Distinct Pharmacologic Properties of Neuromuscular Blocking Agents on Human Neuronal Nicotinic Acetylcholine Receptors: A Possible Explanation for the Train-of-four Fade

Background: Nondepolarizing neuromuscular blocking agents (NMBAs) are extensively used in the practice of anesthesia and intensive care medicine. Their primary site of action is at the postsynaptic nicotinic acetylcholine receptor (nAChR) in the neuromuscular junction, but their action on neuronal nAChRs have not been fully evaluated. Furthermore, observed adverse effects of nondepolarizing NMBAs might originate from an interaction with neuronal nAChRs. The aim of this study was to examine the effect of clinically used nondepolarizing NMBAs on muscle and neuronal nAChR subtypes.

Methods: Xenopus laevis oocytes were injected with messenger RNA encoding for the subunits included in the human [alpha]1[beta]1[varepsilon][delta], [alpha]3[beta]2, [alpha]3[beta]4, [alpha]4[beta]2, and [alpha]7 nAChR subtypes. The interactions between each of these nAChR subtypes and atracurium, cisatracurium, d-tubocurarine, mivacurium, pancuronium, rocuronium, and vecuronium were studied using an eight-channel two-electrode voltage clamp setup. Responses were measured as peak current and net charge.

Results: All nondepolarizing NMBAs inhibited both muscle and neuronal nAChRs. The neuronal nAChRs were reversibly and concentration-dependently inhibited in the low micromolar range. The mechanism (i.e., competitive vs. noncompetitive) of the block at the neuronal nAChRs was dependent both on subtype and the NMBA tested. The authors did not observe activation of the nAChR subtypes by any of the NMBAs tested.     

Deficits in spatial coding and feature binding following damage to spatiotopic maps in the human pulvinar.

We report a patient with unilateral damage to the rostral part of the pulvinar who was impaired in localizing stimuli in the inferior visual field contralateral to the lesion and who made errors in the binding of shape and color in that quadrant. The findings demonstrate the importance of the pulvinar in spatial coding and provide support for the function of the thalamus in binding of features. They also provide evidence for a homology between the visual field maps of the inferior and lateral subdivisions of the pulvinar in monkeys and in humans, such that the inferior visual field is represented in the rostral part of the nucleus.     

Volvulus of the sigmoid colon. Emergency resection and anastomosis]

Eleven cases of sigmoid volvulus in patients aged 76 years in average, without visible signs of necrosis on endoscopy, are reported. All patients were treated within 6 to 48 hours by colic resection and immediate restoration of continuity with a mechanical anastomosis. Morbidity was low, including one case of evisceration and one of pneumonia, and there was no mortality after three months. Early resection seems to prevent the risks of necrosis and recurrence, and to have a good prognosis for survival.     

Changes in intra-abdominal pressure and central venous and brain venous blood pressure in patients during extracorporeal circulation.

BACKGROUND: The aim was to analyze IAP changes and the relationships between IAP, CVP, and brain venous blood pressure, which are still unknown, in patients undergoing coronary artery bypass grafting (CABG) with extracorporeal circulation. MATERIAL/METHODS: Twenty-five male patients (aged 53-67 years) underwent CABG under general anesthesia with normovolemic hemodilution. IAPs were measured in the urinary bladder, CVP by left internal jugular vein cannulation, and brain venous blood pressure by retrograde cannulation of the right jugular vein bulb (JVP, jugular vein pressure) at seven time-points: 1) after induction of anesthesia before the operation, 2) during internal thoracic artery preparation, 3) 10 minutes after heart-lung machine disconnection, 4) after procedure completion, before sending the patient to the intensive postoperative care unit, 5) one hour after the procedure, 6) 6 hours after the procedure, and 7) 18 hours after the procedure. RESULTS: IAP increased from points 3 to 6. CVP increased from points 3, 4, and 5 and decreased at point 7. Similar changes were noted in JVP. There were significant correlations between IAP and CVP at points 1, 2, 3, 4, and 5, IAP and JVP at points 3, 4, and 5, and CVP and JVP at all points. The overall analysis showed correlations between IAP and CVP and JVP and very strong correlation between CVP and JVP. CONCLUSIONS: 1) CABG with extracorporeal circulation resulted in increases in IAP, CVP, and brain venous blood pressure. 2) The changes in CVP and brain venous blood pressure correlated with intra-abdominal pressure.     

Mapping the architecture of the ATP-binding site of the KATP channel subunit Kir6.2

ATP-sensitive potassium (K_ATP) channels comprise Kir6.2 and SUR subunits. The site at which ATP binds to mediate K_ATP channel inhibition lies on Kir6.2, but the potency of block is enhanced by coexpression with SUR1. To assess the structure of the ATP-binding site on Kir6.2, we used a range of adenine nucleotides as molecular measuring sticks to map the internal dimensions of the binding site. We compared their efficacy on Kir6.2–SUR1, and on a truncated Kir6.2 (Kir6.2ΔC) that expresses in the absence of SUR. We show here that SUR1 modifies the ATP-binding pocket of Kir6.2, by increasing the width of the groove that binds the phosphate tail of ATP, without changing the length of the groove, and by enhancing interaction with the adenine ring.     

Über die Rolle von Makrophagen in der Pathogenität des Vacciniavirus für junge Ratten

Zusammenfassung Das Vacciniavirus vermehrt sich schnell in den Organen von 1 tägigen Ratten, und die Tiere verenden am 2. oder 3. Tag nach der Infektion. In den Organen von 7 tägigen Ratten kann sich das Virus anfangs vermehren, später wird es aber eliminiert und die Tiere überleben. Bei 15tägigen Ratten wird das Virus eliminiert und die Tiere verenden nicht.Eintägige Ratten, die vor der Infektion Makrophagen erwachsener Tiere erhalten haben, kamen nicht ad exitum. Die Makrophagen von erwachsenen Ratten haben im Gegensatz zu Makrophagen von jungen Tieren die Fähigkeit, das phagozytierte Virus zu inaktivieren.Es wird daraus der Schluß gezogen, daß für die hohe Empfindlichkeit junger Ratten gegenüber Vacciniavirusinfektionen die funktionelle Unreife ihrer Makrophagen verantwortlich ist.

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The role of macrophages in the pathogenicity of vaccinia virus for young rats

Summary Vaccinia viruses grew rapidly in organs of 1-day-old rats, and the animals died 2 or 3 days after infection. In the organs of 7-day-old rats the viruses replicated initially, but were later eliminated and the animals survived. The 15-day-old rats were capable of eliminating the viruses completely and did not die. When macrophages of adult animals were transferred to 1-day-old rats before infection the rats did not die. The macrophages of adult rats destroyed phagocytized viruses while those of young animals did not.The results suggest that this susceptibility of young rats to vaccinia virus infection is due to the functionally immature state of their macrophages.