Biomedical subjects
Publications and source records attributed to M Li.
The possibility of using near-infrared reflectance spectroscopy for the evaluating quality of analgini powder pharmaceuticals was investigated. We used the multivariate statistical classification technique to identify true, poor and false phamaceuticals of analgini from their first derivative spectra successfully. The results are satisfactory.
The time course of nicotine metabolite appearance in brain from 5 min-18 hr after subcutaneous administration of S-(-)-[3H-N-methyl]nicotine was determined. Results demonstrated that metabolite appearance in brain was greatest at 4 hr postadministration, whereas levels of nicotine were greatly diminished at this time point. For determination of N-demethylated metabolites, (+/-)-[2'-14C]nicotine was administered subcutaneously to rats, and the presence of nicotine and nicotine metabolites in brain supernatant was determined 4 hr postadministration. Using high-performance liquid radiochromatographic analysis, nicotine and three nicotine metabolites (cotinine, nornicotine, and norcotinine) were identified in brain, together with a fourth minor, unidentified metabolite. After subcutaneous administration of S-(-)-[G-3H]cotinine, significant amounts of cotinine were found in brain over an 18-hr postadministration period; however, no cotinine metabolites were detected. Therefore, cotinine is able to pass the blood-brain barrier and access the central nervous system, but is not biotransformed in brain. Thus, this is the first report of norcotinine as a central nervous system nicotine metabolite. Data indicate that norcotinine detected in brain after peripheral nicotine administration most likely originates from 5'-C-oxidation of brain nornicotine, rather than from N-demethylation of cotinine, as occurs peripherally. Because peripheral biotransformation of nicotine to nornicotine is a minor pathway, the relatively high levels of nornicotine found in brain after peripheral nicotine administration suggest that nornicotine is formed via oxidative N-demethylation of nicotine locally in brain. Nornicotine is pharmacologically active; thus, its presence in brain after peripheral nicotine administration indicates that nornicotine may contribute to the neuropharmacological effects of nicotine and tobacco use.
1-[(3-Fluoro-4-pyridinyl)amino]-3-methyl-1(H)-indol-5-yl methyl carbamate (P10358) is a potent, reversible acetylcholinesterase inhibitor that produces central cholinergic stimulation after oral and parental administration in rats and mice. P10358 is a 2.5 times more potent acetylcholinesterase inhibitor than THA in vitro (IC50 = 0.10 +/- 0.02 microM vs. IC50 = 0.25 +/- 0.03 microM). It also inhibits butyrylcholinesterase activity as potently as THA (IC50 = 0.08 +/- 0.05 microM vs. IC50 = 0.07 +/- 0.01 microM). Ex vivo, P10358 (0.2 - 20 mg/kg, p.o.) produced dose-dependent inhibition of brain acetylcholinesterase activity. At 10 and 20 mg/ kg, it produced profound and long-lasting hypothermia in mice. P10358 enhanced performance in rats in a step-down passive avoidance task (0.62 and 1.25 mg/kg) and in a social recognition paradigm (0.32, 0.64 and 1.25 mg/kg) in mice. It reversed scopolamine-induced deficits in the Morris Water maze in rats (1.25 and 2.5 mg/kg) and a higher dose elevated striatal homovanillic acid levels. These behavioral and biochemical effects are consistent with central cholinergic stimulation. Hemodynamic studies in the rat demonstrated a 16-fold separation between behaviorally active doses (1.25 mg/kg) and those that elevated arterial pressure (20 mg/kg). Lethality in rats occurred at an oral dose of 80 mg/kg, but not at lower doses. Chemically, P10358 is an N-aminoindole and may not have the hepatotoxic liability associated with aminoacridine structure of tacrine. P10358 had weak affinity (>10 microM) at a variety of aminergic and peptidergic receptors and uptake carriers. These properties suggest that P10358 may be a safe and promising symptomatic treatment for Alzheimer's disease.
This paper reviews the Iodine Deficiency Disorders (IDD) Elimination Program of the People's Republic of China (PRC). Over 700 million people live in iodine deficient regions of China and the social and economic consequences of IDD are profound. National and international organisations have supported China's advocacy, social mobilisation and health education programs. Many countries affected by IDD have benefited from discoveries emerging from China's aggressive and effective multisectoral approach to this massive public health problem. The challenge of the next decade is to sustain the momentum through the use of cost-effective monitoring and quality improvement strategies, particularly, in those regions in which a large proportion of babies continue to be at risk of brain damage due to iodine deficiency. This paper sets China's IDD Program in an international context by reference to the literature and through consultation with public health experts.
A randomized, double blind, placebo controlled Phase I trial of a prototype human immunodeficiency virus type 1 (HIV-1) synthetic peptide vaccine was conducted in Bangkok, Thailand, to evaluate the safety and immunogenicity of the vaccine in a population of healthy adults at low risk for HIV infection, and to establish essential infrastructure for future HIV vaccine trials in Thailand. Thirty volunteers (25 males; 5 females) were recruited and randomized into 3 groups, receiving 3 intramuscular injections of either 100 micrograms vaccine (N = 12) or 500 micrograms vaccine (N = 12) or alum placebo (N = 6) on weeks 0, 4 and 25. The vaccine was well tolerated without any serious adverse effects. HIV-1 specific ELISA responses were detected in 20/24 subjects who received the vaccine, with V3 binding antibody titers ranging from 1:69 to 1:5,041. HIV-1 (MN) specific neutralizing antibody was detected in 19/20 of subjects with detectable HIV-1 specific binding antibody. Neutralization titers ranged from 1:14 to 1:1,294, which were less than titers observed in HIV-infected subjects. The results of this study indicate that the vaccine was well tolerated, and that the vaccine stimulated anti-HIV humoral immune responses in Thai subjects. The successful undertaking of this first HIV vaccine trial conducted in Thailand provided important preparatory information surrounding volunteer recruitment and motivations, and paves the way for future trials of HIV vaccines in Thailand.
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The herpesvirus protease is a recently identified enzyme which is essential for viral replication. It is found in all herpesviruses and offers a new molecular target for therapeutic intervention. Its genomic structure has recently been described and consists of a large open reading frame which encodes a fusion protein containing an amino-terminal protease domain in-frame with a carboxyl-terminal "assembly protein-like" domain. Auto-processing releases the amino-terminal protease as a maturational enzyme. The herpesvirus protease has been characterized as a novel serine protease. Four surface accessible sulfhydryl groups have been identified in the human cytomegalovirus (HCMV) protease. Utilizing a fluorogenic DABCYL-EDANS substrate assay, directed screening has identified a class of sulfhydryl-modifying benzimidazolylmethyl sulfoxides which inhibits recombinant HCMV protease. Site-directed mutagenesis studies suggest oxidative modification of surface-accessible HCMV protease Cys138 (and possibly Cys161) by this class of inhibitors. The benzimidazolylmethyl sulfoxide 1 inhibits HCMV protease (IC50 = 1.9 microM), exhibits selectivity vs. mammalian serine proteases, and exhibits antiviral activity in an HCMV infected cell culture assay.
A Phase 1, double-blind, placebo controlled trial was conducted in Longchuan County, China, to evaluate the safety and immunogenicity of a prototype HIV-1 synthetic peptide vaccine in a target population at risk for HIV infection, and to establish the infrastructure for future large-scale HIV vaccine efficacy trials. Subjects were randomly assigned to receive 100 microg or 500 microg of vaccine or alum placebo, and were given three injections at an accelerated 0, 1, and 2 month schedule. The vaccine was well tolerated with no significant local or systemic reactions observed in any subjects. Fifty-five percent (100 microg dose) and 64% (500 microg dose) of subjects who received the vaccine produced binding antibody to the immunogen as determined by ELISA. However, HIV-1 (MN) neutralizing antibody was detected in only 23% (3/13) of subjects with detectable HIV-1 specific binding antibody. It was concluded that this prototype HIV-1 synthetic peptide vaccine was well tolerated, safe and immunogenic, and that a 0, 1, 2 month schedule was not as effective in stimulating HIV-1 specific neutralizing antibodies compared with previous trials utilizing a 0, 1, 6 month schedule. Finally, this trial demonstrated that well-designed HIV vaccine trials can be performed at this clinical trials site in Yunnan, China, and that this site should be considered for conducting larger safety, immunogenicity and efficacy trials of candidate HIV vaccines.
OBJECTIVE: To observe the safety and cardiovascular stability of on-line hemofiltration (HF) or hemodiafiltration (HDF) and evaluate the clinical effectiveness of one HF or HDF session in addition to two hemodialysis (HD) sessions weekly. METHODS: Forty patients were randomly divided into four groups: group predilutional (PRD) HF (filtration rate: 259-333 ml/min) group predilutional HDF (filtration rate: 167 ml/min) group postdilutional (POD) HDF (filtration rate: 83 ml/min) and group bicarbonate HD. The reduction rate of parathyroid hormone (PTH), beta 2-microglobulin (beta 2MG), alpha 1-microglobulin (alpha 1MG) and KT/V in the initial treatment of every month was observed, and the incidence of hypotension and pyretic reaction during each treatment was evaluated. RESULTS: After 4-month observation, the KT/V for Group POD HDF is better than that for the other three groups, and for Group PRD HDF is better than that for Group HF and HD. Serum level of PTH and beta 2MG was not decreased after every treatment in Group HD, and so was serum level of alpha 1MG in all groups. Significant removal of PTH and beta 2MG was observed in Group HF, PRD HDF and POD HDF. The monthly serum level of beta 2MG and KT/V were stable in all groups, but the monthly serum level of PTH tended to be decreased in Group HF, PRD, HDF, and POD HDF. The incidence of pyretic reaction in HF or HDF was the same as in HD. Although the ultrafiltration volume was significantly higher during HF or PRD HDF than during HD, the incidence of hypotension in HF or PRD HDF was similar to that in HD. CONCLUSIONS: On-line HF or HDF proved to be a safe and reliable method. POD HDF mode seems to have the best KT/V, HF or PRD HDF offers a better choice for preventing intradialytic hypotension. One HF or HDF session in addition to two HD sessions weekly is similarly effective to decrease the serum level of PTH and the proof of the clinical effectiveness of such a therapy awaits a long-term observation.
OBJECTIVE: To study the relationship between patient age, cycle day 3 basal ovarian status, serum estradiol (E2) level and the ovarian response in an in vitro fertilization and embryo transfer (IVF-ET) program. METHOD: 102 cases and 102 cycles of IVF-ET patients with regular menstrual period and normal cycle day 3 basal follicular-stimulating hormone (FSH < 20 IU/L) level were studied. The same superovulation regimen was employed. The ovarian response was classified as low when follicle number (diameter > 10 mm) was fewer than 3 on the day of hCG injection, moderate when the number was 3-14, and high when follicle number exceeded 14. RESULTS: (1) Patients older than 35 years tended to be low responders; women younger than 30 years usually responded well with production of more than 15 follicles. (2) The number of cycle day 3 follicles was positively correlated with the number after stimulation with gonadotropin. When total basal follicle number in both ovary exceeded 20, ovarian an hyperstimulation syndrome should be watched out. (3) On cycle day 3 the diameter of the largest follicle was negatively correlated with the ovarian response. In low responders the diameter of the largest follicle was usually larger than 4 mm. (4) Despite of the different size and number of the cycle day 3 follicles the serum E2 level was quite similar. CONCLUSION: Age and basal ovarian status including the number and size of the antral follicles are valuable factors to be considered in the prediction of ovarian response to the same gonadotrophic stimulation protocol.
OBJECTIVE: To study the role of epidermal growth factors (EGFs) in the regulation of ovarian follicular development in in vitro fertilization (IVF) superovulation cycles. METHODS: In situ hybridyzation and immunochemistry were used to locate EGF, transforming growth factor alpha (TGF alpha) and their receptor (EGFR) in 10 normal ovarian specimens and in 5 granulosa cell samples obtained from IVF egg retrieval procedure. Radioimmunoassay was used for 6 sex hormones and radioreceptor assay for EGFs (mainly including EGF and TGF alpha) determinations in the serum and follicular fluid. RESULTS: (1) EGF was not detected in the ovary, while EGFR and TGF alpha were found to be present in human granulosa cells. (2) Serum EGFs levels increased with the development of follicles, and EGFs levels in the follicular fluid were higher than those of the matched plasma. No correlation was found between EGFs and sex hormones. CONCLUSIONS: TGF alpha but not EGF might be synthesized locally, acting on the granulosa cells in an autocrine fashion through EGFR in granulosa cells. Serum EGFs levels (including EGF and TGF alpha) might be stimulated by exogenous gonadotropins.
OBJECTIVE: To study the difference of structure and function of HSV-2 gD gene among the wild strain, G and Sav strain. So as to provide theoretical basis for future production of HSV-2 vaccine. METHOD: The partial glycoprotein D gene sequence of HSV-2 strain Sav and wild strain isolated from recurred genital herpes simplex were amplified and cloned with PCR. RESULTS: The homology comparison showed that the homology of DNA and amino acid were 99.2% and 99.1% respectively. CONCLUSIONS: There are high homology of HSV-2 gD gene among the wild strain G and Sav strains, but some variations existed.
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OBJECTIVE: To investigate the role of insulin growth in factor-1 (IGF-1) in the development of ovarian follicles under the stimulation of gonadotropins in an in-vitro fertilization (IVF) program. METHODS: Radioimmuoasssy was used to determine the levels of sex hormones and IGF-1 in the serum and follicular fluid samples. In situ hybridyzation was used to detect the expression of IGF-1 and IGF-1 receptor (IGF-1R) in the granulosa cell obtained from follicular aspiration in women undergoing IVF egg retrieval procedures. RESULTS: (1) Levels of plasma IGF-1 increased with the development of follicles (P < 0.001); follicular fluid (FF) IGF-1 levels were lower than those of matched plasma; FF-IGF-1 decreased with increase of follicle numbers (P < 0.01), e.g. in patients with less than 2 follicles (diameter > or = 15 mm) at the tine of ovum pick-up the FF-IGF-1 levels were much higher than patients with more than 2 follicles (P < 0.05). (2) Significant negative correlation was found between plasma IGF-1 and plasma E2 and also between FF-IGF-1 and FF-follicle-stimulating hormone (FSH) during ovum pick-up (P < 0.01). (3) IGF-1 mRNA was not, while IGF-1R mRNA was found to be present in the human granulosa cells taken at ovum pick-up. CONCLUSIONS: Plasma IGF-1 production might be stimulated by gonadotropins and distributed into the ovarian follicles by diffusion from peripheral circulation, acting upon the granulosa cells and therefore plays a complementary role with the gonadotropins in the regulation of follicular development.
We detected the effect of non-toxic doses of sodium selenite (Se) on the expressing effect of nuclear antigen (EBNA) of Epstein-Barr virus (EBV) in Raji cell line by microfluorescence spectrophoto-quantitation (MFS) and studied the inhibing transformation in B lymphocytes from human umbilical cord blood (BL) with EBV in vitro by Se. We found that Se (0.01-0.50 microgram/ml) can lower EBNA-MFS value 8.4%-21.8% in Raji cell line. The transformation effect of BL with EBV was markedly inhibited by Se (0.1-1.0 microgram/ml) in pretreatment and cotreatment. The inhibition rates of BL transformation were 73.4%-92.1% and 60.3%-77.2% respectively. EBV is associated with nasopharyngeal carcinoma (NPC). The Se levels of serum and hair in NPC patients were markedly lower than those in healthy persons. The results suggest that supplement Se to persons for active expression of EBV gene and NPC patients may help protect againt and treat NPC and diseases associated with EBV.
The effects of media buffered with HEPES of different concentrations and different incubation periods on the proliferation and differentiation of CFU-GM were studied under the standard condition for culture. The results exhibited that when the incubation period prolonged, the pH values of culture system raised and the colony formation of CFU-GM decreased; the culture system added with proper HEPES buffer solution could maintain and increase the colony formation of CFU-GM, especially the culture system in which the pH value was not adjusted before the experiment. We also found that media buffered with HEPES could change the ratio of different colony types. This showed that media buffered with HEPES could not only stimulate the proliferation of CFU-GM, but also affect its differentiation. The results suggest that media buffered with HEPES are better than those without HEPES for the culture of hematopoietic progenitor cells, and the optimum concentration is 10-20 mmol.L-1.
Advanced glycation end products (AGEs) in the brain were immunohistochemically examined in Alzheimer's disease (AD) and aging using anti-AGE antibody recognizing mainly carboxymethyllysine. AGE positive staining diffusely located in the neuronal perikarya of hippocampus and parahippocampus in AD and aged brains without dementia, but not in young brains less than 17 years of age. Extra-neuroperikaryal AGE deposits were also detected in the neuropil of AD and aged brains. The extra-neuroperikaryal AGE deposits markedly increased in AD brains as compared to aged brains. These AGE-positive deposits in the neuropil were not related to the senile plaque identified by anti-beta amyloid protein antibody. These findings suggest a potential link of AGE accumulation in the central nervous system to the aging process of neurons and the degenerating process of AD neurons.
The comparison of the protective effects of four components of "green tea polyphenols' (GTP) - (-)-epigallocatechin gallate, EGCG; (-)-epicatechin gallate, ECG; (-)epigallocatechin, EGC; and (-)epicatechin, EC - against iron-induced lipid peroxidation in synaptosomes showed that: (1) the inhibitory effects of those compounds on TBA reactive materials from lipid peroxidation decreased in the order of EGCG > ECG > EGC > EC; (2) the scavenging effects of those compounds on lipid free radicals produced by lipid peroxidation could be classified as follows: ECG > EGCG > EC > EGC. Furthermore, we investigated the iron-chelating activity and the free radical scavenging activity of those compounds as their protective mechanisms against lipid peroxidation in synaptosomes. As for the iron-chelating activity, the ratio of EGC, EGCG, ECG or EC to iron(III) was 3:2, 2:1, 2:1 and 3:1, respectively. The hydroxyl radical (HO) scavenging activity of those compounds was investigated in a photolysis of the H2O2 system. It was found that their ability to scavenge hydroxyl radicals decreased in the order of ECG > EC > EGCG >> EGC. It was also found that they could scavenge lipid free radicals in the lecithin/lipoxidase system and their scavenging activity was classified as follows: ECG > EGCG >> EGC > EC. Moreover, we found that their antioxidant active positions were different from each other and the stability of the semiquinone free radicals produced by those compounds in NaOH solution decreased in the order of EGCG > ECG >> EC. The results indicated that the ability of those compounds to protect synaptosomes from the damage of lipid peroxidation initiated by Fe2+/Fe3+ was dependent not only on their iron-chelating activity and free-radical scavenging activity, but also on the stability of their semiquinone free radicals.