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Biomedical subjects

T Sugano

Publications and source records attributed to T Sugano.

At least 145 records · Page 8Linked to original sources

Effects of alanine on malate-aspartate shuttle in perfused livers from cold-exposed rats.

The role of glucocorticoids in the increase by cold-exposure of the effect of alanine on the malate-aspartate shuttle was studied in perfused rat liver. The capacity of the shuttle was evaluated by measurement of changes in both the rate of glucose production from sorbitol and the ratio of lactate to pyruvate during ethanol oxidation (Biomed. Res. 6, Suppl., 1986). The effect of alanine on the shuttle capacity was decreased by adrenalectomy. When 1.5 mg/kg dexamethasone sulfate was administrated to adrenalectomized rats kept at 24 or 4 degrees C, once daily for 5 days, the effect of alanine on the shuttle increased its capacity to the level of sham-operated rats that had been exposed to 4 degrees C for 5 days. The effects of dexamethasone were blocked by the coadministration of tetracycline with the agent. Cold exposure and steroid replacement had little effect on the alanine-induced elevation of the levels of aspartate, glutamate, and alpha-ketoglutarate in liver cells. The increase of the effect of alanine could not be explained only by changes in the activity of NAD+ malate dehydrogenase and aspartate aminotransferase. The results suggest that cold exposure and replacement treatment with glucocorticoids modulate equally the effect of alanine on the capacity of the malate-aspartate shuttle.

Adrenalectomy↗

Effect of norepinephrine on gluconeogenesis in perfused livers of cold-exposed rats.

The effects of norepinephrine and glucagon on gluconeogenesis were studied in hemoglobin-free perfused liver from rats kept for 1-20 days at 4 degrees C. When rats were starved for 24 h at 4 degrees C, the plasma glucose level of rats exposed to cold for 5, 10, and 20 days was significantly higher than that of rats for 1 day, but hepatic glycogen decreased to the same level in all groups. In the isolated perfused liver, basal rates of oxygen consumption and glucose production increased slightly through 5 days of cold exposure and returned to control levels after 20 days of cold exposure. The rates of glucose production from lactate, pyruvate, sorbitol, and glycerol increased by 20-30% after 5 days of cold exposure. The stimulation of gluconeogenesis from these substrates by norepinephrine and phenylephrine increased markedly at all time periods from 1 to 20 days in the cold, with a maximum at 5 days. The stimulation of glycogenolysis by norepinephrine was not affected by cold exposure. The response to catecholamines decreased markedly in liver perfused with calcium-free medium and/or with phentolamine. The stimulation of gluconeogenesis by glucagon increased only in rats exposed to cold for 20 days. The results obtained suggest that the stimulation of hepatic gluconeogenesis by cold is due to an alpha-adrenergic response, and the activation occurs beyond the interaction of norepinephrine with its receptor.

Acclimatization↗

Role of fructose 2,6-bisphosphate in the regulation of glycolysis and gluconeogenesis in chicken liver.

Glucagon and dibutyryl cyclic AMP inhibited glucose utilization and lowered fructose 2,6-bisphosphate levels of hepatocytes prepared from fed chickens. Partially purified preparations of chicken liver 6-phosphofructo-1-kinase and fructose 1,6-bisphosphatase were activated and inhibited by fructose 2,6-bisphosphate, respectively. The sensitivities of these enzymes and the changes observed in fructose 2,6-bisphosphate levels are consistent with an important role for this allosteric effector in hormonal regulation of carbohydrate metabolism in chicken liver. In contrast, oleate inhibition of glucose utilization by chicken hepatocytes occurred without change in fructose, 2,6-bisphosphate levels. Likewise, pyruvate inhibition of lactate gluconeogenesis in chicken hepatocytes cannot be explained by changes in fructose 2,6-bisphosphate levels. Exogenous glucose caused a marked increase in fructose 2,6-bisphosphate content of hepatocytes from fasted but not fed birds. Both glucagon and lactate prevented this glucose effect. Fasted chicken hepatocytes responded to lower glucose concentrations than fasted rat hepatocytes, perhaps reflecting the species difference in hexokinase isozymes.

Animals↗

Double-blind comparison of piroxicam and indomethacin in the treatment of cervicobrachial syndrome and periarthritis scapulohumeralis (stiff shoulder).

In a 14-day double-blind multicenter trial the efficacy and safety of piroxicam was compared with that of indomethacin among patients with extra-articular rheumatic conditions marked by cervicobrachial pain. The drugs were found to have comparable overall efficacy, with over 75% of the patients in both drug groups experiencing some improvement. Piroxicam appeared to provide somewhat better results in the subpopulation with cervicobrachial syndrome, while indomethacin was marginally better among patients with periarthritis scapulohumeralis. There was a trend toward better relief of nighttime pain with piroxicam in the cervicobrachial syndrome group at week 2. Fewer adverse reactions were observed with piroxicam, and the number of patients discontinued for side effects was also lower for piroxicam (4.1%) than for indomethacin (9.5%).

Adolescent↗

Intracellular redox state and control of gluconeogenesis in perfused chicken liver.

The role of the cellular redox state in the control of gluconeogenesis was studied in hemoglobin-free perfused chicken liver, by fluorimetric measurement of the redox states of intracellular pyridine nucleotides. The aminotransferase inhibitor, aminooxyacetate, completely inhibited gluconeogenesis from lactate in the perfused rat liver and to a small extent in the perfused chicken liver. In chicken liver, the highest rate of glucose production was seen with lactate, followed by fructose, pyruvate, and glycerol. When compared at 5 mM, the rate of glucose production from pyruvate was only 10% of that from lactate. Glucose production from a pyruvate/lactate mixture decreased with increasing proportions of pyruvate, together with redox changes of pyridine nucleotides to a more oxidized state. Increased reduction of pyridine nucleotides upon infusion of ethanol was associated with an increased glucose production from pyruvate, and the increase was abolished during octanoate infusion. This abolishment was accompanied by an increase in the acetoacetate to beta-hydroxybutyrate ratio with an oxidation of pyridine nucleotides. The octanoate-inhibited gluconeogenesis occurred at the higher lactate concentration (10 mM) with a transient oxidation of pyridine nucleotides. No significant inhibition was observed at 1 mM lactate, although an instant reduction of pyridine nucleotides was taking place. The rate of beta-hydroxybutyrate generation during octanoate infusion was 2.2 times higher at 1 mM than at 10 mM lactate. The inhibitory effect of octanoate on glyconeogenesis was completely relieved by the addition of NH4Cl. The results demonstrate that the regeneration of NADH in the cytosol is limited in chicken liver, and that gluconeogenesis is regulated, in part, by alteration in the redox states of mitochondria and cytosol.

Ammonium Chloride↗

Stimulation of gluconeogenesis by glucagon and norepinephrine in the perfused chicken liver.

The effects of glucagon and norepinephrine on gluconeogenesis by perfused chicken liver were studied with fluorimetric monitoring of the redox states of the intracellular pyridine nucleotides. Glucagon stimulated glucose production from precursors entering the pathway both above and below the level of triose phosphates without causing a detectable effect on the redox states of pyridine nucleotides. Glucagon stimulation was not abolished by subsequent infusion of octanoate or ethanol. The presence of a pyruvate/lactate mixture plus NH4Cl resulted in a maximum efficacy of glucagon. Glucose production from lactate and fructose was stimulated by norepinephrine. Norepinephrine always caused a change towards increased reduction of pyridine nucleotides with an increase in the beta-hydroxybutyrate/acetoacetate ratio, but displayed no stimulation of glucose and lactate production from pyruvate. As a result of octanoate infusion with lactate, the changes induced by norepinephrine were reversed. The responses to norepinephrine and phenylephrine were decreased markedly in liver perfused with a calcium-free medium and/or with phentolamine. Infusion of calcium into the calcium-deficient liver caused an abrupt elevation of glucose production together with a reduction of pyridine nucleotides, and the original response to norepinephrine was recovered. The results demonstrate that the effects of glucagon and norepinephrine on gluconeogenesis are not identical, and that norepinephrine stimulation is mediated through an alpha-adrenergic and calcium-dependent mechanism in which redox changes of mitochondrial pyridine nucleotides are involved.

Animals↗

Effect of experimental herpes simplex virus vaccine on established ganglionic latency.

Mice were inoculated with herpes simplex virus type 1 by the corneal route beforehand. Ten weeks after the inoculation, one group of mice was repeatedly treated with infectious virus-free, detergent-soluble extract of virus-infected cells (DSE) by the intraperitoneal route and the other group served as the controls. The virus recovery rate from the trigeminal ganglia of DES-treated mice was markedly reduced as compared with that of untreated mice, when a small amount of inocula was used. However, no significant decrease in the virus recovery rate was obtained when a large amount of inocula was used, suggesting that treatment with DSE had a limited effect on established ganglionic latency. The level of neutralizing antibody titers in the serum did not seem to be correlated with the efficacy of DSE in mice infected with a small amount of inocula.

Animals↗

Effect of bursal perfusate on IgG antibody production in incomplete surgically and hormonally bursectomised chickens.

Bursa of Fabricius tissues of untreated four-week-old and of cyclophosphamide-treated 10-day-old chickens were cultured by a perfusion method and the perfusate used in a study on the enhancement of antibody production and conversion in chickens. The bursal perfusates were given to incompletely immunosuppressed chickens (surgical bursectomy or hormonal bursectomy) and to control chickens which were immunised with either sheep red blood cells or Brucella abortus. The results indicated that bursal perfusate was successful in accelerating the IgM production in surgically bursectomised chickens and in stimulating IgG production. We were able to stimulate IgG production in IgM producing hormonally bursectomised chickens and to shorten the latent period of antibody production against B abortus antigen in normal chickens.

Animals↗

Prevention of syngeneic tumor growth in vaccinia virus-primed mice by immunization with vaccinia virus-modulated tumor cells.

Immunization with vaccinia virus-infected and then X-ray-irradiated murine hepatoma MH134 cells provided C3H/He mice with strong resistance to challenge with viable MH134 cells. Male C3H/He mice of 5 to 6 weeks old were primed intraperitoneally (IP) with 1 x 10(7) PFU of live vaccinia virus (Ikeda strain) after irradiation with 250 R of X-ray. Three weeks after priming, the mice were immunized IP 3 times at weekly intervals with 1 x 10(7) X-ray-irradiated MH134 cells that had been infected with vaccinia virus 8 h before irradiation. Over 60% of these cells showed vaccinia virus-induced antigen on their surface (membrane antigen). Challenge with viable MH134 cells was done by inoculating 1 x 10(5) cells IP one week after immunization. During a 4-week observation period, all the untreated control mice died with ascites. On the contrary, all the mice that were X-ray-irradiated, primed and immunized survived challenge with the tumor cells for at least 4 weeks. The mortalities of mice in other groups that were not irradiated, or not primed, or immunized with only X-ray-irradiated tumor cells, were at lowest 50%.

Animals↗