Variabilidad de la interacción parásito-hospedador de diferentes genotipos Mus musculus al desafío experimental con Trichinella spiralis

Parasite-host interaction is a complex relationship that determines the outcome of infection. Trichinella spiralis is a nematode that affects a wide range of animals and can transmit infection to humans. Studying its interaction with the host is essential for developing strategies to reduce the impact of this parasitosis. The aim of this study was to evaluate potential differences in parasite-host interaction in response to a Trichinella spiralis challenge among different host genotypes, consisting of four mouse lines selected by body weight and a control line derived from the CF1 strain (s, h, s’, h’, and t, respectively). Male mice from the lines were infected with a dose of 400 muscle larvae. The expulsion index at 15 days post-infection indicated that the t line was the most efficient, whereas the h line was the least efficient in this process, showing the highest number of adult worms in the intestine. In the chronic stage of infection, the number of encysted muscle larvae (relative parasitic load) was significantly higher in the light h line and lower in the t and h’ lines, indicating differences in the host-parasite interaction among the genotypes. Histopathological evaluation of the duodenum also revealed differences among the studied lines. The observed variability may result from the systematic process of phenotypic artificial selection for body weight, along with dispersive effects - such as the founder effect and genetic drift - associated with the low effective population size.La interacción parásito-hospedador es una relación compleja que determina el resultado de una infección. Trichinella spiralis es un nematodo que afecta a una amplia gama de animales, los que pueden transmitir la infección al humano. El estudio de la interacción con su hospedador es fundamental para obtener estrategias que permitan reducir esta parasitosis. El objetivo de esta investigación fue evaluar las potenciales diferencias en la interacción parásito-hospedador frente al desafío con Trichinella spiralis por parte de diferentes genotipos de hospedadores, conformados por cuatro líneas de ratones seleccionadas por peso y una línea testigo derivadas de la cepa CF1 (s, h, s´, h´ y t, respectivamente). Fueron infectados ratones macho de las líneas con una dosis de 400 larvas musculares. El índice de expulsión, a los 15 días posinfección, demostró que la línea t fue la más eficiente, mientras que la línea h fue la más ineficiente en este proceso, al presentar el mayor número de gusanos adultos en el intestino. En la etapa crónica de la infección, el número de larvas musculares enquistadas (carga parasitaria relativa) fue significativamente mayor en la línea liviana h, y menor en t y h´, mostrando diferencias en la interacción entre las líneas. La evaluación de los cambios histopatológicos del duodeno también mostró diferencias entre las líneas estudiadas. Esta variabilidad hallada sería producto del proceso sistemático de selección artificial fenotípica por peso corporal a los que se suman los efectos dispersivos -efecto fundador y deriva génica- asociados al bajo tamaño efectivo de las poblaciones

Molecular beacons immobilized within suspended core optical fiber for specific DNA detection

We propose and experimentally demonstrate a new class of sensor for specific DNA sequences based on molecular beacons (MB) immobilized on the internal surfaces of suspended core optical fibers (SCF). MBs, a type of hairpin structured DNA probe, are attached on the surface of the SCF core using a fuzzy nanoassembly process used in conjunction with a biotin-streptavidin-biotin surface attachment strategy. The proposed DNA sensor detects complementary DNA sequences (cDNA) while discriminating sequences differing from the target by just one base. This enables the detection of DNA in unprecedentedly small sample volumes (nL scale) and is, to the best of our knowledge, the first specific DNA detection using a DNA probe immobilized within a microstructured optical fiber.Linh Viet Nguyen, Stephen C. Warren-Smith, Alan Cooper, and Tanya M. Monr

Effect of Adjunct Metformin Treatment in Patients with Type-1 Diabetes and Persistent Inadequate Glycaemic Control. A Randomized Study

Despite intensive insulin treatment, many patients with type-1 diabetes (T1DM) have longstanding inadequate glycaemic control. Metformin is an oral hypoglycaemic agent that improves insulin action in patients with type-2 diabetes. We investigated the effect of a one-year treatment with metformin versus placebo in patients with T1DM and persistent poor glycaemic control.One hundred patients with T1DM, preserved hypoglycaemic awareness and HaemoglobinA(1c) (HbA(1c)) > or = 8.5% during the year before enrolment entered a one-month run-in on placebo treatment. Thereafter, patients were randomized (baseline) to treatment with either metformin (1 g twice daily) or placebo for 12 months (double-masked). Patients continued ongoing insulin therapy and their usual outpatient clinical care. The primary outcome measure was change in HbA(1c) after one year of treatment. At enrolment, mean (standard deviation) HbA(1c) was 9.48% (0.99) for the metformin group (n = 49) and 9.60% (0.86) for the placebo group (n = 51). Mean (95% confidence interval) baseline-adjusted differences after 12 months with metformin (n = 48) versus placebo (n = 50) were: HbA(1c), 0.13% (-0.19; 0.44), p = 0.422; Total daily insulin dose, -5.7 U/day (-8.6; -2.9), p<0.001; body weight, -1.74 kg (-3.32; -0.17), p = 0.030. Minor and overall major hypoglycaemia was not significantly different between treatments. Treatments were well tolerated.In patients with poorly controlled T1DM, adjunct metformin therapy did not provide any improvement of glycaemic control after one year. Nevertheless, adjunct metformin treatment was associated with sustained reductions of insulin dose and body weight. Further investigations into the potential cardiovascular-protective effects of metformin therapy in patients with T1DM are warranted.ClinicalTrials.gov NCT00118937

Do decision support systems influence variation in prescription?

<p>Abstract</p> <p>Background</p> <p>Translating scientific evidence into daily practice is problematic. All kinds of intervention strategies, using educational and/or directive strategies, aimed at modifying behavior, have evolved, but have been found only partially successful. In this article the focus is on (computerized) decision support systems (DSSs). DSSs intervene in physicians' daily routine, as opposed to interventions that aim at influencing knowledge in order to change behavior. We examined whether general practitioners (GPs) are prescribing in accordance with the advice given by the DSS and whether there is less variation in prescription when the DSS is used.</p> <p>Methods</p> <p>Data were used from the Second Dutch National Survey of General Practice (DNSGP2), collected in 2001. A total of 82 diagnoses, 749811 contacts, 133 physicians, and 85 practices was included in the analyses. GPs using the DSS daily were compared to GPs who do not use the DSS. Multilevel analyses were used to analyse the data. Two outcome measures were chosen: whether prescription was in accordance with the advice of the DSS or not, and a measure of concentration, the Herfindahl-Hirschman Index (HHI).</p> <p>Results</p> <p>GPs who use the DSS daily prescribe more according to the advice given in the DSS than GPs who do not use the DSS. Contradictory to our expectation there was no significant difference between the HHIs for both groups: variation in prescription was comparable.</p> <p>Conclusion</p> <p>We studied the use of a DSS for drug prescribing in general practice in the Netherlands. The DSS is based on guidelines developed by the Dutch College of General Practitioners and implemented in the Electronic Medical Systems of the GPs. GPs using the DSS more often prescribe in accordance with the advice given in the DSS compared to GPs not using the DSS. This finding, however, did not mean that variation is lower; variation is the same for GPs using and for GPs not using a DSS. Implications of the study are that DSSs can be used to implement guidelines, but that it should not be expected that variation is limited.</p

Residual B-cell function in type 1 (insulin-dependent) diabetes mellitus: its relation to clinical and metabolic features

The aim of the present study was to investigate whether or not residual B-cell function could be related to insulin sensitivity as well as to duration of disease, insulin requirement, and indices of metabolic control in a population of Type 1 (insulin-dependent) diabetic patients. A positive correlation was found between fasting C-peptide and age at onset of diabetes, whereas a negative relationship occurred between C-peptide and duration of disease. Fasting C-peptide negatively correlated also to mean daily plasma glucose, 24-h glycosuria, and fasting free fatty acid concentration. Moreover, a negative correlation was found between C-peptide and daily insulin requirement. Conversely, a positive relationship occurred between C-peptide levels and the parameter we used for estimating insulin sensitivity, i.e. glucose disappearance rate after i.v. insulin injection. These results once more emphasize the importance of residual B-cell function in Type 1 (insulin-dependent) diabetes mellitus, and suggest that the residual endogenous insulin secretion might play an important role in glucose homeostasis of Type 1 diabetes by influencing the sensitivity to insulin

Insulin metabolism is a major factor responsible for high or low peripheral insulin levels in response to oral glucose loading in the healthy man

In the present study we evaluated C-peptide peripheral levels after an oral glucose load in 30 healthy subjects (18 females, 12 males, aged from 15 to 55) with high or low insulin response to glucose challenge in order to clarify whether or not their beta-cell secretion rate keeps pace with peripheral insulin levels. Moreover, by the study of the relations between C-peptide and insulin in peripheral blood, we had an insight into the extent of insulin metabolism. On the basis of an insulin incremental area higher or lower than the mean +/- 1 SD after a 100-gram oral glucose load, 6 subjects were classified as 'high insulin responders' and 6 other subjects as 'low insulin responders'. Their insulin incremental area after glucose averaged 0.25 +/- 0.01 nmol X 1-1 X min and 0.078 +/- 0.005 nmol X 1-1 X min, respectively (p less than 0.001). The two groups were matched for sex, age and body weight. The glycemic profile after oral glucose load was higher in low insulin responders than in high insulin responders. C-peptide concentrations after glucose load were similar in the two groups, as well as C-peptide incremental areas (0.92 +/- 0.12 vs. 0.74 +/- 0.08 nmol X l-1 X min in high insulin responders and low insulin responders, respectively). The molar ratios of C-peptide to insulin after oral glucose load, as well as the relations between the incremental areas of the two peptides, were significantly lower in high insulin responders than in low insulin responders.(ABSTRACT TRUNCATED AT 250 WORDS