Efficacious In Vitro and In Vivo Effects of Dihydrosphingosine-Ethambutol Analogues Against Susceptible and Multi-drug-resistant Mycobacterium tuberculosis.

BACKGROUND AND AIMS: Tuberculosis (TB) is a major worldwide health problem in part due to the lack of new drugs and the emergence of multidrug-resistant strains (MDR). The aim of this study was to select anti-tuberculosis drug candidates from a collection of 69 synthetic sphingosine-ethambutol analogues through in vitro and in vivo evaluations. METHODS: The 69 compounds were evaluated in vitro against two Mycobacterium tuberculosis strains, a drug susceptible (H37Rv) and a MDR clinical isolate (CIBIN-99). Four selected compounds, those that exhibited the highest potency in vitro, were tested in vivo using a model of progressive TB in BALB/c mice infected with the drug susceptible strain, either alone or combined with conventional chemotherapy, as well as in mice infected with the MDR strain. The acute toxicity was evaluated on male and female adult BALB/c mice. RESULTS: Ten of the evaluated compounds resulted more potent in vitro than ethambutol. The experimental compound 2b (2-aminopalmitol benzyl ether) was the most efficacious and also showed additive effects in combination with conventional chemotherapy. It did not exhibit toxicity (LD50 >2000 mg/kg). CONCLUSIONS: Compound 2b can be considered as a new drug candidate to continue its development against M. tuberculosis MDR strains.

Mecanismos moleculares de la adicción a la marihuana / Molecular Mechanism of Addiction to Marihuana

Introducción: Desde la antigüedad, la planta Cannabis sativa (cáñamo o marihuana), de la familia Cannabaceae, se ha usado con múltiples fines: industriales, medicinales o religiosos; sin embargo, en los últimos años, el fenómeno de la farmacodependencia ha mostrado una expansión social, y a pesar de las medidas ejercidas para controlarlo, su consumo masivo se ha tendido a incrementar cada vez más en las poblaciones más jóvenes de colombianos. Objetivos: Presentar un enfoque adecuado del paciente que presenta adicción a la marihuana y mostrar diferentes aspectos relacionados con esta sustancia, al tiempo que pone el relieve en el sistema endocanabinoide, para explicar su mecanismo de acción. Método: El artículo presenta las generalidades de la marihuana, su cinética (absorción, distribución, metabolismo y excreción), su toxicodinamia y los efectos de su uso crónico. Conclusiones: Pese a que el consumo de la marihuana se ha aceptado en muchos países, porque produce menos efectos nocivos que otras drogas, sólo entendiendo los mecanismos moleculares de la adicción, en un futuro se podrán diseñar estrategias farmacológicas que disminuyan o eliminen los síntomas de abstinencia que, finalmente, llevan a la perpetuación de la dependencia.

Dating from antiquity, the Cannabis sativa plant (marihuana) of the Cannabaceae family has been put to multiple uses: industrial, medicinal and religious. Lately, however, the phenomenon of addiction has expanded socially and in spite of measures taken to control it, massive consumption of marihuana has grown among Colombian youth. Objectives: To establish an approach that is appropriate for patients addicted to marihuana and to show different aspects related to this substance, as well as to lay significance on the mechanis of action of the endocannabinoid system. Method: The article describes the generalities of marihuana, its kinetics (absorption, distribution, metabolism and excretion), toxicology and the effects of chronic use. Conclusions: In spite of the fact that marihuana consumption is accepted in several countries, as its effects are considered less deleterious than those of other substances, only by understanding the molecular mechanisms of addiction will it be possible in the future to design pharmacological strategies that will diminish or eliminate marihuana-related withdrawal symptoms.

[Peripheral neuropathy and deterioration of the cognitive functions associated to chronic exposure to organophosphates]. / Neuropatía periférica y deterioro de las funciones cognitivas asociados a exposición crónica a organofosforados.

OBJECTIVE: To analyze the relationship between the chronic exposure (EC) to organophosphated insecticides (IOF) with the presence of peripheral neuropathy (NP) and the deterioration of cognitive functions (DFC). DESIGN OF THE STUDY: Cross-section, comparative and observational. MATERIAL AND METHODS: Workers with more than three months of seniority, who participated in any stage of the process of production of IOF were included, and those with alterations in the neurological function were excluded. Two control groups were made up: the first one, without direct exposure to IOF, and the second one, without any exposure whatsoever to IOF. A physical examination was practiced on inferior limbs and a motor neuroconduction of the fibular nerves was carried out. The Minimum Exam of the Mental State was set (Mental Mini). The sampling was not random. RESULTS: It was found that the presence of DFC and the clinical data for NP were greater in the exposed group than in the controls, (p < 0.05). Besides, data with a tendency to the continuation in the parameters of latencies, widths and waves F for the motor neuroconduction of inferior limbs were presented. CONCLUSIONS: The long term exposure to IOF is related to deterioration in the cognitive function; as well as to the neurological manifestations in inferior limbs that condition an injury in the peripheral nerve, without being conclusive about the loss of its function.

Evaluation of the mutagenic and cytotoxic effects of mercurous chloride by the micronuclei technique in golden Syrian hamsters.

The aims of this study were to evaluate the mutagenic and cytotoxic activity of mercurous chloride by the micronucleus technique in vivo on the bone marrow of golden Syrian hamsters after a single i.p. drug administration. Forty male golden Syrian hamsters were classified into eight groups: negative control, positive control and six groups treated with different doses of mercurous chloride (1.25, 2.5, 5, 10, 20 and 40 mg/kg). The negative control was injected with physiological saline i.p. and the positive control with cyclophosphamide at a dose of 80 mg/kg i.p. With respect to mutagenic effect, the average number of micronucleated polychromatic erythrocytes (MPE) in hamsters treated with different doses of mercurous chloride was not significant compared with the negative control. With respect to cytotoxic effect, the average polychromatic erythrocyte/red blood cell ratio showed a significant decrease when the doses were higher than the 2.5 mg/kg dose compared with the negative control. In conclusion, this preliminary study shows a cytotoxic effect but not a mutagenic effect of calomel in vivo at one time point (24 h).

Estudio de la posible actividad anticonvulsiva de la raíz de Ipomoeastans / Possible anticonvulsive activity of Ipomoea stans

Se hizo un estudio sobre la posible actividad anticonvulsivante de extractos acuosos crudos de la raíz de Ipomoea stans Cav, que es usada en la medicina herbolaria empírica, en el tratamiento de los ataques epileptiformes. Se emplearon dos modelos farmacológicos para la evaluación de los posibles efectos anticonvulsivantes de la planta: el de Estimulación Supramáxima y el de Estimulación Química con Pentilentetrazol, ambos en ratones Balb-C. Los resultados se compararon con los que se habían obtenido en los mismos modelos, pero utilizando drogas anticonvulsivantes de referencia (definilhidantoína en el modelo elétrico y trimetadiona en el químico). Los resultados mostraron una tendencia a la disminución de la actividad convulsiva evocada en los animales a los que se les administró el extracto; sin embargo, no se observó una diferencia que fue se estadísticamente significativa (p >0.05) al comparar los resultados con testigos apropiados. Estos resultados nos impiden asegurar que la raíz de Ipomoea tenga actividad anticonvulsivante, al menos, en los modelos empleados en este estudio