Early imaging in heart failure: Exploring novel molecular targets

Conclusions  Noninvasive imaging of neurohumoral upregulation in remodeled myocardium suggests that an imaging strategy can be developed for predicting the rate of remodeling and likelihood of HF development. This should allow a more judicious use of neurohumoral antagonists especially in subjects who do not have manifest HF.⁷⁴ In others specific targeted imaging may allow timely selection of individualized treatment strategies and ensure optimization of therapeutic intervention. Similar to ACE and AII receptors, multiple other targets in the hormonal cascades can identify the likelihood of adverse and favorable remodeling.⁷⁴     

Two-stage treatment of skeletal Class III malocclusion during the early permanent dentition.

A patient with skeletal Class III malocclusion was treated in 2 phases during the early permanent dentition. In phase 1, maxillary protraction was combined with rapid palatal expansion; in phase 2, fixed appliances were placed. The results were good posttreatment, and, 1 year later, a favorable growth tendency could be observed. This report shows that treatment for a patient with skeletal Class III malocclusion can be started in the early permanent dentition, with very good final results.     

Production and characterization of monoclonal antibody against colon cancer associated antigen in Chinese]

Although many monoclonal antibodies have been made in human colon cancer, none of them are from the Chinese species. Recently, a colon cancer cell line CC-M2 established from a Chinese patient has been completely characterized and used as immunogen to produce monoclonal antibodies. Monoclonal antibodies were produced by standard hybridoma technique. The fusion rate was 95.8%. An isotype IgG1 of high proliferation named as Sam-2 was used in this study. The titers were measured around 10(4). Further studies on MoAb Sam-2 through indirect immunofluorescent and immunoperoxidase tests revealed its good specificity and sensitivity in colorectal cancer tissue. In CEA study, the result indicated that Sam-2 may react on a non-CEA related antigen. For further clinical application, the antigen was identified as a glycoprotein by chemical resistant test. In preliminary studies using sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting techniques, Sam-2 could recognize two closed antigens or a dimer antigen with molecular weight 25.2 and 27 Kd respectively.     

Activity-dependent Decay of Early LTP Revealed by Dual EPSP Recording in Hippocampal Slices from Young Rats

The early maintenance of long-term potentiation (LTP) was studied in the CA1 region of hippocampal slices from 12- to 18-day-old rats in a low-magnesium solution (0.1 mM). The α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) and N-methyl-D-aspartate (NMDA) receptor-mediated components of the field excitatory postsynaptic potential were estimated in parallel using early and late measurements of the composite potential. At the normal test stimulus frequency of 0.1 Hz, LTP was seen initially as a predominant increase in the AMPA component, but converted, via a substantial decay of this component and a gradual growth of the NMDA component, into nearly equal changes of the two components. Interrupting the test stimulation for 10 min, changing the test stimulus frequency to 1/60 Hz after LTP induction, or using a test stimulus frequency of 1/60 Hz during the entire experiment significantly reduced the decay of the potentiation of the AMPA component while enhancing the potentiation of the NMDA one. The ratio between the magnitudes of the two excitatory postsynaptic potential (EPSP) components showed a decaying time course that was independent of the manipulations used. Application of the NMDA antagonist D(-)-2-amino-5-phosphonopentanoic acid (50μM) after LTP induction stabilized the LTP of the AMPA component until washout was started. On the other hand, the phosphatase inhibitor okadaic acid (1 μM) resulted in decay of the potentiation of both EPSP components back to around baseline and altered the time course of the ratio between the components. Our results show that the early maintenance of LTP is controlled in an activity-dependent and NMDA-dependent manner. This process accelerates the decay of LTP of both AMPA and NMDA components in parallel, suggesting that it is similar to homosynaptic long-term depression, although it operates at the normal test stimulus frequency. The data support a scenario in which LTP ensues as a selective AMPA receptor modification and subsequently converts to another modification, possibly a presynaptic one.     

Clinicopathological features of bladder cancer associated with chronic exposure to arsenic.

A high incidence of bladder cancer has been documented in an area of chronic arsenic (As) exposure. This study investigates the characteristics of As-associated (n = 49) and other (n = 64) bladder cancers. A higher histological grading was observed for the As-exposed tumours (P = 0.04), but no other difference in pathobiological features or prognosis was found between the two groups.     

美沙酮联用丁丙诺啡对海洛因依赖重度药瘾戒毒治疗临床研究

目的　探索对海洛因依赖重度药瘾较理想的戒毒治疗方法。　　方法　采用美沙酮与丁丙诺啡联合用药方案 ,对海洛因依赖重度药瘾 41例行戒毒治疗 ,1 2天为一疗程 ,并与单用美沙酮组 2 0例进行比较。　　结果　联合用药组控制症状较彻底 ,鸦片类药物戒断症状量表 (OWS)总分平稳下降 ,症状波动小 ,减药顺利 ,两药替换平稳 ,戒毒成功率 73 2 %。　　结论　我们认为美沙酮联用丁丙诺啡是一种值得推荐的戒毒治疗方法。     

The bioavailability and nonlinear pharmacokinetics of MK-679 in humans

MK-679 (R(?)-3-((3-(2-(7-chloro-2-quinolinyl)ethenyl)phenyl)(3-(dimethylamino)-3-oxopropyl)thio)methyl)thio(propanoic acid) is a potent and specific LTD₄-receptor antagonist. The disposition of MK-679 was investigated in a three-way crossover study in 12 healthy males receiving single intravenous doses of 75, 250, and 500 mg of MK-679. A greater than proportional increase in the area under the plasma concentration—time curve of MK-679 was observed with increase in dose. The plasma concentration data for each subject fitted well to the differential equations for a two-compartment model with linear tissue distribution and Michaelis-Menten elimination from the central compartment, indicating that the elimination of MK-679 in humans is saturable. In a previous study, the disposition of MK-679 in humans was also dose-dependent when given together with its S(+)-isomer, L-668,018. Thus, the disposition of MK-679 in humans is dose-dependent regardless of the presence of its stereoisomer. Also, the bioavailability of MK-679 was determined in six healthy males receiving simultaneously an oral dose of 250 mg of MK-679 and intravenous infusion of 1 mg ¹⁴C-MK-679. Results of this study indicate that the oral bioavailability of MK-679 is nearly quantitative.