Thiazine-derived compounds in inhibiting efflux pump in Staphylococcus aureus K2068, mepA gene expression, and membrane permeability alteration.

Staphylococcus aureus is a bacterium responsible for resistance to multiple drugs and the efflux system is widely studied among the resistance mechanisms developed by this species. The present study evaluates the inhibition of the MepA efflux pump by thiadiazine-derived compounds. For this purpose, thiadiazine-derived compounds (IJ-14 to IJ-20) were tested against S. aureus K2068 strains. Microdilution tests were initially conducted to assess the Minimum Inhibitory Concentration (MIC) of the compounds and their efflux pump inhibition activity. In addition, fluorimetry tests were performed using BrEt emission and tests were conducted to inhibit the expression of the mepA gene. This involved comparing the bacterial gene expression with the antibiotic alone to the gene expression after combining compounds (IJ-17 and IJ-20) with the antibiotic. Furthermore, membrane permeability assessment tests and in silico molecular docking tests were performed. It was observed that the IJ17 and IJ20 compounds exhibited direct activity against the tested strain. The IJ17 compound produced significant results in the gene inhibition tests, which was also evidenced through the membrane permeability alteration test. These findings suggest that thiadiazine-derived compounds have promising effects against one of the main resistance mechanisms, with the IJ17 compound presenting observable mechanisms of action.

Limonene, a food additive, and its active metabolite perillyl alcohol improve regeneration and attenuate neuropathic pain after peripheral nerve injury: Evidence for IL-1ß, TNF-α, GAP, NGF and ERK involvement.

BACKGROUND: Limonene (LIM) and its main metabolite perillyl alcohol (POH) are ingredients found in food with promising chemical entities due to their pharmacological profile. In this study, we hypothesized that LIM and POH are two molecules capable of accelerating the regenerative process and alleviating neuropathic pain. METHODS: Animals were treated daily (LIM, POH and saline) for 28 days and during this period evaluated for mechanical hyperalgesia, astrocyte participation by immunofluorescence for GFAP, and ELISA was used to quantify IL-1ß and TNF-α in the spinal cord. Western blot analysis of the following proteins was also performed: GFAP, GAP-43, NGF and ERK. For motor deficit analysis, tests were performed to assess hind paw muscle strength and footprints through gait (SFI). RESULTS: Both POH and LIM accelerated the regenerative process and improved motor deficits comparing to positive control; however, POH was more effective, particularly between the 2nd and 3rd week after the nerve injury, increasing GAP-43, NGF and the phosphorylated ERK immunocontent. Moreover, POH and LIM were able to reduce hyperalgesia and astrocytosis. CONCLUSIONS: Both substances, LIM and POH, improved the regeneration process and sensory and motor function recovery in the PNI model in mice by mitigating the inflammatory reactions and up-regulating the neurotrophic process.

GC-MS Profile and Enhancement of Antibiotic Activity by the Essential Oil of Ocotea odorífera and Safrole: Inhibition of Staphylococcus aureus Efflux Pumps.

Considering the evidence that essential oils, as well as safrole, could modulate bacterial growth in different resistant strains, this study aims to characterize the phytochemical profile and evaluate the antibacterial and antibiotic-modulating properties of the essential oil Ocotea odorífera (EOOO) and safrole against efflux pump (EP)-carrying strains. The EOOO was extracted by hydrodistillation, and the phytochemical analysis was performed by gas chromatography coupled to mass spectrometry (GC-MS). The antibacterial and antibiotic-modulating activities of the EOOO and safrole against resistant strains of Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa were analyzed through the broth microdilution method. The EP-inhibiting potential of safrole in association with ethidium bromide or antibiotics was evaluated using the S. aureus 1199B and K2068 strains, which carry genes encoding efflux proteins associated with antibiotic resistance to norfloxacin and ciprofloxacin, respectively. A reduction in the MIC of ethidium bromide or antibiotics was used as a parameter of EP inhibition. The phytochemical analysis identified 16 different compounds in the EOOO including safrole as the principal constituent. While the EOOO and safrole exerted clinically relevant antibacterial effects against S. aureus only, they potentiated the antibacterial activity of norfloxacin against all strains evaluated by our study. The ethidium bromide and antibiotic assays using the strains of S. aureus SA1119B and K2068, as well as molecular docking analysis, indicated that safrole inhibits the NorA and MepA efflux pumps in S. aureus. In conclusion, Ocotea odorifera and safrole presented promising antibacterial and antibiotic-enhancing properties, which should be explored in the development of drugs to combat antibacterial resistance, especially in strains bearing genes encoding efflux proteins.

Evaluación del estado nutricional de adultos mayores que viven en un centro geriátrico en Caracas, basada en técnicas de despistaje de desnutrición Mini Nutritional Assessment (MNA) / Evaluation of the nutritional status of older adults living in a geriatric center in Caracas, based on malnutrition screening techniques Mini Nutritional Assessment (MNA)

La valoración del estado nutricional constituye un aspecto clave en la atención de la población adulta mayor, aunque no existe una herramienta de referencia que permita definir de forma inequívoca la situación nutricional de un paciente, la intervención nutricional a través del diagnóstico-planificación-acción-evaluación, mejora la calidad de vida y garantiza la salud. Con el propósito de realizar diagnostico nutricional de 66 adultos mayores, que se encuentran viviendo en un centro geriátrico de larga estancia de Caracas, se elaboró y aplicó un formato de historia nutricional que incluiría la encuesta MNA y otros parámetros de interés. Este instrumento detectó de forma rápida, sencilla, económica y poco invasiva 25,76% casos de malnutrición y 40,91% riesgo de malnutrición en los evaluados, así como las posibles condiciones que las generan como demencia senil tipo Alzheimer, hipertensión arterial que requiere polimedicación y discapacidad motora. La evaluación antropométrica permitió detectar que el 70,59% de la malnutrición es de tipo calórica protéica. La dificultad para vivir sólos, el envejecimiento y la poca ingesta de alimentos, especialmente de aceite de oliva y frutos secos, influyen en el deterioro de la salud de estos pacientes. Un IMC promedio inferior a 23 kg/m² y la circunferencia de pantorrilla inferior a 31cm, demuestran un socavado estado nutricional y un déficit protéico. La información obtenida, permitió realizar un informe nutricional individualizado que se incluyó en la historia médica de cada paciente, que podrían ser utilizada en un futuro para realizar cambios al menú, recomendaciones, suplementación e interconsultas médicas a quienes requirieran mayor intervención de acuerdo a cada caso.

The assessment of nutritional status is a key aspect in the care of older adults, although there is no reference tool that can unmistakenly define the nutritional status of a patient, nutritional intervention through diagnosis-planning-actionevaluation improves the quality of life and guarantees health. In order to perform nutritional diagnosis to 66 older adults, who are living in a long stay nursing home in Caracas, a format of nutritional history was developed and applied, which included the MNA survey and other factors of interest. This method detected in a quick, simple, inexpensive and minimally invasive manner 25.76% cases of malnutrition and 40.91% cases of malnutrition at risk within the assessed, as well as the possible conditions that generate them such as senile dementia (Alzheimer’s type), high blood pressure which requires multiple medication, and motor disabilities. The anthropometric assessment allowed us to detect that 70.59% of malnutrition is of a protein calorie kind. The difficulty of living alone, aging and a low intake of food, particularly olive oil and nuts, influence the deteriorating health of these patients. An average BMI below 23 kg/m² and the circumference of less than 31cm calf, show an undercut nutritional status and a protein deficit. The information obtained allowed an individualized nutritional report that was included in the medical history of each patient, one which could be used in the future to make changes to the menu, to give recommendations, supplementation and medical interconsultations to those who require greater intervention according to each case.

Mulheres e HIV/Aids: informação, ação e recursos relativos as mulheres e HIV/Aids, saúde reprodutiva e relações sexuais

Manual de informações dirigido especialmente para pais, estudantes, professores e agentes multiplicadores de informações. O manual traz informações sobre comportamentos sexuais, o conhecimento do corpo humano e o seu funcionamento, a sexualidade em diferentes fases, os principais problemas sexuais, todos métodos anticoncepcionais, as diferentes formas de manisfestação da sexualidade e os fatores que podem melhorar o prazer sexual

Acid excretion and serum electrolyte patterns in patients with advanced chronic renal failure.

Hyperchloremic metabolic acidosis can be seen in advanced chronic renal failure (CRF). To study this further, we measured acid excretion under controlled conditions in 19 patients with severe but stable CRF. Twelve patients had a hyperchloremic metabolite acidosis, 3 had an elevated anion gap acidosis ('delta acidosis'), while the 4 remaining patients had a slightly decreased tCO2 with a normal anion gap and serum chloride level ('mild acidosis'). Ammonium excretion was markedly reduced in CRF patients (11 +/- 1 vs. 32 +/- 2 mEq/day in normal subjects, p less than 0.005), and likewise urinary titratable acid was diminished (18 +/- 2 mEq/day in patients, vs. 28 +/- 3 mEq/day in normal subjects; p less than 0.005). When expressed per 100 ml GFR, ammonium and titratable acid excretion were markedly increased in all groups of patients compared to normal subjects. The Tm for bicarbonate was 22.5 +/- 3.7 mEq/l for all CRF patients and 24 +/- 1 mEq/l for the patients with a hyperchloremic metabolic acidosis. We conclude that the hyperchloremic metabolic acidosis in advanced renal failure is due to diminished excretion of ammonium and titratable acid and is not due to an increased bicarbonate leak. As renal failure advances and renal mass declines, the remaining functioning nephrons hypersecrete acid.

Consequences of smallpox vaccination in leprosy patients

This study illustrates the consequences of smallpox revaccination in 45 lepromatous, 28 tuberculoid, and 47 normal individuals. Results obtained with leprosy were associated with a relative anergy against the vaccinia virus, the anergy being minimal in the tuberculoid leprosy but marked in the cases with lepromatous leprosy.