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Biomedical subjects

N Nishida

Publications and source records attributed to N Nishida.

At least 145 records · Page 8Linked to original sources
PubMed1990

Carnitine metabolism and morphometric change of liver mitochondria in valproate-treated rats.

The effect of the administration for 7 or 28 days of 50 mg/kg/day valproate (VPA) on carnitine metabolism and morphological changes of liver mitochondria in immature rats was evaluated. The dose of VPA was almost the same as that we clinically used. Carnitine concentrations in serum, red blood cells (RBC), muscle, liver and urine were measured. The rats treated with VPA for 7 days showed no significant change in carnitine concentration in each tissue examined or by morphology. In the serum, RBC and muscle of rats treated with VPA for 28 days, free carnitine levels decreased, while acylcarnitine levels and the ratio of acylcarnitine to free carnitine (acyl/free ratio) increased. Mitochondrial enlargement was also induced and urinary acyl/free ratio of VPA treated rats was higher than that of control rats after the 14th day of the treatment. These results suggest that carnitine deficiency and morphometric changes in mitochondria occur time dependent even if the dose of VPA is clinically appropriate.

Animals↗
PubMed1990

Intracellular activity of tosufloxacin (T-3262) against Salmonella enteritidis and ability to penetrate into tissue culture cells of human origin.

The intracellular antimicrobial activity of tosulfoxacin was tested against Salmonella enteritidis C-32 by using human lung fibroid WI-38 cells and was compared with those of ofloxacin and norfloxacin. The intracellular antimicrobial activities of these drugs were evaluated by determining the numbers of viable organisms remaining within cells after treatment with various drug concentrations. At 0.2 and 0.78 microgram/ml, tosufloxacin suppressed intracellular multiplication of S. enteritidis C-32 more effectively than ofloxacin and norfloxacin did. The ability of tosufloxacin to penetrate into WI-38 cells was also determined by the velocity gradient method. The ratio of the intracellular concentration to the extracellular concentration of tosufloxacin was 1.7- and 2.6-fold higher than those of ofloxacin and norfloxacin, respectively. The results indicate that the potent intracellular bactericidal activity of tosufloxacin may be due not only to its high in vitro activity but also to its ability to penetrate into cells at a high level.

Anti-Infective Agents↗
PubMed1990

Physical dependence potential of an enkephalin analog, EK-399, in rats.

The physical dependence potential of Tyr-D-Met(O)-Gly-EtPhe-NHNHCOCH3.AcOH (EK-399), a novel enkephalin analog with a potent analgesic effect, was assessed in rats. The animals were given EK-399 (0.008, 0.032, 0.125, or 0.5 mg/kg), morphine (0.125, 0.5, or 2 mg/kg), pethidine (2 or 8 mg/kg), or pentazocine (2 or 8 mg/kg) every hour through an implanted intravenous cannula. After 3 days of treatment, precipitated withdrawal tests were conducted: naloxone (5 mg/kg) was administered subcutaneously. Rats treated with morphine showed withdrawal signs such as hyperirritability, salivation, diarrhea, and weight loss. Rats treated with pethidine, pentazocine, or EK-399 showed similar signs, but they were less evident than those in morphine-treated rats. In abrupt withdrawal tests after 7 days of treatment, rats treated with morphine, pethidine, or pentazocine showed weight loss, whereas rats treated with EK-399 showed little or no weight loss. In substitution tests, EK-399 suppressed the withdrawal signs in morphine-dependent rats, and vice versa. These results show that EK-399 has a morphine-like physical dependence potential that is weaker than that of morphine, pethidine, or pentazocine in rats.

Animals↗
PubMed1989

Discriminative stimulus effects of enkephalin analogs, EK-209 and EK-399, in rats.

The discriminative stimulus effects of two enkephalin analogs, Tyr-D-Ala-Gly-MePhe-NHNHCOCH2CH3.AcOH (EK-209) and Tyr-D-Met(O)-Gly-EtPhe-NHNHCOCH3.AcOH (EK-399), were assessed in a drug discrimination experiment with rats. The animals were trained to discriminate between the effect of morphine (3 mg/kg s.c.) and saline in a two-lever choice, water reinforced procedure. After the discrimination training had been completed, the animals were used in stimulus generalization tests. A test drug was administered subcutaneously before the test session, and the animals were allowed to select the morphine or saline lever. The animals completely generalized to the effects of codeine, fentanyl and EK-209, but did not generalize completely to the effect of ethylketocyclazocine. After receiving an injection of pentazocine, levallorphan, N-allynormetazocine, or EK-399, the animals pressed the morphine lever, but did not generalize completely to the effects of these drugs. These results suggest that the discriminative stimulus effect of EK-209 is similar to that of morphine, whereas the effect of EK-399 may be different from that of morphine.

Analgesics↗
PubMed1989

Reinforcing effects of the enkephalin analogs, EK-209 and EK-399, in rats.

The reinforcing effects of two enkephalin analogs, Tyr-D-Ala-Gly-MePhe-NHNHCOCH2CH3.AcOH (EK-209) and Tyr-D-Met(O)-Gly-EtPhe-NHNHCOCH3.AcOH (EK-399), were assessed by means of a self-administration technique with rats. The animals were trained to self-administer an intravenous dose of morphine by a lever-press response. A test drug was substituted for morphine after the rats had initiated and maintained its self-administration. When codeine, fentanyl, pentazocine or EK-209 was available, most of the rats increased the number of self-administrations as the unit dose of these drugs was decreased. When levallorphan or EK-399 was available, most of the rats did not increase responding; only one of 4 rats slightly increased the number of self-administrations as the unit dose of EK-399 was decreased. These results indicate that EK-209, like codeine, fentanyl, and pentazocine, possesses a reinforcing effect, whereas EK-399, like levallorphan, has a very weak effect, suggesting that the latter compound possesses low abuse liability.

Animals↗
PubMed1989

Effect of L-carnitine on glycogen synthesis and ATP production in cultured hepatocytes of the newborn rat.

Changes in intracellular carnitine, ATP and glycogen concentration were studied when hepatocytes of newborn or adult rats were incubated with oleate, lactate and/or carnitine. Hepatocytes of adult rats appeared to be able to maintain cellular carnitine concentration without exogenous carnitine supplementation. Hepatocytes of newborn rats appeared to be unable to maintain cellular carnitine concentration without carnitine supplementation. Moreover, ATP concentration and glycogen concentration were significantly increased by the carnitine supplement with oleate and/or lactate compared to the unsupplemented group. Increases in both intracellular ATP and carnitine concentration depended on the concentration of carnitine added to the medium. These results suggest that carnitine may be an important factor in glycogen synthesis and ATP production of newborn infants.

Adenosine Triphosphate↗
PubMed1988

Protective effect of D,L-carnitine on valproate-induced hyperammonemia and hypoketonemia in primary cultured rat hepatocytes.

The effect of D,L-carnitine on sodium valproate (VPA)-induced hyperammonemia and hypoketonemia was investigated in primary cultures of rat hepatocytes. Administration of VPA (0.1 to 1.0 mM) resulted in an increase of ammonia and a decrease of ketone bodies in culture medium. When D,L-carnitine was added with VPA to the medium, the level of ammonia decreased significantly and that of ketone bodies increased. A significant negative relationship was found between the concentrations of ammonia and the ketone bodies in the medium following administration of D,L-carnitine. Our results suggested that VPA suppressed the urea cycle metabolism and that a protective effect of D,L-carnitine on ketone metabolism was probably due to the reversal of the inhibition of beta-oxidation.

Ammonia↗
PubMed1988

Evaluation of the cytotoxicity of sodium valproate on primary cultured rat hepatocytes.

Primary cultured rat hepatocytes were used to study the cytotoxicity of sodium valproate (VPA). Cytotoxicity was monitored by measurement of leakage of intracellular enzymes into the culture medium: lactate dehydrogenase (LDH), glutamate oxaloacetate transaminase (GOT), glutamate pyruvate transaminase (GPT). The effects of D,L-carnitine and albumin administration on the cytotoxicity were evaluated. LDH leakage rose with an increasing dose of VPA. Administrations of D,L-carnitine and albumin reduced VPA hepatotoxicity. Our data suggest that VPA-induced hepatotoxicity is dose-related and may be modulated by serum carnitine and albumin levels.

Alanine Transaminase↗
PubMed1987

Effect of dexamethasone on the adenylate cyclase system of cultured hepatocytes of fetal rats.

During treatment of primary cultured hepatocytes with dexamethasone for several hours, cyclic AMP formation and glycolysis by glucagon increased dose dependently. In the cells pretreated with dexamethasone, the output of intracellular cyclic AMP increased significantly (p less than 0.01) with glucagon of 2.8 X 10(-9) M or more, and the amount of glucose released also increased significantly (p less than 0.01) with glucagon of 2.8 X 10(-8) M or more, compared to the control cells. Moreover, treatment with dexamethasone increased the stimulatory effect of guanosine-5'-triphosphate (GTP), guanyl-5'-yl-imidodiphosphate on adenylate cyclase and significantly increased the stimulatory effect of fluoride. In the rat hepatocytes primarily cultured with dexamethasone for several hours, the stimulatory effect of GTP and fluoride on adenylate cyclase increased time dependently. These data indicate that the glucocorticoid regulates the sensitivity of adenylate cyclase at distinct loci of the postreceptor system.

Adenylyl Cyclases↗
PubMed1987

Carnitine metabolism in valproate-treated rats: the effect of L-carnitine supplementation.

The effect of the administration for 7 days of valproate (500 mg/kg/day) or valproate (500 mg/kg/day) plus L-carnitine (200 mg/kg/day) on carnitine concentrations in serum, red blood cells, muscle, liver, and urine was evaluated. In the serum and muscle of the valproic acid (VPA) group, free carnitine levels decreased, while acyl-carnitine levels and acyl/free ratio increased, when compared to those of the control. When L-carnitine was given to the VPA group, the free carnitine levels increased in the serum, muscle, and liver, and the acyl/free ratio decreased in all tissues when compared to those of the VPA group. The mean of free carnitine level in urine of the VPA group was not different but acylcarnitine increased when compared to values of controls, and after the supplementation with L-carnitine the acylcarnitine (from day 4 to 7) levels were decreased compared to the VPA group. The serum beta-OH-butyrate level in the VPA group was decreased when compared to those of controls and VPA plus L-carnitine groups. These results indicate that L-carnitine supplementation protects against the alteration in carnitine metabolism induced by the administration of VPA.

Animals↗
PubMed1987

[V1P-terminal force evaluated by left ventricular inflow velocity patterns in pulsed Doppler echocardiography].

The relationship between V1P-terminal force (V1-PT) and the characteristics of left ventricular (LV) diastolic filling and atrial contraction were evaluated using LV inflow velocity patterns obtained by pulsed Doppler echocardiography. Subjects consisted of 54 patients with old myocardial infarction, 56 with essential hypertension, 48 with angina pectoris, 19 with dilated cardiomyopathy, and 16 with miscellaneous disease other than of mitral valve lesions. The patients were classified as the positive group: V1-PT less than or equal to -0.04 mmsec, intermediate group: 0 greater than V1-PT greater than -0.04 mmsec, and negative group: V1-PT greater than or equal to 0 mmsec. The following were the results obtained: 1. In the positive group, the rapid filling wave (R) had reduced velocity, the prolonged deceleration time and the decreased acceleration and deceleration ratios. 2. In the positive group, velocity of the atrial contraction wave (A) was increased and the atrial contraction time was prolonged compared to the other groups. 3. In the positive group, the A/R was greater than in the other groups. 4. In the positive and intermediate groups, V1-PT correlated significantly with the A/R (r = 0.83, p less than 0.01), R (r = -0.58, p less than 0.01) and A (r = 0.48, p less than 0.01). In the positive group, LV inflow volume was decreased in the rapid filling phase. In the atrial contraction phase, the inflow volume was increased to compensate for loss of inflow volume in the rapid filling phase. These findings suggested that LV diastolic filling was disturbed in the positive group. In conclusion, the value of V1-PT is influenced by any disturbance of LV diastolic filling.

Adult↗