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Biomedical subjects

Z L Huang

Publications and source records attributed to Z L Huang.

At least 19 recordsLinked to original sources

Genes for prostaglandin d synthase and receptor as well as adenosine A2A receptor are involved in the homeostatic regulation of nrem sleep.

(1) Prostaglandin D2 is essential for the maintenance of the sleep state. (2) The adenosine and A2A receptor system is a link between the humoral and neural mechanisms of sleep-wake regulation. (3) Prostaglandin D2 plays a crucial role in the homeostatic regulation of NREM sleep. Finally, it may not be too far-fetched to say that prostaglandin D2 was most likely the endogenous sleep substance described by Piéron and Ishimori about 100 years ago, and possibly the sleep-inducing factor reported by Professor Jouvet and coworkers some twenty years ago.

Animals↗

Dominant localization of prostaglandin D receptors on arachnoid trabecular cells in mouse basal forebrain and their involvement in the regulation of non-rapid eye movement sleep.

Infusion of prostaglandin (PG) D(2) into the lateral ventricle of the brain induced an increase in the amount of non-rapid eye movement sleep in wild-type (WT) mice but not in mice deficient in the PGD receptor (DP). Immunofluorescence staining of WT mouse brain revealed that DP immunoreactivity was dominantly localized in the leptomeninges (LM) of the basal forebrain but that PGD synthase immunoreactivity was widely distributed in the LM of the entire brain. Electron microscopic observation indicated that DP-immunoreactive particles were predominantly located on the plasma membranes of arachnoid trabecular cells of the LM. The region with the highest DP immunoreactivity was clearly defined as bilateral wings in the LM of the basal forebrain located lateral to the optic chiasm in the proximity of the ventrolateral preoptic area, one of the putative sleep centers, and the tuberomammillary nucleus, one of the putative wake centers. The LM of this region contained DP mRNA 70-fold higher than that in the cortex as judged from the results of quantitative reverse transcription-PCR. PGD(2) infusion into the subarachnoid space of this region increased the extracellular adenosine level more than 2-fold in WT mice but not in the DP-deficient mice. These results indicate that DPs in the arachnoid trabecular cells of the basal forebrain mediate an increase in the extracellular adenosine level and sleep induction by PGD(2).

Adenosine↗

Arousal effect of orexin A depends on activation of the histaminergic system.

Orexin neurons are exclusively localized in the lateral hypothalamic area and project their fibers to the entire central nervous system, including the histaminergic tuberomammillary nucleus (TMN). Dysfunction of the orexin system results in the sleep disorder narcolepsy, but the role of orexin in physiological sleep-wake regulation and the mechanisms involved remain to be elucidated. Here we provide several lines of evidence that orexin A induces wakefulness by means of the TMN and histamine H(1) receptor (H1R). Perfusion of orexin A (5 and 25 pmol/min) for 1 hr into the TMN of rats through a microdialysis probe promptly increased wakefulness for 2 hr after starting the perfusion by 2.5- and 4-fold, respectively, concomitant with a reduction in rapid eye movement (REM) and non-REM sleep. Microdialysis studies showed that application of orexin A to the TMN increased histamine release from both the medial preoptic area and the frontal cortex by approximately 2-fold over the baseline for 80 to 160 min in a dose-dependent manner. Furthermore, infusion of orexin A (1.5 pmol/min) for 6 hr into the lateral ventricle of mice produced a significant increase in wakefulness during the 8 hr after starting infusion to the same level as the wakefulness observed during the active period in wild-type mice, but not at all in H1R gene knockout mice. These findings strongly indicate that the arousal effect of orexin A depends on the activation of histaminergic neurotransmission mediated by H1R.

Animals↗

Evaluation of nasal cavity by acoustic rhinometry in Chinese, Malay and Indian ethnic groups.

Acoustic rhinometry (AR) evaluates the geometry of the nasal cavity by measuring the minimum cross-sectional area (MCA) and nasal volume (V) by means of acoustic reflection. Understanding the normal and pathologic conditions of the internal nasal cavity using AR is important in the diagnosis of structural abnormalities in patients. The aim of this study was to investigate the normal range of AR parameters in healthy volunteers from three ethnic groups in Singapore: Chinese, Malay and Indian. We also attempted to evaluate the role of these measurements in the documentation of structural abnormalities in the nose. A total of 189 Singaporeans, aged > or = 18 years, were recruited from a nationwide survey study. They comprised 83 Chinese, 35 Malays and 71 Indians. Eighty-nine subjects had a rhinoscopically normal nose (Group 1), 77 had significant septal deviation (Group 2) and 23 had inferior turbinate hypertrophy (Group 3). AR was performed to measure the MCA at the anterior 1-5 cm from the nostril and the volume (V) between points at the nostril and 5 cm into the nose. A mean MCA (mMCA; equal to (L + R)/2) and a total volume (Vt; equal to L + R) were then calculated for each subject, where L and R refer to the measurements made for the left and right nostrils, respectively. The results showed that there was no statistically significant difference in mMCA (p = 0.80) and Vt (p = 0.60) among the three ethnic subgroups of Group 1. Statistically significant differences were found only between Groups 1 and 3 (p < 0.001 for both mMCA and Vt) and between Groups 2 and 3 (p = 0.001 for mMCA and p = 0.013 for Vt). Although there was no significant difference between Groups 1 and 2, significant differences in MCA (p = 0.001) and V (p = 0.040) were found between the narrower sides (smaller volume) and the wider sides in Group 2, indicating volume compensation between the nasal cavities. In conclusion, our study demonstrates that there is no significant difference in the normal range of AR measurements among Chinese, Malay and Indian ethnic groups. AR is able to determine the structural abnormality of the internal nasal cavity caused by septal deviation and inferior turbinate hypertrophy.

Acoustics↗

Differentiation of human U937 promonocytic cells is impaired by moderate copper deficiency.

Copper (Cu) deficiency suppresses macrophage activities in animals and humans. Our previous studies indicated that the induction of Cu deficiency in differentiated U937 monocytic cells impairs respiratory burst and bactericidal activities and lipopolysaccharide-mediated secretion of inflammatory mediators. The current investigation examined the roles of Cu in the monocytic differentiation process. Human U937 promonocytic cells were exposed to a high affinity Cu chelator (5 microM 2,3,2-tetraamine [tet]) for 24 hr before inducing differentiation by treatment with 1,25-dihydroxyvitamin D3 plus interferon-gamma (DI). This procedure decreased cell Cu by 55% without compromising cellular Zn, Fe, or general metabolic activities. Lower Cu status significantly attenuated the expression of maturation markers Mac-1 (CD11b), ICAM-1 (CD54), and LPS-R (CD14). This change was associated with a marked suppression in respiratory burst activity and killing of Salmonella. To examine if the adverse effect of inadequate Cu on the DI-induced differentiation represented a more general defect, U937 cells were treated with phorbol 12-myristate 13-acetate (PMA). Lower Cu status also suppressed PMA-mediated differentiation of U937 cells. Supplemental Cu, but not Zn or Fe, blocked the tet-induced declines in cell Cu, expression of maturation markers, and respiratory burst and bactericidal activities. These results demonstrate that Cu is essential for the monocytic differentiation process that contributes to the competency of the host's defense system.

Cell Differentiation↗

Mapping of genes for cooking and eating qualities in Thai jasmine rice (KDML105).

Thai jasmine rice, KDML 105, is known as the best quality rice. It is known not only for its aroma but also for its good cooking and eating qualities. Amylose content (AC), gel consistency (GC) and gelatinization temperature (GT) are important traits determining rice quality. A population of recombinant inbred lines (RIL) derived from KDML105 x CT9993 cross was used to study the genetic control of AC, GC and GT traits. A total of 191 markers were used in the linkage map construction. The 1605.3 cM linkage map covering nearly the whole rice genome was used for QTL (define QTL) analysis. Four QTLs for AC were detected on chromosomes 3, 4, 6 and 7. These QTLs accounted for 80% of phenotypic variation explained (PVE) in AC. The presence of one major gene as well as several modifiers was responsible for the expression of the trait. Two QTLs on chromosome 6 and one on chromosome 7 were detected for GC, which accounts for 57% of PVE. A single gene of major effect along with modifier genes controls GC from this cross. The QTLs in the vicinity of waxy locus were major contributors in the expression of AC and GC. The finding that the position of QTLs for AC and GC were near each other may reflect tight linkage or pleiotropy. Three QTLs were detected, one on chromosome 2 and two on chromosome 6, which accounted for 67% of PVE in GT. Just like AC and GC, one major gene and modifier genes governed the variation in GT resulting from the KDML105 x CT9993 cross. Breeding for cooking and eating qualities will largely rely on the preferences of the end users.

Amylose↗

Copper deficiency suppresses effector activities of differentiated U937 cells.

Dietary copper (Cu) deficiency impairs both innate and acquired branches of immunity. Specific roles of Cu in the activation and effector activities of host-defense cells remain largely unknown. The effects of Cu status on effector activities of a monocytic cell line were investigated as an initial step in the elucidation of specific functions of Cu in phagocytic cells. Exposure of differentiating U937 human promonocytic cells to 5 micromol/L 2,3, 2-tetraamine (tet), a high affinity Cu chelator, for 4 d decreased cellular Cu by 62% without altering cellular Cu,Zn-superoxide dismutase (SOD) activity, Zn content, mitochondrial activity and protein synthesis. In contrast, Cu deficiency suppressed the respiratory burst activity and markedly compromised the ability of U937 cells to kill Salmonella. Similarly, treatment of RAW264.7 murine macrophages with 5 micromol/L tet decreased cell Cu by 78% and Cu,Zn-SOD activity by 15% and increased bacterial survival by 180%. The tet-induced impairment of respiratory burst and bactericidal activities was blocked in cultures supplemented with Cu, but not Zn or Fe. In addition, lipopolysaccharide (LPS)-induced secretion of the inflammatory mediators, tumor necrosis factor-alpha, interleukin (IL)-1beta, IL-6 and prostaglandin E(2) (PGE(2)), was decreased by 30-60% in tet-treated U937 cells. Flow cytometric analysis of the surface antigens CD11b and CD71 showed that the suppressed activities of Cu-deficient cells were not due to an attenuation in the degree of differentiation or secondary iron deficiency. These data demonstrate that U937 cells provide a useful model for examining the biochemical roles of Cu in monocyte activity.

Analysis of Variance↗

Activation of sensory nerves participates in stress-induced histamine release from mast cells in rats.

To elucidate the mechanism by which stress induces rapid histamine release from mast cells, Wistar rats, pretreated as neonates with capsaicin, were subjected to immobilization stress for 2 h, and histamine release was measured in paws of anesthetized rats by using in vivo microdialysis after activation of sensory nerves by electrical or chemical stimulation. Immobilization stress studies indicated that in control rats stress induced a 2.7-fold increase in the level of plasma histamine compared to that in freely moving rats. Whereas pretreatment with capsaicin significantly decreased stress-induced elevation of plasma histamine. Microdialysis studies showed that electrical stimulation of the sciatic nerve resulted in a 4-fold increase of histamine release in rat paws. However, this increase was significantly inhibited in rats pretreated with capsaicin. Furthermore, injection of capsaicin into rat paw significantly increased histamine release in a dose-dependent manner. These results suggest that activation of sensory nerves participates in stress-induced histamine release from mast cells.

Animals↗

Histamine release induced by immobilization, gentle handling and decapitation from mast cells and its inhibition by nedocromil in rats.

The effect of immobilization, gentle handling and decapitation on the level of plasma histamine in Wistar rats was investigated. Mast cell deficient (Ws/Ws) rats were used to characterize the source of elevated histamine in plasma by stress, and the effect of nedocromil, a mast cell stabilizer, on histamine release was assessed in these models in vivo. The plasma histamine concentration of freely moving rats was 93.0+/-2.3 pmol/ml. Gentle handling produced a transient increase in plasma histamine level by 1.9-fold, whereas immobilization resulted in a longer-lasting elevation by 2.6-fold compared to that in the freely moving rats. Decapitation increased the plasma histamine level by 10- to 16-fold compared with that in the freely moving rats. No increase in plasma histamine was found in Ws/Ws rats exposed to stress. Nedocromil inhibited the increase in plasma histamine level induced by stress in a dose-dependent manner. These findings suggest that stress induces histamine release from mast cells in Wistar rats and the extent of this histamine release increases with the severity of stress. Nedocromil proved to be a good pharmacological tool to inhibit stress-induced release of mediators from mast cells.

Animals↗

Biphasic elevation of plasma histamine induced by water immersion stress, and their sources in rats.

The effect of water immersion stress on the plasma concentration of histamine, in Wistar and mast cell-deficient (Ws/Ws) rats, was investigated. The histamine content of the plasma, skin and gastric mucosa, as well as the level of activity of histidine decarboxylase in the gastric mucosa, were determined by high performance liquid chromatography (HPLC)-fluorometry. In Wistar rats exposed to water immersion stress for a total of 6 h, an initial, acute, four-fold, transient increase in the plasma histamine level, followed by a sustained, though lower, elevation of the plasma histamine level, was observed. The initial acute increase in plasma histamine level was also seen in gastrectomized Wistar rats exposed to water immersion stress, but not in Ws/Ws rats exposed to stress. The sustained elevation of the plasma histamine level was observed in the Ws/Ws rats. However, in both the gastrectomized Wistar rats and gastrectomized Ws/Ws rats, the sustained elevation in plasma histamine level was not observed. The histamine content of the skin of Wistar rats after 15 min or more exposure to water immersion stress, was 20% lower than that of control rats. The mucosal histamine content of both Wistar rats and Ws/Ws rats, was 20% lower, whereas histidine decarboxylase activity in the gastric mucosa was enhanced by two-fold, during exposure to stress for 4 h. These findings indicate that water immersion stress causes a biphasic increase in plasma histamine concentration in Wistar rats; the initial acute increase in plasma histamine level originates from mast cells, and the second, sustained increase is attributed to enterochromaffin-like cells.

Animals↗

Anti-inflammatory and ulcerogenic effects of 3-(N,N-diethylamino) propylindometacin HCl.

AIM: To study anti-inflammatory effects of a novel indometacin ester, 3-(N,N-diethylamino) propyl-indometacin HCl (prodrug) and its ulcerogenicity in fats. METHODS: Carrageenin (Car)-induced paw edema and ulcer index were examined. RESULTS: Car-induced paw edema was inhibited by 36.6% (P < 0.01) at 3 h and 34.6% (P < 0.01) at 5 h after a single i.p. injection of the prodrug 7.09 mg.kg-1. On the same molar basis, indometacin (Ind) 5 mg.kg-1 i.p. inhibited edema by 45.6% at 3 h and 39.2% at 5 h, however, there was no statistical significant difference (P > 0.05) between the edema-inhibitory effect of the prodrug and that of Ind. The dose 10 micrograms/paw exhibited 64% inhibition of the swelling, the prodrug > 10 micrograms/paw showed no additional inhibition of swelling; the acute gastric lesion properties of the prodrug were much lower than those of Ind 6 h after p.o. CONCLUSION: The prodrug is a potent anti-inflammatory agent with lower ulcerogenicity in the stomach.

Animals↗

Immobilization of prostaglandin synthetase by hydrophobic adsorption.

In this article, the immobilization of prostaglandin synthetase on n-alkyl or aryl amino-agar beads by hydrophobic adsorption is reported. The effects of different hydrophobic groups in the agar beads, pH of buffer, concentration of salts on the adsorption of prostaglandin synthetase, and the properties of immobilized prostaglandin synthetase were also studied. The results showed that 20-35 mg of microsome containing PG synthetase (protein content 8-15 mg) could be adsorbed on each gram of n-dodecylamino-agar beads after suction drying the gel in the buffer of pH 5.5 (containing 0.5 mol/L KCl), 0.1 mol/L citric-phosphate at 4 degrees C. The remaining immobilized enzyme activity was over 80%. The optimum pH of immobilized PG synthetase is 8.0, similar to that of the native enzymes. The thermostability of immobilized PG synthetase in the buffer containing 0.5 mol/L KCl was increased. Immobilized PG synthetase was used as a catalyst of synthesis of prostaglandin E1. The preservation of activity after 10 working cycles was 86.2%.

Adsorption↗

[Experimental study on tea polyphenols in prevention of hyperlipidemia].

Hyperlipidemia (HP) was induced in quails by feeding high lipid food. Effect of tea polyphenol (TP) on development of HP was observed by feeding various dosage of TP simultaneously and was compared with that of nicotinic acid (NA). The results showed: (1) TP could prevent the increase of serum total cholesterol (TC), triglycerides (TG) and low-density lipoprotein cholesterol (LDL-C). Effect of the group treated with large dose of TP was more significant than that treated with NA (P < 0.05). But no statistically significant difference was observed on the changes of TG and LDL-C between TP and NA treated group. (2) No significant change of HDL-C level was observed in both TP groups and NA group, but both of them could inhibit the elevation of atherogenic index (TC/HDL-C), their effects were similar. It suggested that TP might be a regulator of blood lipid.

Animals↗

Absorption of indomethacin from nasal cavity in rats.

AIM: To investigate if identical bioavailability, rapid Tmax, and Cmax of indometacin (Ind) could be achieved when Ind is administered in rats via intranasal (ina) route. METHODS: The pharmacokinetics of Ind solution at a dosage of 3 mg.kg-1 was studied after i.v., ina, and po in rats using HPLC. RESULTS: It showed that the time to peak (Tmax) of ina Ind 3 mg.kg-1 solution was 0.08 h, approached that after i.v. route the peak concentration (Cmax) following ina was 20.0 mg.L-1, 2.4 times higher than po dosing. CONCLUSION: It demonstrated that the ina administration of Ind was superior to po in rats, and that Ind absorption through nasal mucosa was a reasonable approach at lower doses.

Absorption↗