Effects of vasoactive neuropeptides on human saphenous vein.

OBJECTIVE--To assess the role of neuropeptides in the control of vascular tone in the human saphenous vein the actions of substance P, vasoactive intestinal peptide, calcitonin gene related peptide, neuropeptide Y, and somatostatin on this blood vessel were examined. METHODS--In vitro organ bath techniques were used with preparations of saphenous veins obtained from 29 patients (aged 41-66) who were undergoing coronary bypass surgery. RESULTS--Substance P, vasoactive intestinal peptide, and calcitonin gene related peptide relaxed pre-constricted vessels in a dose dependent manner with a rapid onset of action, taking one to two minutes to reach a plateau at each dose. Substance P (10(-9) to 10(-6) mol/l) induced relaxation with a maximum response (mean (SEM)) 23.0 (6.6)% of the total relaxation induced by glyceryl trinitrate 1 microgram/ml and a 50% maximal effective concentration of 6.8 x 10(-9) mol/l. Vasoactive intestinal peptide (10(-10) to 10(-7) mol/l) produced a relaxation of 27.0 (5.1)% at 10(-7) mol/l. The maximum responses induced by substance P and vasoactive intestinal peptide were significantly reduced, to 3.7 (2.8)% and 4.7 (2.0)% respectively, after removal of the endothelium. Calcitonin gene related peptide (10(-10) to 10(-7) mol/l) elicited only 14.3 (2.6)% relaxation at 10(-7) mol/l, and this was not affected by removal of the endothelium. By contrast, neuropeptide Y and somatostatin exerted concentration dependent constriction on resting vessels. Neuropeptide Y (10(-10) to 10(-7) mol/l) caused prolonged contraction (roughly 20 minutes to reach a maximum plateau at each dose). At 10(-7) mol/l, the constriction amounted to 28.0 (12.0)% of the response to 90 mM KCl, in ring segments with or without endothelium. Somatostatin (10(-10) to 10(-6) mol/l) quickly caused contraction with a maximum response of 42.7 (15.0)% and a maximum response of 42.7 (15.0)% and a 50% maximal effective concentration of 6.7 x 10(-6) mol/l. The constriction was greatly increased when endothelium was removed, with a maximum response of 78.2 (16.8)% and a 50% maximal effective concentration of 4.3 x 10(-7) mol/l. CONCLUSIONS--Vasoactive peptides have diverse effects on the vascular tone these effects are endothelium dependent. The exact physiological role and implication for performance of bypass grafts require further investigation.     

Treatment of chronic experimentalStaphylococcus aureus osteomyelitis with LY146032 and vancomycin

LY146032 and vancomycin were compared as therapeutic agents in the treatment of chronicStaphylococcus aureus osteomyelitis in the rat. Quantitative cultures disclosed that one of 16, none of 16, and two of 17 tibiae were sterile from the control, LY146032, and vancomycin groups, respectively. From positive cultures, geometric mean staphylococcal CFU per gram of bone were as follows: control, 5.13±1.58; LY146032, 5.36±0.43 (p=0.57); and vancomycin, 4.33±1.73 (p=0.078). Mean gross pathology was decreased significantly in both treatment groups. LY146032 was no more effective than vancomycin in reducing bacterial counts.     

Derivatives of methyl vinyl sulfone. Distribution and elimination of methyl (2,2-diphenyl)-vinyl sulfone labelled with 14carbon in mice

The investigation of methyl (2,2-diphenyl)-vinyl sulfone (14C-MDVS) administered i.p. in mice shows that this product appears rapidly in the general circularoty system. The blood concentration of MDVS reaches a maximum 1 h after injection. Part of the MDVS is bound to the plasma proteins. Infrared spectrometry analysis of radioactive products eliminated by the urine confirms that the product is not split, but also reveals the presence of hydroxyl and carbonyl groups in the metabolic conversion products.     

应用AccuMap多焦视觉诱发电位客观视野检测法观察晶状体混浊对青光眼视野检测结果的影响

目的探讨AccuMap多焦视觉诱发电位客观视野检测法观察晶状体混浊对青光眼视野检测结果的影响及与Humphrey自动视野检测结果之间的相关性。方法观察和比较原发性青光眼伴有中等程度晶状体混浊患者白内障术前后AccuMap与Humphrey视野计检测结果。术前由同一位有经验的眼科医师观察并记录(采用LOCSⅢ标准)患者晶状体的混浊程度。结果符合入选标准并完成观察者共22例。(1)AccuMap视野检测平均振幅术前为(308.0±96.6)nV,术后为(382.6±146.7)nV,术前与术后平均振幅差异有统计学意义(P=0.01)。平均视野损害严重程度指数(accumapseverityindex,ASI)术前为90.0±54.8,术后为48.6±42.4,术后比术前ASI显著下降(P<0.001)。潜伏期术前后无明显变化,术前平均为(1207.5±67.7)ms,术后为(1191.2±61.9)ms(P=0.289)。(2)晶状体混浊程度与AccuMap振幅的变化AccuMap振幅的变化与晶状体混浊程度无明显相关性(Spearman秩相关分析,P=0.09)。(3)Humphrey视野计检测结果术前平均偏差(meandeviation,MD)为-12.2±7.8,术后为-9.6±8.8,术后与术前MD差异有统计学意义(P<0.001);而模式标准差(patternstandarddeviation,PSD)术前为6.5±3.2,术后为6.3±4.0,差异无统计学意义(P=0.748)。(4)ASI与MD比较术前、术后ASI分别与MD具有相关性(Pearson相关分析,术前P=0.013,术后P<0.001);且术后与术前ASI的变化与MD的变化也具有相关性(Pearson相关分析,P=0.017)。结论AccuMap视野检测法显示晶状体混浊影响青光眼患者的视野检测结果,其中振幅受影响更明显。与Humphrey视野检测结果比较,AccuMap检测的ASI与MD具有相关性。(中华眼科杂志,2006,42972-976)     

Fine particulate air pollution and hospital admission for cardiovascular and respiratory diseases

Context  Evidence on the health risks associated with short-term exposure to fine particles (particulate matter 2.5 µm in aerodynamic diameter [PM_2.5]) is limited. Results from the new national monitoring network for PM_2.5 make possible systematic research on health risks at national and regional scales. Objectives  To estimate risks of cardiovascular and respiratory hospital admissions associated with short-term exposure to PM_2.5 for Medicare enrollees and to explore heterogeneity of the variation of risks across regions. Design, Setting, and Participants  A national database comprising daily time-series data daily for 1999 through 2002 on hospital admission rates (constructed from the Medicare National Claims History Files) for cardiovascular and respiratory outcomes and injuries, ambient PM_2.5 levels, and temperature and dew-point temperature for 204 US urban counties (population >200 000) with 11.5 million Medicare enrollees (aged >65 years) living an average of 5.9 miles from a PM_2.5 monitor. Main Outcome Measures  Daily counts of county-wide hospital admissions for primary diagnosis of cerebrovascular, peripheral, and ischemic heart diseases, heart rhythm, heart failure, chronic obstructive pulmonary disease, and respiratory infection, and injuries as a control outcome. Results  There was a short-term increase in hospital admission rates associated with PM_2.5 for all of the health outcomes except injuries. The largest association was for heart failure, which had a 1.28% (95% confidence interval, 0.78%-1.78%) increase in risk per 10-µg/m³ increase in same-day PM_2.5. Cardiovascular risks tended to be higher in counties located in the Eastern region of the United States, which included the Northeast, the Southeast, the Midwest, and the South. Conclusion  Short-term exposure to PM_2.5 increases the risk for hospital admission for cardiovascular and respiratory diseases.      

Predictors of treatment failure for pneumatic retinopexy

Objective

The purpose of this study was to define the overall anatomic success rate in pneumatic retinopexy and to identify morphologic features that may be predictive of treatment failure in pneumatic retinopexy.

Design and Participants

Prospective consecutive interventional case series of patients with new-onset primary rhegmatogenous retinal detachments treated with pneumatic retinopexy.

Methods

In this interventional case series, consecutive patients with new-onset primary rhegmatogenous retinal detachments were treated with pneumatic retinopexy and followed prospectively. Morphologic data were collected on 3-colour fundus drawings. The primary outcome measure was treatment failure, defined as requirement for scleral buckle or vitrectomy within the follow-up period. Rates of failure for each morphologic feature were compared and a logistic regression model was fit.

Results

A total of 113 eyes were included in the study. Anatomic success was achieved in 69.6% of patients. Morphologic criteria including the position and number of breaks, position and extent of lattice degeneration, size of the detached area, and macular status were all found not to be significantly related to failure. In multivariate analysis, only 3 predictors, pseudophakic status (p < 0.05, odds ratio [OR] 2.9, 95% CI, 1.06–7.88), presence of retinal break greater than 1 clock-hour (p < 0.05, OR 3.41, 1.06–11.02), and presence of grade C or D proliferative vitreoretinopathy (PVR) (p < 0.01, OR 31.83, 95% CI, 3.59–282.24), gained statistical significance.

Conclusions

Only pseudophakia, a large retinal break, and/or PVR was associated with an increased likelihood of failure.     

Structural characterization of autoinhibited c-Met kinase produced by coexpression in bacteria with phosphatase

Protein kinases are a large family of cell signaling mediators undergoing intensive research to identify inhibitors or modulators useful for medicine. As one strategy, small-molecule compounds that bind the active site with high affinity can be used to inhibit the enzyme activity. X-ray crystallography is a powerful method to reveal the structures of the kinase active sites, and thus aid in the design of high-affinity, selective inhibitors. However, a limitation still exists in the ability to produce purified kinases in amounts sufficient for crystallography. Furthermore, kinases exist in different conformation states as part of their normal regulation, and the ability to prepare crystals of kinases in these various states also remains a limitation. In this study, the c-Abl, c-Src, and c-Met kinases are produced in high yields in Escherichia coli by using a bicistronic vector encoding the PTP1B tyrosine phosphatase. A 100-fold lower dose of the inhibitor, Imatinib, was observed to inhibit the unphosphorylated form of c-Abl kinase prepared by using this vector, compared to the phosphorylated form produced without PTP1B, consistent with the known selectivity of this inhibitor for the unactivated conformation of the enzyme. Unphosphorylated c-Met kinase produced with this vector was used to obtain the crystal structure, at 2.15-A resolution, of the autoinhibited form of the kinase domain, revealing an intricate network of interactions involving c-Met residues documented previously to cause dysregulation when mutated in several cancers.