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Biomedical subjects

T Sakurada

Publications and source records attributed to T Sakurada.

At least 235 records · Page 13Linked to original sources

Human placental thyroxine inner ring monodeiodinase in complicated pregnancy.

Production of rT3 from T4 in the placenta were measured in four patients with induced abortion, in three patients with spontaneous abortion, in 19 patients with various complications of pregnancy including Graves' disease, and in 18 normal pregnancies. The placentas, obtained at delivery, were homogenized and centrifuged at 800 X g. Supernatants (1 mg protein) were incubated with 1 microgram of stable T4 and 50 mmol/L dithiothreitol at 37 degrees C for 60 minutes. The generated rT3 was measured by radioimmunoassay (RIA). In patients who delivered at 38 to 41 weeks with complicated pregnancy, the net placental rT3 production from T4 was 7.3 +/- 2.5 ng/tube, which was not significantly different from that obtained in normal pregnancy (8.5 +/- 2.4) at an equivalent gestational age. In patients with abortions, the net placental rT3 generation from T4 was very high, and there was a significant negative correlation between the net placental rT3 production from T4 and gestational age. These results indicate that the net placental rT3 production from T4 is not affected by complications of pregnancy, but shows a significant change with the progress of gestation.

Abortion, Induced↗

Intrathecal substance P analogue causes motor dysfunction in the rat.

(D-Pro2, Trp7,9)-substance P injected into the subarachnoid space produced a severe faccid extension of hindlimb in a dose-related manner in the rat. This motor dysfunction was neither reversed by naloxone, an opioid receptor antagonist nor by intrathecal SP. SP levels in the lumbar cord were markedly depleted in rats with hindlimb paralysis, though there was not significant changes in rats without paraplegia. These results suggest that DPDT-SP produces motor dysfunction which dose not appear to be mediated by opioid and SP receptors.

Animals↗

Characterization of the hyperalgesic effect induced by intrathecal injection of substance P.

Substance P (SP) was administered to awake rats by injection into the lumbar subarachnoid space via an indwelling cannula. Intrathecal (i.t.) injection of substance P produced a dose-related hyperalgesic response in the tail-pressure assay. This hyperalgesic effect peaked at 1 min and returned to control level within 15 min. Tachyphylaxis to the action of substance P was not observed by successive intrathecal injections. The hyperalgesic effect induced by substance P was increased by pretreatment with naloxone and blocked by a large dose of morphine. A synthetic analogue (D-Pro2, D-Trp7,9)-substance P, was not found to block the action of substance P on mechanical responses. These results suggest that substance P apparently produces a direct action on spinal substance P receptors and the antagonistic effect of morphine on the hyperalgesia induced by substance P may be mediated through a postsynaptic mechanism in the spinal cord.

Animals↗

The analgesic activity of D-Arg2-dermorphin and its N-terminal tetrapeptide analogs after subcutaneous administration in mice.

D-Arg2-dermorphin and its nineteen N-terminal tetrapeptide analogs were prepared, and their analgesic activities after subcutaneous administration in mice and the stability of a D-Arg2-dermorphin tetrapeptide to enzymatic degradation were examined. The analgesic effect was assessed by the tail pressure test. D-Arg2-dermorphin was found to have analgesic potency equal to or slightly greater than that of dermorphin. In a series of tetrapeptide analogs, a very pronounced activity greater than that of morphine was observed for analogs of the following structure, H-Tyr-D-Arg-Phe-X-OH (X = Gly, sarcosine and D-Ala) or its esters. Replacement of D-Arg2 by D-Arg(NO2), D-homoarginine or D-Lys resulted in a decrease in potency, suggesting that the guanidino group and side chain length of D-Arg2 are of great importance for a higher activity. D-Arg2-tetrapeptide (H-Tyr-D-Arg-Phe-Gly-OH) was found to be more stable than the parent tetrapeptide (H-Tyr-D-Ala-Phe-Gly-OH) to cleavage both by aminopeptidase M and by carboxypeptidase Y.

Analgesics, Opioid↗

Localization of thyroxine 5'-monodeiodinase activity in the renal proximal tubules in rabbits and rats.

To determine the localization of T4 5'-monodeiodinase activity in rabbit and rat nephron segments, the formation of tri-iodothyronine (T3) from thyroxine (T4) was measured in kidney homogenate and in isolated nephron segments obtained by the microdissection method. In order of decreasing activity, homogenates of rabbit renal cortex, outer medulla and inner medulla were capable of converting T4 to T3. In the isolated nephron segments of the rabbit cortex, the activities were noted in both proximal convoluted and proximal straight tubules. On the other hand, the activities were not detected in segments including the cortical thick ascending limb of Henle's loop, the distal convoluted tubule, the connecting tubule, and the cortical collecting tubule. It is concluded that both the convoluted and the straight tubules are the sites of T3 production in the kidney.

Animals↗

Measurement of substance P metabolites in rat CNS.

A procedure based on ion-exchange chromatography for chemical separation and radioimmunoassays for quantitation of substance P (SP), the SP(1-7), and C-terminal fragments, respectively, has been developed. The procedure allows the determination of these fragments in the presence of large (i.e., 50- to 100-fold) excess of parent compound. The chemical identity of isolated SP and fragments was studied with preparative electrophoresis on dilute agarose gel and with HPLC. The activity identified as SP(1-7) comigrated with the authentic standard whereas practically all activity isolated as C-terminal fragments comigrated with SP(5-11). The levels of C-terminal fragments in rat brain areas rich in SP and in spinal cord were 1-2% of those of parent compound. The levels of SP(1-7) were always higher, in the spinal cord markedly higher (three to five times). Postmortem storage of samples from brain and spinal cord indicated that SP(1-7) levels fell more rapidly than those of SP or C-terminal fragments.

Animals↗

[Effects of serial administration of vanillyl n-nonoylamide on vocalization responses by arterial algogenics in guinea pigs].

Desensitizing effects of vanillyl n-nonoylamide, one of the synthetic capsaicinoids, were investigated by algogenics induced vocalization in conscious guinea pigs. Intra-arterial administration of bradykinin, acetylcholine and capsaicinoids (capsaicin, dihydrocapsaicin, vanillyl n-nonoylamide) evoked strong vocalization responses. Increasing doses (50 mg/kg, 100 mg/kg, 200 mg/kg, 400 mg/kg) of vanillyl n-nonoylamide were given to guinea pigs by subcutaneous administration for 4 days. Consecutive administration of vanillyl n-nonoylamide produced a weak but not significant desensitizing effect on bradykinin, acetylcholine-evoked vocalization at several doses. However, a complete suppressive effect on capsaicinoids-evoked response was observed in animals treated with serial administration of vanillyl n-nonoylamide. A weak vocalization response reappeared by three kinds of capsaicinoids (3 micrograms), but there were statistically significant effects on vocalization count when compared with the control values. It was therefore concluded that serial administration of vanillyl n-nonoylamide had a selective desensitizing action on chemonociceptors.

Acetylcholine↗

Determination of free triiodothyronine in serum: comparison of radioimmunoassay with equilibrium dialysis method.

In normal volunteers, serum free triiodothyronine (FT3) concentrations determined by Immophase FT3 RIA kit, Amerlex FT3 RIA kit and equilibrium dialysis methods (absolute FT3, AFT3: product of total T3 and percent FT3) were 4.03 +/- 0.65, 3.69 +/- 0.58 and 3.22 +/- 0.65 pg/ml (mean +/- S.D.), respectively. The normal free triiodothyronine index (FT3I) was 38.4 +/- 6.5. In patients with hyper-and hypothyroidism, the FT3 values measured by these methods were clearly abnormal. In patients with decreased thyroxine binding-globulin, the mean FT3 concentrations determined by these methods were not significantly different from the normal. However, the mean FT3I was significantly lower than normal. In pregnant women at delivery, Amerlex FT3 values were subnormal in 7 of 9 subjects. All of these samples except one were within the normal range when evaluated by Immophase FT3 and AFT3, although their mean values were significantly lower than the mean of normal. On the other hand, the mean FT3I was not significantly different from the mean of normal. The correlations between FT3 were all statistically significant. In a clinically euthyroid patient who had chronic thyroiditis and who was shown to have anti-T3 antibody in her serum, Immophase FT3 and Amerlex FT3 values were above the high standards. However, AFT3, calculated by multiplying total T3 (determined after ethanol extraction) by percent FT3 was normal. In conclusion, the evaluation of FT3 by these radioimmunoassay methods proved clinically useful, when appropriate limitations are considered.

Dialysis↗

Effect of carteolol, indenolol and metoprolol on the thyroid hormone of hyperthyroid patients.

Thirty-four hyperthyroid patients were divided into four groups: placebo, carteolol (20 mg/day), indenolol (60 mg/day) and metoprolol (120 mg/day) groups. The heart rate was determined before and two weeks after the treatment with each drug. Serum levels of T4, T3 and rT3 were measured before, and one and two weeks after the treatment. Both indenolol and metoprolol significantly reduced the heart rate (p less than 0.01 and p less than 0.05, respectively), whereas carteolol was ineffective. Carteolol significantly decreased T4 from 23.4 +/- 4.4 micrograms/100 ml to 20.1 +/- 3.2 micrograms/100 ml (p less than 0.01) in one week and to 20.0 +/- 3.7 micrograms/100 ml (p less than 0.01) in two weeks. T3 and rT3 were also decreased significantly (p less than 0.05 and p less than 0.01, respectively) two weeks after the treatment with carteolol. After two weeks of indenolol treatment, T4 was decreased significantly from 26.2 +/- 8.5 micrograms/100 ml to 23.9 +/- 8.2 micrograms/100 ml (p less than 0.05) and T3 from 789 +/- 391 ng/100 ml to 592 +/- 340 ng/100 ml (p less than 0.02). Metoprolol had no effect on serum thyroid hormone levels. The decrease in the serum level of thyroid hormones by carteolol and indenolol but not by metoprolol in patients with hyperthyroidism would be due to the blockade of beta 2-adrenoreceptors concerning with thyroid hormone secretion.

Adrenergic beta-Antagonists↗

Antinociceptive properties of a new tetrapeptide, Asn-Ala-Gly-Ala, in mice.

The effect of intracerebroventricularly (i.c.v.) administered Asn-Ala-Gly-Ala (NAGA), a partial sequence of beta-lipotropin, was investigated using the tail-pressure, hot-plate and phenylbenzoquinone (PBQ)-induced writhing tests in mice. I.c.v. administration of NAGA produced a dose-dependent inhibition of responses as measured by the three different assays. The ED50 of NAGA on the tail-pressure test did not differ from that obtained on the hot-plate test. NAGA showed a prominent reduction in activity on the PBQ writhing as compared with the hot-plate and tail-pressure tests. A low dose of naloxone (0.1-1.0 mg/kg, s.c.) resulted in a dose-dependent antagonism of the effect of NAGA in all assays. These data suggest that the antinociceptive effect induced by NAGA may involve the endogenous opioid system in mice.

Analgesics↗

Substance P levels in various regions of the rat central nervous system after acute and chronic morphine treatment.

Substance P levels were measured in various CNS regions from rats treated acutely and chronically with morphine. There was no observable effect in the group treated with an acute dose of morphine (10 mg/kg) and sacrificed after 2 h. After 35 days chronic treatment with increasing doses of the drug, the rats were divided into three groups and sacrificed 2 h, 24 h and 7 days after the last injection. The substance P level was increased in the corpus striatum 2 h and 24 h and in the medulla oblongata and dorsal part of the spinal cord 2 h after withdrawal. Seven days after the last injection the levels had returned to normal in these areas. No effects were observed in the cerebral cortex, the hypothalamus or the ventral spinal cord at any time of measurement. Earlier studies have demonstrated that morphine inhibits release of substance P. The observed increase in tissue levels after long-term treatment is therefore interpreted as an accumulation of substance P in the neurons.

Animals↗

[Changes in antimicrosomal antibody, serum thyroglobulin and thyrotropin binding inhibitor immunoglobulin in a patient with silent thyroiditis who experienced four thyrotoxic episodes].

Serial changes of thyroid hormones, TSH, anti-thyroidal antibodies, serum Tg and TBII were studied in a patient with silent thyroiditis who experienced four episodes of transient thyrotoxicosis in a follow-up period of five years. The titers of MCHA were high in the thyrotoxic episodes and further increased in the following hypothyroid phases. In the euthyroid phase it became lower. The serum level of Tg was normal or moderated elevated in the thyrotoxic episodes, and it further elevated in the hypothyroid phase. Surgical biopsy, performed in the euthyroid phase about one year after the forth thyrotoxic episode, revealed the findings of Hashimoto's disease. Two different types of transient thyrotoxic episode, one with positive TBII and high uptake and the other with negative TBII and low uptake, were observed in the same patient with silent thyroiditis. In the beginning of the clinical course, the patient showed positive TBII, high 131I-uptake (77%) in the second episode of thyrotoxicosis, no response of TSH to TRH administration and absence of T3-suppressibility. The value of TBII gradually became normal and was negative at the forth episode of thyrotoxicosis when 131I-uptake was low (1.3%). After this last episode, TSH response to TRH administration was normal in euthyroid phase and augmented in hypothyroid phase. The presence of transient positive TBII and of histological changes of Hashimoto's disease was suggestive of the close relationship between Graves' and Hashimoto's diseases.

Antibodies↗