Kv11.1 channel subunit composition includes MinK and varies developmentally in mouse cardiac muscle

The Kv11.1 (also ERG1) K(+) channel underlies cardiac I(Kr), a current that contributes to repolarization in mammalian heart. In mice, I(Kr) current density decreases with development and studies suggest that changes in the structure and/or properties of the heteromultimeric I(Kr)/Kv11.1 channel are responsible. Here, using immunohistochemistry, we report that total Kv11.1 alpha subunit protein is more abundant in neonatal heart and is distributed throughout both adult and neonatal ventricles with greater abundance in epicardia. Immunoblots reveal that the alpha subunit alternative splice variant, Kv11.1a, is more abundant in adult heart while the Kv11.1b variant is more abundant in neonatal heart. Additionally, MinK channel subunit protein is shown to co-assemble with Kv11.1 protein and is more abundant in neonatal heart. In summary, Kv11.1/I(Kr) channel composition varies developmentally and the higher I(Kr) current density in neonatal heart is likely attributable to higher abundance of Kv11.1/I(Kr) channels, more specifically, the Kv11.1b splice variant.     

Affective and Behavioral Stress Outcomes in Alzheimer's Caregivers

Few investigations have looked at behavioral stress outcomes in Alzheimer's caregivers. This study documented concentration deficits to examine behavioral outcomes of stress in 33 Alzheimer's Disease (AD) caregivers and in 33 age-, sex-, and race-matched controls. As hypothesized, caregivers showed less persistence than controls in solving problems from a standard test of problem-solving ability. In addition, caregivers tended to make more errors than controls on a standard proofreading task ( p < .09). In AD caregivers, cognitive deficits (represented by lower scores on problem-solving and concentration tasks) may be representative of a broader deficit in concentration that impairs the ability of caregivers to provide for their own needs and the needs of the family member for whom they are caring.     

Antiphospholipid antibodies and the outcome of pregnancy after the first in-vitro fertilization and embryo transfer cycle

Increased antiphospholipid antibody prevalence has been demonstrated by a number of recent studies in in-vitro fertilization (IVF) patients but the potential effects of antiphospholipid antibodies on the different components of the reproductive process and the consideration of whether to test IVF patients for antiphospholipid antibodies are controversial. The present study was undertaken to investigate the possible association between the presence of circulating antiphospholipid antibodies (namely the lupus anticoagulant and anticardiolipin antibodies), among a series of 21 consecutive IVF patients having a clinical spontaneous abortion after their first embryo transfer. As a control group (n=42), the nearest IVF cycle resulting in an ongoing pregnancy before and after each miscarried IVF cycle (i.e. the closest cycles in temporal relationship to the index cycle) was used. One patient (4.8%) in the study group and two women (4.8%) among controls were seropositive for antiphospholipid antibodies. These low and similar seropositivity rates found in the two groups studied lead us to conclude that antiphospholipid antibodies testing in IVF patients should be considered only in those women having repeated failures of implantation/clinical abortion after embryo transfer but not in an infertile general population reaching an IVF programme.      

Assessment of bioequivalence after subcutaneous and intramuscular administration of urinary gonadotrophins

The objective was to demonstrate bioequivalence between s.c. and i.m. administration of Humegon (FSH/LH ratio 1:1) and Normegon (FSH/LH ratio 3:1). In two randomized, single-centre, cross-over studies, 18 healthy volunteers on each formulation were assigned to one of the two administration sequences. Subjects were given single doses of one of the above gonadotrophins after endogenous gonadotrophin production had first been suppressed using high-dose oral contraceptive. Subsequently, rate (Cmax, tmax) and extent (AUC) of absorption of follicle stimulating hormone (FSH) and luteinizing hormone (LH) were determined for 14 days. For Cmax and AUC, analysis of variance (ANOVA) was performed on log-transformed data and for tmax ANOVA was performed on ranks. Intramuscular and s.c. injections of Humegon were bioequivalent with respect to the main pharmacokinetic parameters, being AUC and Cmax of FSH absorption. Intramuscular and s.c. injections of Normegon were bioequivalent with respect to the AUC of FSH and not bioequivalent with respect to the Cmax of FSH. For tmax of FSH as well as for most LH variables of both preparations, bioequivalence could not be proven due to the high intra- and interindividual variability and/or concentrations being close to the detection limit. Thus, the main pharmacokinetic FSH variables after i.m. and s.c. administration of Humegon and Normegon were bioequivalent.      

Immunologic events in pigeon breeders'' disease

The immunologic and physiologic status of a group of symptomatic and asymptomatic pigeon breeders was studied in an attempt to define the immunologic events occurring in pigeon breeders' disease. Antibody activity to antigen(s) present in pigeon dropping extract (PDE) and pigeon serum (PS) was detected in the serum of both symptomatic and asymptomatic breeders. Antibody activity, however, tended to be greater in the symptomatic pigeon breeders. When subjects were challenged with PS via aerosol, serum complement activity became depressed only in asymptomatic patients. Cellular hypersensitivity to antigens present in PDE was detected in vitro in peripheral lymphocyte populations of 4 of 5 symptomatic breeders and in none of the asymptomatic breeders; cellular hypersensitivity to antigens in PS was not demonstrated in any of the individuals tested. These findings indicate that cell-mediated hypersensitivity, as well as humoral immunologic processes, may be involved in the pathogenesis of the hypersensitivity pneumonitis found in pigeon breeders.