Mapa de evidências sobre a efetividade clínica da Apiterapia: informe executivo / Evidence map on the clinical effectiveness of Apitherapy: executive report

Este Mapa é parte de uma série de Mapas de Evidências sobre aplicação clínica das Práticas Integrativas e Complementares da Saúde (PICS), que estão na Política Nacional de Práticas Integrativas e Complementares (PNPIC). A partir de uma ampla busca bibliográfica (PubMed, BVS e CINAHL) foram incluídos no mapa 51 estudos de revisão, sendo 26 revisões sistemáticas com metanálise, 16 sistemáticas, 7 metanálises e 2 revisões sistemáticas de RCTs. Para avaliar o nível de confiabilidade das 51 revisões, se aplicou a ferramenta AMSTAR2 resultando em 7 revisões de nível alto, 15 revisões de nível baixo e 29 revisões de nível criticamente baixo. Todos os estudos foram avaliados, caracterizados e categorizados por um grupo de pesquisadores da área de Apiterapia. Principais Achados: - O mapa reúne evidências para as seguintes intervenções: mel, própolis, apitoxina, pólen e geleia real; - A maioria das evidências disponíveis concentra-se na intervenção Mel e aplicada para os desfechos mucosite (16 revisões) e ferida (8 revisões); - A Própolis foi a segunda intervenção mais estudada, sendo aplicada para os desfechos mucosite (4 revisões) e placa dentária (3 revisões); - Três revisões sistemáticas avaliaram os efeitos da Apitoxina aplicada em desfechos dos grupos Dor (alívio da dor, dor articular, dor cervical, dor lombar e dor muscular); e Doenças Não Transmissíveis (artrite, bursite, doença de Parkinson, osteoartrite e ovário policístico). Esta intervenção também foi aplicada para os desfechos de função motora e transtorno da articulação temporomandibular; - A geleia real foi aplicada para os desfechos de mucosite, glicemia e hemoglobina glicada, em 2 estudos. Uma revisão sistemática estudou o pólen aplicado para os desfechos de dor pélvica e qualidade de vida.

Epidemiology of the injury with venomous animals in the state of Rio Grande do Norte, Northeast of Brazil.

This report is an investigation of the epidemiological features of injuries with venomous animals in the Rio Grande do Norte state, Northeastern Brazil, from 2007 to 2014. A total of 30,429 cases were analyzed. Cases were distributed over all months of the period studied and occurred mainly in urban areas. Scorpion stings showed the highest percentage of cases, but the chance of death among snakebites was higher. Envenomation predominated in females with age between 20 and 49 years old. Children and elderly showed a higher chance of death. Most victims were bitten on the extremities of the limbs and received medical care within 0-1 hour after being bitten. The main local and systemic symptoms reported were pain and headache, respectively. Cases were mostly classified as mild and progressed to cure. Few victims show local and systemic complications. The high number of accidents with venomous animals shows that Rio Grande do Norte may be an important risk area for such injuries. Furthermore, this study provides data for the development of health actions to promote control and prevention of these injuries in this region.

Epidemiology of envenomation by Africanized honeybees in the state of Rio Grande do Norte, Northeastern Brazil.

INTRODUCTION: In the American continent, accidents caused by honeybees are a public health problem due to the high incidence and severity of the cases. Despite its medical importance, there are few epidemiological studies on this topic in Brazil, especially referring to the Northeastern states. The present study aims to describe the epidemiological features of honeybee envenomation cases in the state of the Rio Grande do Norte, Northeastern Brazil, from 2007 to 2014. METHODS: Data were collected from the Notifiable Diseases Information System database of the Health Department of Rio Grande do Norte. RESULTS: We analyzed a total of 2,168 cases. Cases occurred in all months of the years studied, reaching higher frequencies from June to October. Most incidents happened in urban areas and involved men, with victims aged between 20 and 39 years. Victims were mainly stung on the head and hand, and they received medical care predominantly within 3 hours after the injury. Local manifestations were more frequent than systemic ones. Clinically, most cases were mild and progressed to cure. CONCLUSION: The high number of honeybee sting cases shows that Rio Grande do Norte may be an important risk area for such injury.

Epidemiology of envenomation by Africanized honeybees in the state of Rio Grande do Norte, Northeastern Brazil / Epidemiologia dos envenenamentos por abelhas africanizadas no Estado do Rio Grande do Norte, Nordeste do Brasil

ABSTRACT: Introduction: In the American continent, accidents caused by honeybees are a public health problem due to the high incidence and severity of the cases. Despite its medical importance, there are few epidemiological studies on this topic in Brazil, especially referring to the Northeastern states. The present study aims to describe the epidemiological features of honeybee envenomation cases in the state of the Rio Grande do Norte, Northeastern Brazil, from 2007 to 2014. Methods: Data were collected from the Notifiable Diseases Information System database of the Health Department of Rio Grande do Norte. Results: We analyzed a total of 2,168 cases. Cases occurred in all months of the years studied, reaching higher frequencies from June to October. Most incidents happened in urban areas and involved men, with victims aged between 20 and 39 years. Victims were mainly stung on the head and hand, and they received medical care predominantly within 3 hours after the injury. Local manifestations were more frequent than systemic ones. Clinically, most cases were mild and progressed to cure. Conclusion: The high number of honeybee sting cases shows that Rio Grande do Norte may be an important risk area for such injury.

RESUMO: Introdução: No continente americano, os acidentes causados por abelhas são um problema de saúde pública devido à alta incidência e severidade dos casos. Apesar de sua importância médica, há poucos estudos epidemiológicos sobre esse tema no Brasil, especialmente referentes aos estados do Nordeste. O presente estudo tem como objetivo descrever as características epidemiológicas dos casos de envenenamento por abelhas no estado do Rio Grande do Norte, no Nordeste do Brasil, de 2007 a 2014. Metodologia: Os dados foram coletados da base de dados do Sistema de Informação de Agravos de Notificação da Secretaria Estadual de Saúde do Rio Grande do Norte. Resultados: Um total de 2.168 casos foram analisados. Os casos mostraram distribuição em todos os meses dos anos estudados, com maior frequência de junho a outubro. A maioria dos casos ocorreu em áreas urbanas e envolveu homens, com vítimas entre 20 e 39 anos de idade. As vítimas foram principalmente picadas na cabeça e na mão, e receberam assistência médica predominantemente dentro de 3 horas após serem picadas. As manifestações locais eram mais frequentes do que as sistêmicas. Clinicamente, a maioria dos casos foi leve e progrediu para cura. Conclusão: O alto número casos de picadas de abelhas mostra que o Rio Grande do Norte pode ser uma importante área de risco para tal incidente.

Right ventricular load adaptability metrics in patients undergoing left ventricular assist device implantation.

OBJECTIVE: Several right load adaptability metrics have been proposed as predictors of right heart failure (RHF) following left ventricular assist device implantation. This study sought to validate and compare the prognostic value of these indices. METHODS: This retrospective study included 194 patients undergoing continuous-flow left ventricular assist device implantation. The primary end point was unplanned right atrial assist device (RVAD) need within 30 days after left ventricular assist device implantation; the secondary end points included clinical RHF syndrome without RVAD need and the composite of RHF or RVAD need. Load adaptability indices or interventricular ratios were divided into surrogates of ventriculoarterial coupling (RV area change:end-systolic area), indices reflecting adaptation proportionality (Dandel's index = tricuspid regurgitation velocity-time integral normalized for average RV radius in diastole or systole), and simple ratios (eg, pulse pressure:right atrial pressure or right arterial pressure:pulmonary arterial wedge pressure). RESULTS: Mean age was 55 ± 13 years with 77% of men. RHF occurred in 75 patients with 30 patients requiring RVAD implantation. Among right heart metrics, right arterial pressure (normalized odd ratio, 1.62; 95% confidence interval, 1.15-2.38), right arterial pressure:pulmonary arterial wedge pressure (normalized odds ratio, 1.59; 95% confidence interval, 1.08-2.32) and pulse pressure:right arterial pressure < 2.0 (normalized odds ratio, 2.56; 95% confidence interval, 1.16-5.56) were associated with RVAD need (all P values < .02). These 3 metrics significantly added incremental prognostic value to the Interagency Registry for Mechanically Assisted Circulatory Support classification score in a similar range, whereas only RAP was incremental to the Michigan score. Correlates of RHF not requiring RVAD included RV end-systolic area index and the Dandel indices, which provided similar incremental value to the Interagency Registry for Mechanically Assisted Circulatory Support, Michigan, and European Registry for Patients with Mechanical Circulatory Support scores. CONCLUSIONS: Although associated with outcome, right load adaptability indices do not appear to provide strong incremental value when compared with simple metrics.

The epidemiology of snakebite in the Rio Grande do Norte State, Northeastern Brazil.

This report is a retrospective study of the epidemiology of snakebite cases recorded from 2007 to 2014 in the Rio Grande do Norte State, northeastern Brazil. Data was collected from the Injury Notification Information System database of the Health Department of Rio Grande do Norte. A total of 3,019 cases were studied. Cases were distributed over all months of the period studied and occurred mainly in rural areas. Snakes of the genus Bothrops, Crotalus, Micrurus, Lachesis and non-venomous snakes were responsible for 1,507, 185, 52, 6 and 673 cases, respectively. Snakebites predominated in males with age between 10 and 29 years old. Most victims were bitten on the feet and received medical assistance within 1-3 h after being bitten. Cases were mostly classified as mild and progressed to cure. Envenomation by snakebite in Rio Grande do Norte is an environmental public health problem that needs to be monitored and controlled throughout the year. Additionally, the training of health professionals is urgent in order to improve the registration of epidemiological information and medical care to victims.

Epidemiological study of scorpion stings in the Rio Grande do Norte State, Northeastern Brazil.

This communication is a retrospective epidemiological study of the scorpion sting cases recorded from 2007 to 2014 in the Rio Grande do Norte State, Northeastern Brazil. The data was collected from the Injury Notification Information System database of the Health Department of Rio Grande do Norte State. A total of 20,555 cases were studied. The cases were distributed over all months of the period studied and occurred mainly in urban areas. Victims were predominantly 20-29 year-old women. Most victims were stung on the foot and received medical care within 1-3 h after being stung. The cases were mostly classified as mild and progressed to cure. Scorpion stings in Rio Grande do Norte State are an environmental public health problem that needs to be monitored and controlled throughout the year.

Seroprevalence of toxoplasmosis in pregnant women in a city in Rio Grande do Norte state, Brazil

Toxoplasmosis is caused by Toxoplasma gondii, which is particularly relevant in pregnant women, due to the risk of congenital infection. The aim of this study was to study the serological profile of pregnant women and analyze some factors related to infection in this group. A descriptive and retrospective study was performed analyzing the results of 356 pregnant women in the Mixed Health Unit of Jaçanã-RN from 2009 to 2014. Results of serological tests for IgG and IgM anti-T. gondii antibodies were provided by LACEN-RN. The chi-square test (χ2) was calculated being considered statistically significant for p<0.05. The results showed that: 59% of the pregnant women tested presented serology IgG anti-T. gondii reagent (IgG+) and IgM anti-T. gondii non-reactive (IgM-), 0.6% reagent for both (IgG+ and IgM+) and 40.4% susceptible to infection (IgG- and IgM-). 71.3% of the women were tested in the first trimester of pregnancy; the 20-29 years of age range was the most prevalent (62.5%) and the 11-19 years of age range was the most susceptible (47%). The rural women had the highest incidence of positive serology (60.2%) and those from the urban area were the most susceptible (40.7%). There was no statistical association between serology and the age group (p=0.282) and origin (p=0.881) variables. There is need for investment in prenatal care and health education for the population about toxoplasmosis

Development of Tyrocidine A analogues with improved antibacterial activity.

The development of new antibacterial therapeutic agents capable of halting microbial resistance is a chief pursuit in clinical medicine. Classes of antibiotics that target and destroy bacterial membranes are attractive due to the decreased likelihood that bacteria will be able to generate resistance to this mechanism. The amphipathic cyclic decapeptide, Tyrocidine A, is a model for this class of antibiotics. Tyrocidine A is composed of a hydrophobic and a hydrophilic face, allowing for insertion into bacterial membranes, creating porous channels and destroying membrane integrity. We have used a combination of molecular modeling and solid phase synthesis to prepare Tyrocidine A and analogues 1-8. The minimum inhibitory concentrations (MICs) of these compounds were determined for a host of gram positive species and E. coli as a representative gram negative bacterium. Analogues 2 and 5 demonstrated moderate 2- to 8-fold increases in antibacterial activity over the parent Tyrocidine A for a variety of pathogenic microbes (best MICs for E. coli 32 microg/mL and 2 microg/mL for most gram positives). Examination of the structure- activity relationship between the analogues demonstrated a preference for increased amphipathicity but did not show a clear preference for increasing hydrophilicity versus hydrophobicity in improving antibacterial activity. Of note, movement of positively charged lysine residues or neutral pentafluorophenyl residues to different positions within the cyclopeptide ring system demonstrated improvements in antibacterial activity.

Programmable oligomers targeting 5'-GGGG-3' in the minor groove of DNA and NF-kappaB binding inhibition.

A series of hairpin oligomers containing benzimidazole (Bi) and imidazopyridine (Ip) rings were synthesized and screened to target 5'-WGGGGW-3', a core sequence in the DNA-binding site of NF-kappaB, a prolific transcription factor important in biology and disease. Five Bi and Ip containing oligomers bound to the 5'-WGGGGW-3' site with high affinity. One of the oligomers (Im-Im-Im-Im-gamma-Py-Bi-Py-Bi-beta-Dp) was able to inhibit DNA binding by the transcription factor NF-kappaB.

Programmable oligomers for minor groove DNA recognition.

The four Watson-Crick base pairs of DNA can be distinguished in the minor groove by pairing side-by-side three five-membered aromatic carboxamides, imidazole (Im), pyrrole (Py), and hydroxypyrrole (Hp), four different ways. On the basis of the paradigm of unsymmetrical paired edges of aromatic rings for minor groove recognition, a second generation set of heterocycle pairs, imidazopyridine/pyrrole (Ip/Py) and hydroxybenzimidazole/pyrrole (Hz/Py), revealed that recognition elements not based on analogues of distamycin could be realized. A new set of end-cap heterocycle dimers, oxazole-hydroxybenzimidazole (No-Hz) and chlorothiophene-hydroxybenzimidazole (Ct-Hz), paired with Py-Py are shown to bind contiguous base pairs of DNA in the minor groove, specifically 5'-GT-3' and 5'-TT-3', with high affinity and selectivity. Utilizing this technology, we have developed a new class of oligomers for sequence-specific DNA minor groove recognition no longer based on the N-methyl pyrrole carboxamides of distamycin.

Programmable DNA binding oligomers for control of transcription.

Mapping and sequencing the genetic blueprint in human, mice, yeast and other model organisms has created challenges and opportunities for chemistry, biology and human medicine. An understanding of the function of each of the approximately 25,000 genes in humans, and the biological circuitry that controls these genes will be driven in part by new technologies from the world of chemistry. Many cellular events that lead to cancer and the progression of human disease represent aberrant gene expression. Small molecules that can be programmed to mimic transcription factors and bind a large repertoire of DNA sequences in the human genome would be useful tools in biology and potentially in human medicine. Polyamides are synthetic oligomers programmed to read the DNA double helix. They are cell permeable, bind chromatin and have been shown to downregulate endogenous genes in cell culture.

Challenging the auxiliary donor effect on molecular hyperpolarizability in thiophene-containing nonlinear chromophores: X-ray crystallographic and optical measurements on two new isomeric chromophores.

To reexamine the established "auxiliary donor" effect of thiophene in nonlinear optical (NLO) chromophores, we have prepared two isomeric donor-acceptor azo dyes, differing only in the position of the thiophene. Experimental analysis of these chromophores, including electric field-induced second harmonic generation (EFISH) and X-ray crystallography, contradicts previous experimental findings on similar chromophores but is consistent with the majority of computational precedents. We have found that the thiophene on the donor side produces a compound with a larger dipole moment; however, the isomer with the thiophene on the acceptor side is more nonlinear and has a higher figure of merit for NLO device applications.

Expanding the repertoire of heterocycle ring pairs for programmable minor groove DNA recognition.

The discrimination of the four Watson-Crick base pairs by minor groove DNA-binding polyamides have been attributed to the specificity of three five-membered aromatic amino acid subunits, 1-methyl-1H-imidazole (Im), 1-methyl-1H-pyrrole (Py), and 3-hydroxy-1H-pyrrole (Hp) paired four different ways. The search for additional ring pairs that demonstrate DNA-sequence specificity has led us to a new class of 6-5 fused bicycle rings as minor groove recognition elements. The affinities and specificities of the hydroxybenzimidazole/pyrrole (Hz/Py) and hydroxybenzimidazole/benzimidazole (Hz/Bi) pairs for each of the respective Watson-Crick base pairs within the sequence context 5'-TGGXCA-3' (X = A, T, G, C) were measured by quantitative DNaseI footprinting titrations. The Hz/Py and Hz/Bi distinguish T.A from A.T. Hairpin polyamides containing multiple Hz/Py pairs were examined and were shown to mimic the Hp/Py pair with regard to affinity and specificity. Therefore, the Hz/Py pair may be considered a second-generation replacement for the Hp/Py pair.

DNA minor-groove recognition by 3-methylthiophene/pyrrole pair.

Hairpin polyamides are synthetic oligomers, which fold and bind to specific DNA sequences in a programmable manner. Internal side-by-side pairings of the aromatic amino acid residues 1-methyl-1H-pyrrole (Py), 1-methyl-1H-imidazole (Im), and 3-hydroxy-1-methyl-1H-pyrrole (Hp) confer the ability to distinguish between all four Watson-Crick base pairs in the minor groove of B-form DNA. In a broad search to expand the heterocycle repertoire, we found that when 3-methylthiophene (Tn), which presents a S-atom to the minor groove, is paired with Py, it exhibits a modest threefold specificity for TA>AT presumably by shape-selective recognition. In this study, we explore the scope and limitations of this lead by incorporating multiple Tn residues within a single hairpin polyamide. It was found that hairpin polyamides containing more that one Tn/Py pair exhibit lowered affinities and specificities for their match sites. It appears that little deviation is permissible from the parent five-membered ring 1-methyl-1H-pyrrole-2-carboxamide scaffold for DNA recognition.

Shape selective recognition of T.A base pairs by hairpin polyamides containing N-terminal 3-methoxy (and 3-chloro) thiophene residues.

Hairpin polyamides selectively recognize predetermined DNA sequences with affinities comparable to naturally occurring proteins. Internal side-by-side pairs of unsymmetrical aromatic rings within the minor groove of DNA distinguish each of the four Watson-Crick base pairs. In contrast, N-terminal ring pairs exhibit less specificity, with the exception of Im/Py targeting G.C base pairs. In an effort to explore the sequence specificity of new ring pairs, a series of hairpin polyamides containing 3-substituted-thiophene-2-carboxamide residues at the N-terminus was synthesized. An N-terminal 3-methoxy (or 3-chloro) thiophene residue paired opposite Py displayed 6- (and 3-) fold selectivity for T.A relative to A.T base pair, while disfavoring G,C base pairs by >200-fold. Our data suggests shape selective recognition with projection of the 3-thiophene substituent (methoxy or chloro) to the floor of the minor groove.