicinal chemistry and therapeutic potential

Phospholipases A(2) (PLA(2)s) are commonly found in snake venoms from Viperidae, Hydrophidae and Elaphidae families and have been extensively studied due to their pharmacological and physiopathological effects in living organisms. This article reports a review on natural and artificial inhibitors of enzymatic, toxic and pharmacological effects induced by snake venom PLA(2)s. These inhibitors act on PLA(2)S through different mechanisms, most of them still not completely understood, including binding to specific domains, denaturation, modification of specific amino acid residues and others. Several substances have been evaluated regarding their effects against snake venoms and isolated toxins, including plant extracts and compounds from marine animals, mammals and snakes serum plasma, in addition to poly or monoclonal antibodies and several synthetic molecules. Research involving these inhibitors may be useful to understand the mechanism of action of PLA(2)s and their role in envenomations caused by snake bite. Furthermore, the biotechnological potential of PLA(2) inhibitors may provide therapeutic molecular models with antiophidian activity to supplement the conventional serum therapy against these multifunctional enzymes.

Inteins in pathogenic fungi: a phylogenetic tool and perspectives for therapeutic applications

Inteins or internal proteins are coding sequences that are transcribed and translated with flanking sequences (exteins). After translation, the inteins are excised by an autocatalytic process and the host protein assumes its normal conformation and develops its expected function. These parasitic genetic elements have been found in important, conserved proteins in all three domains of life. Most of the eukaryotic inteins are present in the fungi kingdom and the PRP8 intein is one of the most widespread inteins, occurring in important pathogens such as Cryptococcus neoformans (varieties grubii and neoformans), Cryptococcus gattii, Histoplasma capsulatum and Paracoccidioides brasiliensis. The knowledge of conserved and non-conserved domains in inteins have opened up new opportunities for the study of population variability in pathogenic fungi, including their phylogenetic relationships and recognition or diagnoses of species. Furthermore, inteins in pathogenic fungi should also be considered a promising therapeutic drug target, since once the autocatalytic splicing is inhibited, the host protein, which is typically vital, will not be able to perform its normal function and the fungal cell will not survive or reproduce.

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.