CHANGES IN THE GENETIC STRUCTURE OF A VALLEY IN THE PYRENEES (CATALONIA, SPAIN).

In some situations the use of isonymy is the best strategy for studying the genetic structure of a population and its biological history. In this study different population parameters were calculated for one of the most isolated valleys in the Pyrenees - the region of the Alta Ribagorça in Catalonia, Spain. Surnames from marriage records covering the continuous period from 1638 to 1988 were used. From 1950 onwards this region underwent important social, economic and biological changes related to the introduction of hydroelectric and mining industries, and the change from livestock farming to a society based on services. Two periods were analysed (1638-1950 and 1951-1988) allowing population changes that occurred in the region to be determined. The study focused on calculating the number of surnames by gender, diversity index (H), population sub-structure (RP-RPr)/RPr and inbreeding coefficient (F t) and detection of possible genetic barriers. The results demonstrate the importance that geography initially had in shaping the genetic structure of the population and how this was gradually replaced by other parameters such as roads or the social and economic importance of towns. An interesting phenomenon is that inbreeding has traditionally been associated with rural life, isolation and endogamy. However, for the Alta Ribagorça it was observed that in the second period, 1951-1988, inbreeding mainly depended on the composition of migrant groups and the reaction of the native population to the arrival of migrants from outside the region.

Fatty acid profiles of great tit (Parus major) eggs differ between urban and rural habitats, but not between coniferous and deciduous forests.

Early-life nutrition is an important determinant of both short- and long-term performance and fitness. The avian embryo develops within an enclosed package of nutrients, of which fatty acids (FA) are essential for many aspects of development. The FA composition of yolk depends on maternal nutrition and condition prior to egg formation, which may be affected by the external environment. To test if maternal environment affects yolk FA composition, we investigated whether the FA composition of great tit (Parus major) egg yolks differed between urban and rural habitats, and between deciduous and coniferous habitats. The results reveal differences in FA composition between eggs laid in urban and rural habitats, but not between eggs from the coniferous and deciduous habitats. To a large extent, this difference likely reflects dietary differences associated with urban habitats rather than dominating vegetation type. Specifically, urban yolks contained lower proportions of both ω-3 and ω-6 polyunsaturated FAs (PUFA), which are important for chick development. We also found a positive association between the proportion of saturated fatty acids and laying date, and a negative association between the proportion of ω-6 PUFA and clutch size. Given that urbanization is expanding rapidly, future studies should investigate whether factors such as anthropogenic food in the urban environment underlie these differences and whether they impair chick development.

Does the Treadmill Support Valid Energetics Estimates of Field Locomotion?

SYNOPSIS: Quantifying animal energy expenditure during locomotion in the field is generally based either on treadmill measurements or on estimates derived from a measured proxy. Two common proxies are heart rate (ƒH) and dynamic body acceleration (accelerometry). Both ƒH and accelerometry have been calibrated extensively under laboratory conditions, which typically involve prompting the animal to locomote on a treadmill at different speeds while simultaneously recording its rate of oxygen uptake (V̇o2) and the proxy. Field estimates of V̇o2 during locomotion obtained directly from treadmill running or from treadmill-calibrated proxies make assumptions about similarities between running in the field and in the laboratory. The present study investigated these assumptions, focusing on humans as a tractable species. First we investigated experimentally if and how the rate of energy expenditure during treadmill locomotion differs to that during field locomotion at the same speeds, with participants walking and running on a treadmill, on tarmac, and on grass, while wearing a mobile respirometry system. V̇o2 was substantially higher during locomotion in both of the field conditions compared with on a level treadmill: 9.1% on tarmac and 17.7% on grass. Second, we included these data in a meta-analysis of previous, related studies. The results were influenced by the studies excluded due to particulars of the experiment design, suggesting that participant age, the surface type, and the degree of turning during field locomotion may influence by how much treadmill and field locomotion V̇o2 differ. Third, based on our experiments described earlier, we investigated the accuracy of treadmill-calibrated accelerometry and ƒH for estimating V̇o2 in the field. The mean algebraic estimate errors varied between 10% and 35%, with the ƒH associated errors being larger than those derived from accelerometry. The mean algebraic errors were all underestimates of field V̇o2, by around 10% for fH and varying between 0% and 15% for accelerometry. Researchers should question and consider how accurately a treadmill-derived proxy calibration of V̇o2 will estimate V̇o2 during terrestrial locomotion in free-living animals.

Changes in acetylator phenotype over the lifespan in the Wistar rat.

UNLABELLED: Acetylation capacity during drug metabolism differs between species, gender and age groups. OBJECTIVE: The purpose of this work was to determine variations in the acetylating phenotype (AP), in a longitudinal study, as a function of growth and development. METHODS: Twenty male Wistar rats were studied. AP was determined on days 21, 48, 114, 180, 457 and 780 with oral doses of 30mg/kg of sulphadiazine (SDZ) by urine collection. The Schröeder and Vree methods were used to obtain SDZ concentrations, both acetylated and not acetylated. Rats were classified as slow or fast acetylators in accordance with previously validated metabolic indicators. RESULTS: Of the 20 rats phenotyped at 21 and 48 days of age, 18 were slow and 2 were fast acetylators. As age and consequent growth progressed, changes in the expression of AP were registered. At 114 days, 16 rats were slow and 4 were fast acetylators; at 180 days, 12 were slow and 8 were fast; at 457 days, 6 were slow and 14 were fast; at 780 days, the 20 rats were fast acetylators. Slow acetylation predominates at younger ages. CONCLUSIONS: The effect of growth and developmental progress on AP is evident and relates to previous reports of changes in AP, determined by age in animal and human models. The relevance of changes determined by growth and development should be considered in rational drug management.

Harm reduction actions as a health care construction process at a public health center in Rosario, Argentina.

Even faced with serious numbers of human immunodeficiency virus (HIV) and other infections among injection drug users (IDUs), Argentina lacks large-scale harm reduction programs at national, state, and local levels. We describe the strong relationship of IDUs with the HIV/acquired immunodeficiency syndrome epidemic in Rosario. We discuss a 2-year-long ongoing experience of drug-related harm reduction actions developed at a public health center, which began as a response to a spontaneous demand for needles and syringes and became a permanent and sustainable set of health actions for a group of nearly 50 IDUs, a larger number of drug users who do not inject, and their contacts. These actions comprise voluntary testing and counseling for HIV and other infections, reproductive counseling, condom promotion and distribution, and needle and syringe distribution without needle exchange. This experience, amenable to replication, shows that public health teams can engage successfully in harm reduction actions.

Effect of severe protein-calorie malnutrition on the penetration kinetics of trimethoprim and sulfamethoxazole to the deep tissues of Wistar rats.

This study shows the effect that severe malnourishment has on the kinetics of antibiotic penetration in tissues. A total of 104 male Wistar rats, 21 days old, were randomly divided into eight groups. Five groups of experimental rats were severely malnourished (SM) and three further groups were considered well-nourished control groups (WN). A single dose of trimethoprim-sulfamethoxazole (TMP-SMX) was administered intraperitoneally. Blood samples were taken by heart puncture and five organs were extracted 0-24 h after the administration of the drug. HPLC was used to assess the amount of trimethoprim and sulfamethoxazole in fluids. The elimination half-life for trimethoprim from plasma was longer in SM rats with a median of 3.15 h; in WN rats, it was 0.390 h. Clearance was slower in SM rats: 646.72 mL microg(-1) h(-1) vs 3036.38 mL microg(-1) h(-1) in WN rats (P < 0.05). Tissue penetration was much higher for trimethoprim, with penetration indexes of 0.80-5.66 in WN rats, compared with 0.35-2.14 in SM rats. In the case of sulfamethoxazole, penetration indexes were 0.029-1.13 for WN and 0.075-0.657 for SM rats. Similarly, the penetration ratio to muscle and heart tissue was lower in SM rats. However, penetration to kidney, lung, liver and spleen was greater in SM rats. It is evident that severe SM decreases the capacity of trimethoprim more importantly than sulfamethoxazole biotransformation.

Comparative bioavailability of two oral formulations of ranitidine.

The current requirement of the Mexican Authorities to demonstrate the interchangeability of ranitidine formulations is to establish that the dissolution profile of the drug shows similarity. In order to establish if this requirement is adequate, the bioavailability of two formulations that did not meet this similarity were compared. Twenty-five female volunteers received 150 mg ranitidine (Azantac or Midaven) under fasting conditions in two separate sessions using a cross-over design. Plasma samples were obtained at selected times for a period of 12 h and stored frozen at -80 degrees C until analysed. Ranitidine plasma levels were determined and pharmacokinetic parameters were obtained. Values (mean+/-SEM) were: Cmax 528.85+/-25.34 and 563.03+/-33.25 ng/ml, tmax 2.76+/-0.19 and 2.79+/-0.18 h, and AUC12 h 2694.94+/-99.50 and 2648.51+/-133.38 ng.h/ml, for Azantac or Midaven, respectively. No statistically significant difference was obtained in the parameters evaluated. Moreover, 90% confidence limits were 96.6%-116.2% and 90.7%-105.1% for Cmax and AUC12 h ratios, respectively, indicating that the formulations tested are bioequivalent, despite the dissimilarity in the dissolution profile of the formulations. These results suggest that the comparative dissolution profile is not an adequate test to demonstrate the interchangeability of ranitidine formulations.

Lactancia y transmisión madre-hijo del VIH en niños nacidos en las Maternidades Municipales de Rosario de 1999 a 2010 / Breastfeeding and mother-child transmission of HIV in infants born in maternity hospitals of Rosario Municipal 1999 to 2010

Se revisaron los casos de infección por VIH-1 ocurridos entre niños nacidos en maternidades municipales de Rosario, de 1999 a 2010 notificados al 30 de noviembre de 2011 para identificar el rol jugado por la lactancia materna. Se hallaron 12 casos entre 71.283 partos, de los cuales 479 fueron parturientas VIH positivas. hubo 6 mujeres con serología/s negativas previas o al momento del parto, diagnosticadas como VIH positivas meintras amamantaban sus hijos que resultaron infectados. Se proponen criterios para definir la posibilidad de la asociación. Nombramos estas madres como seroconvertidoras al VIH perinatales con diagnóstico intralactancia. Diez casos mostraron asociación con uso de drogas. La Tasa de Transmisión Vertical hallada fue 2,47 %, y podría reducirse aún más con el diagnóstico de VIH precoz durante la lactancia materna. Proponemos comunicar este problema y promover pruebas de VIH asesoradas ofrecidas regularmente desde los servicios a mujeres que amamantan y sus parejas.

Dosis efecto de la administración de fumarato ferroso en personas ancianas con deficiencia de hierro / Dose effect of ferrous fumarate administration in elderly persons with iron deficiency

Antecedentes: la anemia es un problema hematológico prevalente en ancianos, que afecta a 14 por ciento de los hombres y a 6 por ciento de las mujeres de la población mayor de 60 años de edad en México. Objetivo: determinar el efecto de la administración prolongada de fumarato ferroso en ancianos con deficiencia de hierro. Método: se estudió una población de 178 ancianos con edades entre 65 y 100 años, en 51 de estos sujetos (28.65 por ciento) se diagnosticaron niveles séricos anormales de hierro, menores de 80m g/dL para los hombres y 60 m g/dL para las mujeres, únicamente 21 de estos ancianos (11.8 por ciento) aceptaron participar en el estudio, en los cuales se estudió la respuesta a la administración oral de 5 mg/kg de hierro elemental durante seis meses.Los pacientes fueron clasificados según la alteración de los parámetros del metabolismo del hierro en tres grupos. (grupo 1 = 10.9 por ciento anemia; grupo 2 = 28.0 por ciento y grupo 3 = 63.0 por ciento de anemia). Resultados: la eficacia del tratamiento se evaluó por los cambios ocurridos en los parámetros hematológicos, como concentración de hierro sérico, hemoglobina, ferritina e índice de saturación, a los 0, 30, 90 y 180 días. Se observó que el tratamiento con fumarato ferroso durante seis meses produjo mejoría en la población estudiada determinada por el incremento significativo en los valores de los parámetros del metabolismo del hierro.Conclusiones: los resultados de este estudio sugieren la utilidad del tratamiento prolongado con fumarato ferroso en pacientes ancianos con deficiencia de hierro, para evitar fallas terapéuticas como consecuencia del no cumplimiento, el cual es común en ellos

Kinetic effects of trimethoprim-sulfamethoxazole in children with biliary atresia: a new dosing regimen

Pharmacokinetics for combination trimethoprim/sulfamethoxazole (TMP/SMX) was studied in only four patients with biliary atresia (BA): three girls, 6.2, 8.0 and 8.2 years of age and one boy 8.4 years of age, as this is an uncommon obstructive anomaly of the extrahepatic biliary system and has been described as having a poor prognosis. These four patients are the survivors of 27 initial children who were operated on previously. They have been receiving 2.3 ñ 0.5 mg/kg TMP, and 11.5 ñ2.6 mg/kg SMX every 12 h since 2 weeks after surgical treatment for biliary atresia performed at 2 - 2.5 months of age. The patients have suffered some episodes of cholangitis during their short lives, most of them after interrupting temporally the chemotherapy. Nevertheless, they have a achieved a favorable quality of life. TMP/SMX disposition was well characterized by a one compartment open pharmacokinetic model. Wide interpatient variability was observed for all pharmacokinetic parameters with coefficients of variation for t½ el, ClT, and Vd of 33.2, 49.6, and 26.3 per cent, respectively, for SMX and 108.9, 52.1, and 71.0 per cent, respectively, for TMP. A marked difference in the pharmacokinetics of TMP and SMX was observed, for example; (ClT: mean ñ SD; 90.3 ñ 47.0 ml/kg/g for TMP and 13.7 ñ 6.8 ml/kg/h for SMX), (t½ el with 7.93 ñ 8.64 h for TMP and 10.51 ñ 3.49 h for SMX). In order to develop dosage schedules that would reliably achieve peak serum concentrations of TMP/SMX in the therapeutic range, we found that established dose leads to high fluctuations at steady state between Cmax, ss and Cmin, ss, without maintaining therapeutic levels. Recommended maintenance dose varied from 8 to 30 mg/kg for SMX with a mean of 21.9 ñ 10.89 mg/kg/12 h, and from 0.8 to 4.5 mg/kg/12 h with a mean of 3.2 ñ 1.7 mg/kg/12 h. The present study illustrattes the need for pharmacokinetic studies for the individualization of drug dosing in patients with BA