The growing interest in nicotinic receptors, because of their wide expression in neuronal and non-neuronal tissues and their involvement in several important CNS pathologies, has stimulated the synthesis of a high number of ligands able to modulate their function. These membrane proteins appear to be highly heterogeneous, and still only incomplete information is available on their structure, subunit composition, and stoichiometry. This is due to the lack of selective ligands to study the role of nAChR under physiological or pathological conditions; so far, only compounds showing selectivity between alpha4beta2 and alpha7 receptors have been obtained. The nicotinic receptor ligands have been designed starting from lead compounds from natural sources such as nicotine, cytisine, or epibatidine, and, more recently, through the high-throughput screening of chemical libraries. This review focuses on the structure of the new agonists, antagonists, and allosteric ligands of nicotinic receptors, it highlights the current knowledge on the binding site models as a molecular modeling approach to design new compounds, and it discusses the nAChR modulators which have entered clinical trials.

New I(f) blockers have been designed and tested on HEK293 cells stably expressing the HCN1, HCN2, and HCN4 channels to find compounds able to discriminate among the channel isoforms. Among the synthesized compounds, the cis-butene derivative (R)-5 shows some preference for HCN2 while the pseudodimeric product (R)-6 shows selectivity for HCN1. These compounds can be important pharmacological tools to study the channels in native tissues and may be useful to design safe drugs.

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Two different immunosensors, recently developed for the determination of antibacterial proteins (lactoferrin and immunoglobulin G) in buffalo milk and in other commercial animal milks samples, were used in the present study. The aim was to propose these immunosensor methods for routine control of important diet products, such as cow and goat milks, and in particular buffalo milk. To this end we employed two different kinds of immunosensors: one for the analysis of immunoglobulin G (IgG), the other was a new amperometric immunosensor for lactoferrin analysis. Lactoferrin and IgG immunosensors were also used for the determination of lactoferrin and immunoglobulin G in buffalo milk on different days of lactation.

OBJECTIVE -To investigate the maternal demographic and metabolic factors contributing to the growth of fetal lean and fat body mass in women whose degree of glucose intolerance is less than that defining gestational diabetes in comparison with women with normal glucose metabolism.RESEARCH DESIGN AND METHODS -Longitudinal sonographic examinations of 66 singleton fetuses without anomalies of nonobese mothers with abnormal oral glucose challenge test (GCT) results and without gestational diabetes (group 1) were compared with those of 123 singleton fetuses without anomalies of nonobese mothers with normal GCT values (group 2). Lean body mass measurements included head circumference, femur length, mid-upper arm, and mid-thigh central areas. Fat body mass measurements included the anterior abdominal wall thickness, the subscapular thickness, and the mid-upper arm and mid-thigh subcutaneous areas. All the women performed a 24-h glucose profile on the day preceding the ultrasound scan. Multivariate logistic regression analysis established best-fit equations for fetal sonographic measurements of fat and lean body mass. Independent variables included groups 1 and 2, maternal age, parity, prepregnancy BMI, gestational age, weight gain during pregnancy, fetal sex, and the following averaged 24-h profile maternal capillary blood glucose values: preprandial, 1-h postprandial, and 2-h postprandial. RESULTS -No difference was found between the two groups with respect to fetal lean body mass parameters; the factors that contributed significantly and most frequently were gestational age and fetal sex (male). With respect to fetal fat body mass, all the measurements were significantly higher in group 1 than in group 2. In all instances, the significantly contributing factors were gestational age and maternal 1-h postprandial glucose values, whereas another frequent contributor was prepregnancy BMI.CONCLUSIONS -Our study suggests the possibility of using sonographically determined fetal fat and lean mass measurements as indicators of body composition. The assessment of these parameters, achievable in a noninvasive and reproducible fashion in pregnancies complicated by glucose intolerance, might enable the real-time detection of fetal overgrowth and disproportion, thus opening the possibility of exploring interventions to limit fetal fat accretion, birth weight, and potential resulting morbidity. Diabetes Care 26:2741-2748, 2003G estational alterations in maternal metabolism provide nutrients in excess of those required for normal fetal growth and for maternal and fetal energy requirements. In this context, the presence of any degree of abnormal glucose tolerance, even if less than that conventionally required for the diagnosis of gestational diabetes, represents an altered environment for the growth of the fetus (1-7).The excess supply of nutrients caused by altered glucose tolerance is most easily discerned through fetal fat body mass, which has been shown to be more closely associated with maternal glucose control than birth weig...

These data indicate that the elevated cardiac output is adequately maintained in pregnancy during the postural challenge, due to optimisation of the responses of preload and afterload.

OBJECTIVE -To investigate, in pregnant women without gestational diabetes mellitus (GDM), the relation among obstetric/demographic characteristics; fasting, 1-h, and 2-h plasma glucose values resulting from a 75-g glucose load; and the risk of abnormal neonatal anthropometric features and then to verify the presence of a threshold glucose value for a 75-g glucose load above which there is an increased risk for abnormal neonatal anthropometric characteristics. RESEARCH DESIGN AND METHODS -The study group consisted of 829 Caucasian pregnant women with singleton pregnancy who had no history of pregestational diabetes or GDM, who were tested for GDM with a 75-g, 2-h glucose load, used as a glucose challenge test, in two periods of pregnancy (early, 16 -20 weeks; late, 26 -30 weeks), and who did not meet the criteria for a GDM diagnosis. In the newborns, the following abnormal anthropometric characteristics were considered as outcome measures: cranial/thoracic circumference (CC/TC) ratio Յ10th percentile for gestational age (GA), ponderal index (birth weight/length 3 ϫ 100) Ն90th percentile for GA, and macrosomia (birth weight Ն90th percentile for GA), on the basis of growth standard development for our population. For the first part of the objective, logistic regression models were used to identify 75-g glucose load values as well as obstetric and demographic variables as markers for abnormal neonatal anthropometric characteristics. For the second part, the receiver operating characteristic (ROC) curve was performed for the 75-g glucose load values to determine the plasma glucose threshold value that yielded the highest combined sensitivity and specificity for the prediction of abnormal neonatal anthropometric characteristics.RESULTS -In both early and late periods, maternal age Ͼ35 years was a predictor of neonatal CC/TC ratio Յ10th percentile and macrosomia, with fasting 75-g glucose load values being independent predictors of neonatal CC/TC ratio Յ10th percentile. In both periods, 1-h values gave a strong association with all abnormal neonatal anthropometric characteristics chosen as outcome measures, with maternal age Ͼ35 years being an independent predictor for macrosomia. The 2-h, 75-g glucose load values were significantly associated in both periods with neonatal CC/TC ratio Յ10th percentile and ponderal index Ն90th percentile, whereas maternal age Ͼ35 years was an independent predictor of both neonatal CC/TC ratio Յ10th percentile and macrosomia. In the ROC curves for the prediction of neonatal CC/TC ratio Յ10th percentile for GA in both early and late periods of pregnancy, inflection points were identified for a 1-h, 75-g glucose load threshold value of 150 mg/dl in the early period and 160 mg/dl in the late period.CONCLUSIONS -This study documented a significant association, seen even in the early period of pregnancy, between 1-h, 75-g glucose load values and abnormal neonatal anthropometric features, and provided evidence of a threshold relation between 75-g glucose load results and clinical outcome. Our ...

HBsAg clearance is increased over the years in HDV patients compared to ordinary HBsAg carriers, and is often associated with improvement of HDV disease without seroconversion to anti-HBs.