Efficacy and safety of artemisinin-based combination therapy and chloroquine with concomitant primaquine to treat Plasmodium vivax malaria in Brazil: an open label randomized clinical trial.

BACKGROUND: There is general international agreement that the importance of vivax malaria has been neglected, and there is a need for new treatment approaches in an effort to progress towards control and elimination in Latin America. This open label randomized clinical trial evaluated the efficacy and safety of three treatment regimens using either one of two fixed dose artemisinin-based combinations or chloroquine in combination with a short course of primaquine (7-9 days: total dose 3-4.2 mg/kg) in Brazil. The primary objective was establishing whether cure rates above 90% could be achieved in each arm. RESULTS: A total of 264 patients were followed up to day 63. The cure rate of all three treatment arms was greater than 90% at 28 and 42 days. Cure rates were below 90% in all three treatment groups at day 63, although the 95% confidence interval included 90% for all three treatments. Most of the adverse events were mild in all treatment arms. Only one of the three serious adverse events was related to the treatment and significant drops in haemoglobin were rare. CONCLUSION: This study demonstrated the efficacy and safety of all three regimens that were tested with 42-day cure rates that meet World Health Organization criteria. The efficacy and safety of artemisinin-based combination therapy regimens in this population offers the opportunity to treat all species of malaria with the same regimen, simplifying protocols for malaria control programmes and potentially contributing to elimination of both vivax and falciparum malaria. Trial registration RBR-79s56s.

Using a single tablet daily to treat latent tuberculosis infection in Brazil: bioequivalence of two different isoniazid formulations (300 mg and 100 mg) demonstrated by a sensitive and rapid high-performance liquid chromatography-tandem mass spectrometry method in a randomised, crossover study.

The recommended treatment for latent tuberculosis (TB) infection in adults is a daily dose of isoniazid (INH) 300 mg for six months. In Brazil, INH was formulated as 100 mg tablets. The treatment duration and the high pill burden compromised patient adherence to the treatment. The Brazilian National Programme for Tuberculosis requested a new 300 mg INH formulation. The aim of our study was to compare the bioavailability of the new INH 300 mg formulation and three 100 mg tablets of the reference formulation. We conducted a randomised, single dose, open label, two-phase crossover bioequivalence study in 28 healthy human volunteers. The 90% confidence interval for the INH maximum concentration of drug observed in plasma and area under the plasma concentration vs. time curve from time zero to the last measurable concentration "time t" was 89.61-115.92 and 94.82-119.44, respectively. The main limitation of our study was that neither adherence nor the safety profile of multiple doses was evaluated. To determine the level of INH in human plasma, we developed and validated a sensitive, simple and rapid high-performance liquid chromatography-tandem mass spectrometry method. Our results showed that the new formulation was bioequivalent to the 100 mg reference product. This finding supports the use of a single 300 mg tablet daily strategy to treat latent TB. This new formulation may increase patients' adherence to the treatment and quality of life.

In vitro-in vivo correlation of efavirenz tablets using GastroPlus®.

The aim of the present work was to use GastroPlus™ software for the prediction of pharmacokinetic profiles and in vitro-in vivo correlation (IVIVC) as tools to optimize the development of new generic medications. GastroPlus™ was used to simulate the gastrointestinal compartment and was based on the advanced compartmental absorption and transit model. Powder dissolution and efavirenz tablet dissolution studies were carried out to generate data from which correlation was established. The simulated plasma profile, based on the physicochemical properties of efavirenz, was almost identical to that observed in vivo for biobatches A and B. A level A IVIVC was established for the dissolution method obtained for the generic candidate using the Wagner-Nelson (r (2) = 0.85) and for Loo-Riegelman models (r(2) = 0.92). The percentage of fraction absorbed indicated that 0.5% sodium lauryl sulfate may be considered a biorelevant dissolution medium for efavirenz tablets. The simulation of gastrointestinal bioavailability and IVIVC obtained from immediate-release tablet formulations suggests that GastroPlus™ is a valuable in silico method for IVIVC and for studies directed at developing formulations of class II drugs.

Application of the Southwell Plot method to determine equilibrium time in phosphate adsorption.

Among the different factors that influence the liquid-solid adsorption technique, equilibrium time is one of the most relevant and requires a large number of experiments over a long period of time for its determination. This work evaluates the Southwell Plot as a further tool that can contribute to determining the equilibrium time in adsorption processes. It can also optimize the operating conditions in a batch system for the removal of phosphate in adsorbents produced from domestic sewage sludge and clam shell residue. Sewage sludge and clam shell residues were ground, sieved and sintered at 700 °C for 1 h. The material was characterized by thermal analyses (TG/DTG), chemical analysis (EDX), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR) and adsorption studies. The kinetic studies were investigated by varying the initial concentration of the phosphate solution and mass of the adsorbent. The equilibrium time was determined by applying the Southwell Plot method to the kinetic data and the results showed some fluctuations as a function of the adsorbent mass. At 0.30 g of the adsorbent in 30 mL of the phosphate solution, regardless of the initial phosphate concentration, the equilibrium time determined by the Southwell Plot was 4 h. The maximum phosphate adsorption capacity in this condition, determined by the Langmuir equation, was 49.45 mg g-1.

Structural determination Vitex cymosa Bertero active principle: Diastereoselective synthesis of (+/-)-trans-4-hydroxy-6-propyl-1-oxocyclohexan-2-one and its antinociceptive activity.

The diastereoselective synthesis of (+/-)-trans-4-hydroxy-6-propyl-1-oxocyclohexan-2-one, as a mixture trans:cis (3:1), was accomplished using a protocol that combine the Prins cyclization and RuO(4) oxidation. The synthesis this lactone allowed the elucidation of the correct structure of the substance isolated from the barks of Vitex cymosa. The delta-lactones mixture showed significant antinociceptive properties in preliminary tests using the tail flick model assay.

Bioequivalence studies and sugar-based excipients effects on the properties of new generic ketoconazole tablets formulations and stability evaluation by using direct compression method.

In this work we described the development of a new solid oral formulation of ketoconazole, a broad-spectrum antifungal agent that belongs to the class II of Biopharmaceutics Classification System (BCS). The ketoconazole raw material supplier was selected to present a best flow and compactation. In addition we used direct compression and superdisintegrants associated to polyols to enhance the dissolution of the ketoconazole tablets. The dissolution was evaluated based in level C in vivo/in vitro correlation established. The best formulation was obtained with croscarmellose/maltose association that in the accelerated stability assays presented no differences on quality specifications and no drug-excipients interaction by DSC analyses. In this work it was possible to confirm the use of sugar-based excipients as suitable dissolution enhancers in pharmaceutical technology and real processes conditions.

Decompression Associated with Irrigation with Elixir Sanativo® Before Enucleation of Odontogenic Keratocysts: Report of Two Cases

Odontogenic Keratocyst (OKC) is an aggressive cystic lesion of the jaws and one of the most common odontogenic cysts, usually affecting the posterior region of the mandible. Recurrences are frequently recorded and may be directly related to the treatment modality adopted. Two patients presenting OKC were treated by combining decompression and intralesional irrigation with the drug Elixir Sanativo® for 8 months before enucleation surgery. In both patients, the association between decompression and irrigation with Elixir Sanativo® represented a safe and effective method to reduce the preoperative lesion dimensions.

El queratoquiste odontogénico (QO) es una lesión quística agresiva de la mandíbula y es uno de los quistes odontogénicos más frecuentes, que suele afectar a la región posterior de la mandíbula. Las recidivas se registran con frecuencia y pueden estar directamente relacionadas con la modalidad de tratamiento adoptada. Presentación del caso: Dos pacientes que presentaban OKC fueron tratados combinando descompresión e irrigación intralesional con el fármaco Elixir Sanativo® durante 8 meses antes de la cirugía de enucleación. En ambos pacientes, la asociación entre descompresión e irrigación con Elixir Sanativo® representó un método seguro y eficaz para reducir las dimensiones de la lesión preoperatoria.

Preparation and evaluation of inclusion complexes of commercial sunscreens in cyclodextrins and montmorillonites: performance and substantivity studies.

Herein we describe inclusion complexes of commercial sunscreens in cyclodextrins and montmorillonites to generate new sunscreen derivatives with optimized functional properties such as water resistance and skin adherence. Four cyclodextrins (alpha-, beta-, and gamma-cyclodextrin, and beta-dimethyl cyclodextrin) and two montmorillonites (sodium and alkylammonium) were investigated for encapsulating some commercial sunscreens. Our results reveal a good yield and inclusion products with functional properties obtained by using kneading technique on Eusolex 2292 and Eusolex 6007 in beta-cyclodextrin and solubilization method on Eusolex 6007 and NeoHeliopan MA in montmorillonite. In addition, molecular modeling studies indicated flexibility as important for the intercalation of the host molecule.

[Assessment of the technical adequacy of phytotherapeutics and officinal medicine manufacturers in the State of Rio de Janeiro]. / Avaliação da adequação técnica de indústrias de medicamentos fitoterápicos e oficinais do Estado do Rio de Janeiro.

In this study we evaluated the current profile of manufacturers of officinal medicines and phytotherapeutics in relation to the Brazilian regulatory legislation. Forty-eight industries involved in manufacture and distribution of officinal medicines and phytotherapeutics were identified in one hundred current administrative processes of the National Health Surveillance Agency in Brazil. The analysis of the inspection reports of these companies considered the first nine months after the implantation of Resolution RDC 210/03 and revealed five specific company profiles: satisfactory (29.2%), satisfactory with restrictions (10.4%), unsatisfactory (6.2%), interdicted (39.6%), and applying for cancellation due to lack of conditions for complying with Resolution RDC 210/03 (14.6%). The main irregularities found in these companies involved the operational flow, quality control and product registration issues. Our results revealed a great number of companies whose activities are related to the production of officinal medicines and phytotherapeutics but that are still not totally adequate to the industrial park of Rio de Janeiro. The perspectives for the future of this category of industries are thus not favorable because of their difficulties to meet the current requirements.

Covid-19: perfil epidemiológico dos usuários testados em uma unidade de Atenção Primária à Saúde / COVID-19: epidemiological profile of users tested at a Primary Health Care unit / COVID-19: perfil epidemiológico de los usuarios testeados en una unidad de Atención Primaria de Salud

O segundo semestre de 2019 foi marcado pelo debate mundial acerca de casos de contaminação por um agente etiológico, que, após pesquisas genéticas, foi classificado pela Organização Mundial da Saúde (OMS) como covid-19. No Brasil, o vírus chegou em fevereiro de 2020. A partir de então, a Atenção Primária à Saúde (APS) se tornou fundamental no cenário pandêmico com a oferta de serviços, como testes rápidos, para diagnóstico do vírus. O objetivo deste artigo é descrever o perfil epidemiológico da população usuária de uma unidade de Atenção Primária à Saúde que realizou teste rápido para covid-19. Este é um estudo descritivo, documental, com abordagem quantitativa do tipo perfil epidemiológico. A pesquisa foi feita em Natal, Rio Grande do Norte, entre 10 de junho e 5 de agosto de 2020. Dos usuários testados, observaram-se prevalência do sexo feminino (60%); cor/raça parda (53,8%); faixa etária entre 56 e 60 anos (14%); em relacionamento estável (61,5%); ensino médio completo (45,4%); não praticantes de atividade física (56,9%) e não tabagistas (96,2%). Os resultados permitiram traçar o perfil epidemiológico local e, somados aos demais dados obtidos no curso da pandemia, contribuem para novas medidas de promoção, prevenção e recuperação do processo saúde-doença.

The second semester of 2019 was plunged into a worldwide debate concerning cases of contamination by an etiological agent that, following genetical research, was classified by the World Health Organization (WHO) as COVID-19. In Brazil, the virus was first recorded in February 2020, from then on Primary Health Care (PHC) played a key role during the pandemic by offering services such as the rapid testing for virus detection. Hence, this epidemiological, descriptive, quantitative and documentary study sought to describe the epidemiological profile of PHC users tested for COVID-19 using the rapid test. The research took place in Natal, Rio Grande do Norte, Brazil, between June 10 and August 5, 2020. Most tested users were women (60%), mixed race/brown (53.8%), aged 56 to 60 years (14%), in stable relationships (61.5%), with complete high school (45.4%), sedentary (56.9%), and non-smokers (96.2%). The results allowed us to outline a local epidemiological profile which, when taken with other data obtained throughout the pandemic, has contributed to new measures for promotion, prevention and recovery in the health-disease process.

En el segundo semestre de 2019 estuvo en debate mundial los casos de contaminación por un agente etiológico, que después de investigaciones genéticas la Organización Mundial de la Salud lo clasificó como COVID-19. En Brasil, el virus llegó en febrero de 2020. A partir de ese momento la Atención Primaria de Salud (APS) se convirtió en el elemento fundamental en el escenario de la pandemia con la oferta de servicios, como la realización de exámenes rápidos para diagnóstico del virus. El objetivo de este estudio es describir el perfil epidemiológico de la población usuaria de una unidad de Atención Primaria de Salud que realizaron examen rápido para COVID-19. Este es un estudio descriptivo, documental, con enfoque cuantitativo, del tipo perfil epidemiológico. El estudio se realizó en Natal, Rio Grande do Norte (Brasil), entre 10 de junio a 5 de agosto de 2020. En los usuarios testados, se observó el predominio del sexo femenino (60%); color/raza parda (53,8%); franja etaria entre 56 a 60 años (14%); en una relación estable (61,5%); enseñanza secundaria completa (45,4%); no practicantes de actividad física (56,9%) y no fumadores (96,2%). Los resultados permitieron trazar el perfil epidemiológico local que, sumado con los demás datos obtenidos durante la pandemia, contribuyen con nuevas medidas de promoción, prevención y recuperación del proceso salud-enfermedad.

Solution and Solid State Nuclear Magnetic Resonance Spectroscopic Characterization of Efavirenz.

Samples of efavirenz (EFZ) were evaluated to investigate the influence of the micronization process on EFZ stability. A combination of X-ray diffraction, thermal analysis, FTIR, observations of isotropic chemical shifts of (1)H in distinct solvents, their temperature dependence and spin-lattice relaxation time constants (T1), solution (1D and 2D) (13)C nuclear magnetic resonance (NMR), and solid-state (13)C NMR (CPMAS NMR) provides valuable structural information and structural elucidation of micronized EFZ and heptane-recrystallized polymorphs (EFZ/HEPT). This study revealed that the micronization process did not affect the EFZ crystalline structure. It was observed that the structure of EFZ/HEPT is in the same form as that obtained from ethyl acetate/hexane, as shown in the literature. A comparison of the solid-state NMR spectra revealed discrepancies regarding the assignments of some carbons published in the literature that have been resolved.

Development and validation of a HPLC-UV method for the determination in didanosine tablets.

A simple, rapid, sensitive and specific reversed-phase high performance liquid chromatographic method involving ultraviolet detection (HPLC-UV) was developed for analysis of didanosine in drug substance and formulated products, tablets. Chromatography was carried out on a pre-packed, Lichrospher 100 Rp-8 (5.0 microm, 250 mm x 4.0 mm) column using 0.01 M sodium acetate solution:methanol (85:15, v/v) adjusted to pH 6.5 with acetic acid as mobile phase at a flow rate of 1.5 ml/min and a 248 nm detection. Hypoxantine was confirmed as the main degradation product. The assay was linear over the concentration range of 50-150 microg/ml (R approximately 0.999). The method was validated for accuracy and precision.

Participatory research revealing the work and occupational health hazards of cooperative recyclers in Brazil.

Although informal waste collectors are sometimes organized in cooperatives, their working conditions remain extremely precarious and unsafe. The paper discusses the findings of action oriented, participatory qualitative research with several recycling groups in the metropolitan region of São Paulo, Brazil. During workshops with the recyclers mapping, acting, and drawing methods helped reveal health hazards from collection, separation and transportation of recyclable materials. Major health problems relate to chemical and biological hazards, musculoskeletal damage, mechanical trauma and poor emotional wellbeing. The recent federal legislation on solid waste management opens new avenues for the inclusion of recycling cooperatives in selective waste collection. Nevertheless, we express the need to consider the distinctive characteristics and vulnerabilities of recycling groups, when developing safer work environments in these social businesses. We also suggest that the workspace be ergonomically organized and that public awareness campaigns about selective waste collection are conducted regularly to increase the quality of source separation. The introduction of electric hand pushed carts can further reduce health strains. This research has produced a better understanding of the work of the recyclers and related health risks. The interactive qualitative research methodology has allowed for the co-creation and mobilization of specific knowledge on health and safety in recycling cooperatives.

Using a single tablet daily to treat latent tuberculosis infection in Brazil: bioequivalence of two different isoniazid formulations (300 mg and 100 mg) demonstrated by a sensitive and rapid high-performance liquid chromatography-tandem mass spectrometry method in a randomised, crossover study

The recommended treatment for latent tuberculosis (TB) infection in adults is a daily dose of isoniazid (INH) 300 mg for six months. In Brazil, INH was formulated as 100 mg tablets. The treatment duration and the high pill burden compromised patient adherence to the treatment. The Brazilian National Programme for Tuberculosis requested a new 300 mg INH formulation. The aim of our study was to compare the bioavailability of the new INH 300 mg formulation and three 100 mg tablets of the reference formulation. We conducted a randomised, single dose, open label, two-phase crossover bioequivalence study in 28 healthy human volunteers. The 90% confidence interval for the INH maximum concentration of drug observed in plasma and area under the plasma concentration vs. time curve from time zero to the last measurable concentration “time t” was 89.61-115.92 and 94.82-119.44, respectively. The main limitation of our study was that neither adherence nor the safety profile of multiple doses was evaluated. To determine the level of INH in human plasma, we developed and validated a sensitive, simple and rapid high-performance liquid chromatography-tandem mass spectrometry method. Our results showed that the new formulation was bioequivalent to the 100 mg reference product. This finding supports the use of a single 300 mg tablet daily strategy to treat latent TB. This new formulation may increase patients’ adherence to the treatment and quality of life.

Structural equation modeling in epidemiology.

Structural equation modeling (SEM) is an important statistical tool for evaluating complex relations in several research areas. In epidemiology, the use and discussion of SEM have been limited thus far. This article presents basic principles and concepts in SEM, including an application using epidemiological data analysis from a study on the determinants of cognitive development in young children, considering constructs related to organization of the child's home environment, parenting style, and the child's health status. The relations between the constructs and cognitive development were measured. The results showed a positive association between psychosocial stimulus at home and cognitive development in young children. The article presents the contributions by SEM to epidemiology, highlighting the need for an a priori theoretical model for improving the study of epidemiological questions from a new perspective.

Ácido Poli-L-Láctico: um agente bioestimulador / Poly-L-lactic acid: a biostimulating agent

O ácido poli-L-láctico (PLLA) é polímero biocompatível, reabsorvível, imunologicamente inerte, que induz a neocolagênese através de resposta inflamatória subclínica, indicado para restauração do volume facial associado à lipoatrofia facial em pacientes imunocompetentes ou com imunodeficiência pelo vírus HIV, além das indicações cosméticas em áreas extrafaciais. Há mais de três décadas vem sendo usado em dispositivos médicos como placas, parafusos, implantes intraósseos, de tecidos moles, como vetor biodegradável para medicamentos, em fios de sutura e stents. Este artigo tem como objetivo apresentar uma revisão da literatura sobre indicações ao uso do PLLA, seu modo de aplicação e suas possíveis complicações.

Poly-L-lactic acid (PLLA) is a biocompatible, re-absorbable, immunologically inert polymer that induces neocollagenesis through a subclinical inflammatory response. It is indicated for restoration of facial volume associated with facial lipoatrophy in immunocompetent or HIV-immunodeficient patients. In addition there are cosmetic indications for extra facial areas. For more than three decades it has been used in medical devices such as plates, screws, intraosseous and soft tissue implants, and as a biodegradable vector for drugs, in sutures and stents. The present article is aimed at presenting a literature review on the indications, application method, and complications of the use of PLLA.

Tumor de Merkel: relato de caso / Merkel's tumor: a case report

O carcinoma de células de Merkel é tumor neuroendócrino da pele, altamente agressivo, de prognóstico reservado. Relatamos um caso clínico e enfatizamos a importância do diagnóstico e do tratamento precoces.

Merkel cell carcinomas are highly aggressive neuroendocrine skin tumors that have a poor prognosis. The authors present a case report and emphasize the importance of early diagnosis and treatment.

Nevo melanocítico congênito - tratamento cirúrgico / Congenial melanocytic nevus - surgical treatment

Nevos melanocíticos congênitos gigantes são lesões raras que apresentam risco aumentado de transformação em melanoma cutâneo.Quando localizados na face podem causar deficit neurológicos, incluindo melanocitose leptomeníngea e epilepsia. Implicam risco de comprometimento estético importante. Relata-se caso de paciente do sexo feminino, de 17 anos, com nevo melanocítico congênito acometendo um terço da hemiface direita. Foi submetida à ressecção da lesão e reconstrução com enxerto de pele parcial em um único tempo cirúrgico. O objetivo deste trabalho é demonstrar proposta terapêutica para nevos melanocíticos congênitos localizados em região periorbital.

Phytochemical profile and analgesic evaluation of Vitex cymosa leaf extracts

Vitex cymosa Bertero ex Spreng., Lamiaceae, is found in Central and Amazon regions of Brazil, where it is popularly used as antirheumatic. Extracts from the leaves of V. cymosa were tested in analgesia models such as abdominal contortions induced by acetic acid and formalin to test peripheral analgesia; as well as the tail flick and hot plate models, to test spinal and supraspinal analgesia. A significant reduction was observed in the number of contortions with all extracts and in all doses. In the formalin model, a reduction in the second phase (inflammatory) was observed with all extracts, whereas only the n-butanol extract was able to act in the first, neurogenic, phase. In the tail flick model, all extracts increased latency time. Naloxone treatment reverted analgesic effect of all extracts with the exception of the dichloromethane one. All extracts developed peripheral and central analgesic activity. In the hot plate model no antinociceptive effect was observed for all tested extracts. All these results taken together suggest that V. cymosa leaf extracts were able to promote peripheral and central antinociceptive activity mediated by the opioid system.Twenty three substances were isolated and identified in the extracts and include flavonoids (C-glucosyl flavones, flavones and flavonols), triterpene acids from ursane and oleanane types, iridoids (free and glucosides), as well as simple phenols.