Determination of carbamazepine in fingerprints: a feasibility study to evaluate adherence in epilepsy patients.

Background: Fingerprint drug concentrations can be used as a noninvasive and convenient alternative to evaluate adherence to pharmacotherapy. Methods: Fingerprints were applied over glass slides, extracted and analyzed by ultra-high performance LC-MS/MS. The assay and drug adherence questionnaires were applied to 30 epilepsy patients. Results: The assay had linearity in the range 0.05-10 ng fingerprint-1, with precision of 2.16-7.9% and accuracy of 95.0-102.8%. Carbamazepine (CBZ) levels in fingerprints were stable at 45°C for 15 days. Concentrations in patient samples were 0.06-9.28 ng fingerprint-1. A significant difference (p = 0.003) was found between CBZ concentrations in fingerprints between patient groups divided as low and medium/high adherence. Conclusion: This method can potentially be applied to the identification of epilepsy patients with low adherence to CBZ pharmacotherapy.

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Dissolution test for oral suspension: an overview about use and importance

Abstract This work aims to ascertain the comprehensiveness of dissolution tests for oral suspensions registered in Brazil and the USA. After consulting literature since 1994, a paucity of information about dissolution methods for suspensions was detected. It makes it difficult to establish the most appropriate test parameters. In January, 2019, there were 46 drugs registered in Anvisa (Brazil) as oral suspension, being 47 reference, 173 generic and 114 interchangeable similar (IS) medicines; while in the USA, 90 drugs were registered as oral suspension by FDA, 235 Abreviatted New Drug Application and 111 New Drug Application medicines. Out of 46 and 90, only six and 15 drugs as oral suspension had a pharmacopeial dissolution test, corresponding to 70 (20.9%) and 82 (23.7%) products in Brazil and the USA, respectively. Dissolution studies were found for 17 drugs as oral suspension in the non-compendial literature. Dissolution test conditions were established to few marketable oral suspension drugs, most of which are BCS class II or IV. Thus, investing in dissolution studies could subsidize the registration of these products by regulators, especially for generic and IS drugs, by comparing dissolution profiles, and predicting their in vivo behavior to avoid exposure of healthy individuals to clinical research.

Prenylated flavonoid-enriched fraction from Maclura tinctoria shows biological activity against Staphylococcus aureus and protects Galleria mellonella larvae from bacterial infection.

BACKGROUND: The Atlantic Forest biome extends along the entire Brazilian coast and is home to approximately 20,000 plant species, many of which are endemic; it is considered one of the hotspot regions of the planet. Several of these species are sources of natural products with biological activities that are still unknown. In this study, we evaluated the antimicrobial activity of 90 extracts derived from native Atlantic Forest tree species against Staphylococcus aureus, an important human and veterinary pathogen. METHODS: Extracts from native Atlantic Forest tree species were evaluated for their antimicrobial activity against S. aureus by in vitro standard methods. Phytochemical fractionation of the extract from Maclura tinctoria was performed by liquid-liquid partitioning. LC-DAD-ESI-MS was used for identification of constituents in the most active fraction. Damage of cells and alterations in the permeability of cell membrane were determined by atomic force microscopy (AFM) and crystal violet uptake assay, respectively. In vivo antimicrobial activity was evaluated using Galleria mellonella larvae infected with S. aureus with survival data collected using the Kaplan-Meier method. RESULTS: Among the organic or aqueous extracts tested here, 26 showed biological activity. Eight species showed relevant results, with a minimum inhibitory concentration (MIC) below 1 mg/mL. Antibacterial activity was registered for three species for the first time. An organic extract from Maclura tinctoria leaves showed the lowest MIC (0.08 mg/mL). Fractionation of this extract by liquid-liquid partitioning led to obtaining fraction 11FO d with a MIC of 0.04 mg/mL. This fraction showed strong activity against veterinary S. aureus isolates and contributed to the increased survival of Galleria mellonella larvae infected with S. aureus ATCC 29213. The bacterial surface was not altered by the presence of 11FO d, and no cell membrane damage was detected. The LC-DAD-ESI/MS analyses identified prenylated flavonoids as the major constituents responsible for the antibacterial activity of this active extract. CONCLUSION: A fraction enriched in prenylated isoflavones and flavanones from M. tinctoria showed in vitro and in vivo efficacy as antistaphylococcal agents. These findings justify the need for further research to elucidate the mechanisms of action of these compounds.

Desenvolvimento de pão de forma enriquecido com batata-doce biofortificada / Development loaf of bread enriched with biofortified sweet potato

Objetivo do trabalho foi desenvolver pão de forma adicionado de polpa de batata-doce, cultivar Beauregard, e avaliar sensorialmente o produto, verificando a sua aceitação entre os consumidores. Foram desenvolvidas três formulações com substituição da farinha de trigo pela batata-doce cozida nas porcentagens de 20%, 40% e 60% e comparadas com o padrão, sem substituição. A avaliação sensorial foi feita por 32 provadores, não treinados, utilizando-se escala hedônica para os atributos de sabor, cor, textura, aroma e aceitação global. Os pães de forma elaborados com a batata-doce não apresentaram diferença estatística na análise sensorial para os atributos avaliados. Os pães obtiveram notas relevantes, com boa aceitação entre os consumidores. Em relação ao sabor, as melhores notas foram dadas para a amostra com 20% de substituição de farinha de trigo por batata-doce, comparada com a amostra, sem substituição de farinha de trigo. O aroma dos pães foi destaque também nas amostras com maior porcentagem de substituição, 60% e 40%. Para os demais atributos não houve diferença significativa em relação à amostra padrão, com 100% de farinha de trigo, o que permitiu concluir que a adição de batata-doce com polpa laranja na formulação de pão de forma pode ser considerada uma opção saudável de consumo de alimento biofortificado para combater a "fome oculta", que é a carência dos micronutrientes vitamina A, ferro e zinco, essenciais para a saúde.

The objective was to develop a loaf of bread with sweet potato pulp, Beauregard, evaluate the product by sensory analysis and verify their acceptance among consumers. Three formulations were developed to replace the wheat flour for sweet potatoes baked in percentages of 20%, 40% and 60%, compared with the standard, without replacement. The sensory evaluation was performed by 32 panelists, untrained, using hedonic scale for the attributes of flavor, color, texture, aroma and global acceptance. The loaf of breads elaborate with sweet potato showed no statistical difference in sensory analysis for the evaluated attributes. The breads obtained relevant notes, with good acceptance among consumers. Regarding the taste, the best grades were given for the sample with 20% wheat flour substitute for sweet potatoes, compared with the sample without wheat flour replacement. The aroma of bread was also featured in the samples with the highest percentage of replacement, 60% and 40%. For other attributes there was no significant difference from the standard sample, 100% wheat flour, which showed that the addition of sweet potatoes with orange pulp in the form of bread formulation can be considered a healthy option consumption biofortified of food to fight "hidden hunger", which is the lack of micronutrients vitamin A, iron and zinc, essential for health.

Key biomechanical characteristics of complete-arch fixed mandibular prostheses supported by three implants developed at P-I Brånemark Institute, Bauru.

PURPOSE: To determine the range of vertical cantilever (VC), real cantilever (RC), and height of the imaginary triangle (h) formed by the bases of the three implant cylinders in full-arch mandibular prostheses supported by three implants. MATERIALS AND METHODS: The sample comprised 203 patients (147 women, 56 men; mean age, 58 years, range, 37 to 79 years) with full-arch mandibular rehabilitations. Their prostheses were measured in relation to implant placement to characterize numerical values for VC, force arm of the lever system (represented by the distal cantilever or RC), and resistance arm of the system (represented by the height of the imaginary triangle formed by the bases of the three implants). Data were tabulated and means and standard deviations calculated for all measurements. The range of each of the three measurements was then divided into quintiles for characterizing data distribution. RESULTS: The mean (standard deviation) values found were as follows: VC1 = 17.11 (3.39) mm; VC2 = 17.46 (2.89) mm; VC3 = 16.68 (3.16) mm; RC1 = 14.67 (3.90) mm; RC3 = 15.02 (4.15) mm; h = 8.27 (2.96) mm. CONCLUSION: VC ranged from 7.37 to 26.44 mm, RC ranged from 4.00 to 26.93 mm, and the height of the imaginary triangle formed by the bases of the three implant cylinders ranged from 0.37 to 15.33 mm.

Enterotoxin-Encoding Genes in Staphylococcus spp. from Food Handlers in a University Restaurant.

Food handlers carrying enterotoxin-producing Staphylococcus are a potential source of food poisoning. The aim of this study was to analyze genes encoding enterotoxins in coagulase-positive Staphylococcus (CoPS) and coagulase-negative Staphylococcus (CoNS) isolated from the anterior nostrils and hands of food handlers at a university restaurant in the city of Natal, Northeast Brazil. Thirty food handlers were screened for the study. The isolates were subjected to Gram staining, a bacitracin sensitivity test, mannitol fermentation, and catalase and coagulase tests. CoNS and CoPS strains were subsequently identified by a Vitek 2 System (BioMerieux, France) and various biochemical tests. Polymerase chain reaction was used to detect genes for enterotoxins A, B, C, D, E, G, H, and I (sea, seb, sec, sed, see, seg, seh, and sei) and a disc-diffusion method was used to determine susceptibility to several classes of antimicrobials. All food handlers presented staphylococci on their hands and/or noses. The study found 58 Staphylococcus spp., of which 20.7% were CoPS and 79.3% were CoNS. S. epidermidis was the most prevalent species. Twenty-nine staphylococci (50%) were positive for one or more enterotoxin genes, and the most prevalent genes were seg and sei, each with a frequency of 29.3%. Indeed, CoNS encoded a high percentage of enterotoxin genes (43.5%). However, S. aureus encoded even more enterotoxin genes (75%). Most isolates showed sensitivity to the antibiotics used for testing, except for penicillin (only 35% sensitive). The results from this study reinforce that coagulase-negative as well as coagulase-positive staphylococci isolated from food handlers are capable of genotypic enterotoxigenicity.

West Nile Virus Infection in Humans and Horses, Cuba

West Nile virus was first detected in the Western Hemisphere during an outbreak of encephalitis in New York State in 1999 (1). Genetic analyses showed that the virus responsible for the 1999 outbreak was nearly identical to a WNV strain circulating in Israel in 1998 (2). Recent outbreaks of WNV disease in the United States and Canada have been accompanied by a high proportion of deaths in birds (3,4), substantial illness in equines (4,5), and thousands of cases of severe neurologic disease in humans (6). The range of WNV has rapidly expanded across the continental United States and Canada (7). WNV infection in humans, equines, and birds in Mexico (8), the Caribbean (9), and South and Central America (10,11) shows southward movement of the virus. Because Cuba is close to areas of the United States where WNV is endemic and because of recent evidence that suggests spread of WNV into the Caribbean, surveillance was established to monitor for WNV in Cuba. Beginning in 2002, the Medical Services and Ministry of Agriculture and Veterinarian Services of Cuba established a national surveillance program by using birds, horses, and humans to detect WNV activity. In this report, we summarize the key findings of surveillance activities(AU)

El virus del Nilo Occidental se detectó por primera vez en el Hemisferio Occidental durante un brote de encefalitis en el estado de Nueva York en 1999 (1). Análisis genéticos mostraron que el virus responsable del brote de 1999 fue casi idéntico a una cepa de virus que circulan en Israel en 1998 (2). Los recientes brotes de la enfermedad del VNO en Estados Unidos y Canadá se han visto acompañadas por una elevada proporción de muertes en las aves (3,4), enfermedad importante en equinos (4,5), y miles de casos de enfermedad neurológica en los seres humanos (6 ). La gama de virus se ha expandido rápidamente en todo el territorio continental de Estados Unidos y Canadá (7). La infección por el VNO en los seres humanos, equinos y aves en Mexico (8), el Caribe (9), América del Sur y Centroamérica (10,11) muestra el movimiento hacia el sur del virus. Porque Cuba está cerca de zonas de Estados Unidos, donde el virus es endémico y debido a las pruebas recientes sugieren que la propagación de virus en el Caribe, la vigilancia se estableció para supervisar VNO en Cuba. A partir de 2002, los Servicios Médicos y el Ministerio de Agricultura y Servicios Veterinarios de Cuba estableció un programa nacional de vigilancia mediante el uso de aves, caballos, y los seres humanos para la detección de VNO actividad. En este informe, resumimos las principales conclusiones de las actividades de vigilancia

West Nile Virus infection in humans and horses, Cuba.

A surveillance system to detect West Nile virus (WNV) was established in Cuba in 2002. WNV infection was confirmed by serologic assays in 4 asymptomatic horses and 3 humans with encephalitis in 2003 and 2004. These results are the first reported evidence of WNV activity in Cuba.