Antimalarial effect of two photo-excitable compounds in a murine model with Plasmodium berghei (Haemosporida: Plasmodiidae) / Efecto antimalárico de dos compuestos foto-excitables en un modelo murino con Plasmodium berghei (Haemosporida: Plasmodiidae)

Abstract Malaria represents a major health problem worldwide, affecting around 198 million people in 2016 according to WHO database. For decades, anti-malarial drug therapy has been used in the battle against this disease and its uncontrolled usage in endemic areas has developed the appearance of the drug resistance. Thus, it has emerged the necessity of finding new treatments that could be used as an alternative cure to malaria infection. The aim of this work was the evaluation of two photo-excitable compounds: Compound 1, which is (2E)-3-(4-dimethylamino-phenyl)-1-(4-imidazol-1-yl-phenyl)prop-2-en-1-one) and Compound 2, (1E,4E)1-[4-(dimethylamino)phenyl]-5-(4-methoxyphenyl)-1,4-pentadiene-3-one) as possible anti-malaria drugs with Plasmodium berghei ANKA strain in BALB/c mice as murine model. Cytotoxicity effect was evaluated by a cell proliferation by colorimetry assay (MTS); and the drug incorporation into the parasite was assessed in vitro with Indirect Immunofluorescence Assay (IFA) to determine the localization of the drugs into the parasitized red blood cells (RBCs). Finally, the curative effect of compounds no-radiation (fundamental state) and ration drugs were evaluated by oral drug administration of this drugs in BALB/c mice and chloroquine was used as positive control. This curative effect was determined daily by the parasitemia percentage. The results showed that both compounds were cytotoxic in fundamental state. Furthermore, cytotoxic effect was increased after radiation into the Solar Simulator, and compound 2 was more cytotoxic than compound 1. Curative assays showed that both compounds in fundamental state were non effective as anti-malarial drug. However, in the curative assays in the mice treated with compound 2, when this was ration showed a survival rate of 33 % and a parasitemia percentage decrease in compare to compound 1. Although the compounds did not show a similar or better anti-malarial effect than Chloroquine, Compound 2 presented certain anti-malarial effect after solar radiation. Rev. Biol. Trop. 66(2): 880-891. Epub 2018 June 01.

Resumen La malaria representa un importante problema de salud en todo el mundo, afectando a alrededor de 198 millones de personas en 2016 según la base de datos de la OMS. Durante décadas, se ha utilizado la terapia con fármacos anti-malpricos en la lucha contra esta enfermedad y su uso incontrolado en las zonas endémicas ha desarrollado la aparición de resistencia a los fármacos. Por lo tanto, se ha surgido la necesidad de encontrar nuevos tratamientos que podrían ser utilizados como una cura alternativa para la infección por el paludismo. El objetivo de este trabajo fue evaluar dos compuestos foto-excitables: El compuesto 1, que es (2E) -3- (4-dimetilamino-fenil) -1- (4-imidazol-1-ilfenil) prop-2 1-ona) y el Compuesto 2, (1E, 4E) -1- [4- (dimetilamino) fenil] -5- (4-metoxifenil) -1,4-pentadieno-3-ona) como posibles drogas antimaláricas con la cepa ANKA de Plasmodium berghei en ratones BALB / c como modelo murino. El efecto de la citotoxicidad se evaluó mediante una proliferación celular con el ensayo de colorimetría (MTS); y la incorporación del fármaco en el parásito se evaluó in vitro con Ensayo de Inmunofluorescencia Indirecta (IFA) para determinar la localización de los fármacos en los glóbulos rojos parasitados (RBCs). Finalmente, se evaluó el efecto curativo de los compuestos sin radiación (estado fundamental) y los fármacos irradiados mediante la administración oral de los fármacos en los ratones BALB / c, y se usó cloroquina como control positivo de cura. Este efecto curativo se determinó diariamente por el porcentaje de parasitemia. Los resultados mostraron que ambos compuestos eran citotóxicos en estado fundamental. Además, el efecto citotóxico se incrementó después de la radiación en el Simulador Solar, y el compuesto 2 fue más citotóxico que el compuesto 1. Los ensayos curativos mostraron que ambos compuestos en estado fundamental no eran eficaces como fármacos antimaláricos. Sin embargo, en los ensayos curativos en los ratones tratados con el compuesto 2, cuando fue irradiado, se observó una tasa de supervivencia del 33 % y una disminución del porcentaje de parasitemia en comparación con el compuesto 1. Aunque los compuestos no mostraron un efecto similar o mejor antimalárico que la cloroquina, el compuesto 2 presentó cierto efecto antimalárico después de la radiación solar.

Occupational Neurotoxic Diseases in Taiwan

Occupational neurotoxic diseases have become increasingly common in Taiwan due to industrialization. Over the past 40 years, Taiwan has transformed from an agricultural society to an industrial society. The most common neurotoxic diseases also changed from organophosphate poisoning to heavy metal intoxication, and then to organic solvent and semiconductor agent poisoning. The nervous system is particularly vulnerable to toxic agents because of its high metabolic rate. Neurological manifestations may be transient or permanent, and may range from cognitive dysfunction, cerebellar ataxia, Parkinsonism, sensorimotor neuropathy and autonomic dysfunction to neuromuscular junction disorders. This study attempts to provide a review of the major outbreaks of occupational neurotoxins from 1968 to 2012. A total of 16 occupational neurotoxins, including organophosphates, toxic gases, heavy metals, organic solvents, and other toxic chemicals, were reviewed. Peer-reviewed articles related to the electrophysiology, neuroimaging, treatment and long-term follow up of these neurotoxic diseases were also obtained. The heavy metals involved consisted of lead, manganese, organic tin, mercury, arsenic, and thallium. The organic solvents included n-hexane, toluene, mixed solvents and carbon disulfide. Toxic gases such as carbon monoxide, and hydrogen sulfide were also included, along with toxic chemicals including polychlorinated biphenyls, tetramethylammonium hydroxide, organophosphates, and dimethylamine borane. In addition we attempted to correlate these events to the timeline of industrial development in Taiwan. By researching this topic, the hope is that it may help other developing countries to improve industrial hygiene and promote occupational safety and health care during the process of industrialization.

Occupational Neurotoxic Diseases in Taiwan

Occupational neurotoxic diseases have become increasingly common in Taiwan due to industrialization. Over the past 40 years, Taiwan has transformed from an agricultural society to an industrial society. The most common neurotoxic diseases also changed from organophosphate poisoning to heavy metal intoxication, and then to organic solvent and semiconductor agent poisoning. The nervous system is particularly vulnerable to toxic agents because of its high metabolic rate. Neurological manifestations may be transient or permanent, and may range from cognitive dysfunction, cerebellar ataxia, Parkinsonism, sensorimotor neuropathy and autonomic dysfunction to neuromuscular junction disorders. This study attempts to provide a review of the major outbreaks of occupational neurotoxins from 1968 to 2012. A total of 16 occupational neurotoxins, including organophosphates, toxic gases, heavy metals, organic solvents, and other toxic chemicals, were reviewed. Peer-reviewed articles related to the electrophysiology, neuroimaging, treatment and long-term follow up of these neurotoxic diseases were also obtained. The heavy metals involved consisted of lead, manganese, organic tin, mercury, arsenic, and thallium. The organic solvents included n-hexane, toluene, mixed solvents and carbon disulfide. Toxic gases such as carbon monoxide, and hydrogen sulfide were also included, along with toxic chemicals including polychlorinated biphenyls, tetramethylammonium hydroxide, organophosphates, and dimethylamine borane. In addition we attempted to correlate these events to the timeline of industrial development in Taiwan. By researching this topic, the hope is that it may help other developing countries to improve industrial hygiene and promote occupational safety and health care during the process of industrialization.

Evaluación terapéutica del maleato de trimebutina en estudios colonoscópicos: comparación con el etobromuro de piperidina / Therapeutic evaluation of the trimebutine maleate in colonoscopy study: comparing with piperidine etobromuro

El maleato de trimebutina (TMB) es un fármaco procinético que actúa sobre la motilidad intestinal. Se indica para síndromes de colon irritable, transtornos funcionales del aparato digestivo, prevención y tratamiento del íleo paralítico postoperatorio o como coadyuvante en procedimientos endoscópicos. Nuestro interés ha sido evaluar sus efectos clínicos y endoscópicos y compararlo con el etobromuro de piperidina (EBP), farmaco procinético usado como coadyuvante para estudios colonoscópicos en el Servicio de Gastroenterología del Hospital Universitario de Maracaibo. Se llevó a cabo un ensayo prospectivo y comparativo en una muestra de 56 pacientes adultos que acudieron para estudio colonoscópico. La mitad de los pacientes, seleccionados al azar, recibieron 5 mgrs de TMB por vía endovenosa en inyección lenta en un tiempo de 3 a 5 minutos y la mitad de la población restante recibió 10 mgrs de EBP, también por vía endo-venosa. La evaluación de la eficacia fue realizada a ciegas en tres áreas: colonoscópica, clínica y evaluación global. Es de hacer notar que las evaluaciones fueron tomadas por diferentes observadores y por tanto hay un rango inevitable de subjetividad al respecto. La aplicación de la prueba estadística X2 señala diferencias significativas entre ambos medicamentos, solo al comparar la data referente a "Evaluación colonoscópica" y "Dolor después del procedimiento". Nuetros resultados señalan una acción muy parecida de ambos medicamentos sobre la motilidad intestinal, ya que si bien el TMB, produjo excelentes efectos sobre el colón, con el EBP se obtuvieron mejores resultados en la distension y dolor abdominal durante y después del procedimiento colonoscópico. Evaluación terapéutica del maleato de trimebutina en estudios colonoscópicos. Comparación con el etobromuro de piperidina

Participación de la dexametasona y las vitaminas E y C en la modulación del efecto hepatotóxico inducido por los herbicidas fomesafén y 2,4-D amino, en ratas / Participation of dexamethasone and E and C vitamins in the modulation of the hepatotoxic effect induced by fomesafen and 2,4-D amino herbicides, in rats

RESUMEN: Los herbicidas fomesafén y el 2,4-D amino inducen importantes efectos tóxicos a nivel hepático en ratas, tales como: hepatomegalia, cambios hiperplásicos y aumento en la actividad de enzimas que participan en la b-oxidación lipídica a nivel peroxisomal como lo es la oxidasa de acidos grasos (FACO: Fatty Acyl CoA.oxidase). En el presente trabajo se evaluó el efecto de la vitamina E y C, así como de la dexametasona, en la modulación de los efectos hepatotóxicos inducidos por estos herbicidas. Ratas Sprague-Dawley fueron tratadas tanto con los herbicidas como con los agentes a evaluar, solos o simultáneamente. Los diferentes tratamientos fueron suministrados durante 15 días por vía oral y una vez transcurrido este tiempo, las ratas fueron pesadas y sacrificadas. Se evaluó el tamaño del hígadoy fragmentos de hígado fueron obtenidas para determinar la actividad enzimática (FACO) y la hiperplasia. Los resultados muestran que la hepatomegalia inducida por el fomesafén fue inhibida tanto por las vitaminas como por la dexametasona (DXMO), mientras que no se observó efecto alguno en el grupo de ratas tratadas con 2,4-D amino. Ninguno de los agentes modulo la actividad FACO observada en el hígado de ratas tratadas con los herbicidas. Sin embargo, la dexametasona mostró un efecto protector en la hiperplasia inducida por los dos herbicidas. Nuestros resultados demuestran que los dos herbicidas comparten una vías de inducción de efectos hepatotóxicos similares ya que la DXMO inhibe la hiperplasia inducida por los dos. Sin embargo, cuentan simultaneamente con mecanismos propios diferentespara inducir otras lesiones tales como hepatomegalia y proliferación de peroxisomas. Bajo las condiciones experimentales de este estudio, la utilización de estos agentes, como moduladores de toxicidad, no garantiza protección contra los efectos hepatotóxicos inducidos por los herbicidas evaluados.

Blockade of Na+/H+ exchanger contracts the portal vein of spontaneously hypertensive and Wistar Kyoto rats.

It has been claimed that the activity of Na+/H+ exchanger (NHE) is altered in spontaneously hypertensive rats (SHR) suggesting a possible role for it in the pathophysiology of hypertension. The purpose of this study has been to investigate the effect of blockade of NHE on the noradrenaline (NA) and 26K+ induced tone and on the recovery of tone from acid induced contractions in the portan vein of spontaneously hypertensive rats (SHR) as compared to their controls of Wistar Kyoto rats (WKY). Blockade of NHE by 10(-4) dimethylamiloride (DMA) raised the tone of NA and 26K+ activated preparation of both strains, the contractions being higher with NA activation. Total blockade of NHE by replacement of Na in solution with N-methy-D-Glucamine (NMDG) raised the tone of the NA activated preparations by 45+/-10%, n=8, P<0.01 and 33+/-4%, n=12, P < 0.01 in SHR and WKY respectively. The time for 50% relaxation from NH4Cl washout contraction was significantly prolonged by 10(-5) and 10(-4) M DMA in both strains under NA or 26K+ activation. DMA effect was greater on NA than on 26K+ activated preparations, and was not significantly different when comparing SHR to WKY results. In conclusion the results reported in this study indicate that NHE has similar activity in WKY and SHR portal veins and that its blockade contracts both preparations. Therefore, it is unlikely that increased NHE activity, acting directly on vascular smooth muscle tone, could be a primary cause for hypertension.

Reactions with spiroepoxy-alkanones. part III+ reaction of spirooctanones with dimethylamine aldehyde and then thiourea

Spirooctanones I react with dimethylamine at different conditions to give compounds II and III, and in the presence of aldehydes give IV. Compounds IV react with thiourea to give V, which undergoes cyclization with chloroacetic acid to give VI. Compounds VI condensed with dimethylamino-benzaldehyde to give VII. Some of the prepared compounds are biologically active

Local anaesthetic activity of some new substituted acylamides II.

Six new substituted acylamides, chemically related to lignocaine were studied for local anaesthetic activity and toxicity in mice, frogs and guinea pigs. Only one of these compounds, w-pyrrolidino 2, 3, 5, 6 tetramethyl acetanilide was found to possess potency comparable to lignocaine with a slightly higher therapeutic index. Study of the S.A.R. of this group indicated that by removal of two methyl groups at position 3 and 5 in the above compound, a local anaesthetic with greater potency than lignocaine may be obtained. Further exploration of the potentialities of a compound having pyrrolidine group as a part of basic side chain is indicated.