Adolescent ; Adult ; Blood Pressure ; Gravity Suits ; Heart Function Tests ; Humans ; Male ; Positive-Pressure Respiration ; Young Adult

OBJECTIVETo study the mechanism of learning and memory dysfuction in the transgenic mouse expressing human tau 40 isoform with P301L mutation (F10).

METHODSThe human tau protein expression and phosphor-tau protein levels were detected with Western blot method. The neurofibrillary tangles were observed with Bielshowsky silver stain. The behavior changes of learning and memory were observed by open field test and passive avoidance test. Acetyleholine level, activities of acetycholinesterase and choline acetyltransferase of whole brain was detected by colorimetry method. The nitric oxide level of whole brain was detected by nitrate enzyme reduction method.

RESULTSExogenous human tau gene was expressed and an elevation of phosphor-tau protein level in 7 and 3-month transgenic mice's hippocampus andcerebrocortex was observed. The neurofibrillary tangles were observed in cerebrocortex of 7-month transgenic mice; the 7-month transgenic mice also presented an evident reduction of learning and memory ability and nitric oxide level of the whole brain, but not changes in acetylcholine level, acetycholinesterase activity, choline acetyltransferase activity and expression in whole brain.

CONCLUSIONTau transgenic mice (F10) can still inherit their parents' biologiccal characters, and develop learning and memory dysfunction awnodh san obvious decrease in nitric oxide level of whole brain in the 7-month old mice, suggesting a decrease of nitric oxide level of whole brain would be involved in the mechanism of learning and memory dysfunction in these transgenic mice.

Acetylcholine ; metabolism ; Acetylcholinesterase ; metabolism ; Animals ; Brain ; physiopathology ; Choline O-Acetyltransferase ; metabolism ; Humans ; Membrane Proteins ; genetics ; Memory Disorders ; genetics ; physiopathology ; Mice ; Mice, Transgenic ; Mutation ; Nitric Oxide ; metabolism

The aim of this paper was to investigate the effect of terpene penetration enhancers on membrane fluidity and membrane potential using HaCaT keratinocytes, and study the potential mechanisms of these terpene compounds using as natural transdermal penetration enhancer. Six terpene compounds, namely menthol, limonene, 1,8-cineole, menthone, terpinen-4-ol and pulegone, were chosen in this study on account of their good penetration-enhancement activities. The cytotoxicity of these terpene compounds was measured using an MTT assay. The fluorescence recovery after photobleaching (FRAP) technique was employed to measure the change of membrane fluidity of HaCaT cells. The flow cytometer was used to study the alteration of membrane fluidity of HaCaT cells, and investigate the effect of terpene compounds on intracellular Ca2+. It was found that 6 terpene compounds possessed low cytotoxicity in comparison to the well-established and standard penetration enhancer azone. Those terpene compounds could significantly enhance HaCaT cells membrane fluidity and decrease HaCaT cells membrane potentials. Meanwhile, after treated with various terpene compounds, the Ca2(+)-ATPase activity and intracellular Ca2+ of HaCaT cells was decreased significantly. Terpene penetration enhancers perhaps changed the membrane fluidity and potentials of HaCaT cells by altering the Ca2+ balance of the cell inside and outside, resulting in the low skin permeability to increase the drug transdermal absorption.
Cell Line ; Drugs, Chinese Herbal ; pharmacokinetics ; Humans ; Keratinocytes ; drug effects ; metabolism ; Membrane Fluidity ; drug effects ; Skin Absorption ; drug effects ; Terpenes ; pharmacokinetics

OBJECTIVETo study the effects of beta-amyloid peptide (Abeta) on cell membrane lipids and cholinergic receptors of human neuroblastoma cells.

METHODSHuman SH-SY5Y neuroblastoma cells were treated with different concentrations of Abeta(1-42) with and without pretreatment of vitamin E. MTT [3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide] reduction, lipid peroxidation, protein oxidation and phospholipids were measured by spectrophotometry. Levels of cholesterol and unbiquinone were determined by high-performance liquid chromatography (HPLC). The numbers of cholinergic receptor binding sites were determined by receptor binding assay and the protein levels of nicotinic receptor alpha3 and alpha7 subunits were studied by Western blotting.

RESULTSSH-SY5Y cells showed decreased reduction rates of MMT and phospholipids, and increased lipid peroxidation and protein oxidation after exposure to Abeta (0.1 micromol/L) as compared to the control. The number of cholinergic receptor binding sites, the protein level of nicotinic receptor alpha3 and alpha7 subunits and the content of ubiquinone decreased in cells treated with high dose of Abeta (1 micromol/L). Although the level of cholesterol was not changed in any way, vitamin E partially prevented the neurotoxic effects of Abeta.

CONCLUSIONbeta-amyloid peptide reduces the level of cell membrane lipids and cholinergic receptors in human SH-SY5Y neuroblastoma cells, likely through the induction of an enhanced oxidative stress.

Amyloid beta-Peptides ; administration & dosage ; metabolism ; toxicity ; Cell Line, Tumor ; Cell Membrane ; metabolism ; Cholesterol ; metabolism ; Dose-Response Relationship, Drug ; Humans ; Lipid Peroxidation ; drug effects ; Malondialdehyde ; metabolism ; Membrane Lipids ; metabolism ; Neuroblastoma ; metabolism ; pathology ; Oxidative Stress ; drug effects ; Peptide Fragments ; administration & dosage ; metabolism ; toxicity ; Phospholipids ; metabolism ; Receptors, Nicotinic ; metabolism ; Ubiquinone ; metabolism ; Vitamin E ; metabolism ; pharmacology

Objective To investigate the prevalence of unintended pregnancy (UP) and exploring the risk factors of UP for married women of child-bearing age from Qingshan district,Wuhan.Methods A cross-sectional study was adopted in this study.Cluster sampling method was used with 3256 women recruited,in 2010.Information on history and risks related to social-demographic factors of UP were collected,using a self-administered questionnaire.Results Of the 3256 participants,over half of them (53.8％) reorted ever having had the history of UP and 9.1％ reported UP in the past year.Rate of UP in the past year for different age cohorts (18-30,31-40,41-49 years) were 31.8％,10.5％ and 1.8％ respectively.The most frequently reported reason for UP across all the age cohorts was "Did not use any contraceptive methods",with proportions on the reason that reported by women at 18-30,31-40 and 41-49 year-olds,were 69.7％,51.1％ and 42.4％ respectively.The second frequently reported reasons for UP were "Failure of traditional contraception" for younger cohort ( 18-30 years:13.0％ ) and "IUD dropped or pregnancy with IUD" for older-age cohorts (23.4％ at 31-40 year-olds and 37.0％ at the 41-49 year-oplds).The most frequently cited reason for "Did not use any contraceptive methods" was "Believe we were lucky so far,not to get pregnant" (59.6％).The risk factors of UP were being at older age,experiencing sex debut at younger age and got married at younger age.Conclusion The prevalence of lifetime UP history was high among women at child-bearing age from Qingshan district,Wuhan.Reproductive health services and interventions should be taken according to the needs from different age cohorts of women.Younger cohort of women should receive more attention.

OBJECTIVETo study the influence of beta-amyloid protein (Abeta) and cholesterol on the pathological changes of Alzheimer's disease (AD) and on the expression of nicotinic acetylcholine receptor (nAChR) subunits in the brains of rats.

METHODThe rats were treated by intracerebroventricular injection of Abeta1-42 and fed with a diet containing 5% cholesterol to establish animal model of AD. The pathological changes, learning and memory, and expression of nAChRs of rats were analyzed by Bieoschowsky staining, immunohistochemistry, water-labyrinth, Western blot, and RT-PCR.

RESULTSAbeta intracerebroventricular injection induced Abeta deposition in rat brains and high-cholesterol diet resulted in hypercholesterolemia in the animals. Injection of Abeta caused a reduction of learning and memory of rats and modifications of the expression of nAChRs. Cholesterol enhanced these effects of Abeta on neuropathology and expression of nAChRs.

CONCLUSIONSAbeta can induce marked neuropathological changes, influence the learning and study ability, and modify the expression of nAChRs. Cholesterol can enhance the neurotoxicity of Abeta.

Alzheimer Disease ; chemically induced ; metabolism ; pathology ; physiopathology ; Amyloid beta-Peptides ; metabolism ; Animals ; Cerebral Cortex ; metabolism ; pathology ; Cholesterol ; blood ; Drug Synergism ; Female ; Hypercholesterolemia ; blood ; Learning ; drug effects ; Male ; Peptide Fragments ; metabolism ; RNA, Messenger ; metabolism ; Random Allocation ; Rats ; Rats, Wistar ; Receptors, Nicotinic ; biosynthesis ; genetics

[Objective]To investigate the etiology,clinical manifestation,treatment and prognosis of optic disc vas-culitis.[Method]Twenty-four eyes of 21 patients were enrolled in this retrospective study.Eye examinations,treatment, and effect were recorded.[Result]Six were male and 15 were female.The age was between 19 and 43 years old(average:28.7±1.6).85.7% of the patients referred to the clinic with mild to moderate decreased vision.Edema of the optic disc can be seen in both types while tortuous veins can also be found in type 2.Similar characteristics were noticed in OCT,FFA, and etc.With a follow-up of 4.52±0.98 months after treatment(prednisone:initial dose 1.0-1.2 mg/kg),the BCVA of the affected eyes improved significantly.[Conclusion]Optic disc vasculitis is affected by autoimmune disorder,infection,hy-perlipidemia,and etc.Edema of the optic disc with/without tortuous veins and retinal hemorrhage can be noticed.Similar diseases should be excluded in avoidance of misdiagnosis. Systemic examination and complete solution should be per-formed.Glucocorticoid helps to improve the visual function.The application of anti-VEGF is effective in secondary macu-lar edema.However,the long-term efficacy is awaiting being confirmed.

BACKGROUNDTalaromyces (Penicillium) marneffei (TM) is an emerging dimorphic human pathogenic fungus that is endemic to Southeast Asia. TM mostly occurs as an opportunistic infection in patients with human immunodeficiency virus (HIV). The objective of this study was to compare the clinical and laboratory parameters of patients with TM infections who were HIV-positive and HIV-negative and to assess therapies and outcomes.

METHODSThis was a retrospective analysis of 26 patients diagnosed with disseminated TM infection from September 2005 to April 2014 at Fujian Provincial Hospital, China.

RESULTSPatients with TM infection tend to present with fever, weight loss, and anemia. The time from symptom onset to confirmed diagnosis was greater for HIV-negative patients (n = 7; median: 60 days, range: 14-365 days) than for HIV-positive patients (n = 19; median: 30 days, range: 3-90 days, Mann-Whitney U = 31.50, P= 0.041). HIV-negative patients were more likely to have dyspnea (57.1% vs. 5.3%, χ2 = 8.86, P= 0.010), low neutrophil count (Mann-Whitney U = 27.00, P= 0.029), high CD4 count (Mann-Whitney U = 0.00, P= 0.009), and high lymphocyte count (Mann-Whitney U = 21.00, P= 0.009). There were no significant differences in other demographic, clinical, or biochemical characteristics. Among all the patients, 12 HIV-positive patient and 1 HIV-negative patient received amphotericin and fluconazole treatment, 9 of whom improved, 1 died, 2 had kidney damage, 1 had hypokalemia due to exceeded doses.

CONCLUSIONSHIV-negative patients with TM infections tend to have a longer diagnostic interval, a higher percentage of dyspnea, higher levels of CD4 and lymphocytes, and lower neutrophil counts than TM infection in HIV-positive patients. Treatment programs with amphotericin and fluconazole are mostly effective.

Adult ; Aged ; CD4 Lymphocyte Count ; Female ; HIV Infections ; complications ; Humans ; Male ; Middle Aged ; Mycoses ; diagnosis ; drug therapy ; immunology ; Retrospective Studies ; Talaromyces ; drug effects

Nicotine enhances the function of learning and memory, but the underlying mechanism still remains unclear. Hippocampal long-term potentiation (LTP) is assumed to be a cellular mechanism of learning and memory. Our previous experiments showed that with the single pulses evoking 80% of the maximal population spike (PS) amplitude, nicotine (10 μmol/L) induced LTP-like response in the hippocampal CA1 region. In the present study, the nicotinic acetylcholine receptor (nAChR) subtypes and relevant neurotransmitter releases involved in LTP-like response induced by nicotine were investigated by extracellularly recording the PS in the pyramidal cell layer in the hippocampal CA1 region in vitro. LTP-like response induced by nicotine was blocked by mecamylamine (1 μmol/L) or κ-bungarotoxin (0.1 μmol/L), but not by dihydro-β-erythtroidine (DHβE, 10 μmol/L). Moreover, it was inhibited by propranolol (10 μmol/L), but not by phentolamine (10 μmol/L) or atropine (10 μmol/L). The results suggest that noradrenaline release secondary to the activation of κ-bungarotoxin-sensitive nAChRs participates in LTP-like response induced by nicotine in the hippocampal CA1 region.
Animals ; Bungarotoxins ; CA1 Region, Hippocampal ; physiology ; Long-Term Potentiation ; drug effects ; Nicotine ; pharmacology ; Norepinephrine ; secretion ; Receptors, Nicotinic ; metabolism

This study was purposed to evaluate the effects of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on hematopoietic reconstruction and survival in beagles exposed to mixed fission neutron and γ-ray. 13 beagles were unilaterally exposed to single dose of 2.3 Gy 90% neutrons. The experiments were divided into 3 groups: irradiation control group (no any treatment, n = 4), supportive care group (n = 5) and rhG-CSF plus supportive care group (n = 4, abbreviated as rhG-CSF group) in which the beagles were subcutaneously injected with 200 µg/kg of rhG-CSF early at half an hour and 24 hours post-irradiation respectively. The results showed that 2.3 Gy 90% neutron irradiation induced a severe acute radiation sickness of bone marrow type. The administration of rhG-CSF increased the survival rate from 60% in supportive care group to 100%. Twice injection of rhG-CSF in the first 24 hours reduced duration of neutropenia, enhanced neutrophil nadir and promoted neutrophil recovery when compared with control cohort administered clinical support. The number of colony-forming cells (CFU-GM, CFU-E, and BFU-E) in peripheral blood of rhG-CSF treated canines increased 2-to 5-fold relative to those of the supportive care group on day 3. All canines treated with rhG-CSF achieved hematopoietic reconstruction as evidenced by the pathological section of sternum while severe shortage of hemopoietic cells remained in the cohorts given supportive care alone. It is concluded that the combination of supportive care and high-dose rhG-CSF can accelerate hematopoietic recovery and enhance survival of dogs exposed to 2.3 Gy mixed neutron and gamma ray.
Animals ; Dogs ; Gamma Rays ; adverse effects ; Granulocyte Colony-Stimulating Factor ; administration & dosage ; pharmacology ; Hematopoietic System ; drug effects ; radiation effects ; Neutron Diffraction ; Recombinant Proteins ; administration & dosage ; pharmacology ; Survival Rate