2-[对-(二甲氨基)苯乙烯]氯化甲基吡啶对大鼠心电图、豚鼠左心房收缩及乳头肌动作电位的影响

2-[对-(二甲氨基)苯乙烯]氯化甲基吡啶(DSPM-Cl),是由氯取代2-[对-(二甲氨基)苯乙烯]碘化甲基吡啶(DSPM)上的碘而得。本文应用心电图、机械收缩描记方法及细胞内标准微电极技术,研究DSPM-Cl对大鼠心电图(ECG)、豚鼠心房肌量效曲线及对豚鼠乳头肌快反应动作电位(AP)、高钾除极慢反应动作电位(SAP)的影响。结果显示,DSPM-Cl(2mg·kg^-1)对大鼠有明显的负性频率、负性传导作用,分别使PP间期、PR间期延长达66.2%(P<0.01),17.0%(P<0.01),50μmol·L^-1能明显抑制左心房收缩力,非竟争性拮抗Iso及CaCl₂对豚鼠左心房的正性肌力作用,PD^2'分别为4.6,4.34,100μmol·L^-1DSPM-Cl延长动作电位时程APD₉₀,有效不应期(ERP),降低高钾除极豚鼠乳头肌0期最大上升速率Vmax,其作用与Ver相似,提示DSPM-Cl可能为钙拮抗剂。     

The Role of Serotonin (5-HT) in Behavioral Control: Findings from Animal Research and Clinical Implications

The neurotransmitters serotonin and dopamine both have a critical role in the underlying neurobiology of different behaviors. With focus on the interplay between dopamine and serotonin, it has been proposed that dopamine biases behavior towards habitual responding, and with serotonin offsetting this phenomenon and directing the balance toward more flexible, goal-directed responding. The present focus paper stands in close relationship to the publication by Worbe et al. (2015), which deals with the effects of acute tryptophan depletion, a neurodietary physiological method to decrease central nervous serotonin synthesis in humans for a short period of time, on the balance between hypothetical goal-directed and habitual systems. In that research, acute tryptophan depletion challenge administration and a following short-term reduction in central nervous serotonin synthesis were associated with a shift of behavioral performance towards habitual responding, providing further evidence that central nervous serotonin function modulates the balance between goal-directed and stimulus-response habitual systems of behavioral control. In the present focus paper, we discuss the findings by Worbe and colleagues in light of animal experiments as well as clinical implications and discuss potential future avenues for related research.     

2-Amino-3-aroyl-4,5-alkylthiophenes: agonist allosteric enhancers at human A(1) adenosine receptors.

2-Amino-3-benzoylthiophenes are allosteric enhancers (AE) of agonist activity at the A(1) adenosine receptor. The present report describes syntheses and assays of the AE activity at the human A(1)AR (hA(1)AR) of a panel of compounds consisting of nine 2-amino-3-aroylthiophenes (3a-i), eight 2-amino-3-benzoyl-4,5-dimethylthiophenes (12a-h), three 3-aroyl-2-carboxy-4,5-dimethylthiophenes (15a-c), 10 2-amino-3-benzoyl-5,6-dihydro-4H-cyclopenta[b]thiophenes (17a-j), 14 2-amino-3-benzoyl-4,5,6,7-tetrahydrobenzo[b]thiophenes (18a-n), and 15 2-amino-3-benzoyl-5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophenes (19a-o). An in vitro assay employing the A(1)AR agonist [(125)I]ABA and membranes from CHO-K1 cells stably expressing the hA(1)AR measured, as an index of AE activity, the ability of a candidate AE to stabilize the agonist-A(1)AR-G protein ternary complex. Compounds 3a-i had little or no AE activity, and compounds 12a-h had only modest activity, evidence that AE activity depended absolutely on the presence of at least a methyl group at C-4 and C-5. Compounds 17a-c lacked AE activity, suggesting the 2-amino group is essential. Polymethylene bridges linked thiophene C-4 and C-5 of compounds 17a-j, 18a-n, and 19a-o. AE activity increased with the size of the -(CH(2))(n)()- bridge, n = 3 < n = 4 < n = 5. The 3-carbethoxy substituents of 17a, 18a, and 19a did not support AE activity, but a 3-aroyl group did. Bulky (or hydrophobic) substituents at the meta and para positions of the 3-benzoyl group and also 3-naphthoyl groups greatly enhanced activity. Thus, the hA(1)AR contains an allosteric binding site able to accommodate 3-aroyl substituents that are bulky and/or hydrophobic but not necessarily planar. A second region in the allosteric binding site interacts constructively with alkyl substituents at thiophene C-4 and/or C-5.     

Venous clots: evaluation with MR imaging

In vitro and in vivo studies were performed to determine the proton relaxation and imaging characteristics of static blood and acute and organized clot in canine jugular veins. In vivo, it was found that two inversion recovery sequences using a short inversion time (100 msec) demonstrated better differentiation of signal intensity of intravascular clot from surrounding soft tissues than did standard T1- and T2-weighted sequences. In vitro, quantitative measurements showed marked reduction of both T1 and T2 relaxation time of acute clot compared with stagnant blood. In addition, the T1 relaxation time, and to a lesser extent the T2 relaxation time, shortened as the clot aged, indicating a potential role for magnetic resonance imaging in determining the age of venous thrombi.     

Significance of diastolic pulmonary artery pressure peaks

We describe a patient undergoing elective surgery for treatment of an abdominal aortic aneurysm in whom an abrupt change in the contour of the pulmonary artery pressure (PAP) trace indicated the development of an intermediate (20 mm Hg) V wave in the pulmonary artery wedge pressure (PAWP) trace. As the PAP trace is displayed continuously, attention to its contour may allow for early detection of changes to the underlying PAWP trace.FC Anaesth     

Trichinella infection and clinical disease

Trichinellosis is caused by ingestion of insufficiently cooked meat contaminated with infective larvae of <it>Trichinella</it> species. The clinical course is highly variable, ranging from no apparent infection to severe and even fatal disease. We report two illustrative cases of trichinellosis. Returning to Denmark a few days after having eaten roasted pork in the Republic of Serbia, a female patient suffered from severe vomiting, epigastric pain, diarrhoea, and later myalgia, generalized oedema, and prostration. A biopsy showed heavy infestation with <it>Trichinella spiralis</it>, 2000 larvae/g of muscle. Life-threatening cardiopulmonary, renal and central nervous system complications developed. The patient recovered after several months. Her husband, who also ate the pork, did not have clinical symptoms, but an increased eosinophil count and a single larva in a muscle biopsy confirmed infection. The epidemiology, clinical manifestations, diagnosis, treatment and prevention of trichinellosis are reviewed.      

Autoantibodies against bactericidal/permeability-increasing protein in patients with cystic fibrosis

Cystic fibrosis (CF), a genetic disorder, is characterized by chronic pulmonary infection/inflammation which leads to respiratory failure. The presence of anti-neutrophil cytoplasmic autoantibodies (ANCA) has previously been observed in the sera of patients with CF. In view of the known relationship of ANCA with primary vasculitis and of their putative pathogenetic role in these disorders, we studied the presence, specificity and isotype of ANCA and their clinical associations in 66 adult CF patients. None of the 66 CF samples had autoantibodies to the major ANCA antigens, proteinase 3 or myeloperoxidase. However, 60/66 (91%) CF samples contained IgG and 55/66 (83%) IgA, autoantibodies to bactericidal/permeability increasing protein (BPI), a recently characterized ANCA specificity. All the IgA anti-BPI-positive samples were also IgG anti-BPI-positive. The autoantibody specificity was confirmed by inhibition assay and immunoblotting of CF sera against a neutrophil granule preparation. Furthermore, in this cross-sectional study, anti-BPI levels were inversely correlated with the observed reductions in FEV1 and FVC (IgA anti-BPI and FEV1: r = 0.508, <it>p</it> &lt; 0.0001), and both IgG and IgA anti-BPI levels were higher in CF patients with secondary vasculitis (<it>n</it> = 6) than in those without (<it>p</it> &lt; 0.05). ANCA with specificity for BPI were present in the majority of CF sera in this study and autoimmune processes may be associated with the development of pulmonary injury in CF.