Different effects of halothane, isoflurane and sevoflurane on sarcoplasmic reticulum of vascular smooth muscle in dog mesenteric artery

Background: The direct effect of halothane on vascular smooth muscle is mediated in part via its effects on the sarcoplasmic reticulum (SR). Little information is available concerning the effects of other volatile anesthetics including isoflurane and sevoflurane, whose vascular effects differ from those of halothane. The aim of the present study was to compare the effects of halothane, isoflurane and sevoflurane on the SR by testing the contraction induced by caffeine in vascular smooth muscle. Methods: Rings without endothelium from isolated canine mesenteric artery were mounted in physiological saline solution (PSS) for isometric tension recording. After complete depletion of Ca²⁺ from the SR by adding 35 mM caffeine, the rings were exposed to normal Ca²⁺ containing PSS (Ca²⁺ loading), to Ca²⁺-free PSS for 10 min, and then to 15 mM caffeine to induce contraction. Anesthetics were administered during Ca²⁺ loading, the Ca²⁺-free phase and simultaneously with caffeine administration. Results: Halothane (0.5-2%) attenuated the caffeine-induced contraction of canine mesenteric artery when administered during Ca²⁺ loading in the SR (P<0.001), whereas isoflurane and sevoflurane (1–4%) failed to affect the contraction. When given simultaneously with caffeine, halothane (1–2%) potentiated the caffeine-induced contraction (P<0.05), but isoflurane and sevoflurane had no effect. When given before caffeine administration, halothane (0.5-2%), isoflurane (24%) and sevoflurane (4%) all potentiated the caffeine-induced contraction (P<0.05). Conclusion: It has been shown that halothane not only potentiates caffeine- induced Ca²⁺ release from the SR, but also induces contraction by releasing Ca²⁺ from the SR. We conclude that halothane decreases Ca²⁺ accumulation in the SR while exerting facilitative and additive effects on caffeine-induced Ca²⁺ release from the SR when applied before caffeine administration and simultaneously with caffeine, respectively, whereas isoflurane and sevoflurane lack both the ability to decrease Ca²⁺ accumulation and an additive effect on caffeine-induced Ca²⁺ release from the SR, but are able to facilitate Ca²⁺ release by caffeine.     

A sighted man with non-24-hour sleep-wake syndrome shows damped plasma melatonin rhythm

Abstract Twenty-four-hour profiles of plasma melatonin, cortisol and rectal temperature were measured longitudinally in a sighted man who has been suffering from sleep disorders for more than 10 years. The sleep-wake rhythm of this subject free-ran, despite his routine life, and occasionally showed a sign of internal desyn-chronization, where sleep was lengthened up to 30 h. These states were classified into the non-24-hour sleep-wake syndrome. Plasma melatonin concentrations in the subjective night remained at a low level and showed a damped circadian rhythm. At the same time, robust circadian rhythms were detected in plasma cortisol and rectal temperature, indicating that the circadian pacemaker was intact. The causal relationship between the damping of nocturnal melatonin rise and a failure of entrainment of the sleep-wake cycle is discussed.     

Long-term effect of α-glucosidase inhibitor on late dumping syndrome

Dumping syndrome commonly occurs after gastrectomy. The late dumping, which is one of the dumping syndromes, is due to postprandial hypoglycaemia caused by an excessive insulin secretion after a sharp rise in plasma glucose. Several treatments, including operation, dietary fibre and somatostatin, have been attempted to relieve dumping symptoms. These treatments take effect through modulation of plasma insulin and glucose levels, but their efficacy is still under consideration. α-Glucosidase inhibitor attenuates the postprandial increase of plasma glucose levels and is widely used for treatment of non-insulin-dependent diabetes mellitus (NIDDM). The acute effect of α-glucosidase inhibitor on late dumping syndrome has been reported by some studies with test meals. The purpose of this study was to evaluate a long-term effect of α-glucosidase inhibitor treatment with ordinary meals in late dumping patients with NIDDM because administration of α-glucosidase inhibitor is only ethically allowed for diabetic patients in Japan. Six late dumping patients with NIDDM were orally administered α-glucosidase inhibitor, acarbose (50 or 100 mg), three times a day before each meal for 1 month. Diurnal changes of plasma glucose, insulin and pancreatic glucagon levels were compared before and after the α-glucosidase inhibitor treatment. All patients had late dumping-related symptoms, such as weakness, palpitation and dizziness before the induction of α-glucosidase inhibitor treatment. Patients suffered from a rapid fall in plasma glucose levels from hyperglycaemia at the same time as dumping symptoms. These late dumping-related symptoms disappeared and a rapid change of plasma glucose and insulin levels were attenuated after the α-glucosidase inhibitor treatment. These data suggest a long-term therapeutic efficacy of α-glucosidase inhibitor for late dumping patients.     

Effects of Isoquinolinesulphonamide Compounds on Multidrug-resistant P388 Cells

Abstract— The effects of eight isoquinolinesulphonamide compounds on resistance to vinblastine in adriamycin-resistant mouse leukaemia cells (P388/ADR) which overexpress the relative molecular weight (M_r) 140 kDa P-glycoprotein in the plasma membrane were investigated. N-[2-(Methylamino)ethyl]-5-isoquinolinesulphonamide (H-8) and N-(2-aminoethyl)-5-isoquinolinesulphonamide (H-9) did not reverse vinblastine resistance. N-[2-[N-[3-(4-Chlorophenyl)-2-propenyl]amino]ethyl]-5-isoquinolinesulphonamide (H-86) and N-[2-[N-[3-(4-chlorophenyl)-1-methyl-2-propenyl]amino]ethyl]-5-isoquinolinesulphonamide (H-87) caused accumulation of intracellular vinblastine and inhibition of vinblastine efflux from the cells and reversed the resistance. Addition of an aminoethyl group to the nitrogen atom of the sulphonamide group (W-66) or a formyl group at the terminal amino group (H-85) of H-86 reduced those activities. Conversion of the chlorophenyl group of H-87 to pyridinyl (H-31) or furanyl (H-34) markedly decreased activities against the drug resistance. The activity against vinblastine accumulation closely correlated with the apparent partition coefficient of compounds. These compounds dose-dependently inhibited photoaffinity labelling of a photosensitive analogue of vinblastine, N-(p-azido-(3-[¹²⁵I])salicyl)-N′-β-aminoethylvindesine ([¹²⁵I]NASV), and there was a good correlation between inhibition of [¹²⁵I]NASV-photolabelling and hydrophobicity. Although these isoquinolinesulphonamides inhibited protein kinase A with different magnitudes, this activity did not correlate with the effect on the drug resistance. These results indicate that isoquinolinesulphonamide compounds with a hydrophobic group interact with antitumour drugs on P-glycoprotein and reverse multidrug resistance without involvement of their activity on protein kinase A.     

Three-dimensional Ultrasonography Using Ultrasonic Probes by the Transpapillary Approach for Diagnosis of Pancreatobiliary Diseases

Abstract: Three-dimensional (3D) intraductal ultrasonography (IDUS) is more useful than two-dimensional IDUS for the diagnosis of pancreatobiliary disease. We investigated the advantages and disadvantages of the transpapillary approach for 3D-IDUS using a newly developed system for pancreatobiliary application. In total 12 patients with a sufficiently wide orifice were examined, bile duct (BD) scanning being successful in 100% of attempted cases and main pancreatic duct (MPD) scanning in 85.7%. In all cases, acceptable radial and linear images were obtained and 3D diagnosis was accomplished. However, several primary problems were experienced; 1) The 3D probe is relatively inflexible, having a thick shaft and a long tip, such that insertion into the BD or MPD can be somewhat difficult; 2) Clear images of the BD or MPD wall were not always obtained because of artifacts produced by the 3D probe itself; 3) In some cases, linear images could not be reconstructed with BD or MPD scanning despite sufficiently clear radial scan images. In the future, development of new 3D probes with more flexible and thinner shafts, and shorter tips, should considerably enhance the diagnostic capacity of IDUS for the pancreatobiliary system.     

Ocular Membrane Permeability of Hydrophilic Drugs for Ocular Peptide Delivery

The purpose of this study is to investigate the ocular membrane permeability and the permeation mechanism of hydrophilic drugs such as thyrotropin-releasing hormone (TRH), p-nitrophenyl β-cellopentaoside (PNP) and luteinizing hormone-releasing hormone (LHRH). The penetration of hydrophilic drugs was measured across the isolated corneal and conjunctival membranes of albino rabbits using a two-chamber diffusion glass cell. The corneal permeabilities of hydrophilic drugs were much lower than those of beta blockers reported previously. The corneal penetration of TRH was the highest among the hydrophilic drugs studied. Scraping the corneal epithelium increased the penetration of hydrophilic drugs. Conjunctival membranes showed higher permeability to hydrophilic drugs compared with corneal membranes. The permeability of drugs was also analysed by Fick's equation. The partition parameter and diffusion parameter of TRH, PNP and LHRH in the cornea were lower than those in scraped cornea and conjunctiva. In addition to the data of fluorescein isothiocyanate-dextran reported previously, the permeability coefficient of hydrophilic drugs through the cornea, scraped cornea and conjunctiva correlated with molecular weight of the drugs. The diffusion parameters of hydrophilic drugs decreased with an increase of molecular weight for all ocular membranes. The extent of dependency of partition parameters on the molecular weights of drugs varied according to the ocular membrane. These results indicate that ocular membranes are sufficiently different in permeation character and mechanism to control the extent and pathway for ocular absorption of hydrophilic drugs.     

Churg–strauss syndrome: importance of colonoscopy and endoscopic biopsy in establishing diagnosis

A 31‐year‐old Japanese man was admitted with complaints of left lower abdominal pain and diarrhea. He had a history of bronchial asthma since he was 26 years old. On admission, his eosinophil count was 4100/mm ³ and increased as high as 12 000/mm ³ . A neurological examination disclosed mononeuritis multiplex with paresthesia in both lower and upper extremities. Because of hematochezia, colonoscopy was performed and disclosed multiple colonic ulcers and erosions from the rectum to the ascending colon. Endoscopic biopsy showed fibrinoid necrosis of small‐sized vessels with moderate infiltration of eosinophils in the mucosa and submucosa. He was suspected of being a case with Churg–Strauss syndrome (CSS; allergic granulomatous angiitis), and prednisolone of 30 mg/day was administered. After the administration of prednisolone, his eosinophil count decreased dramatically. His symptoms also improved gradually, except for numbness in the extremities. Three weeks later, colonoscopy revealed improvement of the mucosal appearance, but the colonic ulcers and erosions were still present. Endoscopic biopsy showed exravascular granuloma with moderate infiltration of eosinophils in the submucosa. Colonoscopy and endoscopic biopsy may be important in establishing the diagnosis of CSS with intestinal symptoms.     

Liver abscess that developed after a long interval of transcatheter arterial embolization followed by formation of hepatoduodenal fistula

A 55‐year‐old male patient with hepatocellular carcinoma underwent transcatheter arterial embolization (TAE). He became febrile and experienced pain at the right hypochondrial region 323 days later, which led to the discovery of a liver abscess that fistulated into the duodenal bulb. There have been no reports on the fistulation of liver abscesses into the digestive system following TAE. Rhodococcus equi was isolated as a causative agent, which distinguished the case further.