M3 muscarinic receptor-mediated enhancement of NMDA-evoked adenosine release in rat cortical slices in vitro

Acetylcholine plays an important role in cortical arousal. Adenosine is released during increased metabolism and has been suggested to be a sleep-promoting factor. To understand the interaction of acetylcholine and adenosine in regulating cortical excitability, we examined the effect of carbachol on NMDA-evoked adenosine release and identified the muscarinic receptor subtype that mediated this effect in adult rat cortical slices in vitro. Carbachol (to 300 microM) alone did not affect the basal release of adenosine. However, carbachol (100 microM) induced a 253% increase in NMDA (20 microM)-evoked adenosine release in the presence of Mg2+. In the absence of Mg2+, carbachol's potentiating effect was less (60% increase). The nonselective muscarinic antagonist atropine (1.5 microM) blocked the facilitatory effect of carbachol on NMDA-evoked adenosine release, and this was mimicked by the M3-selective antagonist 4-diphenylacetoxy-N-methylpiperidine (1 microM). Neither an M1-selective dose of pirenzepine (50 nM) nor the M2-selective antagonist methoctramine (1 microM) affected carbachol's action on NMDA-evoked adenosine release. Carbachol had no effect on adenosine release evoked by alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA). These results suggest that acetylcholine does not affect basal adenosine release but enhances NMDA receptor-mediated evoked adenosine release by acting at M3 receptors in the cortex. This interaction may have a role in regulating cortical neuronal excitability on a long-term basis.     

鼎桥公司TD-SCDMA系统测试和性能

TD—SCDMA是2005年通信行业特别关注的一个焦点，从TD—SCDMA的研发与产业化进展、技术试验、政府引导等各个方面，可以明显看出国家对TD—SCDMA的关注达到了一个新的高度。2005年也可以说是TD—SCDMA的专项测试年，为了进一步支持和检验TD—SCDMA的产业化进展，TD—SCDMA研发和产业化专项专家组为TD—SCDMA网络技术试验制定了总体方案。     

Reducing saturated fat intake is associated with increased levels of LDL receptors on mononuclear cells in healthy men and women

1. Previous studies in our laboratory have shown that the synthetic xanthine analogue denbufylline, a selective type 4 phosphodiesterase (PDE-4) inhibitor, is a potent activator of the hypothalamo-pituitary-adrenal (HPA) axis when given orally or intraperitoneally (i.p.) to adult male rats. This paper describes the results of experiments in which well established in vivo and in vitro methods were used to compare the effects of denbufylline on HPA function with those of two other selective PDE-4 inhibitors, rolipram and BRL 61063 (1,3-dicyclopropylmethyl-8-amino-xanthine). For comparison, parallel measurements of the immunoreactive- (ir-) luteinising hormone (LH) were made where appropriate. 2. When injected intraperitoneally, rolipram (40 and 200 micrograms kg-1, P < 0.005), denbufylline (0.07-0.6 microgram kg-1, P < 0.05) and BRL 61063 (30 micrograms kg-1, P < 0.005) each produced marked rises in the serum ir-corticosterone concentrations. However, lower doses of rolipram (1.6 and 8 micrograms kg-1) and BRL 61063 (0.25-6 micrograms kg-1) were without effect (P > 0.05). By contrast, intracerebroventricular (i.c.v.) injection of rolipram (8 ng-1 micrograms kg-1) or denbufylline (50 ng-1 microgram kg-1) failed to influence the serum ir-corticosterone concentration. BRL 61063 (8-120 ng kg-1, i.c.v.) was also ineffective in this regard although at a higher dose (1 microgram kg-1, i.c.v.) it produced a small but significant (P < 0.05) increase in ir-corticosterone release. Denbufylline also increased the serum ir-LH concentration when given peripherally (0.2-0.6 microgram kg-1, i.p., P < 0.05) or centrally (100 ng kg-1, i.c.v., P < 0.05) but rolipram (1.6-200 micrograms kg-1, i.p. or 8 ng-1 microgram kg-1, i.c.v.) and BRL 61063 (0.25-30 micrograms kg-1, i.p. or 1 ng-1 microgram kg-1, i.c.v.) did not (P > 0.05). 3. In vitro rolipram (10 microM, P < 0.01), denbufylline (1 mM, P < 0.001) and BRL 61063 (1 and 10 microM, P < 0.05) stimulated the release of corticotrophin releasing hormone (ir-CRH-41) but lower concentrations of the drugs were without effect as also was BRL 61063 at 100 microM (P > 0.05); the rank order of potency was thus BRL 61063 > rolipram > denbufylline. The adenylyl cyclase activator forskolin (100 microM, P < 0.01) also stimulated the release of ir-CRH-41, producing effects which were additive with those of rolipram and denbufylline but not with those of BRL 61063. The secretory responses to forskolin (100 microM) were accompanied by a highly significant increase in the cyclic AMP content of the hypothalamic tissue (P < 0.005). Rolipram (10 microM) also significantly (P < 0.05) elevated the hypothalamic cyclic AMP but denbufylline (10 mM) and BRL 61063 (10 microM) did not. However, all three PDE-inhibitors potentiated the rise in cyclic AMP induced by forskolin (P < 0.05). None of the drugs tested, alone or in combination, modified the release of arginine vasopressin (ir-AVP) from the hypothalamus. 4. Rolipram (100 microM), denbufylline (100 microM) and BRL 61063 (100 microM) stimulated the release of corticotrophin (ir-ACTH) from pituitary tissue in vitro (P < 0.05) but in lower concentrations they were without significant effect. In addition, rolipram (10 microM, P < 0.05), denbufylline (0.1 microM, P < 0.05) and BRL 61063 (10 microM, P < 0.05) potentiated the significant (P < 0.05) rises in ir-ACTH secretion induced by forskolin (100 microM). Forskolin (100 microM) also produced a highly significant increase (P < 0.01) in the tissue cyclic AMP content which was further potentiated by rolipram (10 microM), denbufylline (10 microM) and BRL 61063 (10 microM) which, alone did not affect the cyclic AMP content of the tissue. 5. Since both denbufylline and BRL 61063 possess significant adenosine A1 receptor blocking activity, further studies examined the potential influence of these receptors on the secretion in vitro of CRH-41, AVP and ACTH. The release of ir-CRH-41 was increased significantly by adenosine deaminase (ADA, 5microml-1, P<0.05) and the A1-receptor antagonist, 1,3-dicyclopropyl-8-cyclopentylxanthine (DPCPX, 0.1-10nM, P<0.05). The responses to ADA were abolished by the A1 receptor agonist N6-cyclo-hexyladenosine (CHA, 100nM, P<0.05) which alone had no significant effect on ir-CRH-41 release. ADA (0.1-10microml-1) and DPCPX (1nM) had weak stimulant and inhibitory effects, respectively, on the release of ir-ACTH from the pituitary gland while CHA (0.1-10nM) was without effect. Ligand binding studies with [3H]-DPCPX as a probe demonstrated the presence of specific high affinity A1 binding sites in the hypothalamus (Kd=0.7nM; Bmax=367+/-32fmolmg-1 protein) and in the hippocampus (Kd=1nM; Bmax=1165 +/-145fmolmg-1 protein). In both tissues binding of the ligand was displaced by CHA (IC50=1nM (hypothalamus) and 2nM (hippocampus)), BRL 61063 (IC50=80nM (hypothalamus) and 100nM (hippocampus)) and denbufylline (IC50=5microM (hypothalamus) and 9microM(hippocampus)) but not by rolipram. 6.The results suggest that rolipram, denblufylline and BRL 61063 stimulate the HPA axis in the rat, acting at the levels of both the hypothalamus and the pituitary gland. Their actions may be explained, at least in part, by inhibition of PDE-4 but additional actions including blockade of hypothalamic adenosine A1 receptors by denbufylline and BRL 61063 cannot be excluded.     

Estrogen-androgen for hormone replacement. A review

OBJECTIVE: To critically examine the role of androgens as part of postmenopausal hormone replacement therapy. STUDY DESIGN: Examination of original reports and reviews obtained by electronic database searches and supplemented by manual search of bibliographies. RESULTS: As compared to estrogens alone, estrogen-androgen therapy may better protect against osteoporosis and increase libido, energy levels and general sense of well-being. However, estrogen-androgen replacement also reduces the beneficial increases in high-density lipoprotein induced by estrogens alone, although this effect may be offset at least partially by decreases in atherogenic triglycerides. The long-term net effect of estrogen-androgen replacement on cardiovascular disease remains unknown. CONCLUSION: Although the literature includes relatively few clinical trials or well-controlled studies and is further limited by the subjective nature of outcomes, such as sexual and psychological function, the available data suggest that for many postmenopausal women, estrogen-androgen replacement may provide benefits beyond those provided by estrogen-only replacement therapy.     

Accuracy of single-photon emission computed tomography myocardial perfusion imaging in patients with stents in native coronary arteries

Strategies to noninvasively evaluate patients after coronary stenting have not been evaluated. To determine the accuracy of single-photon emission computed tomography (SPECT) myocardial perfusion imaging in patients after coronary stenting, 209 patients who had undergone stenting followed by late stress SPECT myocardial perfusion imaging were evaluated. Quantitative coronary angiography was performed in 33 patients following SPECT imaging. SPECT restenosis was defined as a reversible or fixed defect within the stented vascular territory. Angiographic restenosis was examined using 2 definitions: total area narrowing > or =50% or > or =70% of the stent site or stented artery. The SPECT and angiographic findings were concordant in 22 of 33 stented vascular territories using the 50% definition of restenosis and in 29 of 33 stented territories using the 70% definition. Use of the 70% definition of restenosis resulted in improved accuracy of SPECT to detect a significant stenosis in the stented artery. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of SPECT were 95%, 73%, 88%, 89%, and 88% respectively. In patients with positive SPECT scans, the most significant stenosis in the stented artery was outside the stent site in 50% of cases. SPECT imaging appears to be accurate to predict significant stenosis in the stented artery, although the most severe stenosis is frequently distant from the stent site.     

White coat effect detected using self-monitoring of blood pressure at home: comparison with ambulatory blood pressure

The objective of the study was to investigate whether home blood pressure (HBP) is a reliable alternative to ambulatory blood pressure (ABP) for the detection of the white coat effect (WCE). Hypertensive patients were randomized to measure HBP for 2 weeks or ABP for 24 h. The alternative measurement was then performed. Clinic blood pressure (CBP) was measured in the beginning and end of the study. Subjects with a difference of > or = 20 mm Hg systolic or > or = 10 mm Hg diastolic BP between CBP and awake ABP or CBP and HBP, were classified as clinic reactors. A total of 189 patients completed the study (79 on stable antihypertensive treatment). There was no difference in the magnitude of WCE assessed using the ABP or the HBP method (mean discrepancy, systolic BP: -1.5 +/- 11.7 mm Hg, 95% CI -3.2, 0.2; diastolic BP: 0.9 +/- 7.0, 95% CI -0.1, 1.9). A strong association existed between WCE calculated using the HBP or the ABP method (r = 0.64/0.59 systolic/diastolic, P < .001). The proportion of patients classified as clinic reactors was identical using the HBP or the ABP method (25.9%). Agreement between methods in the classification of clinic reactors was found in 147 patients (78%). The sensitivity and specificity of the HBP method to classify correctly clinic reactors (ABP method used as the standard) were 57% and 85%, respectively, whereas its positive and negative predictive value were 57% and 85%. These results indicate that HBP is not appropriate as an alternative to ABP diagnostic testing in the detection of WCE. Nevertheless, HBP appears useful as a screening test for the detection of this phenomenon.     

Apneic oxygenation associated with patient-controlled analgesia

A confusing number of measures are used to describe the effect sizes from clinical trials or systematic reviews. Absolute measures (absolute risk reduction, number needed to treat) and relative measures (relative risk reduction, relative risk or odds ratio) may give not just different numerical answers but convey different messages. This paper describes the role and meaning of the different measures, advises on their interpretation, and highlights the importance of taking into account the initial risk when assessing effect sizes from published studies.     

HIV-1 seroconversion in a prospective study of female sex workers in northern Thailand: continued high incidence among brothel-based women

OBJECTIVES: To determine the incidence of HIV-1 infection, temporal trends in incidence, and risk factors for seroconversion in a cohort of female commercial sex workers (CSW) in upper northern Thailand, the region of Thailand with the highest rates of HIV-1 infection. METHODS: CSW were enrolled from 1991 through 1994 and evaluated prospectively with interviews, physical examination, testing for sexually transmitted diseases (STD), and serologic testing for HIV-1 infection. RESULTS: The incidence of HIV-1 seroconversion in the first year of follow-up was 20.3 per 100 person-years among 126 brothel-based CSW and 0.7 per 100 person-years among 159 other CSW who worked in other venues such as bars or massage parlors. Incidence remained elevated among brothel-based CSW who were enrolled later in the study compared with those who enrolled earlier. Through 1996, 30 women seroconverted. In a multivariable proportional hazards model, seroconversion was significantly associated (P < 0.05) with brothel-based sex work (adjusted risk ratio, 7.3) and Chlamydia trachomatis cervical infection (adjusted risk ratio, 3.3). CONCLUSION: Despite national HIV control efforts and declining rates of infection among young men in Thailand, brothel-based CSW may continue to be at high risk for HIV-1 infection. Additional efforts are needed to provide alternative economic choices for young women, to ensure universal condom use during commercial sex, and to develop new prevention technologies.     

Implications of a diagnosis of anorexia nervosa in a ballet school

A growth curve is presented, that using the Tanner and Whitehouse's 50th centile, plots the height versus weight, both for males and females. The age is gives as parameter on the curves. In this way, weight, height and age are merged on a single chart for every sex. After exemplifying its advantages, the simpler relief of deviation from the values of the height-weight medians on the various ages, because the values of weight refer to the real height (and back), not to the age. With the same rule, curves relating to 10th and 90th centiles are processed by Tanner and Whitehouse's values. Collating between them, curves allow some morphological relief. Moreover, for both referred to the 50th centile of Tanner and Whitehouse curves (for the male sex and the female one), is presented a simple mathematical expression of interpolation, which shows and excellent representation of the measured dates. This expression is composed of a third-degree polynomial (cubic), which is fitted to the dates by the method of least square. The result of the correlation height-weight allows both to synthesize the dates in a sole expression and a simpler relief of discordance in the growth.