Does the beneficial effect of HRT on endothelial function depend on lipid changes

OBJECTIVES: To determine whether improvement in endothelial function of the brachial artery observed in women treated with hormone replacement therapy (HRT) may be explained by changes in lipid profile or blood pressure, information was used obtained in a single-centre, randomised, double blind, placebo-controlled trial. METHODS: Hundred-and-five healthy postmenopausal women, aged 50-65 years, were treated with 0.625 mg conjugated equine estrogens (CEE) combined with 2.5 mg medroxyprogesterone acetate (MPA) (CEE+MPA), 2.5 mg tibolone or placebo for 3 months. At baseline and after 3 months, endothelial function was assessed using flow-mediated dilatation (FMD) and nitro glycerine-mediated dilatation (NMD). Furthermore, lipids were measured. Multivariate linear regression analysis was applied to address the research question. RESULTS: Treatment with CEE+MPA resulted in an improvement in FMD of 2.0% (95% CI: -0.1; 4.1). CEE/MPA reduced total cholesterol with 13% (95% CI: -18%; -7%), LDL-cholesterol with 23% (95% CI: -30%; -15%) and lipoprotein(a) (Lp(a)) with 14% (95% CI: -26%; -2%). The magnitude of the relation of CEE/MPA with endothelial function was attenuated to from 2.0 to 1.6% when change in Lp(a) was taken into account. Adjustments for other lipids or blood pressure did not attenuate the association. CONCLUSIONS: The improvement in endothelial function in postmenopausal women treated with CEE+MPA appears to be partially mediated by change in Lp(a), and apparently not by changes in other lipids.     

NMDA receptors trigger neurosecretion of 5-HT within dorsal raphé nucleus of the rat in the absence of action potential firing

Activity and calcium-dependent release of neurotransmitters from the somatodendritic compartment is an important signalling mechanism between neurones throughout the brain. NMDA receptors and vesicles filled with neurotransmitters occur in close proximity in many brain areas. It is unknown whether calcium influx through these receptors can trigger the release of somatodendritic vesicles directly, or whether postsynaptic action potential firing is necessary for release of these vesicles. Here we addressed this question by studying local release of serotonin (5-HT) from dorsal raphé nucleus (DRN) neurones. We performed capacitance measurements to monitor the secretion of vesicles in giant soma patches, in response to short depolarizations and action potential waveforms. Amperometric measurements confirmed that secreted vesicles contained 5-HT. Surprisingly, two-photon imaging of DRN neurones in slices revealed that dendritic calcium concentration changes in response to somatic firing were restricted to proximal dendritic areas. This implied that alternative calcium entry pathways may dominate the induction of vesicle secretion from distal dendrites. In line with this, transient NMDA receptor activation, in the absence of action potential firing, was sufficient to induce capacitance changes. By monitoring GABAergic transmission onto DRN 5-HT neurones in slices, we show that endogenous NMDA receptor activation, in the absence of postsynaptic firing, induced release of 5-HT, which in turn increased the frequency of GABAergic inputs through activation of 5-HT₂ receptors. We propose here that calcium influx through NMDA receptors can directly induce postsynaptic 5-HT release from DRN neurones, which in turn may facilitate GABAergic input onto these cells.     

Molecular epidemiology of hepatitis B virus in Afro-Venezuelan populations

Summary.  Hepatitis B virus (HBV) infection among Venezuelan populations of African origin was analyzed. These populations exhibited lower HBV prevalence than the one found in the African continent. Sequence analysis of 6 isolates showed that 3 belonged to genotype F, while the 3 others were HBV genotype A. HBV genotype A was more common in the Afro-Venezuelan groups than in the general Venezuelan population. This might reflect the introduction of genotype A during the slavery period. The absence of the African genotype E among these isolates supports the hypothesis of a recent origin for this HBV genotype. HBV genotype F has already been introduced to these relatively isolated communities. Received February 18, 2002; accepted March 8, 2002 Published online July 22, 2002     

Controlling the statistics of action: obstacle avoidance

Task optimization in the presence of signal-dependent noise (TOPS) has been proposed as a general framework for planning goal-directed movements. Within this framework, the motor command is assumed to be corrupted by signal-dependent noise, which leads to a distribution of possible movements. A task can then be equated with optimizing some function of the statistics of this distribution. We found the optimal trajectory for obstacle avoidance by minimizing the mean-squared error at the end of the movement while keeping the probability of collision with the obstacle below a fixed limit. The optimal paths accurately predicted the empirical trajectories. This demonstrates that controlling the statistics of movements in the presence of signal-dependent noise may be a fundamental and unifying principle of goal-directed movements.     

Bleeding patterns in recent postmenopausal outpatients with uterine myomas: comparison between two regimens of HRT

Objectives: To evaluate and to compare the bleeding patterns obtained with two regimens of hormone replacement therapy given to early postmenopausal women with asymptomatic uterine leiomyomas. Methods: In this randomised prospective 1-year study 50 early postmenopausal women with one to four asymptomatic uterine leiomyomas were enrolled into two study-groups to take two regimens of hormone replacement therapy for 12 28-day cycles: (A) Tibolone, 2.5 mg/day; (B) conjugated equine estrogens (CEE), 0.625 mg/day plus medroxyprogesterone acetate (MPA), 5 mg/day. The bleeding patterns and the changes in uterine volume of the 47 outpatients who completed the study were evaluated and compared. Results: Amenorrhea incidence was higher in group A (75.0% of the cycles) than in group B (65.6% of the cycles), while irregular bleeding and irregular spotting incidences were higher in group B (29.7 and 4.7% of the cycles, respectively) compared to group A (22.6 and 2.4% of the cycles, respectively). The mean bleeding and spotting lengths were not statistically different between patients in group A and those in group B. Finally, at the end of the study period transvaginal ultrasonography showed no significant change in leiomyoma size. Conclusions: The results demonstrate that, in early postmenopausal patients with asymptomatic uterine leiomyomas, Tibolone treatment seems to be preferable compared to CEE–MPA continuous combined treatment in relation to the lesser occurrence of irregular bleeding. Furthermore, neither Tibolone nor CEE–MPA therapy, at the doses used here, promote fibroid growth.     

Association of fibroblastoid features with the invasivephenotype in human bronchial cancer cell lines

The acquisition of a metastatic phenotype by epithelial cells implicates a series of changes altering their differentiation, their overall behavior and morphology. In the present study, we have examined the relationships between the cellular morphology, E-cadherin expression, matrix metalloproteinases expression and in vitro invasive properties in two human bronchial immortalized cell lines. The (16HBE14o-) cell line which did not show any invasive abilities in the Boyden chamber assay displayed a typical epithelial morphology in monolayer, expressed high levels of E-cadherin and synthesized neither MMP-2 and MT1-MMP nor vimentin. In contrast, the BZR cell line which was highly invasive displayed a more elongated phenotype in monolayer, did not produce E-cadherin but expressed vimentin, MMP-2 and MT1-MMP. Our data therefore suggest that the metastatic progression of broncho-pulmonary cancer cells results in a cellular dedifferentiation and the gain of some mesenchymal attributes (loss of E-cadherin and expression of vimentin) associated with enhanced degradative properties (expression of metalloproteinases).© Rapid Science 1998     

Effect of timing of oocyte denudation and micro-injection on survival, fertilization and embryo quality after intracytoplasmic sperm injection

In human in-vitro fertilization (IVF), the oocytes are surrounded by cumulus and corona cells at the time of insemination so that their maturity cannot easily be evaluated. The best IVF results are obtained if the oocytes are inseminated 2-6 h after retrieval. In the intracytoplasmic sperm injection (ICSI) procedure, the oocytes are denuded by enzymatic and mechanical treatment in order to be able to perform the injection. As a consequence, the nuclear maturity of the oocytes can be evaluated and only those that have extruded the first polar body are injected. However, metaphase-II oocytes that have not yet reached cytoplasmic maturity cannot be recognized. The purpose of this study was to investigate the effect of different timing of cumulus- corona cell removal and injection on the outcome of ICSI. For this we allowed the oocytes to complete in-vitro cytoplasmic maturation in two different culture conditions: (i) surrounded by their cumulus and corona cells or (ii) totally denuded. We performed three different studies on sibling oocytes obtained after a standardized buserelin/human menopausal gonadotrophin (HMG) protocol. We investigated the effect of early (1-2 h after retrieval) and late (5-6 h after retrieval) oocyte denudation and injection on the survival and fertilization of the injected oocytes and on embryo cleavage after fertilization. We found no statistically significant differences between early and late injection, indicating that after a standardized buserelin/HMG protocol the metaphase-II oocytes do not need time for further cytoplasmic maturation. Furthermore, a different timing of cumulus-corona cell removal has no effect on the outcome of ICSI, suggesting that the surrounding cells are not necessary for survival, fertilization and cleavage after ICSI.      

Virtually full-length subtype F and F/D recombinant HIV-1 from Africa and South America

For reliable classification of HIV-1 strains appropriate reference sequences are needed. The HIV-1 genetic subtype F has a wide geographic spread, causing significant epidemics in South America, Africa, and some regions of Europe. Previously only two full-length sequences of each of the HIV-1 subtype F subclusters F1 and F2 have been described. To extend the knowledge of subtype F variation on a complete genome level, three new virtually full-length F1 sequences were cloned and sequenced, two from Africa and one from South America. Comparison of the new and previously described sequences showed that monophyletic clustering of the subcluster F1 of subtype F is consistent and highly supported in all genome regions. Two additional full-length strains were shown to be mosaics of subtypes F and D. These epidemiologically unrelated F/D sequences showed similar chimeric structure, suggesting that they may represent a previously undescribed circulating recombinant form (CRF). This was supported by partial sequences from three additional unlinked F/D recombinants. Genetic distances in the phylogenetic trees suggest that the recombination event leading to the putative CRF occurred relatively long ago, close to the divergence of the F1 and F2 subclusters. Furthermore, all five F/D recombinants are linked to the Democratic Republic of Congo, suggesting that the original recombination event took place in central Africa.