Acute myocardial ischemia: MR imaging with Mn-TP

Cardiac-gated magnetic resonance (MR) imaging was performed in rats to determine the effects of manganese ethylenediaminetetraphosphonate (TP). Ten normal rats received Mn-TP in a dose of 50 mumol/kg through a tail-vein injection. Spin-echo MR images were obtained before and every 10 minutes after Mn-TP injection for 1 hour. Cardiac signal intensity (SI) increased more than 70% after Mn-TP injection and remained nearly unchanged 1 hour after injection. Myocardial T1 was 517 +/- 49 msec in eight control rats and 282 +/- 61 msec (P less than .001) in six rats 81 +/- 0 minutes after injection. Nine rats underwent occlusion of the left anterior descending coronary artery prior to MR imaging. Images were obtained before and 15, 30, and 60 minutes after Mn-TP injection. In normal myocardium, SI increased up to 82% and remained elevated for 1 hour. In ischemic myocardium, SI rose 11%, leading to a marked contrast between the two tissue zones. T1 was also different in the two regions: In normal tissue, it was 206 msec +/- 54; in ischemic tissue, 338 +/- 82 (P less than .001). With T1-weighted MR imaging, Mn-TP showed a potential for delineating the jeopardized area after acute myocardial ischemia.     

Muscle necrosis in the extremities: evaluation with Tc-99m pyrophosphate scanning--a retrospective review

A retrospective review was done of 34 extremities studied between 1981 and 1985 with technetium-99m pyrophosphate scanning; 22 were subsequently amputated. Results of detailed pathologic examination or immediate postoperative examination of the resected extremity were available in 16 cases. In these cases, scanning had allowed correct prediction of the level of amputation and of the specific areas of muscle infarction in 13 cases. In the one case in which amputation was performed for infection rather than muscle necrosis, the lack of necrosis was correctly predicted with the scan. The limited results of this study indicate that the Tc-99m pyrophosphate scan allows the location of necrotic muscle to be predicted accurately and may therefore be a useful adjunct in determining the best level for ultimate amputation. Special caution is required in those cases in which muscle necrosis is due to acute causes (e.g., traumatic thrombosis) rather than chronic vascular disease.     

Impairment of chemoattractant-stimulated hexose uptake in neonatal neutrophils

Neonatal neutrophils (polymorphonuclear leukocytes [PMN]) exhibit a well-documented deficiency in chemotaxis, the nature of which has not been fully elucidated. To determine whether impaired ability of neonatal PMN to increase hexose uptake in response to chemoattractants could contribute to this defect, we compared uptake of 2-deoxy-D- glucose (2-DOG) in stimulated versus resting PMN from neonates (cord blood) and healthy adults. Compared with unstimulated values; N-formyl- methionyl-leucyl-phenylalanine (fMLP) (optimal at 10 nmol/L) caused a threefold to fourfold increase in 2-DOG uptake by adult PMN. Unstimulated 2-DOG uptake by neonatal PMN was slightly higher than that for adult cells, but fMLP caused only a minimal (less than twofold) increase, and optimally stimulated uptake was significantly lower than for adult PMN (P < .01 for adult versus neonatal stimulated uptake; n = 6). Findings were similar when ionomycin or C5a was used as a stimulus. Optimal fMLP stimulation of adult PMN was associated with a marked decrease in the Km for 2-DOG uptake, from 0.74 +/- 0.11 to 0.23 +/- 0.03 mmol/L (delta Km = -0.51 +/- 0.12 mmol/L; n = 6). In contrast, there was relatively little fMLP-induced change in the Km for uptake of 2-DOG by neonatal PMN (from 0.44 +/- 0.04 mmol/L to 0.32 +/- 0.019 mmol/L n = 6); delta Km = -0.12 +/- 0.04 mmol/L; P = .011 for adult versus neonatal delta Km. Stimulation with fMLP was not accompanied by a significant change in the Vmax for 2-DOG uptake with either adult or neonatal PMN, and the respective values for Vmax were similar. We conclude that the chemoattractant-induced increase in hexose uptake by PMN is deficient in neonates compared with adults and that this deficiency involves mechanisms that determine the Km for this process. This impairment may contribute to defective chemotaxis in neonatal PMN.     

Genetic polymorphisms and drug interactions modulating CYP2D6 and CYP3A activities have a major effect on oxycodone analgesic efficacy and safety

Background and purpose:

Thrombus formation is commonly associated with pulmonary arterial hypertension (PAH). Thrombin may thus play an important role in the pathogenesis and pathophysiology of PAH. Hence, we investigated the contractile effects of thrombin and its mechanism in pulmonary artery.

Experimental approach:

The cytosolic Ca²⁺ concentrations ([Ca²⁺]_i), 20 kDa myosin light chain (MLC20) phosphorylation and tension development were evaluated using the isolated porcine pulmonary artery.

Key results:

Thrombin induced a sustained contraction in endothelium-denuded strips obtained from different sites of a pulmonary artery, ranging from the main pulmonary artery to the intrapulmonary artery. In the presence of endothelium, thrombin induced a transient relaxation. The contractile effect of thrombin was abolished by either a protease inhibitor or a proteinase-activated receptor 1 (PAR₁) antagonist, while it was mimicked by PAR₁-activating peptide (PAR₁AP), but not PAR₄AP. The thrombin-induced contraction was associated with a small elevation of [Ca²⁺]_i and an increase in MLC20 phosphorylation. Thrombin and PAR₁AP induced a greater increase in tension for a given [Ca²⁺]_i elevation than that obtained with high K⁺-depolarization. They also induced a contraction at a fixed Ca²⁺ concentration in α-toxin-permeabilized preparations.

Conclusions and implications:

The present study revealed a unique property of the pulmonary artery. In contrast to normal arteries of the systemic circulation, thrombin induces a sustained contraction in the normal pulmonary artery, by activating PAR₁ and thereby increasing the sensitivity of the myofilament to Ca²⁺. This responsiveness of the pulmonary artery to thrombin may therefore contribute to the pathogenesis and pathophysiology of PAH.     

肩周炎20例的综合疗效

1 临床资料 2004-04以来收治肩周炎20(男8,女10)例;年龄42～55岁19例,70岁1例;右侧16例,左侧4例;病史7 d～1.5 a,均无外伤史,患侧肩部活动受限,手臂上提小于40°,肩关节外展,外旋活动受限,不能自如穿、脱衣和梳理头发及摸背. 分型与药物组方见表1.