Biomedical subjects

Y Morimoto

Publications and source records attributed to Y Morimoto.

At least 379 records · Page 21Linked to original sources

PubMed1991

Effects of the new anti-ulcer agent KB-5492 on experimental gastric mucosal lesions and gastric mucosal defensive factors, as compared to those of teprenone and cimetidine.

Effects of KB-5492, a new anti-ulcer agent, on various experimental gastric mucosal lesions and mucosal defensive factors in rats were compared with those of teprenone and cimetidine. KB-5492 administered orally at 12.5-200 mg/kg inhibited water-immersion stress- and indomethacin-induced gastric mucosal lesions in a dose-dependent manner with ED50 values of 46 and 27 mg/kg, respectively, indicating that KB-5492 was more potent than teprenone but less potent than cimetidine. KB-5492, administered orally at 12.5-100 mg/kg, also inhibited ethanol-induced gastric mucosal lesions in a dose-dependent manner with an ED50 of 23 mg/kg, so KB-5492 was 3 times more potent than teprenone, whereas cimetidine produced no obvious inhibition. In addition, KB-5492, administered orally at 25 and 50 mg/kg twice daily for 10 consecutive days, significantly accelerated the healing of acetic acid-induced gastric ulcers more potently than teprenone and cimetidine. KB-5492 at anti-ulcer doses significantly increased gastric mucosal blood flow in normal anesthetized rats and inhibited the reduction of gastric mucosal hexosamine content induced by aspirin, but did not affect gastric acid secretion in pylorus-ligated rats. These results indicate that KB-5492 has potent and broad anti-ulcer properties, which are probably exerted by its enhancement of gastric mucosal defensive factors through increasing gastric mucosal blood flow and/or retaining gastric mucus, and not by its inhibition of gastric acid secretion.

Administration, Oral↗

PubMed1991

A kinematic analysis of walking and physical fitness testing in elderly women.

Walking ability and physical fitness were assessed in 57 elderly Japanese women. Self-selected walking velocity at normal and fast speeds decreased markedly after age 60. The older age groups exhibited significant reductions in the lower limb joint displacements, due particularly to decreased angles at toe-off. The angular velocity of ankle plantarflexion during the stance phase declined markedly with age. A decrease in toe elevation during the swing phase and an increase in stance time in the process of aging suggested an increasing risk of stumbling over obstacles. Reductions in walking parameters with age correlated significantly with aspects of physical fitness tested, especially with items related to neuromuscular functions.

Aged↗

PubMed1991

[Cefepime in the treatment of patients with surgical infections].

Between March 1988 and June 1990, we gave cefepime to 5 subjects after surgery and studied the pharmacokinetics of the drug. In the same period, we treated 23 patients with surgical infections with the same drug and evaluated its clinical efficacy. In the pharmacokinetic study, 1 g was given intravenously to each individual over a 30 minutes period. The peak levels in the plasma, 59.9-118 micrograms/ml, were obtained at around the end of this time. The peak levels in the bile, 7.1-28.2 micrograms/ml, were reached at 1-5 hours after administration, depending on the patient. At hours 5 and 6, the range of plasma concentration was 3.7-12.3 micrograms/ml. In the 22 patients with surgical infections, clinical efficacy of the drug was excellent in 12, good in 5, fair in 1, and poor in 4, with an overall efficacy rate of 77%. The bacteriological response was evaluated in the 16 patients for whom the species of the probable causative organisms were identified. Those bacteria were eradicated in 10 patients, decreased in 3, and were persisted in 3, with an eradication rate of 63%. Against 5 strains of Escherichia coli isolated, the highest MIC was 0.05 micrograms/ml, and against 2 strains of Pseudomonas aeruginosa isolated, the MIC was 1.56 micrograms/ml, so this drug should be highly effective toward these species. Three strains of Staphylococcus aureus were isolated, one of which was resistant to methicillin. It was not eradicated.

Adolescent↗

PubMed1991

Enhanced skin permeation of papaverine by a medium chain glyceride.

The mode and mechanism of action of Sefsol-318, a medium chain glyceride and a potent percutaneous absorption enhancer, on the in vitro permeation of papaverine hydrochloride through hairless rat skin were investigated and compared with those of laurocapram (Azone). The total amount of the drug delivered through excised skin over 28 h from aqueous solutions of the drug in which 5% S-318 or Azone was suspended was about 820 or 420 times higher, respectively, than from the solution alone. Experiments using liposomes as models, indicated that both the enhancers markedly increased the fluidity of lipid membranes. Skin conductance measurements in hairless rats indicated that they both also increased in vivo skin moisturizing and water holding capacity. These results suggest that the mechanism of action of Sefsol-318 and Azone in enhancing skin permeation are similar. But following in vitro pretreatment of the excised skin with 5% Sefsol-318 and aqueous emulsion for 2 h, skin permeation of papaverine hydrochloride through the pretreated skin was much lower than through non-treated skin in the presence of Sefsol-318. In contrast, the enhancing effect of Azone on the pretreated skin was similar to that of Azone on the in vitro non-treated skin. We found that, unlike Azone, Sefsol-318 disappeared from skin completely one day after 24 h-in vivo pretreatment of skin with aqueous gels containing each agent. In agreement, drug permeation through skin excised one day after the in vivo pretreatment with Sefsol-318 was almost the same as in non-pretreated controls without Sefsol-318. This difference in the mode of action of Sefsol-318 and Azone may arise from the difference in the residence times of these enhancers in skin.

Administration, Cutaneous↗

PubMed1991

[The effect of dopamine or dobutamine on plasma concentration of magnesium in dogs].

Plasma magnesium (Mg) concentration of dogs was determined with atomic absorption spectrophotometry during the infusion of dopamine (DOA) or dobutamine (DOB). Other electrolytes were also measured with same samples. Normoventilation was maintained during this experiment in order to avoid the respiratory interference. DOA 15-20 micrograms.kg-1.min-1 decreased Mg concentration significantly. DOB 5-20 micrograms.kg-1.min-1 did not change Mg concentration. Potassium (K) values were almost constant during infusion of both drugs, but DOB reduced K concentration at the dose of 20 micrograms.kg-1.min-1. Ionized calcium ion tended to decrease in DOA and to increase in DOB while the dose of the catecholamines was increased. These were not significant changes. These changes of concentration returned to control values 1 hour after stopping drug administrations. We speculate that beta-receptor, especially beta 2-receptor stimulation by DOA is responsible for the decrease of Mg in the mechanism of Mg uptake into cells of such tissues as liver or muscle.

Animals↗

PubMed1991

[Analysis of the clinical effect of Adelavin infusion during enflurane anesthesia on post-operative hepatic function].

The protective effect of Adelavin, which is made of liver essence, for maintaining postoperative hepatic function was analysed in 85 patients who had enflurane anesthesia. The patients who showed hepatic dysfunction preoperatively were excluded from this trial. Adelavin was infused at a speed of 0.1 mg.kg-1.hr-1 during anesthesia. The group who had upper abdominal surgery in the Adelavin group showed significantly lower incidence of postoperative hepatic dysfunction. The group who had only enflurane anesthesia in the Adelavin group showed significantly lower incidence of postoperative hepatic dysfunction. These results suggest that the Adelavin infusion has a significant protective effect on hepatic function after enflurane anesthesia.

Anesthesia, Inhalation↗

PubMed1991

[A case report of anesthetic management of orthotopic liver transplantation from a living donor to his son].

In November 1989, transplantation of a liver graft from a living related donor was performed at Shimane Medical University Hospital. The donor was a 26-year-old man and the recipient his 1-year-old son. The child had been in end stage of liver cirrhosis. Before the surgery, he required intensive care because of massive bleeding from varices. Anesthesia of the recipient was rapidly induced with ketamine and the trachea was intubated with succinylcholine using cricoid pressure. Anesthesia was maintained with enflurane, fentanyl and pancuronium. Nitrous oxide was used only in the preanhepatic period. Total surgical time and anesthetic time were 945 min and 1065 min, respectively. Total estimated blood loss was 3650 ml and 2780 ml of fresh whole blood was transfused. Careful attention was paid to body temperature, serum potassium, ionized calcium and blood coagulation function, as well as to general cardiovascular and respiratory functions. During anhepatic period, the inferior caval vein was not clamped. Hemodynamic function was relatively stable throughout the operation. At the time of reperfusion of the transplanted graft, there was little change in serum potassium levels or other parameters. Postoperative mechanical ventilation was required for 8 days.

Adult↗

PubMed1990

X-ray crystallographic characterization of two polymorphs of 8-(2-methoxycarbonylamino-6-methylbenzyloxy)-2-methyl-3-(2- propynyl)-imidazo [1,2-a]pyridine.

Structural characterization of two polymorphs (Forms A and B) of 8-(2-methoxycarbonylamino-6-methylbenzyloxy)-2-methyl-3-(2-p ropynyl)-imidazo [1,2-a]pyridine (1) was accomplished by X-ray crystallographic analysis. Form A crystallized in the monoclinic space group C2/c, with a = 42.936 (14), b = 4.356 (1), c = 21.536 (6) A, beta = 109.92 (4) degrees, z = 8, and dcal = 1.275 g/cm3. Form B crystallized in the monoclinic space group P2(1)/c, with a = 4.367 (1), b = 38.214 (3), c = 11.253 (1) A, beta = 95.47 (2) degrees, z = 4, and dcal = 1.292 g/cm3. Some subtle conformational differences between the polymorphs were observed. Although the Form B crystal has a somewhat more compactly packed structure than Form A, this compactness is thought to be disadvantageous to conformational features and to the crystal structure of Form B. The intramolecular hydrogen bonding force between N(1) and NH(22) atoms of Form B is weaker than that of Form A, and the stacking force between the imidazopyridine rings of Form B may also be weaker than that of Form A. Thus, Form A is considered to be a more stable structure than Form B. In DSC analysis, Form B transformed to Form A. Based on these results, phase transformation from Form B to A occurs during a transient fluid state.

Crystallization↗

PubMed1990

Heterogeneity of islet cell autoantibodies in terms of insulin release from rat islets and insulinoma cells.

The clinical significance of cytoplasmic islet cell autoantibodies (ICA) has been studied since their discovery by Bottazzo et al. in 1974. Some ICAs destroy pancreatic B cells in the presence of complement, whereas others take no part in this destruction. This suggests that islet function varies with the amount of ICA produced. In the present investigation we report the heterogeneity of monoclonal islet cell antibodies produced by one of us in terms of insulin release from isolated rat islets as well as from rat insulinoma cells (RINr).

Adenoma, Islet Cell↗

PubMed1990

Lack of favorable effect of immunomodulators on outbred syngeneic rodent islet transplantation.

We studied the effect of two immunomodulators, lobenzarit disodium and OK-432, on outbred syngeneic islet transplantation. Six hundred fresh islets taken from two male Wistar rats were transplanted intraportally into other male Wistar rats that had been made diabetic with streptozotocin. Lobenzarit was given to 12 recipients and OK-432 to seven recipients intraperitoneally for 1 month, while nine controls received only intraperitoneal saline. Both drug-treated groups could not maintain lower fasting plasma glucose levels or higher fasting body weights at each time as compared with controls. The islet survival time in lobenzarit-treated (23.5 +/- 8.0 days) and OK-432-treated (25.3 +/- 13.4 days) groups was not longer than that (21.6 +/- 9.4 days) of the control group. All the pancreatic insulin contents of the seven surviving controls, ten surviving lobenzarit and five surviving OK-432 recipients were less than 0.8% of the mean insulin content obtained from 12 normal male rats. The hepatic insulin content of both drug-treated groups was not higher than that of the control group. These results suggest that lobenzarit disodium and OK-432 cannot protect outbred syngeneic islet grafts.

Adjuvants, Immunologic↗

PubMed1990

Motion analysis of the cervical spine in athetoid cerebral palsy. Extension-flexion motion.

Frequently instability and premature onset of spondylosis of the cervical spine are found in athetoid cerebral palsy (CP) patients. These structural abnormalities appear to be related to athetoid motion of the neck in CP. Through motion analysis, the authors aimed to clarify the abnormalities of cervical motion that could precipitate structural abnormalities. The gross characteristic feature of cervical motion in athetoid CP is "whip movement." Both velocity and acceleration during extension-flexion motion were greater than in normal subjects, especially at the upper cervical levels. Also, a sudden increase in velocity and acceleration occurred during rapid motions at certain levels, followed by a larger range of motion of the cervical spine. Such kinematic abnormalities were thought to generate a greater shearing force and bending moment exerted on the corresponding cervical articulations-discs and facets. Olisthetic instability often accompanied disc degeneration at the upper cervical levels. A large range of extension--flexion motion of the cervical spine, analogous to a cantilever, caused a repeated bending moment of extraordinary magnitude and was regarded as a precipitative factor for disc degeneration and osteophytosis common at the middle and lower levels of the disc.

Adult↗

PubMed1990

A disintegration test for vaginal tablets: comparison with BP test.

To improve the disintegration test for vaginal tablets described in the British Pharmacopoeia (BP), a monitoring apparatus was added, and tested with seven effervescent and five non-effervescent tablets. A tablet was placed on the metal disc of the BP disintegration apparatus, and the guided plate was placed on the tablet. The guided plate moved downward smoothly in a cylinder as the tablet disintegrated. The movement was recorded by using a kymograph. The end-point and process of disintegration of the tablet were automatically recorded and the results obtained suggest that the modified test is a useful tool for the quality control of vaginal tablets.

Female↗

PubMed1990

Disintegration test to measure lot-to-lot variations of vaginal tablets.

Attempts were made to investigate the disintegration test for vaginal tablets. Disintegration tests were done for four different commercial vaginal tablets (three lots each) by the watch glass method and Japanese Pharmacopoeia (JP) disintegration method, and the resulting profiles were compared to those by the modified British Pharmacopoeia (BP) method on a point of lot-to-lot variation of the disintegration times. The disintegration time of every tablet by the modified BP method was longest, followed by the watch glass method, and finally by the JP disintegration method. The results for lot-to-lot differences in disintegration times by the modified BP method were similar to those by the watch glass method. However, such lot-to-lot differences as found by the modified BP method and watch glass method were not always observed by the JP disintegration method. It was concluded from these results that the modified BP method was most suitable for investigating lot-to-lot differences in the disintegration of vaginal tablets.

Administration, Intravaginal↗

PubMed1990

Enhanced transdermal delivery of zidovudine in rats and human skin.

Zidovudine (azidothymidine, AZT), a potent antiviral agent acting on acquired immunodeficiency syndrome virus, was examined with regard to permeation through rat and human skin. A steady state plasma concentration of AZT after transdermal application in rats estimated from both pharmacokinetics data after i.v. administration and penetration rate through excised rat skin from 10% oleic acid (OA) aqueous solution shows penetration about 85 times higher compared to that from 10% OA would be needed for therapeutic efficacy. A mixed-solvent system consisted of 5% Sefsol-318 (S-318), 10% OA, 10% N-methyl-2-pyrrolidone (MP), 20% propylene glycol (PG) and water showed promising characteristics as a vehicle in terms of permeability of AZT through excised rat skin. The maximum flux of 0.41 mumol/cm2/h was observed in excised human skin after application of a gel formulation including S-318, OA, MP and PG. The result suggests a possible use of the gel formulation to gain an effective plasma concentration in humans.

Administration, Cutaneous↗

PubMed1990

Prediction of skin permeability of drugs. I. Comparison with artificial membrane.

In order to measure the contribution of lipid and pore (aqueous) pathways to the total skin permeation of drugs, and to establish a predictive method for the steady state permeation rate of drugs, the relationship between permeability through excised hairless rat skin and some physicochemical properties of several drugs were compared with those through polydimethylsiloxane (silicone) and poly(2-hydroxyethyl methacrylate) (pHEMA) membranes, as typical solution-diffusion and porous membranes, respectively. A linear relationship was found between the permeability coefficients of drugs for the silicone membrane and their octanol/water partition coefficients. For the pHEMA membrane, the permeability coefficients were almost constant independent of the partition coefficient. On the other hand, the skin permeation properties could be classified into two types: one involves the case of lipophilic drugs, where the permeability coefficient is correlated to the partition coefficient, similar to the silicone membrane; and the other involves hydrophilic drugs, where the permeability coefficients were almost constant, similar to pHEMA membrane. From the above results, the stratum corneum, the main barrier in skin, could be described as a membrane having two parallel permeation pathways: lipid and pore pathways. An equation for predicting the steady state permeation rate of drugs was derived based on this skin permeation model.

Animals↗

PubMed1990

Membrane permeation-controlled transdermal delivery system design. Influence of controlling membrane and adhesive on skin permeation of isosorbide dinitrate.

A membrane permeation-controlled transdermal delivery system (MC-TDS) of isosorbide dinitrate (ISDN), a model drug, was prepared from polyvinyl alcohol aqueous gel containing the drug, a membrane consisting of ethylene-vinyl acetate copolymer membrane and acrylic adhesive (EV-a). The permeability of ISDN through the EV-a membrane was 2.5 times higher than that through excised hairless rat skin. The ratio of plasma concentration of ISDN after application of MC-TDS on stripped (damaged) skin relative to intact skin was lower than that after application of Frandol tape-S, a marketed ISDN TDS, which suggests that the EV-a membrane might work as a control membrane for overall delivery rate of ISDN to the body. When MC-TDS stored at 30 degrees C for 13.5-48h was applied to the damaged skin, however, the initial plasma concentration of ISDN was very much higher than the expected therapeutic level and was not controlled by the EV-a membrane. The initial high plasma concentration of ISDN after application of the stored MC-TDS on the damaged skin was due to migration of ISDN from the reservoir to the adhesive during storage at 30 degrees C. The migration of drugs into the adhesive might be an important problem in developing efficient MC-TDS.

Administration, Cutaneous↗

PubMed1990

[Studies on the synthesis of condensed pyridazine derivatives. III. Synthesis and benzodiazepine receptor binding studies of condensed triazolopyridazine derivatives].

A series of 6H-(1)benzothiopyrano[3,4-e][1,2,4]triazolo[4,3- b]pyridazines and 6,7-dihydro-(1)benzothiepino[4,5- e][1,2,4]triazolo [4,3-b]pyridazines were prepared and tested for their ability to displace [3H] diazepam from rat brain membranes. An approximately planar shape of these molecules was essential for high affinity to the benzodiazepine receptor. Among them, 11-aryl compounds in the latter series were found to have high affinity to the benzodiazepine receptor. 11-Phenyl- and 11-thienyl- 6,7-dihydro-(1)benzothiepino[4,5-e][1,2,4]triazolo[4,3- b]pyridazine (3b-5 and 3b-11 respectively) showed the potent affinity comparable to that of diazepam. The structure-activity relationships are also discussed.

Animals↗

PubMed1990

[Studies on the synthesis of condensed pyridazine derivatives. I. Synthesis and benzodiazepine receptor binding studies of 2-substituted-4,4a,5,6-tetrahydrobenzo[h]cinnolin-3(2H)-ones and related compounds].

A series of 2-substituted-4,4a,5,6-tetrahydrobenzo[h]cinnolin-3(2H)-ones and related compounds were synthesized and tested for their ability to displace [3H]diazepam from rat brain membranes. Among them, compounds bearing 4-methoxyphenyl, 4-chlorophenyl, or 4-methylphenyl group at the position-2 were found to have high affinity to the benzodiazepine receptor. 2-(4-Methoxyphenyl)-9-methyl- and 2-(4-methoxyphenyl)-9-methoxy-4,4a,5,6-tetrahydrobenzo[h]cinnolin- 3(2H)-ones (8b-14 and 8b-15, respectively) showed a potent affinity comparable to that of diazepam. These results suggest that a topographical planarity or pseudoplanarity of these molecules is essential for high affinity to the benzodiazepine receptor. The structure-activity relationships are discussed.

Animals↗