Derivates of 1,1-dioxo-1,4,2-benzoditiazines. Part XII. Synthesis and pharmacology of some 6-chloro-3-carboxyalkylamino-7-methyl-1,1-dioxo-1,4,2-benzodithiazines

Preparation of some novel 6-chloro-3-carboxyalkylamino-7-methyl-1,1-dioxo-1,4,2-benzodithiazines (I-V) and its sodium salts (Ia, IVa) have been elaborated. Their chemical structures have been confirmed by elemental analysis, IR and 1H-NMR spectrometry. In preliminary pharmacological examination compounds I, Ia, IV and IVa exhibited low acute toxicity, moreover investigated compounds shown hypertensive and cholagogic activity (I, Ia) and also hypotensive (IV, IVa) or diuretic (Ia, IVa) activity, on the other hand above mentioned compounds didn't exhibit antiarrhythmic activity. Some relationships between the chemical structure and pharmacological activity of the investigated compounds have also been discussed.     

Aristolochic acids in Aristolochia chilensis

The major components of the acid fraction of the leaves and tender stems of Aristolochia chilensis Miers are aristolochic acids I and Ia. Aristolochic acid Ia has been isolated from plant material for the f?rst time, and its PMR spectrum is discussed.     

Income differences in persons seeking outpatient treatment for mental disorders: a comparison of the United States with Ontario and The Netherlands

BACKGROUND: Variations in the relationships among income, use of mental health services, and sector of care are examined by comparing data from 3 countries that differ in the organization and financing of mental health services. METHODS: Data come from the 1990-1992 National Comorbidity Survey (n = 5,384), the 1990-1991 Mental Health Supplement to the Ontario Health Survey (n = 6,321), and the 1996 Netherlands Mental Health Survey and Incidence Study (n = 6031). Analysis of the association between income and use of mental health services was carried out for the population that was between ages 18 and 54 years. Differential use of mental health treatment was examined in 3 sectors: the general medical sector, the specialty sector, and the human services sector. RESULTS: No significant association between income and probability of any mental health treatment was observed for persons with psychiatric disorders in any of the 3 countries. However, there were significant differences among countries in the association between income and sector of mental health care treatment. In the United States, income is positively related to treatment being received in the specialty sector and negatively related to treatment being received in the human services sector. In the Netherlands, patients in the middle-income bracket are less likely to receive specialty care, while those in the high-income bracket are less likely to be seen in the human service sector. Income is unrelated to the sector of care for patients in Ontario. CONCLUSIONS: Future research should examine whether differential access to the specialty sector for low-income people in the United States is associated with worse mental health outcomes.     

Stimulating amino acids in epilepsy: possibilities of treatment

Stimulating amino acids (glutamine and aspargine) play an essential role in epileptogenesis. Activating receptors NMDA, AMPA, kainate and metabotropic influence a conduction of ion canals and a beginning, duration and extinction of epileptic discharges. Some of the new anti-epileptic drugs introduced in the recent years modify functioning of glutamine receptors subtypes. It is expected that they can also decrease a release of glutamines, amplify a GABA-ergic suppression and block sodium channels. Most information about these drugs in epileptogenesis was received in animal experiment which is an excuse for a lack of certainty in a parallel referring their mechanisms to the central nervous system in a man. Treatment resistant focal or general epilepsies and some epileptic syndromes are the most often appearing indications for using agents producing an effect on activating amino acids system. They are most often used in an added therapy, more rarely in a monotherapy. Some negative comments concern not very clear influence on cognitive functions, however some hope arises due to a potential neuroprotective mechanism being a result of a decreased glutamine release. The drugs blocking a stimulating transmission should be a good supplement for a present possibilities of epileptic treatment.     

Participation of low-threshold calcium spikes in excitatory synaptic transmission in guinea pig medial frontal cortex

We studied the activation of low-threshold calcium spikes (LTS) by excitatory postsynaptic potentials in pyramidal neurons from guinea pig medial frontal cortex with intracellular recording. We used extracellular bicuculline and phaclofen and intracellular QX-314 to block inhibitory synaptic potentials and sodium currents. Postsynaptic potentials were evoked by stimulation of layer I. We found that large (> 10-15 mV) excitatory synaptic potentials evoked from membrane potentials more negative than -75 mV were able to trigger LTS. The activation of LTS resulted in an increase of the rising slope or amplitude of the synaptic potentials depending on the size of the excitatory postsynaptic potential (EPSP). We used 100 microM NiCl2 to confirm the presence of LTS as part of the EPSPs. The N-methyl-D-aspartate (NMDA) and non-NMDA components of the excitatory synaptic potentials were isolated using (+/-)2-amino-5-phosphonovaleric acid (APV; 50 microM) or 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 20 microM); both components could, independently, trigger an LTS. With recordings made with K+ acetate-filled electrodes, we show that the activation of LTS was critical to allow excitatory synaptic potentials to reach the threshold of action potential firing; also, this amplification of synaptic responses produced the firing of more than a single action potential by the postsynaptic cell. These results demonstrate that in cortical pyramidal neurons the activation of low-threshold calcium spikes results in the amplification of synaptic responses.     

Serotonergic and noradrenergic function in depression: clinical correlates

The present study was conducted in order to investigate the relationships between central noradrenergic (NA) and serotonergic (5-HT) function and clinical characteristics of a major depressive episode according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. We measured growth hormone response (ΔGH) to clonidine (CLO) (an α2 NA agonist), as an index of central NA function, and prolactin response (APRL) to d-fenfluramine (d-FEN) (a specific 5-HT releaser/uptake inhibitor), as an index of central 5-HT function, in 53 medication-free depressed inpatients. On the basis of their CLO and d-FEN test responses, patients were classified into 4 groups. Group 1 (blunted ΔPRL(d-FEN) alone [11 %]) was characterized by a recent violent suicide attempt, a high degree of medical damage, and mild anxiety. Group 2 (blunted ΔGH(CLO) alone [32%]) was characterized by an absence of a history of suicide attempt and by severe anxiety. Group 3 (combination of blunted ΔGH(CLO) and APRL(d-FEN) [18%]) was characterized by a history of suicide attempts, total duration of the illness of over W years, age over 40 years, and more than 3 previous hospitalizations. Group 4 (no abnormality [39%]) had no specific clinical profile. These results suggest that, in depression, specific psychopathological features may be linked to 5-HT and/or NA dysfunction. However, our results also suggest that NA and/or 5-HT dysfunction are less likely to be the primary cause of mood disorders but are more indicative of failure of compensatory mechanisms involved in affective homeostatic processes.     

Dural enhancement in pituitary macroadenomas

We describe the normal dural enhancement patterns of the sellar region and determine whether the duramater is affected by pituitary macroadenomas. Dural enhancement appeared to be usually abnormal in 20 patients with pituitary macroadenoma compared with 20 control patients, mainly at the planum sphenoidale and carotid sulcus. However dural changes are subtle and their recognition requires knowledge of the normal enhancement patterns. Dural changes, reported in a variety of inflammatory and infectious dural diseases and after surgery, are not specific and may be also seen in pituitary macroadenomas. Received: 12 December 1998 Accepted: 3 November 1999     

穴位注射治疗溃疡性结肠炎临床观察

为探讨和分析穴位注射治疗溃疡性结肠炎的作用及其机制 ,运用穴位注射治疗溃疡性结肠炎 44例 ,有效率 93 3 %。西药治疗组 46例 ,有效率 93 5 %。经统计学处理 ,穴位注射组与西药治疗组比较 ,近期疗效差异无显著性意义 ,P >0 0 5 ;其复发率两组比较差异具有显著性意义 ,P <0 0 5。