Longitudinal Association between Selenium Levels and Hypertension in a Rural Elderly Chinese Cohort.

OBJECTIVES: Results from previous studies have been inconsistent on the association between selenium and hypertension, and very few studies on this subject have focused on the elderly population. The purpose of this study is to examine the relationship between selenium level and hypertension in a rural elderly Chinese cohort. DESIGN: A longitudinal study was implemented and data were analyzed using logistic regression models and Cox proportional hazards regression model adjusting for potential confounders. The associations between selenium level and prevalent hypertension at baseline and between selenium and incident hypertension were examined. SETTING: Community-based setting in four rural areas in China. SUBJECTS: A total of 2000 elderly aged 65 years and over (mean 71.9±5.6 years) participated in this study. MEASUREMENTS: Nail selenium levels were measured in all subjects at baseline. Blood pressure measures and self-reported hypertension history were collected at baseline, 2.5 years and 7 years later. Hypertension was defined as systolic blood pressure 140 mmHg or higher, diastolic blood pressure 90 mmHg or higher, or reported use of anti-hypertensive medication. RESULTS: The rate of baseline hypertension was 63.50% in this cohort and the mean nail selenium level is 0.413±0.183µg/g. Multi-covariate adjusted cross-sectional analyses indicated that higher selenium level was associated with higher blood pressure measures at baseline and higher rates of hypertension. For the 635 participants with normal blood pressure at baseline, 360 had developed hypertension during follow-up. The incidence rate for hypertension was 45.83%, 52.27%, 62.50%, 70.48%, and 62.79% from the first selenium quintile to the fifth quintile respectively. Comparing to the lowest quintile group, the hazard ratios were 1.41 (95%CI: 1.03 to1.94), 1.93 (95%CI: 1.40 to 2.67), 2.35 (95%CI: 1.69 to 3.26) and 1.94 (95%CI: 1.36 to 22.77) for the second selenium quintile to the fifth quintile respectively. CONCLUSIONS: Our findings suggest that high selenium may play a harmful role in the development of hypertension. Future studies are needed to confirm our findings and to elucidate a plausible biological mechanism.

Predicting precipitation on nonpoint source pollutant exports in the source area of the Liao River, China.

The source area of the Liao River is an important grain growing area in China which experiences serious problems with agricultural nonpoint source pollution (NPS) which is impacting the regional economy and society. In order to address the water quality issues it is necessary to understand the spatial distribution of NPS in the Liao River source area. This issue has been investigated by coupling a wavelet artificial neural network (WA-ANN) precipitation model with a soil and water assessment tool (SWAT) model to assess the export of nonpoint source pollutants from the Liao River source area. The calibration and validation of these models are outlined. The WA-ANN models and the SWAT model were run to generate the spatial distribution of nonpoint source nutrient (nitrogen and phosphorus) exports in the source area of the Liao River. It was found that the SWAT model identified the sub-catchments which not only receive high rainfall but are also densely populated with high agricultural production from dry fields and paddy fields, which are large users of pesticides and chemical fertilizer, as the primary source areas for nutrient exports. It is also concluded that the coupled WA-ANN models and the SWAT model provide a tool which will inform the identification of NPS issues and will facilitate the identification of management practices to improve the water environments in the source area of the Liao River.

Anti-allergic action of anti-malarial drug artesunate in experimental mast cell-mediated anaphylactic models.

BACKGROUND: Allergy is an acquired hypersensitivity reaction of the immune system mediated by cross-linking of allergen-specific IgE-bound high-affinity IgE receptors, leading to immediate mast cell degranulation. Artesunate is a semi-synthetic derivative of artemisinin, an active component of the medicinal plant Artemisia annua. Artesunate is a clinically effective anti-malarial drug and has recently been shown to attenuate allergic asthma in mouse models. This study investigated potential anti-allergic effects of artesunate in animal models of IgE-dependent anaphylaxis. METHODS: Anti-allergic actions of artesunate were evaluated in passive cutaneous anaphylaxis and passive systemic anaphylaxis mouse models, and in ovalbumin-induced contraction of bronchial rings isolated from sensitized guinea pigs. Direct mast cell-stabilizing effect of artesunate was examined in RBL-2H3 mast cell line and in mature human cultured mast cells. Anti-allergic signaling mechanisms of action of artesunate in mast cells were also investigated. RESULTS: Artesunate prevented IgE-mediated cutaneous vascular hyperpermeability, hypothermia, elevation in plasma histamine level, and tracheal tissue mast cell degranulation in mice in a dose-dependent manner. In addition, artesunate suppressed ovalbumin-mediated guinea pig bronchial smooth muscle contraction. Furthermore, artesunate concentration-dependently blocked IgE-mediated degranulation of RBL-2H3 mast cells and human culture mast cells. Artesunate was found to inhibit IgE-induced Syk and PLCγ1 phosphorylation, production of IP(3) , and rise in cytosolic Ca(+2) level in mast cells. CONCLUSIONS: We report here for the first time that artesunate possesses anti-allergic activity by blocking IgE-induced mast cell degranulation, providing a foundation for developing artesunate for the treatment of allergic asthma and other mast cell-mediated allergic disorders.

Lentiviral vector-mediated knockdown of SOCS3 in the hypothalamus protects against the development of diet-induced obesity in rats.

AIM: Leptin resistance is a feature of most cases of obesity in both humans and rodents. The suppressor of cytokine signalling 3 (SOCS3) is a negative-feedback regulator of leptin signalling involved in leptin resistance; therefore, the suppression of SOCS3 is a potential therapy for leptin resistance in obesity. In the studies, we investigated whether hypothalamic silencing of SOCS3 would attenuate diet-induced obesity in rats. METHODS: First we established hypothalamic SOCS3-deficient rats through lentiviral vector (LV)-mediated RNA interference (RNAi) technique, then provided a high-fat diet or a chow diet to the rats. After 8 weeks of the diet, the serum leptin and insulin concentrations were measured by RIA, and the gene expressions of SOCS3 and the long form of leptin receptor in hypothalamus were detected by a real time RT-PCR. The leptin-induced Stat3 activation was examined by Western blot. RESULTS: The RNAi protocol specifically knocked down the expression of SOCS3 mRNA by 50% approximately. The rats treated with LV-SOCS3-shRNA exhibited enhanced leptin-induced Stat3 activation, decreased body weight gain and improved metabolic parameters when exposed to a high-fat diet. CONCLUSION: Our results provide evidence that the rats treated with hypothalamic SOCS3 silencing are significantly protected against the development of diet-induced obesity and SOCS3 is a potential target molecule for therapeutic intervention of obesity.

Study on the interaction between 3 flavonoid compounds and alpha-amylase by fluorescence spectroscopy and enzymatic kinetics.

The interaction between alpha-amylase and 3 flavonoid compounds from tartary buckwheat bran, namely, quercetin (Que), its monoglycoside isoquercetin (Iso), and its diglycoside rutinb (Rut), has been studied by fluorescence spectroscopy and enzymatic kinetics. The results indicate that Que, Iso, and Rut could bind with alpha-amylase to form a new complex, which exhibits an obvious fluorescence quenching. We deduce that such a quenching is a static quenching via nonradiation energy transfer. Results from plots and calculations show that the sequence of binding constants (KA) is Iso > Que > Rut. Calculation on thermodynamic parameters reveals that the main driving force of above-mentioned interaction is hydrophobic. Enzyme activity measurements show that all of the 3 flavonoid compounds are effective inhibitors toward alpha-amylase, and the inhibitory mode belongs to a competitive type. The sequence of affinity (1/Ki) is in accordance with the results of binding constants (KA) from fluorescence experiments.

Hydrogen sulphide in the hypothalamus causes an ATP-sensitive K+ channel-dependent decrease in blood pressure in freely moving rats.

Hydrogen sulfide (H2S) is a naturally occurring gas that may act as an endogenous signaling molecule. In the brain, H2S is mainly produced by cystathionine beta-synthase (CBS) and its cellular effects have been attributed to interactions with N-methyl-D-aspartate (NMDA) receptors and cyclic adenosine 3',5'-monophosphate (cAMP). In contrast, direct vasodilator actions of H2S are most probably mediated by opening smooth muscle ATP-sensitive K+ (K(ATP)) channels. In the hypothalamus, K(ATP) channel-dependent mechanisms are involved in CNS-mediated regulation of blood pressure. In this report, we investigated the hypothesis that H2S may act via K(ATP) channels in the hypothalamus to regulate blood pressure. Mean arterial blood pressure (MAP) and heart rate were monitored in freely moving rats via a pressure transducer placed in the femoral artery. Drugs were infused via a cannula placed in the posterior hypothalamus. Infusion of 200 microM sodium hydrogen sulfide (NaHS), an H2S donor, into the hypothalamus of freely moving rats reduced MAP and heart rate. Infusion of 300 nM to 3 microM gliclazide dose-dependently blocked the effect of 200 microM NaHS. Infusion of the CBS activator, s-adenosyl-L-methionine (0.1 mM and 1 mM), likewise decreased MAP. Infusion of the CBS inhibitors aminooxyacetic acid (10 mM) and hydroxylamine (20 mM) increased MAP but did not block the effects of infusion of 200 microM NaHS. These data indicate that actions of H2S in the hypothalamus decrease blood pressure and heart rate in freely moving rats. This effect appears to be mediated by a K(ATP) channel-dependent mechanism and mimicked by endogenous H2S.

Obesity reduced the gene expressions of leptin receptors in hypothalamus and liver.

The expression of leptin receptor (OB-R) is downregulated by leptin in some cell lines. This study investigated the expressions of leptin receptors at central nerve system and peripheral site in a dietary model of obesity. Rats in the 8 week high-diet and control group were classified based on body weight gain into obese and control groups. Serum leptin and insulin concentrations were measured and gene expressions of short form of leptin receptor (OB-Ra) and long form (OB-Rb) in hypothalamus and liver were detected by RT-PCR. The levels of serum leptin in obese rats were increased compared with control rats (p<0.05). The levels of OB-Ra and OB-Rb gene expressions in both hypothalamus and liver in obese rats were reduced significantly (p<0.01). Serum leptin concentrations of obese rats had a significant negative relationship with both of OB-Ra or OB-Rb gene expression levels in hypothalamus and liver (p<0.01). On the other hand, serum insulin levels had no relationship with OB-Ra or OB-Rb gene expression levels in neither liver nor hypothalamus. Rats with diet-induced obesity have hyperleptinemia and reduced expressions of leptin receptors in hypothalamus and liver. The results suggest that a leptin downregulated OB-R expression is one of leptin resistant mechanisms for maintaining obesity.

Piperbetol, methylpiperbetol, piperol A and piperol B: a new series of highly specific PAF receptor antagonists from Piper betle.

Piperbetol, methylpiperbetol, piperol A, and piperol B, isolated from Piper betle, selectively inhibited the washed rabbit platelet aggregation induced by platelet activating factor (PAF) in a concentration-dependent manner. The IC50 values of piperbetol, methylpiperbetol, piperol A, piperol B, and ginkgolide B were about 18.2, 10.6, 114.2, 11.8, and 4.8 mumol/l, respectively. The inhibitory potency of ginkgolide B was about 2.8, 1.2, 22.8, and 1.4 times higher than those of piperbetol, methylpiperbetol, piperol A, and piperol B. The concentration-response curve of PAF-induced platelet aggregation was shifted to the right by 50 mumol/l of piperbetol, methylpiperbetol, piperol A, piperol B, and ginkgolide B. The EC50 of PAF was increased by these compounds from 1.5 nmol/l to 14.3, 23.1, 2.4, 20.6, and 47.2 nmol/l, respectively. The compounds also inhibited the binding of [3H]-PAF to washed rabbit platelets with IC50 values of 8.7, 5.3, 88, 6.2, and 1.8 mumol/l. Correlating with the inhibitory potency for platelet aggregation, the inhibitory potency of ginkgolide B for binding of PAF was about 3.8, 1.9, 48, and 2.4 times higher than those of piperbetol, methylpiperbetol, piperol A, and piperol B. However, the aggregation of washed rabbit platelets induced by threshold ADP and arachidonic acid were unaffected by piperbetol, methylpiperbetol, piperol A, and piperol B. Furthermore, piperbetol, methylpiperbetol, piperol A, and piperol B had no effects on the cAMP contents in rest washed rabbit platelets. In conclusion, these data indicate that piperbetol, methylpiperbetol, piperol A, and piperol B are effective PAF receptor antagonists in vitro.

[Accumulation and excretion of fluorine and effect of selenium on them in rats with chronic fluorosis].

2 groups of Wistar rats with chronic fluorosis were duplicated with 30 and 50 mg/L fluorine (F) in drinking water. 2. 0 mg/kg selenium (Se) in fodder was supplemented in the other 2 groups of rats with fluorosis. The amount of drinking water and diet, the excretion of urine and the contents of urine F were tendentiously surveyed every month in one year and then, intake and excretion of F were calculated per day. The contents of Se in urine, liver and serum and F in bone, liver, kidney and serum were measured in the 4th, 8th, and 14th month. The results showed that F absorption increased and F excretion/F absorption rate decreased in 2 groups of rats with fluorosis compared with control group and there were positive correlations between concentration of urine F and water F, as well as concentration of F urine and time of drinking F water. The accumulation of F in bone and liver occurred in the middle period of fluorosis and then, the increase of serum F was observed in the late period of fluorosis in 2 groups of rats with fluorosis. After supplement of Se, urine, liver and serum Se ascended. At the same time, state of eating and drinking improved, the weight rose and the amount of urine excretion heightened, as well as there was an increase of urine F and excretion F/absorption F rate and there was a decrease of bone, live, kidney and serum F in rat of Se supplementation with fluorosis compared with non-Se groups.

[Protective effects of chrominum on myocardial damage in rats].

To prove the protective effects of trivalent chromium (Cr3+) on myocardial damage, its ultrastructure and electro-physiological changes were observed in different groups of rats with intraperitoneal injection of normal saline, Cr3+ and selenium, and injection of adriamycin (ADR) by their tail vein. Results of ultrastructural observations showed nuclear margin of myocardial cells was obscure, cytoplasm became coarse and sparse, mitochondria vacuolar, myocardiofibril loose, broken and lytic in the group treated with ADR, myocardiopathic changes reduced and myocardial filaments arranged in good order in that with Cr3+ and selenium. QRS complex, Q-T interval, APD50 and APD90 in electrocardiograph (ECG) prolonged in the group with ADR and selenium, and no changes were observed in that with Cr3+. It suggests Cr3+ and selenium have apparently protective effects on rat's myocardium, and Cr3+ also can reverse the changes in ECG caused by ADR, which is of importance in prevention and treatment of cardiovascular diseases.

[Acute toxicity and anti-inflammatory effect of processed products of gamboge].

The acute toxicity and anti-inflammatory effect of processed and raw Gamboge were compared. The results showed that the acute toxicity of processed Gamboge was less than that of the raw one, while both had significant anti-inflammatory effect alike. Among the differently processed products, those boiled with lotus leaf juice and steamed by high pressure were better.

[Frequency dependence of substance P release by electroacupuncture in rat spinal cord].

Previous studies in our laboratory have shown that electroacupuncture (EA) using different frequencies produced differential opioid peptides release in the spinal cord of rats and human beings. In the present study we observed the frequency dependence of substance P (SP) release from rat spinal cord, with the frequencies of EA set at 2, 4, 8, 15, 30 and 100 Hz. The spinal perfusate was collected in 3 periods of 30 min before, during and after EA, and the immunoreactive SP (SP-ir) was measured by radioimmunoassay (RIA). The effectiveness of EA-induced analgesia was assessed by tail flick latency (TFL). Rats showing an increase of TFL over 40% was considered as EA responder. The results showed that in the responders, SP-ir in spinal perfusate showed a moderate decrease during 2 Hz EA, (P < 0.01 compared with baseline level), no change in the 4 Hz EA group, and a marked increase during 8, 15, 30 and 100 Hz EA (P < 0.01), with maximal increase occurring at 15 Hz (P < 0.001). The above results suggest that EA may induce upward or downward modulation in SP-ir release depending on the frequency of EA. However in the non-responder rats no change in spinal fluid SP-ir content was observed. This suggests that changes in SP-ir release have same causal relation with the analgesia induced by EA stimulation.

[Study on a role of substance P in the spinal mechanisms of electroacupuncture analgesia].

It was found in the present study that low frequency (2Hz) electroacupuncture (EA) stimulation caused a decrease of the content of substance P immunoreactivity (SP-ir), whereas medium-(15Hz), high-(100Hz) and dense-disperse (D-D)- (2/15Hz) frequencies EA stimulation induced an increase of the content of SP-ir in the rat spinal fluid. EA analgesia induced by medium-, high- or D-D mode frequency was suppressed by nonpeptide SP (NK1) receptor antagonists CP96345 or RP67580 administered intrathecally (i.t.). Both the attenuation of SP release by low frequency EA and the potentiation of SP release by medium frequency EA in the spinal cord were blocked by the opioid receptor antagonist naloxone (i.t.). These results suggest that a decrease of release of SP-ir by low frequency and an increase of it by medium-, high- and D-D mode frequencies in the spinal cord facilitate analgesia.

Feasibility of milk fluoridation and trends in dental caries of children in China.

The aim of the study is to investigate the feasibility of milk fluoridation as a vehicle for caries prevention, based on the current epidemiological status and its trends of dental caries in preschool children in the area of the Haidian District of Beijing, where the indications exist: Fluoride level in drinking water is low (0.2-0.3 ppm), and water fluoridation and other systemic uses of fluorides are unlikely. From 75.9 to 79.7% of 3-6-year-old children were identified as having high caries experience (dmft 4.29-4.35). It was found that 60% of the preschool children who attended kindergarten were 3-6 years old, and 40% of the 1-2-year-olds were living with their families. There is a local dairy to produce milk for the population living in this district. The amount of fresh milk produced daily is about 50,000-60,000 kg. A special kind of milk with vitamins A and D is also available for the preschool children. Data available from the Community MCH Centre indicated that the percentage of breast-feeding is 12% only. The first choice by parents for artificial feeding to the babies is fresh or powdered milk. Therefore, the breast-feeding project started in 1992. It is recommended that mothers' milk should be provided to the babies for at least four months after birth, when a specially prescribed milk for the babies, produced by the dairy, will be provided on a daily basis. The cost of milk is cheaper than others. In this connection, a five-year project on milk fluoridation as a pilot study at the community level for caries prevention of preschool children is now planned. The project is supported by BDMF, WHO, and Chinese MOPH.

Reversal of electroacupuncture tolerance by CCK-8 antiserum: an electrophysiological study on pain-related neurons in nucleus parafascicularis of the rat.

Two varieties of neurons were found in nucleus parafascicularis (pf) of the rat: one responds to noxious stimuli with an increase in firing (pain-excited neuron, PEN), the other with a decrease in firing (pain-inhibited neuron, PIN). Electroacupuncture (EA) has been shown to suppress PEN and excite PIN, which can be taken as an electrophysiological index for EA analgesia. This effect of EA subsided after prolonged (6 h) EA stimulation, suggesting the development of tolerance to EA. Intracerebroventricular (icv) injection of CCK-8 antiserum aiming at neutralizing endogenously released CCK-8 resulted in a complete restoration of the EA effect. Normal rabbit serum was not effective. CCK-8 antiserum per se did not affect the firing pattern of the PEN or PIN in nontolerant rat. The results obtained from single neuron recording in anesthetized animals thus confirmed those obtained in intact animals using the tail flick as the end point, implying that an excess of endogenously released CCK-8 may constitute one of the mechanisms for the development of EA tolerance.

[Effects of noxious stimuli on the discharges of pain-excitation neurons and pain-inhibition neurons in the nucleus ventralis posterolalis of thalamus in the rat and a modulating action of electroacupuncture on its electric activities].

The somatic and visceral noxious stimuli could simultaneously induce the increase of discharges of pain-excitation neurons (PEN) and the decrease of discharges of pain-inhibition neurons (PIN) in the Nucleus Ventralis posterolalis (VPL) of thalamus in the rat, and the electric activities of the two kinds of neurons cooperated each other. By the injection of morphine (5 mg/kg) and the electroacupuncture of "zusanli", the discharges of PEN were reduced and the discharges of PIN were enhanced. The results suggested that VPL of thalamus in the rat be involved in the modulating action on pain sensation and the analgesic effects of morphine and electroacupuncture by the simultaneous electric activities of PEN and PIN in VPL.