Stimulatory action of mitemcinal (GM-611), an acid-resistant non-peptide motilin receptor agonist, on colonic motor activity and defecation: spontaneous and mitemcinal-induced giant migrating contractions during defecation in dogs.

The aim of this study was to characterize giant migrating contractions (GMCs) during spontaneous defecation in dogs and to investigate the effect of mitemcinal (an orally active and highly acid-resistant motilin receptor agonist) on colonic motility to assess the possibility of using it for the treatment of colonic motility disorders. To assess colonic motility, strain-gauge force transducers were implanted on the gastrointestinal tract of five dogs, and the behaviour of the dogs was monitored with a noctovision-video camera system. The effect of mitemcinal (0, 3, 10 or 30 mg per dog) and sennoside (300 mg per dog) on colonic motility was assessed 24 h after oral administration. During a 39-day period, the starting point of most of the 140 GMCs was between the transverse colon and the descending colon, but some variation was observed. In the daytime, the GMCs originated from somewhat more proximal positions than at night. Mitemcinal caused an increase in the GMC-index (integration of contractile amplitude and duration) and proximal translocation of the GMC starting point, but did not cause an increase in the number of defecations 12 h after administration. Sennoside, however, caused a significant increase in the number of defecations, an increase in the GMC-index, and prolongation of the duration of GMCs. The GMC starting point in the canine colon varied during spontaneous defecation. Mitemcinal was a potent prokinetic drug to mimic a spontaneous defecation compared with sennoside. Mitemcinal evacuates more intestinal luminal contents during the defecation than does sennoside.

Development of SCAR markers to the PVY resistance gene Ryadg based on a common feature of plant disease resistance genes.

Sequence-characterized amplified regions (SCARs) were developed, based on nucleotide differences within resistance gene-like fragments isolated from a potato plant carrying the Ryadg gene, which confers extreme resistance to potato Y potyvirus (PVY). It originates from Solanum tuberosum subsp. andigena, and a susceptible potato plant. SCARs were tested using 103 potato breeding lines and cultivars with diverse genetic backgrounds derived from Europe, North America, and Japan. Two markers showed high accuracy for detection of the Ryadg gene. The SCAR marker RYSC3 was generated only in genotypes carrying Ryadg. The SCAR marker RYSC4 was detected in all genotypes carrying Ryadg but also in four PVY-susceptible genotypes. Neither marker was detected in genotypes carrying other Ry genes originating from different species than S. tuberosum subsp. andigena. Therefore, these SCAR markers should be powerful tools in marker-assisted selection for Ryadg in potato breeding programs, and should also be useful for cloning of the Ryadg gene.

Effects of ginkgo biloba extract on impairment of learning induced by cerebral ischemia in mice.

The effect of Ginkgo biloba extract (GbE) on cerebral ischemia induced by 10-min bilateral occlusion of the carotid arteries in mice was studied. Severe impairment of memory was apparent when the passive avoidance test was carried out 48 hr after bilaterally induced ischemia. When GbE at doses of 50 and 100 mg/kg was given p.o. 1 hr before the 10-min occlusion, there was a significant improvement in memory. The i.p. injection of ifenprodil (30 mg/kg) also showed improvement on learning tasks. The p.o. administration of flavonoid, a fraction isolated from GbE, showed high step-through latency on scopolamine-induced amnesia. All these findings indicate that GbE is beneficial for clinical use in amnesia accompanied with cerebral vascular disease.

Nodular lymphoid hyperplasia of the terminal ileum: report of a case and the findings of an immunological analysis.

The immunological and immunohistochemical characteristics of a patient with nodular lymphoid hyperplasia (NLH) of the terminal ileum were investigated pre- and post-operatively. The patient presented with diarrhea, lower abdominal pain, and weight loss, and an abdominal X-ray following barium enema revealed multiple small nodules in the terminal ileum which were subsequently confirmed to be NLH by histological examination. Preoperatively, although the serum immunoglobulin levels were normal, the T-cell responses in the peripheral blood, including the phytohemagglutinin (PHA)-blastogenesis and the T4/T8 ratio, were impaired. However, following an ileocecal resection, the PHA-blastogenesis became augmented and the T4/T8 ratio recovered to within the normal range. The immunohistochemical findings revealed a more marked accumulation of T cells in the interstitium around the hyperplastic follicles than in the interstitium of the normal intestine.

Potassium/energy and phosphorus/calcium ratios reflect the quality of nutrition.

A nutritional survey and questionnaire regarding dietary habits were administered to 649 men ranging in age from 35 to 64 years receiving a one-day health screening examination. First, comparisons of nutrient intake based on the nutrient rate of the Recommended Dietary Allowances for Japanese (RDA), and the total score on the questionnaire regarding dietary habits according to the RDA rates of total energy and calcium (Ca) were investigated. Then, the comparisons of intake of food groups, intake of nutrients and the total score on the questionnaire regarding dietary habits according to potassium/energy (K/E) ratio and phosphorus/calcium (P/Ca) ratio were determined. Last, differences between comparisons with the nutrient rates of RDA and comparisons with K/E ratio and P/Ca ratio were investigated. The following results were obtained: 1. Even in the group with RDA rates of total energy or Ca of > or = 90% and < or = 110% the RDA rates of some other nutrients were out-side the appropriate range. 2. In the group with high K/E ratios, as compared to the group with low ratios, the intake of potatoes, pulses, fruits, green/yellow vegetables, other vegetables, soy sauce, other beverages, fish/shellfish, and milk products showed high values, while cereals and fats/oils showed low values. For this reason, in the former group as compared to the latter, the intake and RDA total energy rate showed low values whereas the intake and RDA rates of nutrients such as Ca, Fe, and vitamin A were low. 3. In the group with high P/Ca ratios, as compared to the group with low ratios, the intake of beer and meats showed high values while that of pulses, green/yellow vegetables, and milk products showed low values. For this reason, in the former group as compared to the other groups, despite the fact that the intake and RDA total energy rate tended to be higher, the intake of nutrients such as Ca, P, K, and vitamin A showed lower values. 4. The RDA rates of all of the nutrients of group with a high K/E ratio and the group with a low P/Ca ratio generally showed largely appropriate values. 5. These results suggest that indices reflecting the balance of minerals such as the K/E and P/Ca ratios more objectively reflect the quality of nutrition than comparisons based on the RDA rates of total energy and specific-nutrient.

[Effects of levocarnitine chloride (LC-80) on the cardiovascular system].

The cardiovascular effects of levocarnitine chloride (LC-80) were investigated in in vitro and in vivo experiments, and the following results were obtained: (1) In isolated rabbit cardiac muscle preparations, LC-80 at the high concentration of 10(-2) M had little influence on the atrial rate of spontaneously beating right atria, while it caused a gradual increase in the contractile tension of both spontaneously beating right atria and electrically driven papillary muscle that reached a maximum level after 10 min of administration and lasted for 20-30 min. However, the LC-80-induced positive inotropic effect may be negligible in whole animal experiments or clinical trials, since it was elicited only after the administration of LC-80 in an extremely large dose. Furthermore, LC-80 in a high concentration (10(-2) M) had no influence on the isoproterenol-induced positive inotropic effect in electrically driven papillary muscles. (2) LC-80 in high concentrations of 10(-3)-10(-2) M did not affect the high K+-induced contraction in isolated canine left circumflex coronary artery and saphenous vein. (3) In anesthetized dogs, intraarterial injection of LC-80 in high doses of up to 10 mg did not change the blood flow of coronary, femoral, renal, mesenteric or vertebral arteries and on the adenosine-induced vasodilator action. (4) In anesthetized dogs, intravenous injection of LC-80 in doses of 100-300 mg/kg did not modify the blood pressure responses induced by norepinephrine, acetylcholine, carotid occlusion and vagal stimulation. These results suggest that the cardiovascular effects of LC-80 are extremely mild or negligible. Therefore, LC-80 may be a drug having a new pharmacological feature in its mechanism which enables it to exert a beneficial effect in the treatment of ischemic heart disease, being different from the commonly used antianginal drugs.

[Study on effectiveness of carmofur (Mifurol) in urogenital carcinoma, especially bladder cancer, as a post-operative adjuvant chemotherapeutic agent].

This study was carried out to evaluate the effects of carmofur (Mifurol), a masked compound of 5-fluorouracil (5-FU), in preventing postoperative recurrence of urogenital carcinoma (especially in bladder cancer). Carmofur was given orally at the dose of 300 approximately 600 mg/day to 134 patients (90 males and 44 females) after the resection. Out of 134 patients, 121 patients were evaluable and the rate of their recurrence was 10.7%. The rate of cumulative nonrecurrence for 65 patients it was 96.0, 73.0 and 60.8% in 1, 2 and 3 years, respectively. The group of curative resection demonstrated a higher cumulative nonrecurrence rate than that of noncurative or palliative resection group. In considering the resection methods, transurethral resection of bladder tumor group demonstrated a higher rate than partial or total cystectomy. The average concentration of 5-FU in serum was 0.65 microgram/ml at 120 minutes after oral administration of 200 mg of carmofur. Moreover, the concentration of 5-FU (15 approximately 35 micrograms/ml) in urine was higher than that of carmofur. The rate of side effects that appeared was 19.6%. The side effects were hot feeling (12.2%), pollakisuria (4.3%), anorexia (4.3%), an antabuse-like reaction by drinking (3.8%) and so on. These results were similar to those already reported.

Hypothalamic control of the pituitary-testicular relation in fetal rats: measurement of collective volume of Leydig cells.

On the 20th day of gestation in pregnant rats, the male fetuses were subjected to surgical hypophysectomy by decapitation or to intracranial paraffin injection which compressed the fetal brain. Autopsy was done on the 22nd day of gestation. The collective volume of Leydig cells in the left fetal testis was estimated by Chalkley's method. Decapitation of a fetus caused a significant retardation in increase of the collective volume of Leydig cells 2 days later. In fetuses given an intracranial paraffin injection, the Leydig cell volume was increased significantly compared with normal fetuses on the 20th day of gestation but was far smaller than that in their intact littermates. This effect of paraffin compression was completely prevented by injections of LRH. The Leydig cell volume remained extremely small in decapitated fetuses given LRH. The observations suggest that in the male rat the hypothalamus begins to govern a pituitary gonadotropic function before birth.