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Zhu Li

Publications and source records attributed to Zhu Li.

At least 55 records · Page 3Linked to original sources

Aripiprazole, a novel antipsychotic drug, preferentially increases dopamine release in the prefrontal cortex and hippocampus in rat brain.

Aripiprazole,7-(4-[4-(2,3-dichlorophenyl)-1-piperazinyl]butyloxy)-3,4-dihydro-carbostycil (OPC-14597), a novel atypical antipsychotic drug, is a dopamine D2 receptor partial agonist with functional 5-HT2A receptor antagonist, and 5-HT1A receptor partial agonist properties as well. Other atypical antipsychotic drugs, e.g. clozapine, but not typical antipsychotic drugs, e.g. haloperidol, produce significant increases in dopamine and acetylcholine release in the medial prefrontal cortex in rats, effects believed to be related to the ability to improve cognitive function. The increase in the medial prefrontal cortex dopamine release by the atypical antipsychotic drugs has been shown to be partially inhibited by N-[2[4-)2-methoxyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl)cyclohexanecarboxamide trihydrochloride (WAY100635), a selective 5-HT1A receptor antagonist. Aripiprazole, 0.1 and 0.3 mg/kg, significantly increased dopamine release in the hippocampus. Moreover, aripiprazole, 0.3 mg/kg, slightly but significantly increased dopamine release in the medial prefrontal cortex but not in the nucleus accumbens. These increases were significantly inhibited by WAY100635. By contrast, aripiprazole, 3.0 mg/kg and 10 mg/kg, significantly decreased dopamine release in the nucleus accumbens but not the medical prefrontal cortex. However, aripiprazole 10 mg/kg significantly decreased dopamine release in the both regions. Aripiprazole had no effect on acetylcholine release in the medial prefrontal cortex, hippocampus, or nucleus accumbens at any dose, except for 3.0 mg/kg, which decreased acetylcholine release in the nucleus accumbens only. Aripiprazole, 0.3 mg/kg, transiently potentiated haloperidol (0.1 mg/kg)-induced dopamine release in the medial prefrontal cortex but inhibited that in the nucleus accumbens. The present study demonstrated that aripiprazole, at low doses of 0.1 and 0.3 mg/kg, increases dopamine release in the medial prefrontal cortex and hippocampus. It also suggests that the function of both the medial prefrontal cortex and hippocampus may contribute to the ability of aripiprazole to improve negative symptom and cognition.

Acetylcholine↗

Radiofrequency power deposition utilizing thermal imaging.

Wavelength effects influence radiofrequency (RF) power deposition distributions and limit magnetic resonance (MR) medical applications at very high magnetic fields. The power depositions in spherical saline gel phantoms were deduced from proton resonance shift thermal maps at both 1.5 T and 3.0 T over a range of conductivities. Phase differences before and after RF heating were measured for both a quadrature head coil and a circular surface coil. A long echo time (TE) pulse sequence with a 3D phase unwrap algorithm provided increased thermal sensitivity. The measured thermal maps agreed with a model of eddy-current heating by circularly polarized oscillating RF fields in a conducting dielectric sphere. At 3.0 T, thermal maps were acquired with a <0.32 degrees C temperature rise at 4 W. Proton resonance shift thermal maps provided a measure of hot spots in very-high-field MR imaging (MRI), in which both the phase sensitivity and signal-to-noise ratio (SNR) were increased. The method provides a means of studying the heat distribution generated by RF coils excited by clinical pulse sequences.

Magnetic Resonance Imaging↗

Education-related gender differences in health in rural China.

We investigated gender differences in education-related health inequalities in rural China. Household interview data were obtained from 6 provinces in 1993 and 2001. Remarkable health inequalities existed and favored the higher educational groups; among women, the inequalities were greater and health inequalities increased from 1993 to 2001. Education serves as a more powerful mediating factor for health inequalities among women than among men in rural China.

China↗

[Comparative study of the detection of plasma folate with microbial assay and radioimmunoassay].

OBJECTIVE: To compare two methods (microbial assay and radioimmunoassay) for measuring plasma folate concentrations, and to examine the relationship between plasma folate levels, and alcohol consumption, tobacco use and body mass index, and the risk of hyperhomocysteinemia in China. METHODS: We used a microtiter plate microbial assay and a radioimmunoassay to measure the folate concentration in 88 plasma samples. After comparing the results of these two methods and fitting a regression line, we examined the geographical, seasonal, and gender differences in folate concentration of plasma collected from 2,422 adults in south and north areas in China, and evaluated the association of plasma folate concentration, with alcohol consumption, cigarette smoking, and body mass index, and with the risk of hyperhomocysteinemia, using the data from the two assays. RESULTS: The data from the two assays had a linear relationship (r=0.879, P=0.000); the regression was Y=0.683X+0.308 (where X and Y were nature logarithmic transformations of plasma folate by microbial assay and radioimmunoassay, respectively); however, the mean plasma folate levels by microbial assay were much higher than those obtained by radioimmunoassay. Both data sets showed similar plasma folate distributions among Chinese adults, associations with other risk factors, and the risk of hyperhomocysteinemia. We estimated that 19.9% of the Southerners and 67.1% of the Northerners had plasma folate concentrations by radioimmunoassay lower than the 6.8 nmol/L used to define plasma folate deficiency. CONCLUSION: There is a linear relationship between plasma folate levels determined by microbial assay and radioimmunoassay, but because of the different levels obtained in the two assays, it is difficult to use the microbial assay results to evaluate folate status at this time. The use of 10.5 nmol/L as a cut-off for plasma folate deficiency by microbial assay needs further study.

Adult↗

[Study on reduced folate carrier gene (RFC1) polymorphism in the southern and northern Chinese population].

OBJECTIVE: To describe the distribution of reduced folate carrier gene (RFC1)genotype and allele frequency between southern and northern, female and male Chinese population. METHOD: RFC1 (A80G) genotype was detected, using polymerase chain reaction-restriction fragment length polymorphism (RFLP-PCR) on 720 blood spot DNA from the normal subjects. RESULTS: The frequencies of the northern population with AA, GG and GA genotypes were 22.28%, 31.09% and 46.63%, and the frequencies of the southern population were 18.56%, 22.75% and 58.68%, respectively. Findings showed that there were significant differences between southerners and northerners in RFC1 (A80G) genotype (P < 0.01). There was no significant difference between G allele frequency of the northern (52.10%) and southern population (54.40%). The frequencies of male with RFC1 (A80G) AA, GG and GA genotype were 24.88%, 25.85% and 49.27%, and among female were 18.83%, 27.77% and 53.40%, respectively. There were no significant differences between male and female in RFC1 genotype (P > 0.05), or between G allele frequency in female (50.49%) and that in male (54.47%). CONCLUSIONS: The distribution of RFC1 genotype seemed to be consistent with neural tube defects (NTDs) while its prevalence among the northerners was higher than that of southerners, with female having a higher NTDs prevalence. This study provided genetic epidemiological data for etiological hypothesis between RFC1 and diseases relative to folate metabolism.

Alleles↗

[Advances in the study of the etiologic relationship between reduced folate carrier gene (RFC1) and neural tube and craniofacial defects].

Neural tube and craniofacial defects are common birth defects which are ascribed to the combination of genetic and environmental factors. The population epidemiological studies suggested that periconceptional use of multivitamins containing folic acid can reduce a woman's risk of having a child with neural tube and craniofacial defects. It's a major environmental factor that periconceptional women with deficiency of folic acid may increase their risk for delivering babies with neural tube and craniofacial defects, but the mechanism by which folic acid facilitates this risk reduction is unknown. This paper reviews folate transport carrier, Reduced Folate Carrier (RFC)'s characteristics in biological chemistry, physiological function, the folate transport mechanism, structure, function, regulation and expression of reduced folate carrier gene (RFC1), and the relationship between RFC1 with plasm or erythrocyte folate level and neural tube defects, et al. It is suggested a etiologic hypothesis in investigation of candidate gene encoding specific folate-related pathways of neural tube and craniofacial defects.

Carrier Proteins↗

[Study on the association between reduced folate carrier gene polymorphism and congenital heart defects and cleft lip with or without cleft palate].

OBJECTIVE: To study the association between reduced folate carrier gene (RFC1) polymorphism and congenital heart defects (CHD) as well as cleft lip with or without cleft palate (CLP) and to provide epidemiological evidence on genetic markers of CHD and CLP. METHODS: RFC1 (A80G) genotype was detected using RFLP-PCR for blood DNA of the 67 triads with nonsyndromic CHD-affected child, the 82 triads with child-affected cleft lip with or without CLP and the 100 control families without child-affected birth defects. We performed a family-based association test and analyzed the interaction between RFC1 A80G genotype and maternal periconceptional supplementation of folic acid. RESULTS: Offspring of mothers who did not take folic acid had an elevated risk for CHD when comparing with offspring of mothers who did (OR = 2.68, 95% CI: 1.14 - 6.41). There was a statistical association between the risk of CHD and maternal periconceptional folic acid supplementation (chi(2) = 6.213, P < 0.05). In the family-based association test, G allele was positively associated with an increased risk for children CHD (Z = 2.140, P < 0.05) while G allele of RFC1 (A80G) polymorphism might increase the risk for CHD. Elevated risks for either CLP group were not observed between RFC1 genotype using or not using folic acid. CONCLUSION: Our findings suggested that the G allele was likely to be a genetically susceptible allele for CHD. There was possible association between offspring with GG, GA genotype and maternal periconceptional folicacid deficiency.

Abnormalities, Multiple↗

A comparison of the effects of loxapine with ziprasidone and thioridazine on the release of dopamine and acetylcholine in the prefrontal cortex and nucleus accumbens.

RATIONALE: Atypical, but not typical, antipsychotic drugs (APDs), produce preferential increases in dopamine (DA) and acetylcholine (ACh) release in rat medial prefrontal cortex (mPFC) compared to the nucleus accumbens (NAC). The increase in DA release has been attributed, in part, to their greater serotonin (5-HT)(2A) relative to D(2) receptor occupancy, while the basis for the increase in ACh has not yet been determined. Loxapine, a dibenzoxazepine congener of clozapine, is generally considered to be a typical APD because it produces significant extrapyramidal symptoms (EPS) in humans, at generally recommended clinical doses (60-100 mg/day), and catalepsy in rodents, although several studies have found it to be effective at lower doses which do not produce significant EPS. Moreover, loxapine, like its congener clozapine, has higher affinity for serotonin (5-HT)(2A) than dopamine D(2) receptors, in vitro, suggesting the possibility it could be an atypical APD with clozapine-like potential. OBJECTIVES: The purpose of this study was to compare the effects of loxapine on DA and ACh release in the mPFC and NAC with those of ziprasidone, a novel atypical APD, and thioridazine, which is generally classified as a typical APD. RESULTS: Loxapine, 0.03-10 mg/kg, increased prefrontal dopamine release with the magnitude of this increase exceeding that in the NAC, at all doses, other than the 10 mg/kg dose. The effect of loxapine (0.3 mg/kg) on DA release in the prefrontal cortex was attenuated by WAY 100635 (0.2 mg/kg), a 5-HT(1A) antagonist, as is the case for other atypical APDs. Ziprasidone (0.1-3 mg/kg) also preferentially increased DA release in the mPFC compared to NAC. Thioridazine (5 and 20 mg/kg) did not increase DA release in either the mPFC or NAC. Loxapine (3 mg/kg) and ziprasidone (1 and 3 mg/kg), but not thioridazine (10 and 20 mg/kg), significantly increased cortical ACh release. CONCLUSION: Loxapine has effects on cortical and NAC DA and ACh release which are comparable to those of known atypical APDs. Ziprasidone and thioridazine have effects on cortical DA and ACh characteristic of atypical and typical APDs, respectively. It is concluded that further clinical studies of the atypical APD properties of loxapine are indicated.

Acetylcholine↗

Folic acid supplements during early pregnancy and likelihood of multiple births: a population-based cohort study.

BACKGROUND: Folic acid supplements are recommended for women of childbearing age to prevent neural tube defects in their offspring. Results of some studies, however, suggest an increase in multiple births associated with use of vitamin supplements that contain folic acid during pregnancy. Our aim was to assess this association. METHODS: We used data from a population-based cohort study from which we assessed the occurrence of multiple births in women (n=242015) who had participated in a campaign to prevent neural tube defects with folic acid supplements (400 microg per day) in China. Folic acid use was ascertained before pregnancy outcome was known. We studied the relation between multiple births and any use of folic acid pills before or during early pregnancy; additionally, we investigated mechanisms by which folic acid could potentially affect the occurrence of multiple births by examining pill-taking at three time periods: before ovulation, around the time of fertilisation, and after conception. FINDINGS: 1496 (0.62%) multiple births occurred in a cohort of 242015 women who had registered with the study between October, 1993, and September, 1995, and who had a pregnancy not affected by a birth defect; the rate of multiple births in women who did and did not take folic acid before or during early pregnancy was 0.59% and 0.65%, respectively (rate ratio 0.91; 95% CI 0.82-1.00). INTERPRETATION: Our findings suggest that consumption of folic acid supplements during pregnancy is not associated with an increased occurrence of multiple births.

Adult↗

Characterization of effects of mean arterial blood pressure induced by cocaine and cocaine methiodide on BOLD signals in rat brain.

A total of 45 male Sprague-Dawley rats were employed to determine whether cocaine or cocaine methiodide (CM) administration can induce a significant increase in mean arterial blood pressure (MABP) in rats, and whether such an increase in MABP can produce a global increase in blood oxygenation level-dependent (BOLD) contrast in the rat brain detectable by functional magnetic resonance imaging (fMRI). Cocaine methiodide is a quaternary derivative of cocaine that shares the same cardiovascular effects of cocaine, but does not penetrate the blood-brain barrier (BBB). Experimental results demonstrated that both CM (with doses of 2.5 and 7.5 mg/kg) and cocaine (with doses of 1.25 and 5.0 mg/kg) can induce a significant MABP change (30-80%). It was found that CM can only produce scattered, weak, and transient BOLD signals in a few voxels of the rat brain, and that these MABP-induced BOLD signals are not dose-dependent. In contrast, the administration of cocaine induced dose-dependent biphasic BOLD signals that were consistent with pharmacologically-induced cerebral vascular constriction and neuronal activity in the mesolimbic systems of the rat brain. The potential confounding factor of the MABP changes had little effect on the interpretation of drug-induced BOLD signal changes. These results confirm that the BOLD-weighted fMRI method can be extended to map drug-induced neuronal activity.

Animals↗

Serotonin receptors: their key role in drugs to treat schizophrenia.

Serotonin (5-HT)-receptor-based mechanisms have been postulated to play a critical role in the action of the new generation of antipsychotic drugs (APDs) that are usually referred to as atypical APDs because of their ability to achieve an antipsychotic effect with lower rates of extrapyramidal side effects (EPS) compared to first-generation APDs such as haloperidol. Specifically, it has been proposed by Meltzer et al. [J. Pharmacol. Exp. Ther. 251 (1989) 238] that potent 5-HT2A receptor antagonism together with weak dopamine (DA) D2 receptor antagonism are the principal pharmacologic features that differentiate clozapine and other apparent atypical APDs from first-generation typical APD. This hypothesis is consistent with the atypical features of quetiapine, olanzapine, risperidone, and ziprasidone, which are the most common treatments for schizophrenia in the United States and many other countries, as well as a large number of compounds in various stages of development. Subsequent research showed that 5-HT1A agonism may be an important consequence of 5-HT2A antagonism and that substitution of 5-HT1A agonism for 5-HT2A antagonism may also produce an atypical APD drug when coupled with weak D2 antagonism. Aripiprazole, the most recently introduced atypical APD, and a D2 receptor partial agonist, may also owe some of its atypical properties to its net effect of weak D2 antagonism, 5-HT2A antagonism and 5-HT1A agonism [Eur. J. Pharmacol. 441 (2002) 137]. By contrast, the alternative "fast-off" hypothesis of Kapur and Seeman [Am. J. Psychiatry 158 (2001) 360] applies only to clozapine and quetiapine and is inconsistent with the "slow" off rate of most atypical APDs, including olanzapine, risperidone and ziprasidone. 5-HT2A and 5-HT1A receptors located on glutamatergic pyramidal neurons in the cortex and hippocampus, 5-HT2A receptors on the cell bodies of DA neurons in the ventral tegmentum and substantia nigra and GABAergic interneurons in the cortex and hippocampus, and 5-HT1A receptors in the raphe nuclei are likely to be important sites of action of the atypical APDs. At the same time, evidence has accumulated for the important modulatory role of 5-HT2C and 5-HT6 receptors for some of the effects of some of the current APDs. Thus, 5-HT has joined DA as a critical target for developing effective APDs and led to the search for novel drugs with complex pharmacology, ending the exclusive search for single-receptor targets, e.g., the D3 or D4 receptor, and drugs that are selective for them.

Animals↗

Effect of repeated administration of phencyclidine on spatial performance in an eight-arm radial maze with delay in rats and mice.

Phencyclidine (PCP) is an N-methyl-D-aspartate (NMDA) glutamate receptor channel noncompetitive antagonist that produces some of the symptoms of schizophrenia, including delusions, hallucinations, and negative symptoms as well as cognitive impairment. Thus, administration of PCP to rodents and nonhuman primates has been suggested to provide a potential animal model for schizophrenia. There have been some reports that 7-14 days of PCP administration can bring about enduring impairments in working memory in rodents but not all studies have been consistent in this regard. The present study determined whether repeated PCP administration impaired spatial performance in rats or mice trained to make minimal errors in an eight-arm radial maze task with a delay. Male Sprague-Dawley rats and C57BL/6J mice received 14 daily injection of vehicle or PCP (10 mg/kg, s.c.) followed by a withdrawal period of 1 week. The number of arm reentry errors and the distance traveled to complete the task were not significantly different between PCP-treated and vehicle-treated rats on 2, 8, and 14 days of PCP administration or 8 days following withdrawal of PCP. Mice treated with PCP for up to 2 weeks also had no significant differences in the number of arm reentry errors, travel distances, the numbers of visits to different arms during the first eight choices, or latencies to take all eight pellets compared to the vehicle-treated group. Thus, the present study failed to demonstrate that repeated administration of PCP to rats or mice produces enduring memory impairment. Factors potentially contributing to the discrepancies between various studies are discussed.

Animals↗

A population-based birth defects surveillance system in the People's Republic of China.

We describe a unique birth defects surveillance system in the People's Republic of China. The system was instituted in March 1992 as a component of an evaluation of the effectiveness of a public health campaign using periconceptional folic acid supplementation to prevent neural tube defects, and currently surveys birth cohorts of approximately 150 000 infants per year. Local health care providers collect information in the form of detailed written descriptions and photographs of affected infants. The system allows for detection of birth defects at the local level with later definitive classification and coding; however, information is limited to structural anomalies that are visible on physical examination. This birth defects surveillance system provides an extensive database of infants with major and minor external structural anomalies, including the unique feature of a photographic record for most cases. These data can be used for aetiological studies, descriptive epidemiology and identification of unusual trends.

China↗

Geographical, seasonal and gender differences in folate status among Chinese adults.

Low blood folate concentrations have been associated with cardiovascular disease, neural tube defects and selected cancers, but little is known about folate status in Chinese adults. In a cross-sectional study we measured the plasma and red blood cell folate concentrations in 2422 Chinese men and women aged 35 to 64 y, living in the North and South of China, who provided blood samples either in March or September of 2001. The geometric mean concentrations of plasma and red blood cell folate were lower among Northerners than Southerners (adjusted geometric means, 8.4 and 502, and 16.7 and 811 nmol/L, respectively) controlling for age, gender, season (spring and fall), area (urban and rural), BMI, multivitamin use, alcohol intake and current smoking status. We estimated that approximately 40% of the Northerners and approximately 6% of the Southerners had plasma folate concentrations lower than the 6.8 nmol/L (3 microg/L), and approximately 30% of the Northerners and approximately 4% of the Southerners had red blood cell folate concentrations lower than the 363 nmol/L (160 microg/L), levels used to define folate deficiency. Within each region, men had lower plasma folate concentrations than women (6.9 versus 9.8 nmol/L in the North, and 14.5 versus 19.6 nmol/L in the South). In men, current smokers had a higher risk of folate deficiency compared with nonsmokers [adjusted odds ratios, 1.9 (95% CI, 1.4-2.6) for plasma folate deficiency and 2.5 (95% CI, 1.7-3.6) for red blood cell folate deficiency (P < 0.001)]. Our findings suggest that a large proportion of Chinese adults have a low folate status, especially those living in northern China where 60% of the men are plasma folate deficient in the spring. Further studies are needed to elucidate the factors that influence folate concentrations among middle-aged Chinese and to evaluate possible intervention strategies.

Adult↗

Adverse effects of dietary glycotoxins on wound healing in genetically diabetic mice.

Advanced glycoxidation end products (AGEs) are implicated in delayed diabetic wound healing. To test the role of diet-derived AGE on the rate of wound healing, we placed female db/db (+/+) (n = 55, 12 weeks old) and age-matched control db/db (+/-) mice (n = 45) on two diets that differed only in AGE content (high [H-AGE] versus low [L-AGE] ratio, 5:1) for 3 months. Full-thickness skin wounds (1 cm) were examined histologically and for wound closure. Serum 24-h urine and skin samples were monitored for N(epsilon)-carboxymethyl-lysine and methylglyoxal derivatives by enzyme-linked immunosorbent assays. L-AGE-fed mice displayed more rapid wound closure at days 7 and 14 (P < 0.005) and were closed completely by day 21 compared with H-AGE nonhealed wounds. Serum AGE levels increased by 53% in H-AGE mice and decreased by 7.8% in L-AGE mice (P < 0.04) from baseline. L-AGE mice wounds exhibited lower skin AGE deposits, increased epithelialization, angiogenesis, inflammation, granulation tissue deposition, and enhanced collagen organization up to day 21, compared with H-AGE mice. Reepithelialization was the dominant mode of wound closure in H-AGE mice compared with wound contraction that prevailed in L-AGE mice. Thus, increased diet-derived AGE intake may be a significant retardant of wound closure in diabetic mice; dietary AGE restriction may improve impaired diabetic wound healing.

Administration, Oral↗

[The epidemiology of neural tube defects in high-prevalence and low-prevalence areas of China].

OBJECTIVE: To describe the epidemiology of neural tube defects (NTDs) in high- and low-prevalence areas of China. METHODS: Birth defects surveillance data, collected from 1992 through 1994 was analyzed. These data were collected as part of the Sino-American cooperative project on NTDs prevention. We classified NTDs as anencephaly, encephalocele, high-level and low-level spina bifida (SB) according to location of the lesion (high vs low) and whether the defect was isolated or occurred in association with other birth defects. Rates were compared in the high-prevalence (North) region and the low-prevalence (South) region, after adjusted for classification, urban and rural, season and sex, and calculated the adjusted rate of NTDs. RESULTS: Among seven hundred and eighty-four NTDs cases in 326 874 recorded births (include in livebirth, stillbirth and fetal death with a gestational age of at least 20 weeks), the overall NTDs prevalence in the North was 5.57/1,000 births, and in the South was 0.88/1 000. There were also significant differences in the prevalence of anencephaly, encephalocele, high-level and low-level SB between North (0.97, 0.49, 2.75 and 1.11/1,000 birth) and South (0.36, 0.15, 0.21 and 0.14/1,000 birth) (P < 0.01), with adjusted prevalences in the North 3 - 7 times higher than those in the South. There were significant difference between urban (2.04) and rural areas (6.57/1,000 birth) in the North (P < 0.01), urban (0.52) and rural areas (0.95/1,000 birth) in the South (P < 0.05). Adjusted prevalence rates in the rural were 3 - 4 times higher than those of urban in the North and 1.6 - 1.9 times higher than in the South; The seasonal rate of high-level SB increased between September and November in the North (3.44/1,000 birth), while the seasonal rate of anencephaly decreased between September and November (0.18/1,000 birth) in the South. However there were no seasonal changes in other classified NTDs both in the South and North. CONCLUSIONS: The birth prevalence of NTDs in the North of China was the highest in the world. There were significant differences between the North and the South, urban and rural. There was seasonal change in high-level SB in the North, which was in accordance to the phenotype of NTDs. It was suggested that there might exist etiological heterogeneity among anecephalus, low- and high-level SB.

China↗