Ex vivo trypanocidal activity of 1-(2-hydroxybenzylidene)thiosemicarbazide against Trypanosoma equiperdum.

Trypanosoma equiperdum is the causative agent of dourine, a venereal disease in horses and donkeys. This parasite has a widely distribution, is found in Africa, Asia, Southern and Eastern Europe, Russia, Mexico and Venezuela. The T. equiperdum is morphologically indistinguishable to other Trypanozoon species, however differs from other mammalian trypanosomes due to the fact that it is primarily a tissue parasite, generating cutaneous plaques, swelling of genitalia and neurological signs. The aim of this study was to evaluate the trypanocidal effectiveness of a set of derivatives of thiosemicarbazones on a T. equiperdum ex vivo culture. All compounds appeared to have trypanocidal activity, however one of them shown better solubility and a dose-dependent effect. The median inhibitory concentration (IC50) was 1.2µM. The selected compound exhibits a greater inhibitory activity than diminazene aceturate, a common drug for animal trypanosomosis treatment.

A clinical trial for patients with acute myeloid leukemia or myelodysplastic syndromes not eligible for standard clinical trials.

This corrects the article DOI: 10.1038/leu.2016.303.

Antinociceptive effect of systemically administered dipyrone (metamizol), magnesium chloride or both in a murine model of cancer.

BACKGROUND: Opioid effectiveness to treat cancer pain is often compromised by the development of tolerance and the occurrence of undesirable side effects, particularly during long-term treatment. Hence, the search for more efficient analgesics remains a necessity. The main goal of this study was to relieve neuropathic symptoms associated with tumour growth by administering the non-opioid analgesic dipyrone (DIP) alone or in combination with magnesium chloride (MgCl2 ), an adjuvant that blocks the NMDA receptor channel. METHODS: Mice were inoculated with a melanoma cell line (B16-BL6) in the left thigh and two protocols were used to evaluate the effect of DIP (270 mg/kg), MgCl2 (200 mg/kg), or the combination DIP-MgCl2 . In the therapeutic protocol the drugs, alone or combined, were administered once tumour had promoted increased nociception. In the preventive protocol, drugs were administered prior to the appearance of the primary tumour. Tumour growth was assessed with a caliper and nociception was determined using behavioural tests. RESULTS: DIP promoted antinociception only at the beginning of both protocols due to the development of tolerance. The combination DIP-MgCl2 improved the antinociceptive effect, avoiding tolerance and reducing tumour growth in the preventive treatment, more efficiently than each compound alone. CONCLUSIONS: These results suggest that DIP-MgCl2 may represent a safe, affordable and accessible option to reduce tumour growth and to treat cancer pain avoiding the risk of tolerance, without the typical complications of opioids agents, particularly when long-term treatment is required. SIGNIFICANCE: This study shows a non-opioid analgesic combined with an adjuvant as a therapeutic option to treat cancer pain. The avoidance of antinociceptive tolerance when repeated administration is required, as well as tumor growth reduction, are additional advantages to be considered.

A clinical trial for patients with acute myeloid leukemia or myelodysplastic syndromes not eligible for standard clinical trials.

Most clinical trials exclude patients with poor performance or comorbidities. To study whether patients with these characteristics can be treated within a clinical trial, we conducted a study for patients with acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS) with poor performance, organ dysfunction or comorbidities. Primary endpoint was 60-day survival. Study included stopping rules for survival and response. Treatment consisted on a combination of azacitidine and vorinostat. Thirty patients (16 with MDS, 14 with AML) were enrolled. Median follow-up was 7.4 months (0.3-29). Sixty-day survival was 83%. No stopping rules were met. Main adverse events (AEs) were grades 1 and 2 gastrointestinal toxicities. In view of these results, we expanded the study and treated 79 additional patients: 27 with azacitidine (AZA) and 52 with azacitidine and vorinostat (AZA+V). Median follow-up was 22.7 months (12.6-47.5). Sixty-day survival rate was 79% (AZA=67%, AZA+V=85%, P=0.07). Median overall survival was 7.6 months (4.5-10.7). Median event-free survival was 4.5 months (3.5-5.6). Main AEs included grades 1 and 2 gastrointestinal toxicities. Our results suggest this subset of patients can be safely treated within clinical trials and derive clinical benefit. Relaxation of standard exclusion criteria may increase the pool of patients likely to benefit from therapy.

Determinación de plomo en lápices labiales de diferentes marcas comercializados en Lima / Determination of plumb in lip pencils of different commercial marks in Lima

Objetivo: Determinar la presencia de plomo en los lápices labiales de diferentes marcas que se expenden en la ciudad de Lima. Material y Método: Se utilizó 24 lápices labiales de cinco marcas comerciales operantes en Perú, procedentes del centro comercial Capón en Lima. La presencia de plomo se determinó por el método de espectrofotometría de absorción atómica con horno de grafito. Para la validación estadística, se determinó la media y la desviación estándar. Resultados: Se encontró mayor contenido de plomo en las marcas LAL-04-YHBC (3,02 ppm), LAL-05-BALOE (2,10 ppm), LAL- 02-RW (1,55 ppm) y LAL-03-VCYH (1,22 ppm); contrastada con una marca poco conocida,de código LAL-01-CHOCO PLUSII en la que no se detectó plomo. Conclusiones: De los lápices labiales estudiados, cuatro de ellos superaron los valores permisibles de plomo (0,1 ppm), que es un valor referencial para caramelos.

Objective: To determine the presence of lead in lipsticks from different brands that are sold in the city of Lima. Material and Methods: 24 lipsticks of five different trademarks were used, from the shopping center in Lima Capon. The presence of lead was determined by the method of atomic absorption spectrophotometry with graphite furnace. For statistical validation, the mean and standard deviation was determined. Results: The highest lead content was found in the LAL -04 - YHBC (3.02 ppm) , LAL -05 - BALOE (2.10 ppm) , LAL -02 -RW (1.55 ppm) and LAL -03 marks - VCYH (1.22 ppm ) ; contrasted with a little known brand , LAL -01- CHOCO PLUSII code where no lead was detected. Conclusions: Of the studied lipsticks, four exceeded the permissible values of lead (0.1 ppm), which is a reference value for candy.

Modelling the growth and ethanol production of Brettanomyces bruxellensis at different glucose concentrations.

AIM: To study the effect of glucose concentrations on the growth by Brettanomyces bruxellensis yeast strain in batch experiments and develop a mathematical model for kinetic behaviour analysis of yeast growing in batch culture. METHODS AND RESULTS: A Matlab algorithm was developed for the estimation of model parameters. Glucose fermentation by B. bruxellensis was studied by varying its concentration (5, 9.3, 13.8, 16.5, 17.6 and 21.4%). The increase in substrate concentration up to a certain limit was accompanied by an increase in ethanol and biomass production; at a substrate concentration of 50-138 g l(-1), the ethanol and biomass production were 24, 59 and 6.3, 11.4 g l(-1), respectively. However, an increase in glucose concentration to 165 g l(-1) led to a drastic decrease in product formation and substrate utilization. CONCLUSIONS: The model successfully simulated the batch kinetic observed in all cases. The confidence intervals were also estimated at each phase at a 0.95 probability level in a t-Student distribution for f degrees of freedom. The maximum ethanol and biomass yields were obtained with an initial glucose concentration of 138 g l(-1). SIGNIFICANCE AND IMPACT OF THE STUDY: These experiments illustrate the importance of using a mathematical model applied to kinetic behaviour on glucose concentration by B. bruxellensis.

Estudio botánico y fitoquímico de las hojas secas de maca de la Meseta de Bombón, Junín-Perú / Botanic and phytochemic study of dry maca leaves from the Meseta de Bombón, Junín-Perú

OBJETIVO: Realizamos el estudio botánico (taxonómico e histológico) y fitoquímico de las hojas de maca que se cultivan en la Meseta de Bombón del Departamento de Junín, con el OBJETIVO de determinar la especie a la que pertenece. MATERIAL Y MÉTODOS: Las muestras fueron colectadas entre diciembre-2007 y agosto-2008, siguiendo el método de Cerrate E y Ramagosa et. al. El estudio taxonómico se fundamentó en el sistema de clasificación de Cronquist (1981), claves nacionales e internacionales, descripciones originales fototipos y dibujos. Utilizamos reactivos de grado analítico y un estándar certificado de quercetina. La determinación de la quercetina se realizó por espectrofotometría UV/Vis, en un extracto metanólico hidrolizado, siguiendo la metodología de Sharapin modificada; y por HPLC (método de Piacente modificado). La identificación de los ácidos grasos poliinsaturados se realizó por cromatografía de gases acoplado a espectrofotometría de masa (GC-EM). RESULTADOS: La morfología de las hojas demostró que la planta es anual, pubescente, herbaceae-sufrútice; hojas pinnasectas, sépalos persistentes; raíz globosa tuberosa, características propias del Lepidiun peruvianum Chacón. La histología mostró tricomas unicelulares cónicos y tricomas pluricelulares; la epidermis y el mesófilo contienen cristales de oxalato de calcio. En el extracto metanólico hidrolizado ôBõ encontramos una cantidad significativa de flavonoides, expresados como quercetina (3,55-3,95 mg/ gramo de muestra), tanto por el método espectrofotométrico, como por el de cromatografía líquida de alta precisión. Por CG-EM identificamos ácidos grasos poliinsaturados (palmítico; linoleato, linolenato y palmitato de etilo). CONCLUSIONES: La muestra vegetal colectada proveniente de la Meseta del Bombón del Departamento de Junín corresponde a la especie Lepidium peruvianum Chacón y contiene flavonoides (quercetina) y ácidos grasos poliinsaturados).

ABSTRACT We make a botanic (taxonomic and hystologic) and phytochemic study of the ômacaõ from the Meseta de Bombom-Junìn with the OBJETIVE to deteremine the species to which it belong MATERIALS AND METHOD The samples were collected between December-2007 and Augost-2008 according with the Cerrate E and Ramagosa et al. Method. The taxonomic study was based on the Cronquist clasification system (1981), national and international keys, original descriptions and fototypes and draws. We used reactives of analytic grades and certifayed standars of Quercetine. The test of quercetin was made by spectrophotometry UV/Vis in the methanolic hydrolyzed extract, following the Sharapin modified method and by HPLC following the Piacente modified method. The identification of the insatureted fat acids was made by gas cromatography acopled to mass spectrometry (GC-EM). RESULTS The morphology of the leaves showed tha the plant is annual, pubescent, hebaceae-sufrútice; pinnasectas leaves, permanent sepals; globous tuberous roots. All o these are characteristics of the Lepidiun peruvianum Chacon. The histology showed that the plant has unicelular conic tricomes and pluricelular tricomes; the epidermis and the mesophil has calcium oxalate chystals. In the methanolic hydrolysed ôBõ we found a significant amount of flavonoids, expresed as Quercetine (3,55-3,95 mg/g of sample) tested by spectrophotomety as by HPLC. By CG-EM we found poliinsaturated fat acids such: palimitc acid, etilo linolated, etilo linolenated and etilo palmitated. CONCLUSIONS The sample of ôMacaõ colected in the Meseta de Bombon Department of Junín belongs to the Lepidiun peruvianun Chacon species and has flavonoids (quercetin) and polyunsaturated fat acids.

Evidence of damage in cryopreserved and fresh bovine embryos using the Tunel technique.

The objective of the present study was to evaluate the quality of bovine embryos cryopreserved in different years in Chiapas, Mexico. The embryos were obtained from a government institution (FIMEGEN) dedicated to promoting embryo transfer among dual-purpose cattle farmers. Forty-three embryos frozen in 1988, 1989, 2000 and 2002 were analysed with the Tunel technique to detect programmed cell death (apoptosis). Eleven fresh embryos were used as controls. Analysis of variance was used in embryos stored in the different years with averages tested using Tukey's test. Student's t-test was employed to compare fresh and frozen cells. Embryos with shorter storage time presented a lower number (p < 0.001) of Tunel-positive cells compared with embryos stored for longer time. On the contrary, when comparing the number of apoptotic cells between frozen and fresh embryos a higher number of positive cells (p < 0.05) were found in the former. The present results suggest that the cryopreservation per se caused damage that compromises the viability of the embryo. Another explanation for the lower pregnancy rate found in the tropics could be irreversible damage caused by poor storage technique in these large operations.

Woody plant diversity and structure of shade-grown-coffee plantations in northern Chiapas, Mexico.

Shade-grown coffee is an agricultural system that contains some forest-like characteristics. However, structure and diversity are poorly known in shade coffee systems. In 61 coffee-growers' plots of Chiapas, Mexico, structural variables of shade vegetation and coffee yields were measured, recording species and their use. Coffee stands had five vegetation strata. Seventy seven woody species mostly used as wood were found (mean density 371.4 trees per hectare). Ninety percent were native species (40% of the local flora), the remaining were introduced species, mainly fruit trees/shrubs. Diametric distribution resembles that of a secondary forest. Principal Coordinates Analysis grouped plots in four classes by the presence of Inga, however the majority of plots are diverse. There was no difference in equitability among groups or coffee yields. Coffee yield was 835 g clean coffee per shrub, or ca. 1,668 kg ha-1. There is a significant role of shade-grown coffee as diversity refuge for woody plants and presumably associated fauna as well as an opportunity for shade-coffee growers to participate in the new biodiversity-friendly-coffee market.

Pharmacokinetics of cinnarizine after single and multiple dosing in healthy volunteers.

Cinnarizine (CAS 298-57-7) pharmacokinetics were studied after single and repetitive dosing in healthy volunteers. Six young male healthy subjects received a 75 mg tablet and blood samples were drawn for 72 h after medication. Cinnarizine plasma levels were determined by gas chromatography. Cmax was 275 +/- 36 ng/ml, tmax 3.0 +/- 0.5 h, AUC extrapolated to infinity 4437 +/- 948 ng.h/ml and terminal half-life 23.6 +/- 3.2 h. After a 2-week washout period, 5 of these subjects received 75 mg tablets b.i.d. for 15 days. After the administration of doses 1 and 29, blood samples were drawn for 12 h and cinnarizine plasma levels were measured. Cinnarizine accumulated under these conditions. At steady state (dose 29), the observed accumulation factor was 2.79 +/- 0.23, being not significantly different from that predicted with the terminal half-life obtained from single dose data, which was 3.37 +/- 0.37. AUC0-12 for dose 29 was 5074 +/- 1021 ng.h/ml, being not significantly different from the AUC extrapolated to infinity obtained with the single dose. Results indicate that cinnarizine accumulates with repetitive dosing due to its pharmacokinetic properties.