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.     

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%).     

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。     

Asymmetric alumina membranes electrochemically formed in oxalic acid solution

Alumina membranes were fabricated by anodizing aluminium metal in 0.15 M oxalic acid. The growth kinetics of the porous layer were investigated in the temperature range –1 to 16 °C using linear potential scans up to 70 V. The faradaic efficiencies of metal oxidation and of porous layer formation, determined by applying Faraday's law, were found to be independent of both temperature and electrical charge. SEM analysis of the metal-side and solution-side surfaces revealed different morphologies. After dissolution of the barrier layer in phosphoric acid, the metal-side surface showed circular pores whose size of about 90 nm was found to be uniform and independent of temperature. The pore population was also practically independent of temperature and a value of about 4 × 10¹³ pores m^–2 was determined. On the solution-side surface the presence of a deposit partially occluding the mouths of pores was observed. This coating could be removed by chemical etching in NaOH or thermal treatment at 870 °C, where decomposition of oxalate occurs. This supports the hypothesis that the deposit consists of an aluminium salt containing oxalate anions precipitated from the solution. The results show that it is possible to control the morphological characteristics of the anodic alumina membranes by careful choice of experimental conditions.     

Hydrothermal Synthesis of Acicular Lead Titanate Fine Powders

A pure, acicular lead titanate (PbTiO₃) fine powder with a white color has been prepared by hydrothermal synthesis. It is a new phase of PbTiO₃ with I 4 symmetry, cell parameters of a = 12.358 Å and b = 14.541 Å, and a density of 6.80 g.cm⁻³. The influences of pH (12.5 to 14.4), Pb/Ti ratio (1.0 to 1.6) in the feedstock, reaction temperature (130° to 230°C), time (0.25 to 4 h), starting materials, and additives on the formation of acicular PbTiO₃ under hydrothermal conditions have been investigated. The acicular PbTiO₃ with I 4 symmetry, referred to as the PX phase, can be converted to the perovskite-type (PE phase) of PbTiO₃ at about 605°C while its acicular morphology is essentially unchanged. The preferable conditions for preparing pure acicular PX-phase PbTiO₃ are that the pH is 13.0 to 14.0, Pb/Ti ratio is >1.3, reaction temperature is 170° to 200°C, time is 0.5 to 1.0 h, titanium butoxide (Ti[O(CH₂)₃CH₃]₄) is the starting material, and poly(vinyl alcohol) is an additive. The acicular grain of the PX phase is usually less than 100 nm in diameter and more than 1000 nm in length.     

Multiresidue method for pesticides in drinking water using a graphitized carbon black cartridge extraction and liquid chromatographic analysis

A general liquid-solid extraction procedure for the isolation of pesticides from groundwater and drinking water for high-performance liquid chromatography (HPLC) is presented. This simple and rapid procedure involved passing a 2-L sample through a 250-mg graphitized carbon black (Carbopack B) cartridge at a flow rate of 150-160 mL/min. By taking advantage of the presence of positively charged active centers on the Carbopack B surface, a stepwise elution system allowed the complete separation of base-neutral pesticides from acidic ones. After partial solvent removal, the components in the two fractions were separated and quantified by gradient elution, reversed-phase HPLC with ultraviolet (UV) detection. The performance of the Carbopack cartridge was compared with that of a 500-mg C-18 bonded silica cartridge. With the Carbopack cartridge, the grand mean measurement accuracy of the 35 pesticides considered was 95%. With the C-18 cartridge, the grand mean measurement accuracy of the analytes was 76%. Compared to the C-18 cartridge, additional advantages of using a Carbopack cartridge are that the extraction procedure is about 7 times shorter, no pH adjustment of the environmental sample is necessary for trapping acidic compounds, and one cartridge instead of two suffices to extract base-neutral and acidic pesticides, making the Carbopack cartridge more adaptable than the C-18 one for field use. The detection limits by this method of all the pesticides considered were between 0.003 and 0.07 micrograms/L.