Histological study on healing of cryocautery-induced rat gastric ulcer treated with T-593]

The effect of T-593, a novel anti-ulcer agent, on the healing of cryocautery-induced rat gastric ulcer was investigated histologically in comparison with that of famotidine. Seven days after ulceration, T-593 (30 mg/kg) or famotidine (30 mg/kg) was orally administered twice daily for 8 weeks. Two, 4 and 8 weeks after the start of administration, the ulcer size was measured by a stereoscopic microscope, and the gastric mucosa was observed histologically. The thickness of the regenerated mucosa, the density and the arrangement of gastric glands, the degree of inflammatory-cell infiltration in the submucosal tissue and the number of microvessels in the submucosal tissue were quantified. In macroscopical evaluation, T-593 and famotidine significantly accelerated ulcer healing, and the time courses of the ulcer index were similar in both cases. In histological evaluation of healed ulcers, T-593 normalized the thickness of regenerated mucosa and reduced the degree of inflammatory-cell infiltration and the number of microvessels in the submucosal tissue, while famotidine had no effect. In conclusion, T-593 possesses accelerating effects not only on the restoration of regenerated mucosa but also on the maturation of submucosal tissue. Therefore, T-593 improves the quality of ulcer healing.     

Intrathecal substance P depresses the tail-flick response — Antagonism by naloxone

Summary Substance P injected into the lumbar subarachnoid space of rats depressed the tail-flick response to radiant heat in a dose-dependent way. The effective doses ranged from 0.1 g to 100 g per rat (ED 50: 1.5 g/rat). The maximum of the effect was reached 20 min after intrathecal injection and the effect lasted for about 30 min. An antinociceptive effect was also observed after intrathecal injection of substance P 1 g to spinal rats. The depression of the tail-flick response produced by intrathecal administration of substance P was abolished by intrathecal (5 g/rat) or i.p. (0.5 mg/kg) injections of naloxone.Supported by the Sonderforschungsbereich 38 Membranforschung     

Correlation Between the Inhibitory Effects of Basic Drugs on the Uptake of Cardiac Glycosides and Taurocholate by Isolated Rat Hepatocytes

The role of the multispecific bile acid transporter for cardiac glycoside uptake is still controversial. This study was designed to examine the inhibitory effects of basic drugs (verapamil, dipyridamole, nifedipine, chlorpromazine, disopyramide, quinidine, propranolol, and lidocaine) on taurocholate uptake by isolated rat hepatocytes and to compare these effects with inhibition of ouabain uptake. Sodium-dependent taurocholate uptake was significantly reduced, to 50-70% of the control value, by 50 µM verapamil, dipyridamole, and nifedipine. Sodium-independent taurocholate uptake was more extensively inhibited, to 20-40%, by these basic drugs. The inhibition of ouabain uptake correlated better with sodium-independent taurocholate uptake ( = 0.918) than with sodium-dependent taurocholate uptake ( = 0.714). Taurocholate competitively inhibited ouabain uptake in the absence of sodium. These results indicate that the cardiac glycoside transport system is similar to the sodium-independent taurocholate transport system.     

Free vascularized bone graft for nonunion of the scaphoid

We used a free vascularized small periosteal bone graft to treat scaphoid nonunion. The graft consisted of periosteum, full-thickness cortex, and the underlying cancellous bone and was harvested from the supracondylar region of the femur. The graft was nourished by the articular branch of the descending geniculate artery and vein. Unlike the currently used vascularized bone grafts, this graft can be easily harvested and shaped to accommodate the bone defect of the scaphoid without disturbing its vascularity and can then be transferred with microvascular anastomosis of the nutrient vessels to the radial artery and its venae commitantes. Ten patients with longstanding nonunion of the scaphoid secondary to avascular necrosis, confirmed by radiologic and intraoperative findings, were treated with this vascularized bone graft. Union was achieved in all 10 patients at an average of 12 weeks after surgery. The average follow-up period for all fractures was 3.5 years. The scores for overall outcome, according to the Mayo wrist scoring system, were excellent in 4 patients, good in 4, and fair in 2. Two unsatisfied patients had preoperative signs of early periscaphoid osteoarthrosis. This free vascularized small bone graft from the supracondylar region of the femur is an attractive alternative to the conventional vascularized bone grafting procedures.     

Curative Resection of Microgastrinomas Based on the Intraoperative Secretin Test

The intravenous secretin injection test (secretin test) has been used for the differential diagnosis of gastrinoma. In this study we report that the intraoperative secretin test (IOS test) is also useful for determining the extent of curability in patients with Zollinger-Ellison syndrome (ZES). Twelve patients with ZES underwent surgical exploration and the IOS test. The results of the IOS test were obtained by rapid radioimmunoassay of the serum gastrin level (IRG) within 60 minutes. The test was diagnosed as negative when the maximum increase of serum IRG was less than 80 pg/ml and also less than 20% of the basal serum IRG level. Three of the twelve patients underwent pancreatoduodenectomy (PD), and two patients underwent distal pancreatectomy. Extirpation of duodenal tumors with dissection of regional lymph nodes was performed in seven patients. In two of the seven patients the IOS test remained positive after extirpation of the duodenal tumors and the dissection of regional lymph nodes. In one patient PD was performed on the basis of the positive results, and the IOS test became negative after PD. In the other patient, two tiny metastatic liver tumors were identified and were resected, but the IOS test did not become negative. We closed the abdomen in 11 patients when we obtained negative results from the IOS test. The results of the IOS test were almost identical to the data obtained by the standard assay postoperatively. The serum IRG levels of all but one patient fell to the normal level, and the secretin test became negative postoperatively. The IOS test is thus useful and indispensable for curative resection of microgastrinomas in patients with ZES.     

Binaural advantage on usage of hearing aid together with cochlear implant--examination on speech perception (Japanese monosyllable word list 67-S and Japanese HINT)]

Six cochlear implant recipients with hearing aids in the opposite ear were studied to survey binaural advantage. They were examined in separate tests by using a hearing aid alone, cochlear implant alone, and by using both devices (bimodal condition). Test items used were the Japanese monosyllable word list 67--S and Japanese HINT. Statistically significantly results were obtained in the bimodal condition, three out of six subjects were successful in the monosyllable word test and all successful in the Japanese HINT. We conclude that all subjects enjoyed binaural advantage in speech perception in bimodal condition with no conflict at the recognition level; even when different sounds from cochlear implant and contralateral hearing aid were received. The plasticity of the brain is thought to be of importance in the bimodal condition.     

New technique for producing hybridoma by using laser radiation

BACKGROUND AND OBJECTIVE: With conventional methods, cell fusion rate is extremely low, and fusion of two specific cells is not possible. We developed a new method for inducing cell fusion under the microscope by using a microprocessing device by laser. STUDY DESIGN/MATERIALS AND METHODS: Under a microscope, the target cells were irradiated with laser beams for trapping. Then, the trapped cells were transferred and placed in contact with the corresponding cells, which were also fixed by laser beam. The pulse laser beams are focused on the contact surface to cut small perforations for mutual communication of the cytoplasms. RESULTS: The fusion rate of mouse myeloma cells was 38%. The rate of hybridoma production of myeloma cell and lymphocyte was 2%. We confirmed the proliferation of the newly formed hybridoma in HAT medium and the production of immunoglobulin G. CONCLUSION: This new cell fusion method is characterized by production of hybridomas of target cells, lower cell toxicity, and a high rate of hybrid production.     

Dietary zinc deficiency decreases glutathione S-transferase expression in the rat olfactory epithelium

Zinc deficiency leads to olfactory and gustatory dysfunction, but little is known about the underlying molecular mechanism of this phenomenon. We examined the effect of dietary zinc deficiency on the rat olfactory epithelium. Immunoreactivities of glutathione S-transferase (GST) mu, neuron-specific enolase (NSE) and proliferating cell nuclear antigen (PCNA), and in situ hybridization of GST mu mRNA in the olfactory epithelia were examined under different dietary zinc intake conditions. Adult male rats were fed a zinc-deficient (ZD) diet (0.5 mg zinc/kg diet), whereas control rats, including pair-fed (PF) and zinc-adequate (ad libitum consumption, AL) groups, were fed a zinc-adequate diet (58 mg zinc/kg diet) for 7 wk. We also examined the effect of zinc replacement (ZR) by subsequently feeding half of the ZD group a zinc-adequate diet for 5 wk after the initial 7-wk deprivation. No significant differences in immunoreactivity for NSE in olfactory epithelial receptor cells or for PCNA in basal cells were noted among groups. Intense GST mu immunoreactivity and hybridization signals were observed in olfactory supporting cells of AL, PF and ZR groups, but very minimal or no such signal was noted in ZD rats. Our findings indicated that zinc deficiency reduces GST mu expression in the supporting cells of rat olfactory epithelia but does not affect receptor cell proliferation or maintenance.     

Clotrimazole, an Imidazole Antimycotic, Is a Potent Inhibitor of Angiogenesis

Clotrimazole, an imidazole antimycotic, interferes with the rise in cytosolic Ca²⁺ and inhibits cell proliferation in a reversible manner. Here we describe the effect of clotrimazole on vascular endothelial cells (ECs). Clotrimazole inhibited the proliferation of ECs stimulated with typical angiogenic growth factors; vascular endothelial growth factor and basic fibroblast growth factor (bFGF). This inhibitory effect of clotrimazole was dose-dependent and the maximal inhibition was observed at a concentration of 10 m M . We did not observe any increase in ⁵¹Cr release from ECs during treatment with 10 μ M . clotrimazole. Moreover, clotrimazole inhibited the basal and bFGF-stimulated migration of ECs. As clotrimazole inhibited two principle components of angiogenesis; the proliferation and migration of ECs, we examined whether clotrimazole inhibited angiogenesis. Tube formation by ECs in type 1 collagen gel was investigated, and clotrimazole was found to be significantly inhibitory. The inhibitory effect of clotrimazole on angiogenesis was further confirmed in an in vivo angiogenesis model of murine Matrigel plug assay. These results demonstrate that clotrimazole is a potent inhibitor of angiogenesis.