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Biomedical subjects

M Nakashima

Publications and source records attributed to M Nakashima.

At least 523 records · Page 29Linked to original sources
PubMed1986

Pharmacokinetic study of lenampicillin (KBT-1585) in healthy volunteers.

The pharmacokinetic properties of lenampicillin (KBT-1585), a new ampicillin ester, were investigated in 41 healthy volunteers. The maximum concentration of ampicillin in serum after oral administration of 400 mg of lenampicillin was 6.5 micrograms/ml at 0.70 h, and that after a equimolar dosage of ampicillin was 2.9 micrograms/ml at 0.87 h.

Ampicillin↗
PubMed1986

Conjugation of salicylamide in the intestinal wall of dogs and rabbits.

The intestinal conjugation of salicylamide (SAM) the formation of SAM sulfate (SAMS) and SAM glucuronide (SAMG) were investigated in dogs and rabbits by using in situ intestinal sac preparation with mesenteric vein cannulation. SAM, SAMS and SAMG in the mesenteric venous blood, sampled at successive intervals after injection of SAM solutions into the sac, were determined. Total recoveries in 1 h were not significantly different in dogs (71%) and rabbits (64%). Both animals, however, showed a quantitative difference in intestinal conjugation. Sulfation predominated over glucuronidation in dog intestine while the formation of the glucuronide was exclusively high in rabbit intestine. Furthermore, the dose-dependent conjugation of SAM was investigated in dog intestine at four doses, 2, 3, 6 and 10 mg/one animal. Upon increasing the doses from 2 to 10 mg, the amounts of SAMS appearing in the blood remained unchanged, those of SAMG increased about two times and those of free SAM increased about six times, while the total recoveries increased parallel to the doses, suggesting saturation kinetics in the formation step of the two conjugates. Simultaneous computer-fitting of the experimental data for 2 and 10 mg doses to a simplified model, containing Michaelis-Menten kinetics in the formation of the conjugates, was examined and good agreement between the observed data and the theoretical values was obtained.

Animals↗
PubMed1986

Metabolism of sphingomyelin in cultured skin fibroblasts from patients with different types of Niemann-Pick disease.

The metabolism of [choline-methyl-14C]sphingomyelin in cultured skin fibroblasts from patients with different types of Niemann-Pick disease was measured 1 and 3 days after uptake from the media. The cell lines obtained from type A disease had more than 95% unhydrolyzed sphingomyelin in situ on day 3 while two cell lines obtained from type B had 36.3% and 43.3% unhydrolyzed sphingomyelin on day 3. The cell line derived from one patient with the transitory type disease had 48.1% unhydrolyzed sphingomyelin on day 3, and there was no significant difference in the sphingomyelinase activity measured in vitro or in degradation of sphingomyelin in situ between the type B and transitory type disease. In three cell lines from patients with type C disease, there was 18.5%, 29.6% and 31.1% unhydrolyzed sphingomyelin on day 3, which indicates that this type has a decreased ability to metabolize sphingomyelin. Cell from type E disease metabolized sphingomyelin normally.

Cells, Cultured↗
PubMed1986

[A phase I study on intravenous drip infusion of astromicin].

A phase I study on intravenous drip infusion of astromicin (ASTM, KW-1070), an aminoglycoside antibiotic, was performed on 9 healthy adult male volunteers to investigate the safety and pharmacokinetics of this drug. ASTM 200 mg was dissolved in 250 ml of saline and given to each of 6 volunteers by drip infusion in 1 hour. For comparison, 200 mg of ASTM in 1 ml of saline was injected intramuscularly. No subjective and objective reactions were found, and laboratory test value did not show any change possibly caused by ASTM. In a single administration study, Cmax was 10.8 micrograms/ml by intramuscular injection and 12.0 micrograms/ml by intravenous drip infusion. The areas under the time-serum concentration curve were 35.6 micrograms X hr/ml and 34.9 micrograms X hr/ml, respectively; that is, the serum levels of ASTM after one-hour intravenous drip infusion changed almost identically to those after intramuscular injection. In a multiple administration study, the change in serum levels of ASTM after the ninth administration was approximately the same as that after the first one. This means that no accumulation of ASTM in serum occurred. Recovery rates of ASTM in urine up to 8 hours after a single intramuscular injection and a single intravenous drip infusion were 85.4% and 87.5%, respectively. These results also support the conclusion that there is no accumulation of ASTM in the body by repeated administrations.

Adult↗
PubMed1986

Relationship between elevation of the labellar threshold after raising by increasing sucrose concentrations and impulses of a single sugar receptor in the LL-type hair of the blowfly.

The threshold for proboscis extension to sucrose stimulus of a single sugar receptor on different labellar hairs was elevated by raising blowflies on higher concentrations of sucrose. The reaction time was defined as the duration from stimulus of a single sugar receptor in the LL-type hair until occurrence of proboscis extension. Reaction times at the threshold concentrations of sucrose did not change among blowfiles raised on different sucrose levels. The average value is about 0.35 s. Relationship of the average number of impulses during 0.35 s to log median acceptance thresholds of sucrose for proboscis extension was linear.

Animals↗
PubMed1986

The roles of the recurrent nerve and the ventral nerve cord in the feeding response of the blowfly, Phormia regina M.

The interaction of sensory activities from internal stretch receptors and from external sugar receptors was studied in relation to proboscis extension and sucrose intake of the blowfly. The tarsal threshold for proboscis extension was elevated in flies after the recurrent nerve was cut. Cutting either the recurrent nerve or the ventral nerve cord did not alter the labellar thresholds for proboscis extension but did influence sucrose intake by prolonging the duration of intake. After the ventral nerve cord was cut, the flies did not stop ingestion as long as sugar receptors in the interpseudotracheal papillae were stimulated. Tonic impulse discharges from the intact recurrent nerve were divided into efferent and afferent types. Efferent impulses from the brain were thought to be transmitted to the hypocerebral ganglion-corpus cardiacum complex for regulation of opening and closing of the foregut valves, of peristaltic movements in the foregut. Afferent impulses were thought to be discharged from the foregut stretch receptors which detected peristaltic movements in the foregut.

Animals↗
PubMed1985

Effect of ophthalmic administration of S-596 (Arotinolol) on intraocular pressure and haemodynamics in health volunteers: comparison with timolol.

The effects on intraocular pressure (IOP) and haemodynamics of two beta-blockers, arotinolol and timolol, administered topically to the eye, were studied in 6 healthy volunteers in a cross-over trial. 0.5% timolol or 0.5% arotinolol ophthalmic solutions drop was instilled in both eyes of the volunteers at an interval of 48 hours. Timolol lowered IOP by about 31.9% 1 hour after administration and the effect continued until 3 h, whilst arotinolol lowered it significantly 2 h after instillation and the same maximum effect as that of timolol was obtained after 3 h. Arotinolol was detected in blood in all subject and timolol in blood in one subject, although it was found in all subjects in urine. Both drugs lowered heart rate at rest and attenuated the increase in the double product (products of blood pressure and heart rate) at exercise. The effect of timolol on the double products was larger. Thus, arotinolol and timolol decreased IOP to similar extent, although the maximal effect of arotinolol was delayed. Arotinolol as well as timolol affected haemodynamics through absorption into circulation, but the former had less effect on haemodynamics during exercise.

Adult↗
PubMed1985

The oxygen affinity of mammalian hemoglobins in the absence of 2,3-diphosphoglycerate in relation to body weight.

We studied the oxygenation of mammalian hemoglobins: mouse (Mus musculus molossinus), rabbit (Oryctolagus cuniculus domesticus), Japanese monkey (Macaca fuscata), man (Homo sapiens), sheep (Ovis aries), llama (Lama glama), pig (Sus scrofa domesticus), cow (Bos taurus domesticus) and horse (Equus caballus), in the absence of 2,3-diphosphoglycerate (DPG) and compared their oxygen affinity in relation to the body weight. The negative correlation between body weight and the oxygen affinity of the whole blood, observed by Schmidt-Nielsen and Larimer (1958), was not observed in the absence of DPG. Our results indicated that an adaptive evolution proposed for hemoglobin in terms of its oxygen affinity vs body weight of the animal can only be appreciated with DPG.

2,3-Diphosphoglycerate↗
PubMed1985

Production of monoclonal antibodies against Legionella pneumophila serogroup 1.

Four monoclonal antibodies to Legionella pneumophila Philadelphia 1 were produced by the fusion of immunized BALB/c lymphocytes to a murine myeloma cell line. Two (Lp1-1 and Lp1-3) of the four monoclonal antibodies reacted with 14 L. pneumophila serogroup 1 strains, and the other (Lp1-2 and Lp1-4) reacted with only three out of 20 strains tested. These four monoclonal antibodies did not bind to any strains of L. pneumophila serogroup 2-7 and other Legionella species. In addition, it has been shown that these monoclonal antibodies may be useful not only for subserotyping of L. pneumophila but also for retrospective diagnosis using immunopathological methods.

Antibodies, Monoclonal↗
PubMed1985

Affinities of adrenergic drugs for alpha 2-adrenoceptors in dog saphenous vein in comparison with those in rat brain or human platelets.

The affinities of drugs for the postsynaptic alpha 2-adrenoceptors in the dog saphenous vein were examined and compared with those in human platelets or in rat brain. The pA2 or pD2 values in the vein were determined in the presence of phenoxybenzamine. The pKi values (dissociation constant) of drugs for binding to alpha 2-adrenoceptors in human platelets or in rat brain were determined by radioligand binding assay using 3H-yohimbine (YOH) or 3H-clonidine (CLO) as ligands. The binding of agonists to 3H-YOH binding sites was carried out in the presence of GTP. The pA2 or pD2 values in the vein had a good correlation with pKi values for YOH sites but not with those for CLO sites in rat brain. The pKi values for YOH sites in human platelets had a good correlation with those for YOH sites in the brain or with pA2 or pD2 values in the vein. These results suggested that the affinities of adrenergic drugs for postsynaptic alpha 2-adrenoceptors in the dog saphenous vein are similar to those in brain and in platelets, and it is probable that the adrenergic drugs produce their alpha 2-adrenoceptor-mediated effects on vascular tissues primarily through binding to a low-affinity form of the alpha 2-adrenoceptors.

Adrenergic alpha-Agonists↗
PubMed1985

Anti-arrhythmic effect of nadolol in experimental arrhythmias: comparison with propranolol and alprenolol.

The effects of nadolol on experimental arrhythmias were investigated and compared with those of propranolol and alprenolol. The arrhythmias were induced by either ouabain, holothane plus adrenaline or acute coronary occlusion in anesthetized dogs. All three beta-blocking drugs in a dose range of 10 to 200 micrograms/kg inhibited halothane plus adrenaline-induced arrhythmias. These drugs also attenuated coronary occlusion-induced ventricular arrhythmias as well as other electrical abnormalities such as electrical alternation and conduction delay. Among the three drugs, nadolol was the most potent in suppressing both types of arrhythmias. Contrary to the potent effects on these arrhythmias, nadolol was ineffective against ouabain-induced arrhythmias even in a dose of 3 mg kg, while propranolol and alprenolol were significantly effective in a dose of 100 micrograms/kg. It is probable that the anti-arrhythmic effect of nadolol is exclusively due to its beta-blocking activity.

Alprenolol↗
PubMed1985

Pharmacokinetics of plasma and urine clenbuterol in man, rat, and rabbit.

Therapeutic dose (20, 40 and 80 micrograms/man) of clenbuterol hydrochloride, a beta 2-adrenergic stimulant, was orally administered to healthy volunteers, and the unmetabolized drug in plasma and urine was determined by enzyme immunoassay. The plasma levels of clenbuterol reached the maximum value of 0.1, 0.2 and 0.35 ng/ml, respectively, in a dose-dependent manner within 2.5 h, which lasted for over 6 h after the administration. The half-life of clenbuterol in plasma was estimated to be about 35 h. When the drug was orally administered repeatedly to men twice a day, the plasma level reached the plateau within 4 d after the initial administration. At that time, the plasma levels of the unchanged form were 0.2 to 0.3 ng/ml and 0.5 to 0.6 ng/ml at doses of 20 and 40 micrograms/man, respectively. The bound ratio of the drug to plasma protein was estimated to be 89-98% at a single administration of 80 micrograms of the drug. The cumulative urinary excretion of unchanged compound corresponded to about 20% of the administered dose as measured at 72 h following a single oral administration. When clenbuterol hydrochloride was orally administered to rats at a dose of 2 micrograms/kg, the plasma level reached the maximum at about 1 h after the administration. In rabbits, the plasma concentrations reached the maximum value of about 0.2 and 0.8 ng/ml within 2 h following administration of clenbuterol hydrochloride at doses of 0.5 and 2 micrograms/kg, respectively. The half-life of clenbuterol in plasma was about 30 h in rats and about 9 h in rabbits.

Animals↗