Potential cannabidiol (CBD) repurposing as antibacterial and promising therapy of CBD plus polymyxin B (PB) against PB-resistant gram-negative bacilli.

This study aimed to assess the ultrapure cannabidiol (CBD) antibacterial activity and to investigate the antibacterial activity of the combination CBD + polymyxin B (PB) against Gram-negative (GN) bacteria, including PB-resistant Gram-negative bacilli (GNB). We used the standard broth microdilution method, checkerboard assay, and time-kill assay. CBD exhibited antibacterial activity against Gram-positive bacteria, lipooligosaccharide (LOS)-expressing GN diplococcus (GND) (Neisseria gonorrhoeae, Neisseria meningitidis, Moraxella catarrhalis), and Mycobacterium tuberculosis, but not against GNB. For most of the GNB studied, our results showed that low concentrations of PB (≤ 2 µg/mL) allow CBD (≤ 4 µg/mL) to exert antibacterial activity against GNB (e.g., Klebsiella pneumoniae, Escherichia coli, Acinetobacter baumannii), including PB-resistant GNB. CBD + PB also showed additive and/or synergistic effect against LOS-expressing GND. Time-kill assays results showed that the combination CBD + PB leads to a greater reduction in the number of colony forming units per milliliter compared to CBD and PB alone, at the same concentration used in combination, and the combination CBD + PB was synergistic for all four PB-resistant K. pneumoniae isolates evaluated. Our results show that CBD has translational potential and should be further explored as a repurposed antibacterial agent in clinical trials. The antibacterial efficacy of the combination CBD + PB against multidrug-resistant and extensively drug-resistant GNB, especially PB-resistant K. pneumoniae, is particularly promising.

[Interchangeability among therapeutics equivalents of lamotrigine in the treatment of refractory epilepsy patients: risks and benefits]. / Intercambiabilidad entre equivalentes terapéuticos de lamotrigina en pacientes con epilepsia refractaria: riesgos y beneficios.

INTRODUCTION: Epilepsy is a condition characterized by signs and symptoms of neurological disorder. Lamotrigine has been widely used, mainly due to their greater tolerability and lower rate of drug interactions with other antiepileptic drugs however the newest antiepileptic drugs have high cost to patient. In Brazil there are three different sort of pharmaceutical equivalents (reference, generic and similar), and the Brazilian health care authorities offers to users the possibility to receive them free of charge. Moreover these pharmaceutical equivalents can change during the treatment of epilepsy because this authorities buy the cheapest by public tender two or three times a year. AIM: To evaluate the clinical and laboratory findings related to the most frequently used therapeutic equivalents of lamotrigine (reference drugs and similar products). PATIENTS AND METHODS: Two similar formulations (A and B) and one reference (C) were tested in nine epileptic refractory patients. The study was divided into three periods of 42 days, one for each formulation, and medical data about the frequency of seizures, the occurrence of side effects and measurement of plasma concentrations of lamotrigine were collected. RESULTS: The average number of seizures/week and plasma concentration of lamotrigine for formulations A, B and C were not statistically significant differences. Three patients during the use of the formulation C presented mild and transitory side effects. CONCLUSION: Similar or reference drugs showed satisfactory results, however the interchangeability among the formulations raise the difficulty for the management of seizures in refractory epilepsy.

Tolerability and effectiveness of fluoxetine, metformin and sibutramine in reducing anthropometric and metabolic parameters in obese patients / Tolerabilidade e eficácia da fluoxetina, metformina e sibutramina na redução de parâmetros antropométricos e metabólicos em pacientes obesos

The aim of this study is to assess the effects of sibutramine (S) 15 mg/day, fluoxetine (F) 60 mg/day, and metformin (M) 1,700 mg/day, as an adjunct therapy to a 1,500 kcal/day diet, in reducing anthropometric and metabolic parameters. S (n= 8), F (n= 9), and M (n= 8) were compared to placebo (n= 10) in 35 obese patients in a 90-day trial. Side effects were also studied during the treatment. The data demonstrated that F therapy resulted in a greater average reduction in BMI (11.0 percent), weight (10.0 percent), abdominal circumference (11.0 percent) and percentfatty-tissue (12.8). An elevation in HDL-cholesterol (25.8 percent) and a reduction in average triglyceride levels (28.3 percent) were also shown. S presented a 7.91 percent reduction in the abdominal circumference and a 9.65 reduction in percentfatty-tissue was also found. M group presented reductions in BMI (4.03 percent), waist circumference (6.92 percent), HOMA (23.5 percent) and blood pressure (6.08 percent in systolic and 2.08 percent in diastolic). In general, the three drugs can be considered well tolerated. We concluded that F and S demonstrated a greater mean reduction in anthropometric and metabolic parameters when compared to M, however all of them are useful for that purpose, when the subjectsÆ characteristics are considered.

O objetivo deste estudo foi avaliar o efeito da sibutramina (S) 15 mg/dia, fluoxetina (F) 60 mg/dia, e metformina (M) 1.700 mg/dia, associadas a uma dieta de 1.500 kcal/dia, na redução de parâmetros antropométricos e metabólicos. S (n= 8), F (n= 9) e M (n= 8) foram comparadas ao placebo (n= 10) em 35 pacientes obesos durante 90 dias de tratamento. As reações adversas também foram avaliadas durante o tratamento. O grupo F demonstrou uma redução no IMC (11,0 por cento), peso (10,0 por cento), circunferência abdominal (11,0 por cento) e por cento de tecido adiposo (12,8). Também foram observados um aumento nos níveis de HDL-colesterol (25,8 por cento) e uma redução nos níveis de triglicérides (28,3 por cento), no grupo F. O grupo S apresentou uma redução de 7,91 por cento na circunferência abdominal e de 9,65 na por cento de tecido adiposo. Já o grupo M apresentou reduções no IMC (4,03 por cento), circunferência abdominal (6,92 por cento), HOMA (23,5 por cento) e pressão arterial (6,08 por cento na sistólica, 2,08 por cento na diastólica). Os três fármacos analisados foram bem tolerados durante o tratamento. Concluímos que a F e a S demonstraram maior eficácia na redução dos parâmetros antropométricos e metabólicos dos pacientes obesos quando comparadas à M, entretanto todas podem ser prescritas para essa finalidade, desde que sejam consideradas as características individuais dos pacientes.

Tolerability and effectiveness of fluoxetine, metformin and sibutramine in reducing anthropometric and metabolic parameters in obese patients.

The aim of this study is to assess the effects of sibutramine (S) 15 mg/day, fluoxetine (F) 60 mg/day, and metformin (M) 1,700 mg/day, as an adjunct therapy to a 1,500 kcal/day diet, in reducing anthropometric and metabolic parameters. S (n= 8), F (n= 9), and M (n= 8) were compared to placebo (n= 10) in 35 obese patients in a 90-day trial. Side effects were also studied during the treatment. The data demonstrated that F therapy resulted in a greater average reduction in BMI (11.0%), weight (10.0%), abdominal circumference (11.0%) and %fatty-tissue (12.8). An elevation in HDL-cholesterol (25.8%) and a reduction in average triglyceride levels (28.3%) were also shown. S presented a 7.91% reduction in the abdominal circumference and a 9.65 reduction in %fatty-tissue was also found. M group presented reductions in BMI (4.03%), waist circumference (6.92%), HOMA (23.5%) and blood pressure (6.08% in systolic and 2.08% in diastolic). In general, the three drugs can be considered well tolerated. We concluded that F and S demonstrated a greater mean reduction in anthropometric and metabolic parameters when compared to M, however all of them are useful for that purpose, when the subjects characteristics are considered.