Thrombocytopenia induced by Jui, a traditional Chinese herbal medicine.
Jui is a traditional Chinese herbal medicine. The causal relation between the drug and thrombocytopenia was proved by a rechallenge test.
Drugs, Chinese Herbal↗
Biomedical subjects
K Yaga
Publications and source records attributed to K Yaga.
Regulation of insulin-stimulated glucose transport by chronic glucose exposure in 3T3-L1 adipocytes.
Chronic hyperglycemia causes insulin resistance, termed glucose toxicity. Herein we studied chronic glucose-dependent regulation of the glucose transport system in adipocytes. 3T3-L1 adipocytes were incubated for up to 24 h with low (1 mM) or high (25 mM) glucose, and glucose transport was subsequently analyzed. 100 nM insulin was present throughout the experiments. 24 h incubation with 1 mM glucose caused a 2.3+/-0.4 fold increase in glucose transport activity, compared to the values obtained with 25 mM glucose. This difference was not observed when 24 h incubation was carried out without insulin. Glucose transport activity was not increased at 3 or 6 h incubation with 1 mM glucose, but was increased at 12 h, which closely paralleled increased expression of GLUT1. In addition to increased GLUT1 expression, more efficient translocation of GLUT1 to the plasma membrane was observed when incubated with 1 mM glucose compared to 25 mM glucose. The addition of azaserin or deprivation of glutamine at 25 mM glucose did not increase the glucose transport activity to the level obtained with 1 mM glucose. PD98059 did not affect glucose transport activity when incubated with 1 mM or 25 mM glucose. In conclusion, the present study is the first to show that, in 3T3-L1 adipocytes, chronic exposure to low (1 mM) and high (25 mM) glucose leads to different insulin-stimulated glucose transport activities. These differences result from the difference in the expression and plasma membrane distribution of GLUT1, but not of GLUT4, and the hexosamine biosynthesis pathway or extracellular signal-regulated protein kinase is not involved.
3T3 Cells↗
Chronic graft-versus-host disease and seizure.
Explore the source record for details and available documents.
Adult↗
Melatonin inhibits luteinizing hormone releasing hormone (LHRH) induction of LH release from fetal rat pituitary cells.
The in vitro effect of melatonin on the release of luteinizing hormone (LH) and follicle stimulating hormone (FSH) from fetal rat pituitary cells was investigated. A significant inhibition of LH release induced by 10(-9) M luteinizing hormone releasing hormone (LHRH) was seen when cells were incubated with 10(-9) M melatonin. FSH release was unaffected by either LHRH alone or LHRH in combination with melatonin. In addition, the significant inhibitory effect of melatonin was reduced by pretreatment of the pituitary cells with 10(-10) M melatonin. These findings indicate that melatonin can act directly on the fetal pituitary gland to suppress LHRH-induced release of LH perhaps by a mechanism which eventually involves down-regulation of the melatonin receptors.
Animals↗
Red-light-induced suppression of melatonin synthesis is mediated by N-methyl-D-aspartate receptor activation in retinally normal and retinally degenerate rats.
Pineal gland N-acetyltransferase (NAT) activity and pineal and serum levels of melatonin declined linearly in albino rats acutely exposed to different intensities of red light (600 nm or higher; low, 140 microW/cm2; moderate, 690 microW/cm2; high, 1200 microW/cm2) during the middle of the night. The high intensity red light was as effective as white light (780 microW/cm2) in suppressing NAT activity and pineal and circulating melatonin. Red-light-inhibited nighttime NAT activity and suppressed nocturnal melatonin levels in both retinally degenerate and normal rats. Pretreatment with the N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 (10 mg/kg intraperitoneally) completely prevented the red-light-induced inhibition of nighttime melatonin synthesis. Magnesium chloride (300 mg/kg intraperitoneally) reduced the inhibitory effects of low and moderate intensities of red light but was ineffective when high red-light intensity was used. However, both agents failed to antagonize the suppression of nighttime melatonin synthesis elicted by the exposure to white light. Since retinally degenerate and retinally normal animals respond in the same way to both red-light and pharmacological intervention with the NMDA receptor blocker MK-801, the findings indicate that the activation of central hypothalamic NMDA receptors might mediate the photic inhibition of nocturnal melatonin synthesis in the pineal gland elicited by the exposure to red light at night. Red-light-induced suppression of nocturnal melatonin synthesis possibly can be used to investigate the biochemical mechanisms by which light entrains melatonin synthesis and to study the pharmacological and physiological effects of endogenous and synthetic agents that antagonize the NMDA receptor response.
Animals↗
The pineal melatonin rhythm and its regulation by light in a subterranean rodent, the valley pocket gopher (Thomomys bottae).
The daytime and nightime levels of pineal N-acetyltransferase (NAT) activity, hydroxyindole-O-methyltransferase (HIOMT) activity, and melatonin were measured in adult male and female valley pocket gophers, Thomomys bottae. This species was chosen for study because it is a subterranean rodent that inhabits burrows whose openings to the surface are closed. Therefore, under field conditions it is estimated that the pocket gopher spends roughly 99% of its time in absolute darkness in underground burrows. When wild captured pocket gophers were maintained under a light:dark cycle (light intensity during the day of roughly 140 microW/cm2), nightime levels of pineal NAt activity and melatonin content were higher than values measured during the day; on the other hand, HIOMT activity in the pineal gland was similar in the day and at night. When pocket gophers were exposed to an extended light period (220 microW/cm2) 4 hr into the night, the rise in melatonin synthesis normally associated with darkness onset was not inhibited. Also, when gophers were acutely exposed to a light intensity of 400 microW/cm2 for 1 hr beginning 4 hr after darkness onset, neither high nocturnal levels of pineal NAT nor pineal melatonin contents were reduced. Finally, when pocket gophers were exposed to a 600 microW/cm2 light intensity at either 4 hr or 8 hr into the dark period, pineal melatonin synthesis remained elevated at a level comparable to that measured in dark-exposed controls.(ABSTRACT TRUNCATED AT 250 WORDS)
Acetylserotonin O-Methyltransferase↗
[The circadian dynamics of melatonin concentration in the epiphysis, plasma and retina of silver foxes].
A definite diurnal rhythm of the melatonin concentration was observed in the silver fox pineal gland, plasma and retina, with the maximum at night, the minimum in the morning, and intermediate values in evenings. The interrelationship among the melatonin levels in the tissues under study, is discussed.
Animals↗
Reduction in pineal N-acetyltransferase activity and pineal and serum melatonin levels in rats after their exposure to red light at night.
Pineal gland N-acetyltransferase (NAT) activity and pineal and serum levels of melatonin declined linearly in albino rats exposed to different irradiances (low, 170 microW/cm2; moderate, 420 microW/cm2; high, 1040 microW/cm2) red light during the middle of the night. High intensity red light (1040 microW/cm2) was as effective as white light (670 microW/cm2) in suppressing pineal NAT activity and pineal and serum melatonin levels. The lowered melatonin levels and the reduction in NAT activity following exposure to red light suggest that red light cannot be regarded as 'safe' light when studying circadian melatonin production in the albino rat, at least at the intensities used in this experiment.
Animals↗
Tryptophan loading increases daytime serum melatonin levels in intact and pinealectomized rats.
L-tryptophan (L-Trp) effects on serum and pineal melatonin were studied in fasted and non-fasted rats. Oral administration of L-Trp during the day caused serum melatonin to increase 4-fold compared to that of saline treated rats; this occurred in both fasted and non-fasted animals. In the same animals, neither NAT, HIOMT, not melatonin levels were changed. In a second study, pinealectomized rats were loaded with L-Trp. In these animals, as in those that had an intact pineal gland, L-Trp loading caused a large increase in immunoreactive serum melatonin. The results suggest that the increased melatonin in serum due to L-Trp administration is primarily derived from an extrapineal organ.
Administration, Oral↗
Pineal sensitivity to pulsed static magnetic fields changes during the photoperiod.
The effect of pulsed static magnetic fields on the rat pineal melatonin synthesis was studied at different times of the photoperiod. Exposure to magnetic fields during mid- or late dark phase significantly suppressed pineal N-acetyltransferase activity, the rate-limiting enzyme in melatonin synthesis, as well as the melatonin content in the pineal gland. These parameters were not influenced by magnetic fields when the exposure occurred early in the dark phase or during the day. These results suggest that the responsiveness of the pineal gland to magnetic field perturbations changes throughout the photoperiod.
Animals↗
Unusual responses of nocturnal pineal melatonin synthesis and secretion to swimming: attempts to define mechanisms.
The effect of swimming at night on rat pineal melatonin synthesis was compared with that of light exposure at night. Rats were forced to swim at 0030 hr (lights out at 2000 hr) and sacrificed by decapitation 15 and 30 min later, immediately after swimming. Other groups of animals were exposed to white light (650 muW/cm2) for 15 and 30 min at same time. Swimming caused a rapid and highly significant drop in the melatonin content in the pineal gland; however, the activity of N-acetyltransferase (NAT), the supposed rate limiting enzyme in the melatonin production, was not changed. Despite the drop in pineal melatonin levels, serum concentrations of the indole remained elevated in the rats that swam. In contrast, melatonin levels in the pineal and serum of light exposed rats fell precipitously, accompanied by a significant suppression of NAT activity. Since we anticipated that the strenuous exercise associated with swimming may induce release of artrial natriuretic peptide (ANP) from the heart, which in turn could cause the release of pineal melatonin, in a second study we injected physiological saline intravenously to stretch the cardiac muscle and release ANP. Three milliliters of normal saline was injected during the day into the jugular vein of anesthetized rats that were pretreated with isoproterenol to stimulate pineal melatonin production. Animals were killed 15 min after the saline injection, and pineal NAT activity and pineal melatonin levels were measured. The saline injections caused no alteration in the elevated levels of either NAT or melatonin.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
In vivo and in vitro effects of the pineal gland and melatonin on [Ca(2+) + Mg2+]-dependent ATPase in cardiac sarcolemma.
The possible diurnal variation in cardiac [Ca(2+) + Mg2+]-dependent ATPase (Ca2+ pump) activity and the influence of pinealectomy and melatonin on this enzyme in rat heart have been studied. Lowest levels of cardiac sarcolemmal membrane [Ca(2+) + Mg2+]-dependent ATPase activity were measured in late afternoon in rats kept under a 14:10 light:dark cycle. Late in the dark phase the enzyme activity began to increase with the rise continuing until 0900, 3 hr after light onset. These time-dependent changes in [Ca(2+) + Mg2+]-dependent ATPase activity did not occur in either pinealectomized or light-exposed rats suggesting that melatonin, secreted from the pineal gland during the night, induces the change in [Ca(2+) + Mg2+]-dependent ATPase activity, In vitro studies in which cardiac tissue was incubated in the presence of melatonin over a wide range of doses showed that this indole stimulated the Ca2+ pump. The half-maximal effect of melatonin was observed at a melatonin concentration of 28 ng/ml. These findings suggest that the daily change in [Ca(2+) + Mg2+]-dependent ATPase activity in the sarcolemma of heart tissue is a result of the circadian rhythm in pineal melatonin production and secretion. These findings may be applicable to normal cardiac physiology.
Animals↗
Phototransduction-related circadian changes in indoleamine metabolism in the chick pineal gland in vivo.
The purpose of this study was to examine the day/night levels of pineal melatonin and its rate limiting enzyme N-acetyltransferase (NAT) in relationship to the ratio of 11-cis- to all-trans-retinal. Three-week-old chicks were placed in 12:12 light:dark (LD 12:12) cycle for one week, pineals were collected during the light phase at 1500 (i.e., after 10 hr light), during the dark phase at 1900 (i.e., 2 hr after dark), at 2100 (i.e., 4 hr after dark), and at 2300 (i.e., 6 hr after dark) and after light extension to 1900. The results show that light-sensitive 11-cis-retinal in the chick pineal has the same diurnal rhythm as NAT and melatonin; all constituents increased within 2 hr of darkness onset (at 1900) and reached their peak after 4 hr of dark. All values were lowest during the light phase at 1500. Low values for 11-cis-retinal, NAT, and melatonin were also seen in the group of chicks which experienced light extension to 1900. The data indicate that in vivo light plays a major role in triggering rhodopsin-bound 11-cis-retinal production within 2-4 hr after darkness onset; this change likely serves as the signal for the subsequent formation of the hormonal product of the pineal gland, melatonin.
Acetylserotonin O-Methyltransferase↗
Pulsed static magnetic field effects on in-vitro pineal indoleamine metabolism.
In-vitro rat pineal glands stimulated with the beta-adrenergic receptor agonist isoproterenol to induce melatonin synthesis and exposed for 1 h to a pulsed 0.4-G static magnetic field demonstrated significant inhibition of serotonin-N-acetyltransferase activity and melatonin content. 2-h exposure to pulsed magnetic field also resulted in a significant reduction in isoproterenol-induced serotonin-N-acetyltransferase activity. These results support the idea that the cultured pineal gland can be affected directly by artificially generated weak magnetic fields.
Animals↗
Neuropeptide Y inhibits beta-adrenergic agonist- and vasoactive intestinal peptide-induced cyclic AMP accumulation in rat pinealocytes through pertussis toxin-sensitive G protein.
The effects of neuropeptide Y (NPY) on pineal gland cyclic AMP (cAMP) accumulation were investigated using dispersed pinealocytes from rats. NPY inhibited the intracellular cAMP accumulation stimulated by isoproterenol and norepinephrine in a dose-dependent manner during a 10-min incubation of pinealocytes. NPY (1 x 10(-7) M) also inhibited vasoactive intestinal peptide (VIP)- and cholera toxin-induced cAMP accumulation. The inhibitory effect of NPY on isoproterenol-induced cAMP accumulation was completely abolished by a 5-h pretreatment of pinealocytes with 1 microgram/ml of pertussis toxin (PT). These results suggest that NPY participates in modulation of cAMP production in the rat pineal gland through PT-sensitive G protein. Yohimbine, an alpha 2-adrenergic antagonist, blocked NPY inhibition of isoproterenol-stimulated cAMP accumulation. On the other hand, the alpha 2-adrenergic agonist clonidine by itself did not affect cAMP accumulation stimulated by isoproterenol but significantly potentiated NPY action. The present study demonstrates that NPY inhibits beta-adrenergic or VIPergic stimulation of the pineal gland cAMP accumulation. The inhibitory effect of NPY is mediated through PT-sensitive G protein. Our results also suggest that NPY exerts its action to affect alpha 2-adrenoceptor function.
Adrenergic beta-Agonists↗
Vasoactive intestinal peptide stimulates N-acetyltransferase and hydroxyindole-O-methyltransferase activities and melatonin production in cultured rat but not in Syrian hamster pineal glands.
The purpose of this study was to compare the responses of the Syrian hamster and rat pineal glands in organ culture to vasoactive intestinal peptide (VIP). The endpoints in these studies were the activities of pineal N-acetyltransferase (NAT) and hydroxyindole-O-methyltransferase (HIOMT), as well as pineal and medium melatonin levels. When rat pineal glands were incubated with either VIP (1 microM) or isoproterenol (1 microM), a beta-adrenergic agonist, a significant increase in NAT and HIOMT activities and melatonin levels were observed within 3 hr. Conversely, during the day, VIP (1 microM) was ineffective in stimulating these parameters in hamster pineal gland after incubation times of either 2, 4, 6, or 8 hr. In another experiment, hamster pineal glands were collected from animals killed in the late dark period (after 30 min light exposure). In these glands, isoproterenol promoted NAT activity and melatonin production; however, VIP was ineffective in stimulating either NAT or HIOMT activities; likewise, VIP had no stimulatory effect on pineal melatonin levels at night. Finally, when hamster pineal glands at night were incubated with either 0, 10 nM, 100 nM, 10 microM, or 100 microM VIP, no changes in any parameter of melatonin synthesis were measured. The results indicate that the hamster pineal gland, unlike that of the rat, may not respond to VIP with an increased melatonin production.
Acetylserotonin O-Methyltransferase↗
Antihypertensive and metabolic effects of long-term treatment with amosulalol in non-insulin dependent diabetics.
In this open study, 41 hypertensive patients with non-insulin dependent diabetes mellitus were treated with the combined alpha- and beta-adrenoceptor blocker amosulalol hydrochloride for 24 weeks, either alone or added to existing antihypertensive therapy. The effects on blood pressure, glucose and lipid metabolism were examined. Daily administration of 20 to 60 mg amosulalol caused a significant reduction in both systolic and diastolic blood pressure within 2 weeks. This effect was stable, lasting for the entire trial period. The mean systolic and diastolic blood pressure decreased from 174 +/- 13/92 +/- 9 mmHg at the beginning to 148 +/- 16/80 +/- 11 mmHg at the end of the trial. Heart rate was not affected. Plasma glucose and haemoglobin Alc levels showed a tendency to decrease without any statistical significance. Total and HDL-cholesterol and triglyceride levels also remained unchanged. Although 3 patients had complained of dizziness, all were easily manageable. The results indicate that amosulalol is effective in the treatment of hypertension in non-insulin dependent diabetics and does not affect glucose and lipid metabolism.
Adult↗
Beta-adrenergic and peptide N-terminal histidine and C-terminal isoleucine stimulation of N-acetyl-transferase activity and melatonin production in the cultured rat pineal gland.
The purpose of this investigation was to compare the effect of peptide N-terminal histidine and C-terminal isoleucine (PHI) with that of the beta-adrenergic agonist isoproterenol (ISO) on N-acetyltransferase (NAT) activity and melatonin production in the cultured rat pineal gland. Pineal glands were removed and placed in organ culture containing PHI, ISO, or PHI plus ISO at different dosages, and subsequent changes in NAT activity and melatonin levels were measured. PHI stimulated these parameters in both a time- and dose-dependent manner. Combined treatment with PHI (10(-6) M) and high doses of ISO (either 10(-7) or 10(-8) M) did not potentiate the effect of the peptide in terms of either NAT activity or melatonin levels in the pineal gland. However, at a lower concentration, ISO (10(-9) M) had additive effects to those of PHI in both cultured pineals and medium. The results suggest that PHI modulates melatonin synthesis in the rat pineal gland. Furthermore, stimulation of the pineal with both PHI and ISO demonstrates an additive effect rather than a synergistic action of these compounds. It is presumed that ISO and PHI stimulate pineal melatonin production via separate receptors, but they probably use the same intracellular second messenger, cAMP, to do so. This is the first study showing an effect of the peptide PHI on pineal melatonin production in any vertebrate.
Acetyltransferases↗