Cardiovascular effects of verapamil enantiomer combinations in conscious dogs

We examined the systemic and coronary hemodynamic effects of five combinations of R- and S-verapamil enantiomers (R/S; 100/0, 90/10, 80/20, 50/50, and 20/80%, respectively) in conscious dogs chronically instrumented for measurement of aortic and LV pressure, +dP/dt, subendocardial segment length, coronary blood flow velocity, and aortic blood flow. Dogs received escalating doses (0.1, 0.2, and 0.4 mg kg(-1)) of each verapamil combination over 2 min at 30 min intervals on different experimental days and peak changes in hemodynamics were recorded 2 min after each dose. All verapamil combinations increased heart rate, mean aortic blood flow, and coronary blood flow velocity and decreased calculated systemic and coronary vascular resistance. Alterations in coronary hemodynamics were most pronounced with 20/80 R/S verapamil. Racemic and 20/80 R/S verapamil decreased mean arterial and left ventricular systolic pressure, in contrast to combinations with greater concentrations of the R enantiomer. Left ventricular function was unchanged during administration of 100/0, 90/10, and 80/20 R/S verapamil. Direct negative inotropic and lusitropic effects occurred with 50/50 and 20/80 R/S verapamil. The high dose of 20/80 R/S verapamil also increased left ventricular end-diastolic pressure and the regional chamber stiffness constant, consistent with diastolic dysfunction. The results indicate that combinations of R- and S-verapamil produce differential hemodynamic and left ventricular functional effects in conscious, unsedated dogs that are dependent on the relative ratio of these enantiomers.     

Direct modulation of tumor suppressor connexin 26 gene by human chorionic gonadotropin in rat mammary glands

Human chorionic gonadotropin (hCG) has been shown to reduce the incidence of carcinogen-induced rat mammary tumors. Because connexin 26 (Cx26), a tumor suppressor gene candidate, can be up-regulated in mammary epithelial cells during lactation, we examined the in vivo and ex vivo effects of hCG on Cx26 expression in rat mammary tissues and used its effect on the expressions of beta-casein and Cx43 as controls. The Cx26 mRNA and protein expressions were up-regulated by daily administrations of 100 units of hCG, starting on day 5 and reaching a 14-fold maximum increment on days 16 through 21. It remained elevated above the basal level even 20 days after hCG withdrawal. The changes in beta-casein expression ran parallel to that of Cx26, whereas the expression of Cx43 was down-regulated. There was no correlation between steroidal hormone levels and Cx26 expression, except for the first 5 days of hCG treatment. In the ex vivo organ culture system, exposure of mammary glands to 10 units/ml hCG for 5 days up-regulated Cx26 but had no effect on beta-casein expression. These results imply a direct induction of the tumor suppressor Cx26 gene by hCG in mammary epithelial cells, a mechanism unrelated to lactation.     

Stereospecific effect of bupivacaine isomers on atrioventricular conduction in the isolated perfused guinea pig heart

BACKGROUND: The local anesthetic bupivacaine is an equal mixture of two optically active isomers known to exert different cardiotoxic profiles in vivo. Enantiomer-specific forms of bupivacaine may have differential effects on cardiovascular function, specifically on cardiac electrophysiology. The authors' aim was to determine if there were any direct functional differences in the cardiac effects of bupivacaine isomers. The isolated heart was used to avoid possible indirect cardiac effects of bupivacaine, such as autonomic nervous and hormonal influences, as well as preload and afterload factors. METHODS: The hearts of 12 ketamine-anesthetized guinea pigs were perfused with Krebs-Ringer's solution (97% oxygen, 3% carbon dioxide) at constant perfusion pressure using the Langendorff technique. Atrial and ventricular bipolar electrodes were placed to measure heart rate (HR) and atrioventricular (AV) conduction time. Left ventricular pressure (LVP), coronary flow, and inflow and outflow oxygen tensions were also measured. Oxygen delivery, oxygen consumption (MVO2), and percentage of oxygen extraction were calculated. Each heart was perfused with increasing randomized concentrations (0.5, 1, 5, 10 microM) of both isomers and the racemate of bupivacaine. RESULTS: Racemic and isomeric bupivacaine equally and dose dependently decreased cardiac function. At 10 microM bupivacaine these changes were HR, -17 +/- 2%; LVP, -50 +/- 3%; coronary flow, -20 +/- 4%; and MVO2, -46 +/- 4%. The (+) isomer significantly prolonged AV conduction compared with the racemate and the (-) isomer at all concentrations. At 10 microM, AV time was 54 +/- 6% longer with the (+) isomer and 30 +/- 4% longer with the (+/-) racemate than with the (-) isomer. The greater delay in AV time with the (+) than the racemate or (-) isomer led to a second-degree AV dissociation in 10 of 12 of hearts treated with (+) bupivacaine. CONCLUSIONS: This study shows that bupivacaine has an enatiomer-specific effect to delay AV conduction and to produce second-degree AV dissociation in the isolated perfused heart. This suggests that bupivacaine isomers probably have differential effects on one or more ion-specific channels regulating AV conduction. Other measured direct cardiac effects of bupivacaine appear to be independent of the isomeric form.     

Bilateral hypothalamic dopamine infusion in male Zucker rat suppresses feeding due to reduced meal size

PURPOSE: To determine whether vascular, ischemic, and inflammatory causes of bowel wall thickening in children can be differentiated at gray-scale and color Doppler ultrasonography (US). MATERIALS AND METHODS: Thirty-seven children with acute bowel disease underwent graded compression US. Findings of bowel wall thickness, wall echotexture, location of bowel involvement, and presence of color Doppler flow were evaluated. Diagnoses were classified as inflammation (n = 25), vasculitis (n = 7), or ischemia (n = 5) and were confirmed with findings from colonoscopy and biopsy, stool culture analysis, surgery, and cutaneous biopsy, and with a combination of clinical and laboratory data. RESULTS: Patient age (P = .0022), bowel wall thickness (P = .0001), and color Doppler flow (P = .0013) were statistically significantly related to disease type. Wall thickening and absence of visible color Doppler flow suggested ischemia. Older patient age and visible color Doppler flow suggested inflammation, whereas younger patient age and visible color flow suggested vasculitis. Difference in location of bowel disease in patients with ischemic versus those with vascular wall thickening was statistically significant (P = .0185). No difference was found between disease type and wall stratification. CONCLUSION: Gray-scale and color Doppler flow US can aid in differentiating ischemic, vascular, and inflammatory bowel wall thickening.     

LGA1155 CPU针脚接触不良导致重启变关机

笔者是第一批购买P67主板的用户,因此郁闷地碰上了芯片组瑕疵问题,申请更换B3步进产品后,技嘉在2个月后给我换了一块全新的GA-P67A-UD3R,但此前一直使用存在瑕疵问题的主板,因为磁盘性能下降的问题要长时间使用才会出现,并未对笔者的使用造成太大影响。不过换回来新主板装好之后却出了问题,每次点击重启时,电脑并不按照指令来,而是直接关     

Phage display of intact domains at high copy number: a system based on SOC, the small outer capsid protein of bacteriophage T4

Peptides fused to the coat proteins of filamentous phages have found widespread applications in antigen display, the construction of antibody libraries, and biopanning. However, such systems are limited in terms of the size and number of the peptides that may be incorporated without compromising the fusion proteins' capacity to self-assemble. We describe here a system in which the molecules to be displayed are bound to pre-assembled polymers. The polymers are T4 capsids and polyheads (tubular capsid variants) and the display molecules are derivatives of the dispensable capsid protein SOC. In one implementation, SOC and its fusion derivatives are expressed at high levels in Escherichia coli, purified in high yield, and then bound in vitro to separately isolated polyheads. In the other, a positive selection vector forces integration of the modified soc gene into a soc-deleted T4 genome, leading to in vivo binding of the display protein to progeny virions. The system is demonstrated as applied to C-terminal fusions to SOC of (1) a tetrapeptide; (2) the 43-residue V3 loop domain of gp120, the human immunodeficiency virus type-1 (HIV-1) envelope glycoprotein; and (3) poliovirus VP1 capsid protein (312 residues). SOC-V3 displaying phage were highly antigenic in mice and produced antibodies reactive with native gp120. That the fusion protein binds correctly to the surface lattice was attested in averaged electron micrographs of polyheads. The SOC display system is capable of presenting up to approximately 10(3) copies per capsid and > 10(4) copies per polyhead of V3-sized domains. Phage displaying SOC-VP1 were isolated from a 1:10(6) mixture by two cycles of a simple biopanning procedure, indicating that proteins of at least 35 kDa may be accommodated.     

Mechanical responses of chromium-deficient developing rat heart

Mechanical responses were compared between controls, developing Sprague-Dawley rat papillary muscle and age-matched weanlings fed with Torula yeast, a food source deficient in chromium. At 8 weeks postnatal, deficient rats differed in significant ways from their normal counterparts. Deficient rats in contrast to controls weighed less, their interval-force (I-F) relationship was more negative and their inotropic response to high calcium concentrations was greater. At this time, however, deficient and control rats responded equally to alpha (phenylephrine) and beta (isoproterenol) agonists. At 10 weeks of age, the controls exhibited a less negative I-F and a negative inotropic response to high calcium concentrations while the response to alpha and beta agonists was unchanged. In contrast, at 10 weeks of age, the chromium-deficient rats exhibited a highly negative I-F response and significant inotropic response to high calcium concentrations. The response of the deficient hearts to beta-agonists diminished. At 13 weeks postnatal, control hearts showed only a 10-15% negative I-F response, a persistent response to catecholamines and negative inotropic responses to high calcium concentrations. In deficient hearts, the negative I-F response was reduced and the response to beta-agonists was further diminished but a positive inotropic response to phenylephrine and high calcium concentrations persisted. These observations in deficient animals are explained in terms of a retarded development of the calcium handling elements in the heart and a lack of an insulin-like growth factor.