Effect of destruction of central noradrenergic and serotonergic nerve terminals by systemic neurotoxins on the long-term effects of antidepressants onβ-adrenoceptors and 5-HT2 binding sites in the rat cerebral cortex

Summary The dependence of intact noradrenergic and serotonergic nerve terminals for the decrease in the number ofgif" alt="beta" align="MIDDLE" BORDER="0">-adrenoceptors and 5-HT₂ binding sites in the cerebral cortex produced by long-term treatment of rats with antidepressant drugs was examined. Noradrenergic nerve terminals were destroyed with the selective noradrenaline neurotoxin DSP4, and serotonergic nerve terminals were destroyed with p-chloroamphetamine (PCA). It was found that lesioning of the noradrenergic nerve terminals abolished the decrease ingif" alt="beta" align="MIDDLE" BORDER="0">-adrenoceptors produced by desipramine, mianserin and zimeldine and partially antagonized that of thegif" alt="beta" align="MIDDLE" BORDER="0">-adrenoceptor agonist clenbuterol. PCA pretreatment did not antagonize the long-term effects on thegif" alt="beta" align="MIDDLE" BORDER="0">-adrenoceptor produced by these compounds.Lesioning of serotonergic nerve terminals affected the down-regulation of 5-HT₂ binding sites produced by long-term treatment with mianserin, desipramine and amiflamine. DSP4 pretreatment partially abolished the down-regulation of 5-HT₂ binding sites produced by long-term treatment with desipramine, while the effects of mianserin and amiflamine were unaffected by pretreatment with DSP4.     

The effect of neuroleptic treatment and of high dosage diazepam therapy onβ-endorphin immunoreactivity in plasma of schizophrenic patients

Summary Synapsin I (Protein I), a neuron-specific phosphoprotein enriched in presynaptic nerve terminals, has been used as a quantitative marker for the density of nerve terminals in five brain regions (caudate nucleus, cingulate gyrus, hippocampus, mesencephalon and putamen) from patients who had suffered from Alzheimer disease/senile dementia of Alzheimer type (AD/ SDAT), from patients with multi-infarct dementia (MID), and from agematched controls. Samples were obtained at autopsy. Lower levels of Synapsin I were observed in the hippocampus of patients with AD/SDAT but not with MID. There were no significant differences in Synapsin I levels between patients and controls in any of the other four brain regions examined.     

Huntington's disease: biochemical prediction by determination of GABA synthesis of cultured fibroblasts

Summary GABA synthesis in skin fibroblasts from patients with Huntington's chorea was compared with that in a control group by means of the highly specific ³H-muscimol radioreceptor assay. A significantly increased rate of GABA synthesis was found in the group with Huntington's chorea in an early cell passage. The possible use of this method for early diagnosis of Huntington's chorea is considered.

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Zusammenfassung Die GABA-Synthese in Hautifbroblasten von Chorea Huntington-Patienten im Vergleich zu einer gesunden Kontrollgruppe wurde mittels des hochspezifischen ³H-Muscimol-Radiorezeptoren-Assays untersucht. Wir fanden eine signifikante 8fache Erhöhung der GABA-Synthese bei Chorea Huntington in einer frühen Zellpassage. Es wird erwogen, diese Methode zur Frühdiagnostik von Chorea Huntington einzusetzen.

     

Hypotensive brain stem necrosis in a stillborn

Summary Hypotensive brain stem necrosis is reported in a stillborn. Additional postmortem findings included evidence of intrauterine distress, shock, and a pure blood culture of group B gif" alt="beta" align="MIDDLE" BORDER="0">-hemolytic streptococci. These findings suggest group B gif" alt="beta" align="MIDDLE" BORDER="0">-hemolytic streptococcal sepsis in utero, with a subsequent episode of transitory circulatory failure prior to intrauterine demise.     

Ultrastructural observations on the vincristine-induced neuronal crystalloid inclusion in young rats

Summary Vincristine-induced crystalloid inclusions were examined in the neurons and neuronal processes of young rats by the electron microscope (EM) equipped with a tilting stage. Using a computer system that reproduces three-dimensional organization, an optical transformation method was applied to the microtubules and neurofilaments in an attempt to clarify the morphological appearance and internal pattern of crystalloid inclusions. The dimensional models obtained were compared with actual EM photographs, and the characteristic ultrastructural component and morphology were drawn out.Basically, a crystalloid inclusion is composed of four strands of intermediate 10 nm neurofilaments connected to one another by four side-arms producing a circular profile on a transverse section. These four side-arms seemed to arise from nodules within the filaments at regular intervals simulating a bead-like appearance. These data did not significantly differ from those obtained from EM images. Characteristically, these crystalloid inclusions began to appear 6 h after the administration of 10^–3 M vincristine sulfate and persisted up to a period of 6 days. Beyond that, however, these inclusions were no longer demonstrable suggesting a transient state. This was in contrast to neurofibrillary tangles which appeared to be permanent changes.     

Comparison of the α-adrenoceptor antagonist profiles of idazoxan (RX 781094), yohimbine,rauwolscine and corynanthine

Summary In the present studies the potency and selectivity of idazoxan (RX 781094) were compared with yohimbine and its diastereoisomers rauwolscine and corynanthine in both functional studies and radioligand binding experiments. Prejunctional gif" alt="agr" align="BASELINE" BORDER="0">₂- and postjunctional gif" alt="agr" align="BASELINE" BORDER="0">₁-adrenoceptor antagonist potencies were assessed by determining pA₂ values against clonidine on the stimulated rat vas deferens and noradrenaline on the anococcygeus muscle, respectively. The rank order of prejunctional gif" alt="agr" align="BASELINE" BORDER="0">₂-adrenoceptor antagonist potency was idazoxan > yohimbine > rauwolscine gif" alt="Gt" align="MIDDLE" BORDER="0"> corynanthine. At postjunctional gif" alt="agr" align="BASELINE" BORDER="0">₁-adrenoceptors the rank order of antagonist potency was rauwolscine > corynanthine > yohimbine > idazoxan. The selectivity values (gif" alt="agr" align="BASELINE" BORDER="0">₂/gif" alt="agr" align="BASELINE" BORDER="0">₁) for idazoxan, yohimbine, rauwolscine and corynanthine were 245, 45, 3 and 0.03 respectively. The selectivity and potency profiles established for these antagonists in functional studies were confirmed in radioligand binding studies utilising ³H-idazoxan (gif" alt="agr" align="BASELINE" BORDER="0">₂) and ³H-prazosin (gif" alt="agr" align="BASELINE" BORDER="0">₁) in rat cerebral cortex.In pithed rats intravenously administered idazoxan, yohimbine and rauwolscine fully reversed the inhibitory effects of clonidine on electrically-induced contractions of the vas deferens; idazoxan was approximately ten times more potent than both yohimbine and rauwolscine. Corynanthine was inactive. Idazoxan and yohimbine also fully antagonised the inhibitory effects of guanabenz on electrically-induced contractions of the anococcygeus muscle; idazoxan again was more than ten times more potent than yohimbine in this model. The inhibitory effects of guanabenz were less readily antagonised by rauwolscine indicating that the selectivity of this compound is less than that of yohimbine in this tissue. Corynanthine was again inactive.Studies were also undertaken in which the effects of an extended range of antagonists were examined on contractions of the anococcygeus muscle induced either by electrical stimulation or intra-arterial phenylphrine. Selective gif" alt="agr" align="BASELINE" BORDER="0">₁-adrenoceptor antagonists produced a parallel block of the effects of stimulation and phenylephrine indicating that the postjunctional receptor in this tissue is predominantly gif" alt="agr" align="BASELINE" BORDER="0">₁- character. In this tissue idazoxan potentiated nerve stimulation without inhibiting phenylephrine responses; of the compounds studied only idazoxan failed to influence phenylephrine responses.Under the present experimental conditions idazoxan only produced antagonist properties at gif" alt="agr" align="BASELINE" BORDER="0">-adrenoceptors and consistently displayed improved gif" alt="agr" align="BASELINE" BORDER="0">₂-selectivity and potency with respect to yohimbine and rauwolscine.     

The recovery of α-adrenoceptor function and binding sites after phenoxybenzamine

Summary The recovery of peripheral gif" alt="agr" align="BASELINE" BORDER="0">-adrenoceptor function and binding sites was studied in male New Zealand white rabbits after treatment with the irreversible adrenoceptor antagonist phenoxybenzamine. Phenoxybenzamine (5 mg/kg) was administered intravenously and the animals studied 30 min to 12 days later. Pressor dose response curves to intravenous phenylephrine, noradrenaline and guanabenz were constructed in vivo in conscious animals. The contractile response of abdominal aorta and renal artery to phenylephrine and noradrenaline was examined in vitro and the recovery of specific prazosin and clonidine binding to spleen membranes investigated in radioligand binding studies.The half life (t _1/2) for recovery of maximum pressor response in vivo ranged from 0.9±0.2 days for phenylephrine to 1.4±0.1 days for guanabenz. The t _1/2 for recovery of ED₅₀ was not significantly different to t _1/2 for recovery of maximum pressor response and ranged from 0.8±0.2 days for noradrenaline to 1.3±0.3 days for phenylephrine.Half life for recovery of maximum response and EC₅₀ in the isolated tissues was similar to that obtained in vivo for recovery of pressor responses and ranged from 0.4±0.1 days for the EC₅₀ of noradrenaline in the renal artery to 1.2±0.6 days for maximum response to phenylephrine in the abdominal aorta.The rate of recovery of specific clonidine binding did not differ significantly from the rate of recovery of pressor responses to the gif" alt="agr" align="BASELINE" BORDER="0"> ₂-selective agonist guanabenz. t _1/2 for maximum number of specific clonidine binding sites, B _max was 1.6±0.9 days. However t _1/2 for recovery of specific prazosin binding was significantly longer than recovery of responses to phenylephrine and noradrenaline, t _1/2 for B _max was 3.6 ±0.1 day.     

A social-psychological perspective on successful community control of high blood pressure: A review

This review brings together studies dealing with factors that affect participation in screening, referral, and treatment for high blood pressure (HBP). Community-based screening programs are examined first, in order to describe the changing and the current distribution of hypertensives as gif" alt="ldquo" align="MIDDLE" BORDER="0">unaware,gif" alt="rdquo" align="MIDDLE" BORDER="0"> untreated, treated but uncontrolled, and controlled by treatment. Factors influencing this distribution are examined. Next, data on referral, acceptance of treatment, and staying in treatment are discussed, with a special reference to intervention studies. The review then brings in the broader social science literature on the psychosocial dynamics of health-maintaining and risk-reducing behaviors. The article concludes with an interpretive summary and some suggestions for further action.