Effects of goniopora toxin on bullfrog atrial muscle are frequency-dependent

Summary When goniopora toxin (GPT), a marine toxin isolated from coral, was applied to the bullfrog atrial muscle, the duration of action potential (APD) was prolonged, and a positive inotropic effect was produced. Such effects of GPT were influenced by stimulus frequency. At lower frequencies of 0.1 Hz, GPT (10 to 100 nmol/l) produced a moderate prolongation of APD and positive inotropic effect. At higher prequencies (1.0 Hz), however, the effects of GPT on both APD and contraction were suppressed. In contrast, APD and duration of contraction were prolonged with long intervals of stimulation (1–3 min), in the presence of GPT. The rested-state contraction was also markedly increased and prolonged by GPT. When the membrane potential was conditioned by voltage clamp pulses, the prolonged action potential in GPT-treated muscle was shortened in proportion to the increase in conditioning depolarization. However, the shortening effect of conditioning depolarization was attenuated by lengthening the resting period after the conditioning depolarization. These results, in conjunction with our previous results, suggest that the frequency-dependent effects of GPT on APD and contraction reflect time-and membrane potential-dependent changes of the toxin-modified sodium channels.This work was supported in part by a Grant-in Aid for Special Project Research from the Ministry of Education, Science and Culture of Japan to M. F. (No. 59104007)     

Influence of cigarette smoke on the L-ascorbic acid metabolism and the activities of drug-metabolizing enzyme in rats

This study clarified the influence of cigarette smoke on the L-ascorbic acid (AsA) metabolism and the activities of drug-metabolizing enzyme in rats. The test rats (group T) were exposed to weak sidestream smoke from cigarettes for 2 h, everyday for 57 days. AsA concentration in the tissues and excreted amount of AsA in urine of group T tended to be higher than those of control group (group C). The plasma AsA concentration and the activities of aniline hydroxylase and 7-ethoxycoumarin O-deethylase of group T were significantly higher than those of group C. There was no significant difference in the activity of UDP glucuronosyltransferase or in the liver cytochrome P-450 content between these two groups.     

Gastrectomy Performed with Noninvasive Positive Pressure Ventilation for a Patient with Severe Chronic Obstructive Pulmonary Disease: Report of a Case

We report the case of a patient with severe chronic obstructive pulmonary disease (COPD) for whom gastrectomy was successfully performed with the use of noninvasive positive pressure ventilation (NPPV). A 63-year-old man who had been suffering from chronic pulmonary emphysema for 12 years and receiving home oxygen therapy (HOT) for 9 years was diagnosed with gastric carcinoma. The patient required supplemental oxygen via nasal cannulae even at rest, and had labored breathing through pursed lips after a short conversation. The forced expiratory volume in 1 s was 400 ml. He underwent conventional gastrectomy under general anesthesia, and was extubated 90 min after surgery and given NPPV support. He was successfully weaned from NPPV on postoperative day (POD) 10 and discharged from our hospital on POD 28. Noninvasive positive pressure ventilation is useful for the perioperative management of patients with severe COPD and for extending the possibilities of surgery for patients on HOT.     

Clinical trial of risedronate in Japanese volunteers: single and multiple oral dose studies

The tolerability and pharmacokinetics of risedronate after a single oral administration and during multiple oral administrations were examined in healthy adult male volunteers. In the single dose study, the dose was increased gradually from 1mg to 2.5, 5, 10, or 20mg. Subsequently, risedronate was given by multiple administration, 5mg per dosing, once daily, for 7 days. The observed adverse events, whose causality was possibly related or unknown, included headache, diarrhea, increased body temperature, increased CK-BB, and increased urinary ₂-microglobulin excretion rate. However, none of these adverse events was clinically significant. The results thus showed that risedronate was well tolerated when delivered as a single administration of up to 20mg or as a multiple administration of up to 5mg/day. In the multiple dose study, changes in urinary deoxypyridinoline suggested the bone antiresorptive activity of risedronate. In the single dose study, AUC and C_max, after the administration of risedronate at 1, 2.5, 5, 10, and 20mg, increased dose dependently, and the T_max, t_1/2, and urinary excretion rates were nearly constant. Therefore, the pharmacokinetic profile of risedronate was considered to show linearity in a dosage range of up to 20mg. Furthermore, the results obtained in the multiple administration study indicated that the plasma concentrations of risedronate reached a steady state on day 4 of administration. The plasma concentrations of risedronate after the administration of 2.5mg risedronate to the Japanese population were nearly comparable to the serum concentrations after the administration of 5mg risedronate to the United Kingdom study population.     

Reversible posterior leukoencephalopathy in a patient with Wegener granulomatosis

A 14-year-old girl with rapidly progressive glomerulonephritis was transferred to our hospital because of acute renal failure. A diagnosis of Wegener granulomatosis was made according to the symptom triad of a renal biopsy demonstrating crescentic glomerulonephritis, severe sinusitis, and serological findings of raised proteinase 3 anti-neutrophil cytoplasmic antibody level. In spite of combination therapy with methylprednisolone, cyclophosphamide, and plasma exchange, her renal function gradually deteriorated. Thereafter, she suffered a severe headache and generalized seizures. Brain computed tomography (CT) scan revealed bilateral low-density areas in the parieto-occipital lobes. Magnetic resonance imaging (MRI) disclosed a high-intensity area on T2-weighted images and a low-signal intensity area on T1-weighted images in the same lesion. Follow-up brain CT scan 3 weeks and MRI 2 months after the first studies showed complete resolution of the abnormal lesions, which indicated reversible posterior leukoencephalopathy syndrome. In addition to renal failure, hypertension, and cyclophoshamide, the primary disease may have played a role in the development of this uncommon syndrome in our patient.     

LC/PDA/ESI-MS Profiling and Radical Scavenging Activity of Anthocyanins in Various Berries

Anthocyanin extracts of two blueberries, Vaccinium myrtillus (bilberry)and Vaccinium ashei (rabbiteye blueberry), and ofthree other berries, Ribes nigrum (blackcurrant), Aronia melanocarpa (chokeberry), andSambucus nigra (elderberry), were analyzed by high-performanceliquid chromatography coupled withphotodiode array detection and electrosprayionization - mass spectrometry(LC/PDA/ESI-MS). Both bilberry and rabbiteyeblueberry contained 15 identical anthocyanins withdifferent distribution patterns. Black currant,chokeberry, and elderberry contained 6, 4, and 4 kindsof anthocyanins, respectively. The radicalscavenging activities of these berry extracts wereanalyzed by using 2,2-diphenyl-1-picrylhydrazyl(DPPH). All these extracts showed potent antiradical activities.