A pharmacological study of the angiotensin receptor and tachyphylaxis in smooth muscle.

The interaction of angiotensin with its receptor has been studied on the basis of the tachyphylaxis shown by the rat uterus towards angiotensin II when pH and Ca2+ concentration are below physiological levels. 14C-Angiotensin binding and 45Ca2+-uptake investigations suggest tachyphylaxis to be due to increased binding at low pH and Ca2+ concentration. Studies with alkylating (affinity labeled) angiotensin derivatives containing the N-mustard chlorambucil suggest a "Charnière type" inhibition at the Ca-binding site of receptor and an irreversible inhibition at an anionic site. Angiotensin inhibitors containing chlorambucil do not alkylate tissue but are competitive inhibitors suggesting that the aromatic side chain in angiotensin may induce conformational changes in the receptor. The results obtained lead to a logical model for the angiotensin receptor allowing for normal activation by the hormone as well as for production of tachyphylaxis.     

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.     

Attentional set shifting modulates the target P3b response in the Wisconsin card sorting test

For years the Wisconsin card sorting test (WCST) has been used as a test of frontal lobe function. Recent event-related potential (ERP) research has shown large differences in the amplitude of P3b responses evoked by early and late trials within each WCST series ([8]: Barceló F., Sanz M., Molina V., Rubia FJ. The Wisconsin Card Sorting Test and the assessment of frontal function: A validation study with event-related potentials. Neuropsychologia 1997;35:399-408). In this study, 16 normal subjects performed a WCST adaptation to investigate the role of attentional set shifting in these WCST P3b effects. Two control tasks were designed to examine whether early-late WCST P3b changes reflect category selection (attention) or category storage (memory) operations. Results suggest both a sharp P3b attenuation during shift WCST trials, followed by a gradual P3b build-up during post-shift trials. This P3b modulation could not be attributed to selection or storage of simple sensory stimulus dimensions, nor was it observed when the new rule was externally prompted by the first card in the WCST series. Instead, WCST P3b changes seem related to the endogenously generated shift in the perceptual rule used to sort the cards (i.e., the shift in set). The gradual build-up in P3b amplitude paralleled a progressive improvement in sorting efficiency over several post-shift WCST trials. A model based on formal theories of visual attention and attentional set shifting is proposed to account for these effects. The model offers firm grounds for prediction and bridges the gap between related clinical and experimental evidence.     

Subthalamic neuron activity related to tremor and movement in Parkinson's disease

Single cell activity recorded in the subthalamic nucleus (STN) of Parkinson's patients and the effect of tremor, passive and voluntary movement upon the same cells are described. Three types of cells were distinguished by the pattern of discharge: tonic, phasic and rhythmic. They all demonstrated high mean firing rates (65, 59 and 69 Hz, respectively). Simultaneous recordings of muscle activity and tremor helped in defining cell activity. The implantation of the definitive stimulating electrode in the patients was based on the number of STN cells related to tremor, active and passive movements (mean = 68%) along the track chosen. Cells were related to tremor (n = 21; 11%), modified the discharge with differences in the amplitude of tremor (n = 4), and changed the rate and pattern when tremor stopped spontaneously or artificially (n = 6). Movement-related cells (n = 97; 51%) showed a cyclic activity correlated with phases of the movement, or modified the firing rate along the performance of the movement. Tremor and movement-related cells (n = 11; 6%) revealed an interesting sensory-motor integrative function.     

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     

SIALYL-Tn ANTIGEN DISTRIBUTION IN HELICOBACTER PYLORI CHRONIC GASTRITIS IN CHILDREN: AN IMMUNOHISTOCHEMICAL STUDY

Sialyl-Tn antigen (STn) is a mucin-type carbohydrate normally present in goblet cells of small and large bowel. STn expression has been demonstrated to occur in complete and incomplete intestinal metaplasia as well as in many carcinomas but in no normal gastric cell. The aim of our present study was to evaluate the distribution of STn in Helicobacter pylori chronic gastritis (HpCG) of pediatric patients. Eighteen gastric biopsies from 15 children (mean age: 11.5 years) with HpCG, 9 gastric biopsies from 9 children without H. pylori infection, and 1 heterotopic gastric mucosa in Meckel's diverticulum were immunostained using the anti-STn antibody STn1 (18/18), NCL-MUC-1 (7/18), and NCL-MUC-2 (18/18) antibodies. Also, sulfated mucosubstances were investigated with the Alcian Blue-Periodic Acid Schiff (AB-PAS), pH 1.0 stain. Although with different intensity (weak in 5/18, moderate 9/18, and intense 4/18) all cases with HpCG exhibited STn immunoreactivity. The expression of STn was found to be located mainly to the supranuclear region of the epithelial cells at the foveolae and glandular necks, with occasional cells showing diffuse cytoplasmic staining. When reactivity was intense, it was for the most part found in the cells at the neck of the glands. The mucus out of the luminal border above the positive cells was usually also stained. MUC-1 was negative (2/7) or weakly positive (5/7) in a few surface mucous cells. MUC-2 was negative (16/18) or occasionally detected in some foveolar and surface cells (2/18). AB-PAS pH 1.0 revealed the presence of sulfomucins in the cytoplasm of isolated cells of gastric pits and glands of most cases (11/15). None of these findings was observed in the control group. We conclude that STn can be identified in gastric cells of pediatric patients with HpCG and that this does not correlate with other mucosubtances markers. Thefindings could indicate that minimal intestinal metaplasia takes place in children with HpCG.