Vascular endothelial growth factor receptor signaling is required for cardiac valve formation in zebrafish.

Vascular endothelial growth factor-receptors (VEGF-Rs) are pivotal regulators of vascular development, but a specific role for these receptors in the formation of heart valves has not been identified. We took advantage of small molecule inhibitors of VEGF-R signaling and showed that blocking VEGF-R signaling with receptor selective tyrosine kinase inhibitors, PTK 787 and AAC 787, from 17-21 hr post-fertilization (hpf) in zebrafish embryos resulted in a functional and structural defect in cardiac valve development. Regurgitation of blood between the two chambers of the heart, as well as a loss of cell-restricted expression of the valve differentiation markers notch 1b and bone morphogenetic protein-4 (bmp-4), was readily apparent in treated embryos. In addition, microangiography revealed a loss of a definitive atrioventricular constriction in treated embryos. Taken together, these data demonstrate a novel function for VEGF-Rs in the endocardial endothelium of the developing cardiac valve.     

An Association Between a Microsatellite Polymorphism at the DRD5 Gene and the Liability to Substance Abuse: Pilot Study

We have conducted a population-based association study of substance abuse and a microsatellite at the dopamine D5 receptor locus (DRD5) in a sample of European–American males and females with substance dependence (SA) or without any psychiatric disorder. Overrepresentation of the most frequent allele (148 bp) was found in males in the SA group (OR = 2.2, P= .02); this finding was reproduced in females (OR = 5.4, p< .001). The difference in the frequencies of this allele between SA males and SA females was statistically significant. The genotype coded in accordance with the dose of this allele correlated with substance abuse liability in males and females (stronger in females) and with novelty seeking in females. There was no evidence of correlation between the genotypes of spouses that could be induced by assortative mating for the liability to substance abuse. The data suggest that the DRD5 locus is involved in the variation and sex dimorphism of substance abuse liability.CEDAR is a consortium between St. Francis Medical Center and the University of Pittsburgh.     

A screening study of antidepressant treatment rates and mood symptoms in pregnancy

Summary Study design: As part of a large screening study of perinatal depression, pregnant women were screened for demographic, depression and treatment variables in obstetrics clinics. Women taking antidepressant medication prior to conception were included in the sample as the study aimed to document rates of antidepressant medication use, and relationship to depressive symptomatology.Results: Among women who reported using antidepressant medications within 2 years prior to screening (n = 390, or 11% of all women), 22% reported current use of these medications. Women who reported using antidepressant medications (52%) and those who discontinued them (49%) evidenced elevated depressive symptoms during pregnancy.Conclusions: Both women who discontinue and some who continue antidepressants during pregnancy demonstrate depressive symptoms, suggesting sub-optimal management of both groups. Future studies should carefully assess the adequacy of treatments prescribed as well as the monitoring and adherence of recommended treatments. Full symptom remission should be the goal for antenatal and postnatal depression in order to minimize risk to mother and baby.     

Transdermal progesterone and its effect on vasomotor symptoms,blood lipid levels,bone metabolic markers,moods, and quality of life for postmenopausal women

OBJECTIVE: To determine whether transdermal progesterone cream has any effect on vasomotor symptoms, mood, sexual response, cardiovascular lipid levels, or bone mineral metabolic markers. DESIGN: A parallel, double-blind, randomized, placebo-controlled trial comparing the effect of a transdermal cream containing a progesterone (32 mg daily) with a placebo cream. Eighty postmenopausal women in the Menopause Centre at the Royal Hospital for Women, Sydney, were randomly allocated to receive either the progesterone cream or the placebo. They were evaluated using the Greene Climacteric Scale and the Menopause Quality of Life Questionnaire, as well as blood analysis for lipids and bone markers over a period of 12 weeks. Women were prescribed a cream containing either progesterone at 32 mg daily or a placebo cream for a period of 12 weeks. RESULTS: There was no detectable change in vasomotor symptoms, mood characteristics, or sexual feelings, nor was there any change in blood lipid levels or in bone metabolic markers, despite a slight elevation of blood progesterone levels. CONCLUSION: The use of the transdermal route to administer progesterone at 32 mg daily does not seem to allow sufficient hormone to enter the body to achieve a biological effect on lipid levels, bone mineral metabolic markers, vasomotor symptoms, or moods.     

Effects of stimulant medications on the EEG of children with Attention-Deficit/Hyperactivity Disorder Predominantly Inattentive type.

Stimulant medications are the most commonly-used treatments for Attention-Deficit/Hyperactivity Disorder (ADHD) in North America and Australia, although it is still not entirely known how these medications work. This study investigated the effects of stimulant medications on the EEG of children with the Inattentive type of ADHD. An initial EEG was recorded during an eyes-closed resting condition and Fourier transformed to provide absolute and relative power estimates for the delta, theta, alpha and beta bands. Theta/alpha and theta/beta ratios were also calculated. Subjects were placed on a 6-month trial of a stimulant and a second EEG was recorded at the end of the trial. Subjects were included in this study only if they showed a good clinical response during the trial. The unmedicated ADHD group had significantly greater absolute and relative theta, less relative alpha, and higher theta/alpha and theta/beta ratios than the control group. The stimulant medications resulted in a normalisation of the EEG, with changes in the theta, alpha and beta bands being most evident. These results suggest that stimulants act to increase cortical arousal in children with ADHD, normalising their EEG.     

Biometry and structure of the left internal thoracic and radial coronary arteries

In an attempt to elucidate the causes of occlusion of radial arteries for coronary artery bypass grafts, we studied the biometry and histology of the coronary, radial and left internal thoracic arteries of 20 anatomical subjects (13 males and 7 females). These specimens were calibrated to the various bypass graft sites using coronary calibrators, and were then submitted to histological examination to determine the structure of the vessel wall. Our preliminary results show no correlation between the internal calibres of these various arteries. Like the coronary arteries and their branches, the radial artery is a muscular artery. In contrast, the left internal thoracic artery like the aorta, is an elastic artery.     

Exogenous choline augments transmission at an identified cholinergic synapse in terrestrial mollusk Limax maximus

1. A variety of pharmacological tests indicate that the neuromuscular junction between the salivary burster neuron (SB) and the salivary duct muscle (SD) in the terrestrial mollusk Limax maximus is cholinergic. These include the effects of curare, atropine, and hexamethonium. 2. Exogenously applied choline can act both presynaptically and postsynaptically at the synapse between the SB and SD. a) When the SB-SD synapse is bathed in 30 microM choline, there is no measurable direct postsynaptic effect at the SB-SD synapse. After several hours of choline incubation, however, an increase is observed in the size of SB-elicited junction potentials recorded from the SD. b) When the synapse is bathed in 300 microM choline, a short-term decrease is seen in the amplitudes of junction potentials (JPs) recorded from the SD. This effect is interpreted as competition between choline and acetylcholine (ACh) for postsynaptic receptor sites on the SD, since the response of the denervated SD to ACh is diminished in the presence of 300 microM choline. c) After several hours incubation in 300 microM choline, the amplitudes of JPs elicited by the SB on the SD increase. 3. The long-term effect of exogenous choline is blocked by the choline-uptake inhibitor, hemicholinium 3. 4. We conclude that exogenous choline is taken up by the presynaptic terminals of the SB and converted to ACh. Transmitter output rises with growing transmitter stores, producing an increase in the size of SB-elicited JPs recorded from the SD.     

Immune and autoimmune aspects of diabetes mellitus

The immune and autoimmune aspects of diabetes mellitus are reviewed. Emphasis is given to the clinical association of diabetes with other autoimmune disease; the increased incidence of organ-specific autoimmunity in diabetic patients; the occurrence of humoral and cell-mediated antipancreas (islet) autoimmunity in diabetes; the association of HLA with juvenile-onset, insulin-dependent diabetes mellitus and with certain specific subpopulations of diabetic patients; the possible role of viruses in the etiology of diabetes; and the occurrence of alterations in humoral and cell-mediated immunity, granulocyte function, and the host defense against infectious agents in human diabetics and in animals with experimental diabetes.