Contribution of raloxifene and calcium and vitamin D3 supplementation to the increase of the degree of mineralization of bone in postmenopausal women

Raloxifene has been shown to increase bone mineral density and reduce the risk of vertebral fracture in postmenopausal women with osteoporosis. In this study, we report the results of the first prospective longitudinal study to evaluate the mean degree of mineralization of bone (MDMB) in a group of patients enrolled in the Multiple Outcomes of Raloxifene Evaluation trial. Patients were randomly assigned to one of three treatment groups: placebo (n = 24), raloxifene 60 mg/d (RLX60; n = 22), or raloxifene 120 mg/d (RLX120; n = 18). All patients received daily calcium (500 mg) and vitamin D(3) (400-600 IU) supplementation for the duration of the study. Iliac crest biopsies were taken at baseline and after 2 yr of treatment. Quantitative microradiography was used to analyze the biopsy specimens and revealed a statistically significant (P < 0.05) mean percentage increase in total MDMB of 7.0, 5.3, and 5% for RLX60-, RLX120-, and placebo-treated patients, respectively, compared with baseline. Raloxifene treatment was found to shift the distribution of total bone mineral to higher values of MDMB (RLX60, 29%; RLX120, 8%) with greater heterogeneity, compared with placebo. The profile of MDMB observed in biopsies after treatment with placebo and raloxifene, compared with baseline, closely resembles physiological premenopausal bone.     

Evidence for prolactin feedback actions on hypothalamic oxytocin, vasoactive intestinal peptide and dopamine secretion

Ovariectomized rats, when transplanted with 4 anterior pituitaries (APs) to the kidney capsule for 2-3 weeks, had elevated plasma prolactin (PRL) levels (3.8-fold) and showed decreased in situ AP weights (0.62-fold) and PRL concentrations (0.63-fold). The concentrations of dopamine (DA) and oxytocin (OT) in pituitary portal plasma of hyperprolactinemic rats were increased 1.7- and 1.9-fold, respectively. However, the levels of vasoactive intestinal peptide (VIP) in pituitary portal plasma of these rats were decreased 0.31-fold. The secretion of DA, dihydroxyphenylalanine (DOPA) and OT from fetal hypothalamic cells in primary culture was increased, whereas VIP secretion from these cells was reduced in a dose-dependent fashion following PRL treatment. These data are the first in vivo and in vitro demonstration of a stimulatory action of PRL on OT release and an inhibitory action of PRL on VIP release. Furthermore, these data suggest that a subtle imbalance between the secretion of the PRL-inhibiting factor (DA) and the PRL-releasing factors (VIP and OT) during elevated systemic levels of PRL is responsible for decreased lactotrophic function.     

Ethanol induces hyperprolactinemia by increasing prolactin release and lactotrope growth in female rats

BACKGROUND: Alcohol drinking is known to cause hyperprolactinemia in both humans and laboratory animals. The mechanism by which alcoholism causes hyperprolactinemia is not known. This study investigated whether increased pituitary production of prolactin, which leads to alcohol-induced hyperprolactinemia, results from an increase in cell number and/or cell production of prolactin in the pituitary. METHODS: The effects of ethanol on lactotropes were determined in vivo using female rats as an animal model and in vitro using primary cultures of mixed rat anterior pituitary cells and enriched lactotropes. In vivo experiments involved administration of ethanol for 2 and 4 weeks using a liquid diet containing 8.7% ethanol (v/v), which provides 37% of the calories in cyclic, ovariectomized, and estradiol-17beta-treated ovariectomized Fischer-344 rats. The control group was pair-fed an isocaloric diet minus the ethanol or fed a normal diet ad libitum. These animals were used to determine ethanol's effects on plasma prolactin levels, pituitary wet weights, pituitary total protein levels, and the number of mitotic lactotropes. In vitro studies determined ethanol's effects in the presence and absence of estradiol on prolactin release and lactotropic cell proliferation. Prolactin levels in plasma and media samples were measured using radioimmunoassay. Mitotic lactotropes were determined using bromodeoxyuridine incorporation assay. RESULTS: Ethanol treatment increased in a time-dependent manner the plasma levels of prolactin in cyclic, ovariectomized, and estradiol-treated ovariectomized rats. Ethanol treatment also increased pituitary wet weight and/or pituitary total protein levels and DNA synthesis in lactotropes. Determination of ethanol's action on lactotropic cell proliferation and hormone secretion in vitro using primary cultures of mixed pituitary cells revealed that ethanol stimulated both basal and estradiol-induced prolactin secretion and lactotropic cell proliferation. When ethanol's actions were studied in isolated lactotropes, ethanol alone or in combination with estradiol stimulated prolactin secretion but failed to increase lactotropic cell proliferation. CONCLUSIONS: These results suggest that ethanol causes hyperprolactinemia by elevating prolactin release from lactotropes and by increasing the number of lactotropes in the anterior pituitary gland. The mitotic action of ethanol requires cell-cell communication between lactotropes and other pituitary cells. Furthermore, ethanol's mode of action on prolactin release and lactotrope growth is similar to that observed for estradiol.     

Detection of HBsAg in newborns

Cord blood samples collected from 150 newborns were tested for HBsAg using micro ELISA technique. Only 8 (5.3 per cent) out of 150 samples were found to be positive for HBsAg in variable titres. It is important to identify these HBsAg positive newborns so that appropriate measures could be adopted at the earliest to prevent the complications of HBsAg carriage.     

Histological observations on the anterior olfactory nucleus in human

Aim: Localization of isolated clusters of anterior olfactory nucleus (AON) in a human olfactory bulb and tract. Materials and methods: This investigation was done on human olfactory bulbs and their tracts, collected from the freshly donated cadavers, before embalming, in the Department of Anatomy, IPGMER, Kolkata. H&E stained histological slides were prepared along the whole length of specimens and examined under a Leica DM 2000 microscope and with a Leica Quin image analyzer. Results: The anterior olfactory nucleus was detected in the form of a major cluster and in two smaller clusters of neurons. The major cluster was located at the caudal pole of the bulb and was composed of medium-sized triangular cells which had an average diameter of 13.92 ± 3.43 μm. Out of the two minor clusters, one was detected at the beginning and another at the middle of the olfactory tract. Here neurons were little larger in size and their diameter ranged approximately 15–17 μm. Olfactory striae also accommodated some neurons in a scattered manner. Conclusion: This observation will be helpful in exploration of the complex role of AON in the organization and function of the olfactory system and its clinical significance in human.     

The natural history of a genetic subtype of arrhythmogenic right ventricular cardiomyopathy caused by a p.S358L mutation in TMEM43

To determine the phenotype and natural history of a founder genetic subtype of autosomal dominant arrhythmogenic right ventricular cardiomyopathy (ARVC) caused by a p.S358L mutation in TMEM43. The age of onset of cardiac symptoms, clinical events and test abnormalities were studied in 412 subjects (258 affected and 154 unaffected), all of which occurred in affected males significantly earlier and more often than unaffected males. Affected males were hospitalized four times more often than affected females (p ≤ 0.0001) and died younger (p ≤ 0.001). The temporal sequence from symptoms onset to death was prolonged in affected females by 1–2 decades. The most prevalent electrocardiogram (ECG) manifestation was poor R wave progression (PRWP), with affected males twice as likely to develop PRWP as affected females (p ≤ 0.05). Left ventricular enlargement (LVE) occurred in 43% of affected subjects, with 11% fulfilling criteria for dilated cardiomyopathy. Ventricular ectopy on Holter monitor was common and occurred early: the most diagnostically useful clinical test. No symptom or test could rule out diagnosis. This ARVC subtype is a sex‐influenced lethal arrhythmogenic cardiomyopathy, with a unique ECG finding, LV dilatation, heart failure and early death, where molecular pre‐symptomatic diagnosis has the greatest clinical utility.