Studies on the muscarine receptors in rat gastric smooth muscle

It has been reported that the two types of muscarinic receptors, "M1" and "M2", exist in the opossum lower esophageal sphincter. The presence of these muscarinic receptor subtypes had been confirmed with the discovery of the M1 selective antagonist, pirenzepine. But little is known about muscarinic receptor subtypes in gastric smooth muscle. The aim of this study was to identify the muscarinic receptor subtypes on the gastric smooth muscle responsible for the contraction of rat gastric muscle strip. Also, we examined the mechanism of the action of aclatonium napadisilate on rat gastric smooth muscle in vitro. The stimulation of M2 receptor caused the contraction of the gastric smooth muscle. McN-A-343, selective M1 agonist, caused weak contraction of the gastric smooth muscle, and this response was not affected by the selective M1 antagonist, pirenzepine. Aclatonium napadisilate stimulated M2 receptor and caused the gastric smooth muscle contraction. We conclude that the contraction of the gastric smooth muscle is caused by the stimulation of the M2 receptor and this reaction was not affected by tetrodotoxin, suggesting the M2 receptor is located directly on the gastric smooth muscle. The weak contraction of the gastric smooth muscle caused by McN-A-343 was not affected by the selective M1 antagonist, pirenzepine, suggesting that McN-A-343 may not be a pure M1 selective agonist. The action of aclatonium napadisilate is supposed to stimulate the M2 receptor.     

Changes of the beat amplitude power after partial left ventriculectomy and coronary artery bypass grafting

Partial left ventriculectomy (PLV) was originally introduced as a new surgical approach by patients with an end stage of cardiac disease. Coronary artery bypass grafting (CABG) is a standard procedures used in cardiac surgery. Multichannel ECG (MECG) measurements and body surface mapping (BSM) were used to analyse the normalised beat amplitude power maps (BAM) that reflect an overall cardiac activity. The resulting BAMs show that the amplitude of cardiac signals decrease for approximately 30% after the PLV and stay in the same level during the postoperative monitoring interval while after CABG no significant changes in BAM have been observed. In addition the electrodes from the body surface area above the left ventricle, where surgery was performed, show significant changes in beat amplitudes.     

Novel SARS-CoV-2 Variant in Travelers from Brazil to Japan

Multiple severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with higher transmission potential have been emerging globally, including SARS-CoV-2 variants from the United Kingdom and South Africa. We report 4 travelers from Brazil to Japan in January 2021 infected with a novel SARS-CoV-2 variant with an additional set of mutations.     

Heparin-induced thrombocytopenia with multiple organized thrombi accompanied by unusual cholesterin deposition: Autopsy case after long-term follow up

Heparin-induced thrombocytopenia (HIT) is characterized by a reduction in the platelet count and systemic thromboembolism during heparin therapy. Herein is reported a case of HIT with characteristic thrombus formation. A 68-year-old man who had been treated for hypertension for 27 years suffered a brain infarction and was treated with heparin. After this treatment, other new infarctions occurred in multiple organs. Because serum antibodies against heparin/PF4 complex were detected, he was diagnosed as having HIT, and warfarin and argatroban were administered instead of heparin. He died, however, 119 days after the first onset. At autopsy infarction due to organized thrombi with cholesterin deposition in multiple organs were found, similar to usual atherosclerotic emboli, but different to them with regard to clinical course and distribution of thrombi. This case in which organization and frequent cholesterin deposition were found in thromboembolized lesions of multiple organs after relatively long-term follow up, is unusual. The findings suggest that HIT accompanied by marked hypercholesterolemia of long duration contributes to a characteristic form of thromboembolism that needs careful management.     

Blood-brain barrier permeability precedes senile plaque formation in an Alzheimer disease model

OBJECTIVE: To establish the generality of cerebrovascular pathology frequently observed with Alzheimer disease, we have assessed blood-brain barrier (BBB) integrity using the Alzheimer disease model Tg2576 mice in which cognitive deficits and neuritic plaque formation develop around 10-12 months of age. METHODS: We assessed BBB integrity using well-established methods involving albumin and Evans blue uptake and introduce the use of a novel perfusion protocol using succinimidyl ester of carboxyfluorescein diacetate. RESULTS: BBB permeability is increased in the cerebral cortex of 10-month-old Tg2576 mice preceding Alzheimer disease pathology presentation. Furthermore, when compared with their nontransgenic littermates, 4-month-old Tg2576 mice exhibit compromised BBB integrity in some areas of the cerebral cortex. An age-related increase in albumin uptake by the brains of Tg2576 mice, compared with nontransgenic mice, was also observed. These findings were supported by quantitative Evans blue analysis (p = 0.07, two-way analysis of variance). CONCLUSION: A breakdown of BBB was evident in young 4- to 10-month-old Tg2576 mice. Compromised barrier function could explain the mechanisms of Abeta entry into the brain observed in experimental Alzheimer disease vaccination models. Such structural changes to the BBB caused by elevated Abeta could play a central role in Alzheimer disease development and might define an early point of intervention for designing effective therapy against the disease.     

Increased reactive oxygen species and anti-oxidative response in mitochondrial cardiomyopathy.

A 60-year-old woman was admitted for treatment of congestive heart failure. She had been diagnosed with diabetes mellitus when she was 23 years old, and she began to go deaf when she was 34 years old. She showed symptoms of heart failure at age 51 and was diagnosed with hypertrophic cardiomyopathy. Echocardiography showed progressive diffuse hypokinetic motion of the left ventricle and the left ventricular hypertrophy had gradually regressed. A mitochondrial transition mutation, A3243G, was detected in her peripheral leukocytes (9%) and in those of her 27-year-old son, who also has diabetes and deafness. Electron microscopy of an endomyocardial biopsy specimen showed proliferation and swelling of the mitochondria, and significant generation of reactive oxygen species (ROS), as well as marked induction of heme oxygenase-1, which is an adaptive enzyme to oxidative damage, were also observed in the myocardial tissue. These observations were more prominent than in other patients with heart failure of different etiology, which suggests that the increased ROS generation and anti-oxidative response were involved in the development of the mitochondrial cardiomyopathy.     

New quinolone versus vancomycin/tobramycin for intestinal sterilization in patients who undergo allogeneic bone marrow transplantation

The frequency of infection in recipients of allogeneic bone marrow transplants (BMT) who received oral new quinolones (NQ) was compared with that in BMT recipients who were given oral vancomycin/tobramycin (V/T). Between 1984 and 1997, our hospital treated 79 patients with V/T and 90 patients with NQ. Number of febrile days, duration of intravenous antibiotics administration, and frequency of documented infections were statistically the same for both groups. However, the frequency of grampositive bacterial infections, especially staphylococcal infections, was slightly higher in patients receiving NQ than in patients receiving V/T (p = 0.12). Of the patients who received NQ, those who underwent unrelated donor BMT procedures were generally febrile for slightly longer periods than those who underwent related donor BMT procedures (p = 0.10). These results suggest that oral NQ is as effective as oral V/T for the prevention of serious gramnegative bacterial infections in patients who undergo BMTs.