Calcitonin gene-related peptide: functional role in cerebrovascular regulation.

Distribution studies disclosed that all major cerebral arteries and cortical arterioles of the cat were invested with fine varicose nerve fibers that contained calcitonin gene-related peptide (CGRP)-like immunoreactivity; the trigeminal ganglia likewise contained CGRP immunoreactivity. Sequential immunostaining with antibodies to CGRP and to substance P (SP) revealed identical distributions of these two peptides in trigeminal ganglia and cerebrovascular nerve fibers, suggesting that CGRP and SP are colocalized in these nerves. CGRP completely disappeared from ipsilateral blood vessels after unilateral section of the trigeminal nerve. Exogenous CGRP was a potent relaxant of feline middle cerebral arteries in vitro (maximum relaxation, 10.5 +/- 1.5 mN; concentration eliciting half-maximal response, 9.6 +/- 1.3 nM). Perivascular microapplication of CGRP to individual cortical arterioles of chloralose-anesthetized cats provoked dose-dependent dilatations (maximum increase in diameter, 38 +/- 5%; concentration eliciting half-maximal response, approximately equal to 3 nM). CGRP was significantly more potent than SP as a cerebrovascular dilator, both in vitro and in situ. Chronic division of the ipsilateral trigeminal nerve in cats did not modify the magnitude of arteriolar responses to perivascular microapplication of either vasoconstrictor or vasodilator agents, but the duration of vasoconstrictor responses to norepinephrine (0.1 mM) or alkaline solutions (pH 7.6) was significantly increased. The cerebrovascular trigeminal neuronal system, in which CGRP is the most potent vasoactive constituent, may participate in a reflex or local response to excessive cerebral vasoconstriction that restores normal vascular diameter.     

AMPK在妊娠期糖尿病发病机制中的作用

腺苷酸活化蛋白激酶是一种重要的蛋白激酶,主要作用是协调代谢和能量平衡.腺苷酸活化蛋白激酶被激活后,在增加骨骼肌对葡萄糖摄取、增强胰岛素敏感性、增加脂肪酸氧化以及调节基因转录等方面发挥重要作用.已经证实脂联素有调节糖脂代谢的作用,但其作用机制尚不十分清楚,很可能是通过腺苷酸活化蛋白激酶介导,对脂联素信号转导通路的研究将成为进一步理解脂联素作用的关键所在.而脂联素又是妊娠期糖尿病的预测因子,所以腺苷酸活化蛋白激酶逐渐成为对妊娠期糖尿病研究中的焦点.     

Specific statistical considerations relevantto the design and analysis of gingivitis trials demonstrating

Simulation studies were conducted to address specific statistical issues which arise in the design and analysis of gingivitis studies whose principal aim is the demonstration of superiority or equivalence of one product to another. The effects of measurement scale, using differences or ratios of group means, particular statistical test produces and specific rules demonstrating superiority or equivalence were investigated. An alternative concept to equivalence—denoted “least as good”—was also defined and evaluated. For a wide class of possible distributions of gingivitis scores, characterized by specific gamma distributions, the student-t test applied to means of subject GI gingivitis scores proved to be the most powerful of the test produces considered, having statistical properties quite similar to the randomization or permutation test procedure. Transformations of subject GI mean gingivitis scores did not produce an advantage in demonstrating either superiority or equivalence, and in some cases made it more difficult. Little difference was observed in test results when using the difference in group means as compared with using the ratio of group means for demonstrating either equivalence or superiority. The clinically significant rule produced the lowest false-positive rates for products slightly better than the active control, and similar false-positive and -negative rates as the statistically significant rule for products clearly superior to the active control. Demonstration of product equivalence will require more subjects per group than demonstrating product superiority, the size of this difference being a function of the definition of superiority that is accepted. Showing that the 90% confidence interval for 100*R is completely contained within the [90%, 110%] interval is the preferred method of demonstrating equivalence today, although much more research needs to be done to improve methods for demonstrating product equivalence. The “least as good” alternative to “equivalence” makes it easier to demonstrate “equivalence” for products slightly better than the active control product, but both experience great difficulty in demonstrating equivalence for lest products not quite as good as the active control.     

臂丛神经根性损伤膈神经移位术对青壮年患者早期呼吸功能的影响

目的研究臂丛神经损伤膈神经移位术对青壮年患者早期呼吸功能的影响.方法对16例接受膈神经移位治疗的患者,在术前、术后（10 d）进行肺功能指标的比较,同时定期进行门诊随访,观察呼吸系统自觉症状程度.结果13例术后出现了不同程度的供氧不足症状,16例全部出现一侧膈肌抬高,术后第10天肺活量（VC）、肺活量预计值百分数（VC%）分别比术前减少37.98%和26.88%,两者差异有统计学意义（tvc=11.532、tvc%=0,P＜0.01）.其它项目如残气量（RV）较术前轻度下降,肺总量（TLC）下降值达到术前肺总量的36.49%,残气量/肺总量比值（RV/TLC%）较术前上升了4.75%,上述各指标的差值均有统计学意义.1 s用力呼气量/用力肺活量比值（FEV1/FVC）和术前比基本无改变,但其差值有统计学意义.膈神经移位右侧（10例）与左侧（6例）术前、术后肺活量比较差异有统计学意义.术后随访8个月～2年,所有患者均无明显呼吸困难和胸闷等症状.结论膈神经移位术后对青壮年患者肺容量有较大的丧失,肺通气功能减弱和小气道阻力增加,但其丧失程度在机体自身代偿耐受范围内,不会导致急剧发生的严重呼吸功能障碍.建议对右侧臂丛神经根性损伤的患者,术前进行严格的肺、心功能检查,避免发生较为严重的并发症.     

Cerebrovascular responses to capsaicin in vitro and in situ.

1. The cerebrovascular effects of capsaicin have been examined in vitro, in feline isolated cerebral arteries (circular segments, 2-3 mm long, 300-400 microns extended diameter) and, in situ, in pial arterioles (diameter 40-200 microns) on the cortical surface of chloralose-anaesthetized cats. 2. In isolated middle cerebral arteries, low concentrations of capsaicin (10(-14)-10(-10) M) effected a concentration-dependent relaxation of vessels precontracted with prostaglandin F2 alpha. This relaxant response was markedly attenuated by repeated administration of capsaicin but was minimally affected by the presence of atropine, propranolol, cimetidine or spantide in the tissue bath. 3. In isolated middle cerebral arteries, higher concentrations of capsaicin effected a marked concentration-dependent contraction. This contraction was not modified by 10(-6) M phentolamine or 10(-6) M ketanserin. A markedly reduced contraction by capsaicin was found upon the removal of calcium ions from the buffer solution. Also the calcium entry blocker nimodipine reversed the capsaicin-induced contraction. 4. Subarachnoid perivascular microapplication of capsaicin around individual pial arterioles in situ elicited a biphasic response (an immediate vasoconstriction followed by a sustained vasodilatation). The maximum vasoconstriction was a 60 +/- 6% reduction in diameter from base line and the maximum vasodilatation a 38 +/- 7% increase in diameter. Vasodilatation occurred at lower concentrations of capsaicin (EC50, approximately 5 x 10(-8) M) than those required for vasoconstriction (EC50 3 x 10(-7) M). 5. Trigeminal ganglionectomy 10-16 days before the microapplication abolished the in situ vasodilator effects of capsaicin (10(-6) M) applied perivascularly, but was without effect on the vasoconstrictor actions of this agent.(ABSTRACT TRUNCATED AT 250 WORDS)     

Periodontal disease in adolescents: some clinical and microbiologic correlates of attachment loss

The influence of several clinical and microbiological variables on the site-specific risk of attachment loss was studied in Navajo Indian adolescents aged 14-19. Diagnoses were made at mesio-buccal sites of the four first permanent molars. Case-control analytical methods were used, with A. actinomycetemcomitans, B. gingivalis, and B. intermedius considered the "risk" variables, and with calculus, gingival bleeding, age, and gender treated as possible confounders. The presence of B. intermedius significantly increased the likelihood that attachment loss would be diagnosed at a site (odds ratio = 2.86). However, this association was confounded by calculus and gingival bleeding; when either or both were present, the effect of B. intermedius was markedly weaker. Step-wise multiple logistic regression analyses showed that, of the variables considered, the combination of calculus, gingival bleeding, and B. intermedius gave the most parsimonious explanation of the presence of attachment loss. The chance that attachment loss would be diagnosed was increased five times when calculus was present, 16.5 times in the presence of both calculus and gingival bleeding, and 37 times when these variables plus B. intermedius were observed at a particular site.     

Statistical vs Clinical Significance in Product Testing: Can They Be Designed to Satisfy Equivalence?

Statistical issues associated with demonstrating significance between treatment groups (efficacy or superiority) and nonsignificance (equivalence) are presented and discussed. Methodologies for demonstrating efficacy of a product are proposed and contrasted, incorporating clinical and statistical criteria, with emphasis on situations in which placebo groups are precluded from the study design. Distinctions are drawn between study designs for demonstrating superiority and those for equivalence, including the determination of sample sizes needed for the different approaches. The "at least as good as" criterion is proposed as a reasonable alternative to that of equivalence in active control equivalence studies for demonstrating that dental product modifications or new products are efficacious.