Pharmacological characterization of the voltage-dependent calcium channel of pancreatic B-cell

Pharmacological characteristics of the voltage-dependent calcium channel (VDCC) of the pancreatic B-cell were studied using omega-conotoxin (omega CgTX) and dihydropyridine (DHP) calcium channel blockers. High glucose and potassium (K+) depolarization were employed as the stimulant of insulin release. omega CgTX (greater than 50 nM), a blocker of neural, but not muscular, Ca2+ channels, partially blocked (27%) the second, but not the first, phase of glucose-induced insulin release without a significant effect on K+ depolarization-induced insulin release. The DHP Ca2+ channel blocker nifedipine inhibited both phases of glucose-induced insulin release (ED50 = 200 nM) and completely abolished both phases of response at 10 microM. In contrast, the DHP Ca2+ channel blocker only partially suppressed (75% at 10 microM) K+ depolarization-induced insulin release with an ED50 of 100 nM. We conclude that pancreatic B-cell possesses at least two classes of VDCCs; one is DHP sensitive, and the other DHP insensitive. Partial suppression of the second phase of glucose-induced insulin release by a high concentration of omega CgTX may be due to its toxic effect on the secretory machinery other than VDCC.     

The possible novel treatment of achondroplasia, C-type natriuretic peptide (CNP)

C-type natiruetic peptide (CNP) showed a potent effect on the elongation of the tibial organ culture system. CNP also corrected the dwarfing phenotype of the CNP knockout mice. These results suggest that CNP is the novel promoter of the endochondral ossification, and that CNP/GC-B activation is possible target of the treatment of the achondroplasia.     

Utility of the filtered bipolar esophageal lead in the diagnosis of arrhythmias

Electrophysiologic study was performed in 25 patients with tachycardia or bradycardia attacks. The coronary sinus (CS) and filtered bipolar esophageal electrograms were recorded simultaneously to compare the phase of atrial activations. During sinus rhythm and high right atrial pacing, the esophageal and proximal CS atrial activations were nearly simultaneous but earlier by 26 +/- 5 msec on the average than the distal CS atrial activations. During reciprocating tachycardia due to reentry using a left-side accessory atrioventricular pathway for retrograde conduction the esophageal and CS atrial activations occurred earlier than the low septal right atrial activation, so the esophageal lead can be used as a substitute for the CS lead to clarify the eccentric retrograde atrial activation sequence. By using the filtered bipolar esophageal lead, the interval from Q wave on the surface electrocardiogram to the first rapid deflection in the esophageal atrial activation (Q-AESO interval) was measured in 15 patients with supra-ventricular tachycardia. All patients with reciprocating tachycardia due to reentry using a left side accessory atrioventricular pathway had Q-AESO intervals between 100 to 130 msec and four of five patients with a right side accessory atrioventricular pathway for retrograde conduction had Q-AESO intervals between 130 to 150 msec. In contrast, all patients with reentry in the atrioventricular node had Q-AESO intervals between 30 to 60 msec. The esophageal lead is also of value in the prompt diagnosis of atrial flutter and ventricular tachycardia, since the esophageal electrograms readily reveal the relationship between atrial and ventricular activations. In conclusion, the filtered bipolar esophageal lead provides a non-invasive method for the quick diagnosis of various arrhythmias.     

Survey on clinical isolates from 13 hospitals in Akita Prefecture--changes in frequency and susceptibility of isolates by scale of hospital. Survey Group for Clinical Isolates, Chemotherapy Research Committee of Akita Prefecture

Isolates from various clinical materials in 13 hospitals in Akita prefecture and their drug susceptibility were investigated by the Chemotherapy Research Committee of Akita Prefecture during the period from Dec., 1987 to Feb., 1988. The results were as follows: 1. The total number of isolates was 8,387, including Staphylococcus aureus (18.9%), Pseudomonas aeruginosa (10.9%), Staphylococcus epidermidis (7.3%) and Enterococcus faecalis (6.6%). S, aureus and P. aeruginosa were detected more frequently in the larger hospitals. 2. The detection frequency of S. aureus from the sputum, throat swab and pus exudate was also very high. There was a diversity in isolates from the urine and the frequency of Escherichia coli was low. More than half of the isolates from the blood were S. epidermidis and S. aureus. Many kinds of bacteria were detected from pleural fluid and ascites, but the isolate showed no particular tendency. 3. The susceptibility of S. aureus to oxacillin were variable in hospitals, and the susceptibility to cefazolin were even lower. Low susceptibility were also seen with norfloxacin. S. aureus showed the highest susceptibility to minocycline. The susceptibility was lower for inpatients than for outpatients. P. aeruginosa showed low susceptibility to cefsulodin. The number of ampicillin-resistant Haemophilus influenzae isolates tended to decrease. Enterobacter cloacae showed a low susceptibility for cephems. Serratia marcescens showed low susceptibility to many drugs. Based on the above results, we concluded that attention should be paid to S. aureus, P. aeruginosa and Enterobacter in clinical practice.     

Age-related change in the amount of ubiquitinated histones in the mouse brain

We investigated age-related changes in the ubiquitination of histones in mouse brains. By Western blot analysis using rabbit anti-ubiquitin antibodies, histone H2A and H2B were found to be the only proteins that are ubiquitinated in the acid-extractable nuclear proteins of both young (4-month-old) and senescent (29-month-old) mouse brains. The proportion of ubiquitinated histones was about 30% higher in senescent mice than in young ones. When total brain homogenates were analyzed similarly using somewhat different age groups of the animals, the proportion in the old animals was about 2-fold higher than that in the young.     

Acute myocardial infarction caused by "malignant" anomalous right coronary artery detected by multidetector row computed tomography.

Anomalous coronary arteries are usually identified incidentally by angiography or autopsy, but some "malignant" coronary anomalies are associated with a high incidence of syncope, arrhythmia, myocardial infarction, and sudden death. So far, the pathogenesis of the coronary events in such cases has only been revealed by autopsy. In the present case report, a patient with anomalous origin of the right coronary artery from the left sinus of Valsalva developed acute myocardial infarction, and visualization of the anomaly and assessment of the culprit plaque in the artery were done by multidetector row computed tomography and intravascular ultrasound.     

Inhibition of endotoxin- and antigen-induced airway inflammation by fudosteine, a mucoactive agent

We evaluated the effect of a mucoactive agent (-)-(R)-2-amino-3-(3-hydroxypropylthio) propionic acid (fudosteine), on airway inflammation using endotoxin- and antigen-induced models. Time courses of growth related oncogene/cytokine-induced neutrophil chemoattractant-1 (GRO/CINC-1) production, neutrophil migration and goblet cell hyperplasia were examined in endotoxin-induced rat airway inflammation. GRO/CINC-1 in bronchoalveolar lavage fluid (BALF) increased in response to intratracheal instillation of endotoxin and peaked within 4 h. Neutrophils in BALF and goblet cells on trachea peaked 24 and 96 h after endotoxin instillation, respectively. Fudosteine significantly inhibited increases in GRO/CINC-1 at 10-100 mg/kg, and neutrophils and goblet cells at 30 and 100 mg/kg. These results suggest that inflammatory events including neutrophil chemoattractant production and neutrophil migration play important roles for goblet cell hyperplasia in endotoxin-induced airway inflammation, and fudosteine inhibits goblet cell hyperplasia by inhibiting GRO/CINC-1 production and/or neutrophil migration. Furthermore, fudosteine (100 mg/kg) inhibited ovalbumin-induced eosinophil infiltration into BALF, suggesting it attenuates asthmatic inflammation.     

Endothelial function and coronary spastic angina

Coronary spasm plays an important role in the pathogenesis of not only variant angina but also coronary heart disease in general including acute coronary syndromes, especially in the Japanese population. The vascular endothelium has been reported to be a multifunctional organ whose integrity is essential for normal vascular physiology. Vascular endothelial dysfunction can be a critical factor in the pathogenesis of ischemic heart disease. Acetylcholine and methacholine cause vasodilation by endothelium-derived relaxing factor when the endothelium is functioning normally, whereas they cause vasoconstriction when the endothelium is removed or damaged. Coronary spasm can be induced by a variety of stimuli with different mechanisms of action, including acetylcholine and methacholine. Patients with coronary spasm may have a disturbance in endothelial function as well as local hyperreactivity of the coronary arteries.