Reduction of proline transport in R3230AC mammary carcinomas by estrogens in vitro

The effects of estrogens on proline and leucine transport into enzymatically dissociated cells from the R3230AC mammary adenocarcinoma were studied. Estradiol-17β demonstrated a time- and dose-dependent reduction of proline transport; at 10^?6M, transport of proline was decreased by 50 percent. Kinetic analysis of these effects indicate that estradiol displayed characteristics of a non-competitive inhibitor, with a K_i of 1.79 μM. Other estrogens, and the anti-estrogen tamoxifen, gave somewhat higher estimated K_i values and could be ranked as inhibitors as follows: estradiol-17β > diethylstilbestrol > tamoxifen > estriol-estrone > estradiol-17α. No effects of these estrogens on leucine transport were observed, indicating their selectiveness for the A system. The synthetic glucocorticoid, dexamethasone, was comparable to diethylstilbestrol as an inhibitor of proline transport, but dexamethasone also decreased transport of leucine. Testosterone and progesterone were approximately comparable to estrone in their actions. It is proposed that these actions of estrogens represent one potential mechanism whereby pharmacological levels exert therapeutic benefit in the treatment of advanced breast cancer.     

L-type calcium channels: the low down

L-type calcium channels couple membrane depolarization in neurons to numerous processes including gene expression, synaptic efficacy, and cell survival. To establish the contribution of L-type calcium channels to various signaling cascades, investigators have relied on their unique pharmacological sensitivity to dihydropyridines. The traditional view of dihydropyridine-sensitive L-type calcium channels is that they are high-voltage-activating and have slow activation kinetics. These properties limit the involvement of L-type calcium channels to neuronal functions triggered by strong and sustained depolarizations. This review highlights literature, both long-standing and recent, that points to significant functional diversity among L-type calcium channels expressed in neurons and other excitable cells. Past literature contains several reports of low-voltage-activated neuronal L-type calcium channels that parallel the unique properties of recently cloned CaV1.3 L-type channels. The fast kinetics and low activation thresholds of CaV1.3 channels stand in stark contrast to criteria currently used to describe L-type calcium channels. A more accurate view of neuronal L-type calcium channels encompasses a broad range of activation thresholds and recognizes their potential contribution to signaling cascades triggered by subthreshold depolarizations.     

Children grow and horses race: is the adiposity rebound a critical period for later obesity?

Background  

The adiposity rebound is the second rise in body mass index that occurs between 3 and 7 years. An early age at adiposity rebound is known to be a risk factor for later obesity. The aim here is to clarify the connection between the age at rebound and the corresponding pattern of body mass index change, in centile terms, so as to better understand its ability to predict later fatness.     

Smoking cessation in pregnancy: a review of postpartum relapse prevention strategies

OBJECTIVE: Review and examine existing research, current strategies, and directions for future research on smoking cessation relapse and relapse prevention in pregnancy and postpartum. METHODS: A MEDLINE/PubMed search in 2002 and 2003 for articles containing the key words "smoking," "pregnancy," "cessation," and "cessation relapse prevention" and references of retrieved papers yielded a review of more than 500 articles. Only 14 of these addressed program-based strategies to increase cessation among pregnant women through relapse prevention programs. CONCLUSION: Although there is much information on the rationale and strategies for smoking cessation for pregnant women, fewer studies exist on how to prevent relapse. Maintaining and accelerating progress in cessation during pregnancy and postpartum requires more research that focuses on relapse prevention and cessation. Programs should incorporate stresses particular to postpartum women, should be part of routine health care, and should involve the woman's social support network, including her partner, to maximize effectiveness.     

Prospective brain imaging evaluation of children with sickle cell trait: initial observations

PURPOSE: To determine whether sickle cell trait (hemoglobin AS) is associated with abnormalities in the brain of asymptomatic children. MATERIALS AND METHODS: Magnetic resonance (MR) imaging and MR angiography were performed prospectively in 26 siblings (eight girls, 18 boys; mean age, 10.5 years) of patients with sickle cell disease. Two neuroradiologists, blinded as to whether a child had hemoglobin AS or AA, reviewed images obtained in siblings. With MR imaging, lacunae, loss of white matter volume, encephalomalacia, or leukoencephalopathy was identified. With MR angiography, arterial stenosis, occlusion, or tortuosity was identified. Images with definite or possible abnormalities were mixed with randomly selected images and were referred to a third neuroradiologist for a completely blinded review. In cases in which all neuroradiologists concurred, a score was assigned that indicated the sibling had an abnormality. MR angiographic findings were assigned a score for tortuosity with a new quantitative scale. RESULTS: Among 26 siblings screened, 21 children had sickle cell trait. Among these 21 children, two had mild abnormalities at MR imaging (sample prevalence rate, 10% [95% CI: 1%, 29%]), and four had arterial tortuosity (sample prevalence rate, 19% [95% CI: 5%, 42%]). When children with sickle cell trait were compared with 31 control subjects without the trait, arterial tortuosity was significantly more common in children with sickle cell trait (P =.014). Among children with sickle cell trait, percentage of hemoglobin S was significantly greater in children who had tortuosity than percentage of hemoglobin S in children who had normal blood vessels at MR angiography (P <.03). CONCLUSION: Findings suggest that greater percentage of hemoglobin S is associated with mild vasculopathy. This vasculopathy may explain some of the excess risk of stroke among African Americans.     

Hepatic and Splenic Hydatidosis Managed with Percutaneous Aspiration,Injection, and Reaspiration (PAIR) of the Hepatic Cyst and Laparoscopic Splenectomy

The treatment of hydatidosis traditionally consisted of surgery with a perioperative course of anthelmintic medications. However, percutaneous aspiration, injection, and reaspiration (PAIR) combined with oral albendazole has been recently shown to be as effective as surgery in the treatment of liver hydatidosis. We report a 20-year-old female immigrant from Western Europe who presented with discomfort in her upper abdomen. Computed tomography revealed a 5.7 × 7 × 5.9-cm cyst in segment 7 of the liver and a 17 × 15-cm cyst in the spleen in contiguity with the hilar vessels. Indirect hemaglutination test confirmed hydatidosis. A strategy with two different surgical approaches was designed to treat her condition: laparoscopic splenectomy and ultrasound-guided PAIR of the liver cyst. The patient was discharged on postoperative day 5, and at 18 months follow-up, she is free of symptoms.