Potentiation by deprenyl of the autoreceptor-mediated inhibition of [3H]-5-hydroxytryptamine release by 5-methoxytryptamine

Summary The 5-hydroxytryptamine (5HT) receptor agonist, 5-methoxytryptamine, inhibited in a concentration-dependent manner the electrically-evoked release of ³H-5HT from superfused rat hypothalamic slices, with an IC₅₀ of 560 nmol/l, without affecting the spontaneous outflow of radioactivity. In the presence of the selective monoamine oxidase B (MAO B) inhibitor, (–)-deprenyl (1 mol/l), the concentration-effect curve for 5-methoxytryptamine was shifted significantly to the left, and the IC₅₀ was decreased to 25 nmol/l. Under the same experimental conditions, the potency of the 5HT receptor agonist lysergic acid diethylamide (LSD) at inhibiting the electrically-evoked release of ³H-5HT was the same in the presence as well as in the absence of (–)-deprenyl. The IC₅₀ values for LSD were 34 nmol/l in the absence of deprenyl, and 31 nmol/l in the presence of the MAO B inhibitor. It is concluded that deprenyl potentiates the inhibition by 5-methoxytryptamine of ³H-5HT release, by preventing its inactivation through MAO B. Since 5-methoxytryptamine may be present in the pineal gland of some species, the potent effects of this 5-HT receptor agonist on seretoninergic neutrotransmission may be of physiological relevance.     

Differential effects of α-β-methylene ATP on responses to nerve stimulation in SHR and WKY tail arteries

Summary The effects of ,-methylene-adenosine triphosphate, (,-methylene ATP, a P₂-receptor desensitising agent) have been evaluated on vasoconstrictor responses elicited by exogenous agonists or electrical field stimulation in isolated perfused SHR or WKY tail arteries and on tritium release elicited by electrical field stimulation in SHR-tail arteries pre-labeled with ³H-noradrenaline.Exposure to ,-methylene ATP (0.1 mol/l) significantly inhibited vasoconstrictor responses to electrical field stimulation in SHR tail arteries. These inhibitory effects were not further increased at a higher concentration of ,-methylene ATP (1 mol/l). In WKY tail arteries, ,-methylene ATP (1 mol/l) failed to significantly inhibit vasoconstrictor responses to electrical stimulation.In SHR tail arteries prelabelled with ³H-noradrenaline, ,-methyleneATP (1 mol/l) did not inhibit the stimulation evoked release of tritium. However, at this concentration, ,-methylene ATP significantly antagonized the vasoconstrictor responses of SHR tail arteries induced by exogenous ATP (1 mol/l), ,-methylene ATP (30 mol/l), a stable agonist at P₂-receptors, or 60 mmol/l KCl. These effects of ,-methylene ATP on contractile responses to KCl were not observed in WKY-tail arteries.In tail arteries obtained from reserpine pretreated SHR, despite a 85–95% decrease in endogenous noradrenaline tissue content, the vasoconstrictor responses induced by periarterial field stimulation were greatly diminished, but not abolished. These residual responses to periarterial field stimulation were not antagonized by prazosin (0.1 mol/l), but were practically abolished by the addition of ,-methylene ATP (1 mol/l).In tail arteries from WKY rats pretreated with reserpine, exposure to prazosin (0.1 mol/l) further reduced the residual responses elicited by electrical field stimulation. In these WKY-tail arteries, addition of ,-methylene ATP (1 mol/l) did not further inhibit the remaining vasoconstrictor response obtained in the presence of prazosin.While our results suggest a significantly greater cotransmitter role for ATP with noradrenaline in tail arteries of SHR compared with control normotensive WKY rats, additional effects of ,-methylene ATP not involving P₂ receptors cannot be entirely excluded.     

Brainstem afferents to the omnipause region in the cat: a horseradish peroxidase study

"Omnipause" neurons (OPNs), located in the nucleus raphe pontis and the reticular formation, actively suppress saccadic eye movements during intersaccadic intervals. To determine the brainstem afferents that may inhibit the OPNs and thereby allow a saccade to occur, we injected horseradish peroxidase into the raphe pontis of four cats at the site of physiologically identified OPNs. Labeled neurons were found in a number of brainstem nuclei. The greatest concentrations, composed of small to medium-sized neurons, were located in a group of nuclei around the habenulopeduncular tract, in the rostral mesencephalic reticular formation, in the deep layers of the superior colliculus, and in parts of the subjacent cuneiform and subcuneiform reticular nuclei. Smaller numbers were found in the nucleus reticularis pontis oralis. Caudal to the injection site, labeled neurons were scattered in parts of the nuclei reticularis gigantocellularis, paragigantocellularis dorsalis, and paragigantocellularis lateralis. A few neurons were labeled in a restricted region of the causal part of the nucleus prepositus hypoglossi and in the nucleus reticularis medullaris ventralis. Larger numbers of neurons were labeled in the dorsal column nuclei and in parts of the cochlear nuclei. Smaller numbers were found in the spinal trigeminal nucleus, the lateral nucleus of the superior olive, and the fastigial nucleus of the cerebellum. The nonreticular brainstem projections may contribute sensory information in a number of modalities since OPNs respond to visual, somesthetic, and auditory stimuli. Our findings indicate a number of regions that may contain neural elements impinging on the OPNs. The best prospects for a saccade initiation signal from one of the labeled populations appear to be the meso-diencephalic reticular formation and/or the superior colliculus.     

Management of lung transplantation in the COVID-19 era—An international survey

It is unknown if solid organ transplant recipients are at higher risk for severe COVID-19. The management of a lung transplantation (LTx) program and the therapeutic strategies to adapt the immunosuppressive regimen and antiviral measures is a major issue in the COVID-19 era, but little is known about worldwide practice. We sent out to 180 LTx centers worldwide in June 2020 a survey with 63 questions, both regarding the management of a LTx program in the COVID-19 era and the therapeutic strategies to treat COVID-19 LTx recipients. We received a total of 78 responses from 15 countries. Among participants, 81% declared a reduction of the activity and 47% restricted LTx for urgent cases only. Sixteen centers observed deaths on waiting listed patients and eight centers performed LTx for COVID-19 disease. In 62% of the centers, COVID-19 was diagnosed in LTx recipients, most of them not severe cases. The most common immunosuppressive management included a decreased dose or pausing of the cell cycle inhibitors. Remdesivir, hydroxychloroquine, and azithromycin were the most proposed antiviral strategies. Most of the centers have been affected by the COVID-19 pandemic and proposed an active therapeutic strategy to treat LTx recipients with COVID-19.     

Experience with Radical esophagogastric devascularization procedures (Sugiura) for variceal bleeding outside Japan

The Sugiura operation has been reported to have low operative mortality, rebleeding, and encephalopathy rates when carried out in a predominantly nonalcoholic Japanese population with good liver function. A literature review of reports of the Sugiura procedure outside Japan reveals a high complication and mortality rate when it is used as an emergency procedure in patients with advanced liver disease, especially in those with alcoholic cirrhosis. Uncontrolled studies report results that differ little from the Japanese series when the operation is confined to good-risk patients in the elective situation. Our experience with the Sugiura operation supports its role in these circumstances, especially in patients with portal vein thrombosis and normal liver function. The only good prospective controlled trial has been carried out in patients with schistosomiasis and suggests that the Sugiura operation is far superior to total shunt and may have a slight advantage over the Warren shunt because of its low incidence of postoperative encephalopathy. More controlled trials are required to establish its role in good-to moderate-risk patients with alcoholic cirrhosis.

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Resumen Se ha informado que la operación de Sugiura se asocia con bajas tasas de mortalidad, de hemorragia recurrente y de encefalopatía cuando se la ejecuta en poblaciones no alcohólicas, predominantemente japonesas y con buena función hepática. Una revisión de la literatura sobre los resultados del procedimiento por fuera del Japón, revela elevadas tasas de mortalidad y de morbilidad cuando se la practica como operación de emergencia en pacientes con enfermedad hepática avanzada, especialmente en los cirróticos alcohólicos. Estudios no controlados informan resultados que no difieren grandemente de las series japonesas cuando el uso de la operación es confinado a pacientes de buen riesgo y en condiciones electivas. Nuestra experiencia con la operación de Sugiura da apoyo al rol que quede desempeñar en estas circunstancias, especialmente en pacientes con trombosis de la vena porta y función hepática normal. El único buen ensayo prospectivo y controlado ha sido realizado en pacientes con esquistosomiasis, el cual sugiere que la operación de Sugiura es superior al shunt total y que parece tener una ligera ventaja sobre el shunt de Warren en virtud de su may baja incidencia de encefalopatía postoperatoria. Se requieren ensayos clínicos controlados adicionales para definir y dejar establecido su papel en pacientes de riesgo bueno y moderado con cirrosis alcohólica.

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Résumé L'opération de Sugiura est réputée pour avoir une mortalité opératoire, un taux de récidive hémorragique et d'encéphalopathie réduites lorsqu'il s'agit d'une population japonaise, non-alcoolique avec une bonne fonction hépatique. Une revue de la littérature sur l'opération de Sugiura en dehors du Japon montre des taux de complications et de mortalité lorsqu'elle est utilisée pour les cas opérés en urgence, chez les patients ayant une maladie hépatique avancée et surtout d'origine alcoolique. Des études non contrôlées ont rapporté des résultats qui ne diffèrent que peu des séries japonaises lorsque l'intervention est pratiquée uniquement chez les patients à bon risque et dans un climat non urgent. Notre expérience de l'opération de Sugiura soutient ces notions, surtout lorsqu'il s'agit de patients ayant une thrombose portale et une bonne fonction hépatique. Par ailleurs, dans la seule étude prospective et contrôlée accomplie jusqu'à présent chez le patient ayant une bilharziose, il a été démontré que l'opération de Suguira était très supérieure à l'anastomose portocave complète et pourrait être même supérieure à celle de Warren en raison d'une incidence extrêmement basse d'encéphalopathie postopératoire. D'autres études contrôlées sont nécessaires pour établir son rôle chez le patient cirrhotique et alcoolique, à risque opératoire modéré.

     

Pharmacokinetics and bioavailability of benperidol in schizophrenic patients after intravenous and two different kinds of oral application

Pharmacokinetics and bioavailability of benperidol were determined in 13 schizophrenic patients after acute administration of 6 mg benperidol as an intravenous (i.v.) bolus injection, orally as liquid, and orally as tablets using a partially randomized cross-over design. Drug plasma levels were determined by high performance liquid chromatography with electrochemical detection and subjected to model independent pharmacokinetic analyses. After i.v. dosing the geometric means (mean-g) were 3.2 min for the distribution half-life, 5.80 h for the elimination half-life (t _1/2), 4.21 l/kg for the distribution volume, 7.50 h for the mean residence time (MRT), and 0.50 l/(h*kg) for the clearance. After oral administration as liquid and as tablet mean-g data for the time lag until the first appearance of measurable plasma concentrations were 0.33 and 1.1 h, mean-g t _1/2 values were 5.5 and 4.7 h, respectively, mean-g t _max data were 1.0 h and 2.7 h, mean-g MRT values were 8.44 and 8.84 h, and mean-g C _max ^maxvalues were 10.2 and 7.3 ng/ml. Differences between liquid and tablet administration were statistically significant for time lag,t _max, andC _max. Mean-g absolute bioavailabilities were computed as 48.6% after liquid and 40.2% after tablet administration respectively. All parameters studied exhibited large intersubject variation. The plasma concentrations of the presumed metabolite reduced benperidol were found to be very low.     

MRI of heart morphology. Comparison of nongradient echo sequences with single- and multislice acquisition.

RATIONALE AND OBJECTIVES: A large variety of cardiac MRI sequences have been introduced for heart morphology evaluation. The aim of this study was to establish a practicable and robust examination protocol for standard high-field systems applying nongradient echo sequences with single- and multi-slice acquisition. METHODS: Fifty-one patients received electrocardiogramgated MRI of the heart with "black-blood" preparation, comparing three single-slice and three multislice sequences with a T1-weighted turbo spin echo reference sequence. Demarcation of the left ventricular myocardium and cavity and the extent of flow and motion artifacts were assessed. RESULTS: The myocardium and left ventricular cavity were depicted best with the single-slice T1- and T2-weighted turbo spin echo sequence. The nonbreath-hold multislice sequences produced marked artifacts and therefore were of poor diagnostic value. The TIRM haste sequence was best suited for fat suppression. The T2-weighted breath-hold single-shot sequence with half-Fourier imaging proved to be most appropriate for multislice imaging. CONCLUSIONS: Sufficient depiction of heart morphology with comprehensive evaluation of signal changes can be achieved using nongradient spin echo and turbo spin echo sequences with breath-holding. For rational imaging of myocardial and heart chamber morphology, multislice and single-slice sequences should be combined.     

Cerebral and renal embolization after lymphography in a patient with non-Hodgkin lymphoma: case report

An unusual case of lipid embolization to brain and kidney after lymphography in a patient with non-Hodgkin lymphoma of the upper anterior mediastinum is reported. Contrast material-enhanced echocardiography demonstrated a right-to-left shunt to the left atrium without evidence of a patent foramen ovale. Echo contrast particles were transiently present within the tumor surrounding the great vessels.