The novel inotropic agent CGP 48506 alters force primarily by Ca(2+)-independent mechanisms in porcine skinned trabeculae

OBJECTIVES: The aim was to determine whether, and by what mechanism(s), a novel inotropic agent 5-methyl-6-phenyl-1,3,5,6-tetrahydro-3, 6-methano-1,5-benzodiazocine-2,4-dione (BA 41899) and its enantiomers directly alter the Ca2+ sensitivity of cardiac myofilaments. METHODS: Porcine ventricular trabeculae were permeabilised with Triton X-100. The relationship between force and pCa (-log[Ca2+]) was determined in the presence and absence of ATP. Troponin I was extracted, using vanadate, to produce unregulated maximally activated myofilaments. Force and actomyosin ATPase activity were measured simultaneously to determine tension cost (ATPase activity/tension). The effects of the (+) enantiomer (CGP 48506) on the twitch of intact muscle were demonstrated using rat papillary muscle. RESULTS: 100 microM BA 41899 had a pronounced Ca2+ sensitising effect on force production by porcine skinned cardiac fibres, increasing the pCa required for 50% maximal activation by 0.64 units, while suppressing maximum force by 18.3%. Resting tension was unaffected. These actions were primarily caused by CGP 48506 and were concentration dependent. At concentrations less than 100 microM, CGP 48506 also increased twitch amplitude in intact papillary muscles with no effect on resting tension, whereas 100 microM CGP 48506 increased resting force due to a slowing of relaxation. 100 microM CGP 48506 potentiated Ca(2+)-independent rigor tension in skinned trabeculae, indicating a Ca2+ sensitising mechanism unrelated to Ca2+ binding to troponin C. Tension cost was unaffected by 100 microM CGP 48506 over the entire range of activating Ca2+ concentrations. Suppression of maximum force by CGP 48506 was independent of both Ca2+ concentration and the regulatory troponin complex. CONCLUSIONS: Both the increase in Ca2+ sensitivity during submaximal activation and the depression of maximum force which are induced by CGP 48506 in skinned trabeculae occur at least partly through Ca(2+)-independent mechanisms.     

Morphological variations of the human gastric mucosa after omeprazole treatment: a scanning electron microscopic study

The effects of antiepileptic drugs on cognitive function in 48 healthy volunteers were assessed using event-related potentials (ERP) and the Attention Index included in the Wechsler Memory Scale, revised edition (WMS-R). The study was conducted over 1 week, using a double-blind design. Four drugs, carbamazepine (CBZ), phenytoin (PHT), valproate (VPA) and zonisamide (ZNS) were tested. Using an auditory oddball task, ERP measurements were made under two conditions with different tone intensities: Condition 1 used 70 db SPL; and Condition 2 used 30 db SPL. Results showed that CBZ prolonged target N1 and P3 latencies in Condition 1, and reduced frequent N1 amplitude in Condition 2, which suggests that CBZ may cause a change in sensory memory and prolong stimulus evaluation time. It is suggested that under a low stimulus intensity level, the sensory function itself was affected. Phenytoin was found to prolong target N1 latency in Condition 2, which also indicates a change in the sensory memory function. However, VPA did not significantly affect ERP components, except for the shortened frequent N1 latency, which could not be explained due to the limited information. It was found that ZNS augmented P3 amplitude in Condition 2, and reduced scores on the Attention Index. It is suggested that the augmentation of P3 amplitude was caused by the reduction of processing negativity as a result of the detrimental effect of ZNS on subjects' attention. However, the apparent difference between the ERP and behavioral indices suggests that caution should be exercised in assessing the results obtained only from ERP measurements.     

一种快速跟踪机动目标的并行算法

针对机动目标的跟踪问题,采用一种完全解耦的卡尔曼滤波跟踪算法,即速度滤波器和加速度滤波器并行独立运算,加速度滤波器的输出用于校正速度滤波器的结果。根据探测到的目标机动性情况,加速度滤波器可实时切换。降低了滤波维数,从而使计算量和存贮量减少,提高实时性。仿真结果表明,该算法具有很好的跟踪性能。     

Assessment of the influence of the compliant aortic root on aortic valve mechanics by means of a geometrical model

In recent years several researchers have suggested that the changes in the geometry and angular dimensions of the aortic root which occur during the cardiac cycle are functional to the optimisation of aortic valve function, both in terms of diminishing leaflet stresses and of fluid-dynamic behaviour. The paper presents an analytical parametric model of the aortic valve which includes the aortic root movement. The indexes used to evaluate the valve behaviour are the circumferential membrane stress and the stress at the free edge of the leaflet, the index of bending strain, the bending of the leaflet at the line attachment in the radial and circumferential directions and the shape of the conduit formed by the leaflets during systole. In order to evaluate the role of geometric changes in valve performance, two control cases were considered, with different reference geometric configuration, where the movement of the aortic root was ignored. The results obtained appear consistent with physiological data, especially with regard to the late diastolic phase and the early ejection phase, and put in evidence the role of the aortic root movement in the improvement of valve behaviour.     

Apoptosis in the failing human heart

BACKGROUND: Loss of myocytes is an important mechanism in the development of cardiac failure of either ischemic or nonischemic origin. However, whether programmed cell death (apoptosis) is implicated in the terminal stages of heart failure is not known. We therefore studied the magnitude of myocyte apoptosis in patients with intractable congestive heart failure. METHODS: Myocardial samples were obtained from the hearts of 36 patients who underwent cardiac transplantation and from the hearts of 3 patients who died soon after myocardial infarction. Samples from 11 normal hearts were used as controls. Apoptosis was evaluated histochemically, biochemically, and by a combination of histochemical analysis and confocal microscopy. The expression of two proto-oncogenes that influence apoptosis, BCL2 and BAX, was also determined. RESULTS: Heart failure was characterized morphologically by a 232-fold increase in myocyte apoptosis and biochemically by DNA laddering (an indicator of apoptosis). The histochemical demonstration of DNA-strand breaks in myocyte nuclei was coupled with the documentation of chromatin condensation and fragmentation by confocal microscopy. All these findings reflect apoptosis of myocytes. The percentage of myocytes labeled with BCL2 (which protects cells against apoptosis) was 1.8 times as high in the hearts of patients with cardiac failure as in the normal hearts, whereas labeling with BAX (which promotes apoptosis) remained constant. The near doubling of the expression of BCL2 in the cardiac tissue of patients with heart failure was confirmed by Western blotting. CONCLUSIONS: Programmed death of myocytes occurs in the decompensated human heart in spite of the enhanced expression of BCL2; this phenomenon may contribute to the progression of cardiac dysfunction.     

Ascitic fluid analysis in hepatocellular carcinoma

BACKGROUND: Ascites in patients with hepatocellular carcinoma (HCC) is a poorly characterized subgroup of malignancy-related ascites. Not only the underlying liver disease, but also the tumor growth and spread contributes to the ascites formation. The authors differentiated ascites in HCC from other types of ascites. METHODS: The authors analyzed the ascitic fluid of 185 consecutive patients (89 liver cirrhosis, 33 HCC, 31 peritoneal carcinomatosis, 22 liver metastases, 10 spontaneous bacterial peritonitis). RESULTS: Each subgroup showed a typical pattern. Compared with the cirrhotic patients, those with HCC showed a higher frequency of positive cytologic findings (4 of 33 versus 0/89, P < 0.004), elevated fibronectin concentration (10/33 versus 8/89, P < 0.004), and elevated polymorphonuclear cell count (10/33 versus 5/89 P < 0.004). CONCLUSIONS: A significant number of patients with ascites and HCC patients showed signs of peritoneal infiltration with positive cytologic findings and increased concentration of fibronectin. Moreover, neutrocytic ascites without signs of superinfection is relatively common (30%).     

A comparison of the shake test, optical density, L/S ratio (planimetric and stechiometric) and PG for the assessment of fetal lung maturity

Our aim was to determine the diagnostic accuracy and reliability of four tests for the assessment of fetal lung maturity (FLM): shake test, optical density at 650 nm (OD650), lecithin to sphingomyelin ratio (L/S) by planimetry and stechiometry, and presence of phosphatydylglycerol. Amniotic fluid was obtained from 74 patients at various gestational ages. The shake test and the OD650 were performed according to published methods L/S was determined by TLC (thin-layer chromatography) and the ratio assessed by planimetry and stechiometrically by measurement of organic phosphorus from the chromatographic spots. PG was assessed similarly by TLC. When correlated with gestational age at amniocentesis, all tests correlated positively: shake test (r = 0.46, p < 0.005); OD650 (r = 0.31, p < 0.005); planimetric L/S (r = 0.77, p < 0.005); stechiometric L/S (r = 0.52, p < 0.005) and PG (r = 0.54, p < 0.005). The diagnostic accuracy of each test was as follows: the shake test and the OD650 had a sensitivity of 50%, while the steciometric L/S had a sensitivity of 75%, the planimetric L/S and the presence of PG were 100%. All four tests demonstrated a specificity greater than 64%, the highest for the PG presence being (83%) and the shake test (86%). Predictive negative values for lung maturity were > 93% for all tests, with the highest for the planimetric L/S and presence of PG being (100%). The study confirms that the determination of L/S ratio is still superior to other tests in terms of overall diagnostic accuracy. In addition, it was found that presence of PG was highly associated with the absence of respiratory complications in the newborn.     

薄膜磁头磁轭制备工艺研究

本文重点讨论了用不同的工艺方法来制备薄膜磁头中的关键元件-磁轭。采用多次光刻的方法克服湿法工艺中磁性膜NiFe层的侧向钻蚀问题，从而实现对磁轭几何尺寸的精确控制，并对几种工艺方法的优缺点作了比较详细的分析。     

Feasibility of a long-term low-sodium diet in mild hypertension

The present study set out to assess the feasibility of long-term moderate dietary sodium restriction in patients with mild hypertension in general practice. After screening and a run-in phase of 6-8 weeks, a total of 77 previously undiagnosed mildly hypertensive patients were identified. Half of them were randomized to receive a few simple dietary instructions from their general practitioners in order to reduce salt usage; the others were randomized to receive no advice. The patients were followed up for 12 months with quarterly visits. A total of 56 patients (72.7%) completed the study, 26 on a low-sodium diet (LD) and 30 on their usual diet (UD). At each visit in the diet phase, patients provided 24h urine, which was analysed for volume and sodium concentration in order to assess their sodium intake. Blood pressure, heart the rate and body weight were recorded. The mean urinary sodium excretion for all diet phase visits overlapped in the two groups (177.0 +/- 32.9 vs. 169.3 +/- 49.4 mEq/24h respectively in the LD and UD groups). Nevertheless the mean systolic and diastolic blood pressures for all diet phase visits were significantly lower in the LD than in UD group (144.2 +/- 11.1/91.6 +/- 6.4 and 148.0 +/- 13.7/95.6 +/- 4.7 mmHg respectively, P less than 0.01). Our data suggest that it is not feasible at present to reduce sodium intake in mild hypertensives with simple and inexpensive dietary instructions, the only ones suitable for widespread application in general practice.