This study is to evaluate the effect of resveratrol on carotid baroreceptor activity (CBA). The functional curve of carotid baroreceptor (FCCB) was constructed and the functional parameters of carotid baroreceptor were measured by recording sinus nerve afferent discharge in anesthetized male rats with perfused isolated carotid sinus. Resveratrol (30, 60 and 120 μmol·L-1) inhibited CBA, which shifted FCCB to the right and downward. There was a marked decrease in peak slope (PS) and peak integral value (PIV) of carotid sinus nerve charge in a concentration-dependent manner. Pretreatment with Nω-nitro-L-arginine methyl ester (L-NAME, 100 μmol·L-1), an inhibitor of nitric oxide synthase (NOS), eliminated the inhibitory effect of resveratrol. Pretreatment with Bay K8644 (an agonist of L-type calcium channel, 500 nmol·L-1) abolished the effect of resveratrol on CBA. A potent inhibitor of tyrosine phosphatase (sodium orthovanadate, 1 mmol·L-1) did not influence the effect of resveratrol on CBA. Resveratrol inhibits carotid baroreceptor activity, which may be mediated by the locally released NO and decreased calcium influx. Several studies have showed a cardioprotective effect of resveratrol, with the penetrating study of resveratrol, it may show a potential value in the clinical treatment of cardiovascular disease as an alternative medicine.

AIM To study the relationship between cardioprotective effects of resveratrol and carotid sinus baroreflex (CSB). METHODS The functional curve of the CSB was measured by recording changes in arterial pressure in anesthetized male rats with perfused isolated carotid sinus. RESULTS Resveratrol (30, 60 and 120 μmol·L-1) inhibited the CSB, which shifted the functional curve of the baroreflex to the right and upward. There were a marked decrease in peak slope and a reflex decrease of blood pressure, and also an increase in threshold pressure. Changes of these parameters showed a concentration-dependent manner. Pretreatment with Nω-nitro-L-arginine methylester (100 μmol·L-1), an inhibitor of nitric oxide synthase, and pretreatment with Bay K8644 (500 nmol·L-1), an agonist of L-type calcium channel, could both eliminate the inhibitory effect of resveratrol on CSB. A potent inhibitor of tyrosine phosphatase sodium orthovanadate (1 mmol·L-1) did not influence the effect of resveratrol on CSB. CONCLUSION Resveratrol inhibits carotid baroreflex, which may be mediated by the locally released NO and decreased calcium influx.

Cannabinoid receptors are one of the most expressed G protein-coupled receptors in the central nervous system, which are potential drug targets for inflammation, pain and drug abuse. Cannabinoid receptors are composed of type 1 receptor (CB1R), type 2 receptor (CB2R) and other receptors, of which CB1R plays a vital role in regulating central memory, cognition, and motor function. Therefore, screening CB1R agonists has potential value in treating nervous system diseases. In this study, the intracellular loop 3 (ICL3) domain of CB1R was replaced with a circular-permutated enhanced green fluorescent protein (cpEGFP). After infecting HEK 293T cells with lentivirus particles, we obtained a stable cell line that was overexpressed human CB1R-cpEGFP after puromycin selection. The interaction between receptor agonists and CB1R led to the change of receptor conformation, resulting in de-protonation of the EGFP, and enhancing the fluorescence intensity. Therefore, active CB1R compounds could be verified by measuring the fluorescence intensity. Using CB1R agonist arachidonyl-2′-chloroethylamide (ACEA) as a positive control to evaluate the reliability of this model, studies have shown that ACEA could induce receptor activation and increase fluorescence intensity, while antagonist rimonabant inhibited receptor activation with unchanged fluorescence intensity. In conclusion, this study successfully constructed a fluorescent probe screening model for CB1R agonists.

Accidents, Occupational ; statistics & numerical data ; China ; epidemiology ; Humans

This study is to evaluate the effect of resveratrol on carotid baroreceptor activity (CBA). The functional curve of carotid baroreceptor (FCCB) was constructed and the functional parameters of carotid baroreceptor were measured by recording sinus nerve afferent discharge in anesthetized male rats with perfused isolated carotid sinus. Resveratrol (30, 60 and 120 micromol x L(-1)) inhibited CBA, which shifted FCCB to the right and downward. There was a marked decrease in peak slope (PS) and peak integral value (PIV) of carotid sinus nerve charge in a concentration-dependent manner. Pretreatment with N(omega)-nitro-L-arginine methyl ester (L-NAME, 100 micromol x L(-1)), an inhibitor of nitric oxide synthase (NOS), eliminated the inhibitory effect of resveratrol. Pretreatment with Bay K8644 (an agonist of L-type calcium channel, 500 nmol x L(-1)) abolished the effect of resveratrol on CBA. A potent inhibitor of tyrosine phosphatase (sodium orthovanadate, 1 mmol x L(-1)) did not influence the effect of resveratrol on CBA. Resveratrol inhibits carotid baroreceptor activity, which may be mediated by the locally released NO and decreased calcium influx. Several studies have showed a cardioprotective effect of resveratrol, with the penetrating study of resveratrol, it may show a potential value in the clinical treatment of cardiovascular disease as an alternative medicine.
3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester ; pharmacology ; Anesthesia ; Animals ; Carotid Sinus ; drug effects ; physiology ; Male ; NG-Nitroarginine Methyl Ester ; pharmacology ; Pressoreceptors ; drug effects ; physiology ; Rats ; Rats, Sprague-Dawley ; Stilbenes ; pharmacology ; Vanadates ; pharmacology

OBJECTIVETo observe the temporal and spatial changes in the distribution of Ca2+ in the rat brain following focal cerebral ischemia injury and explore the protective effect of puerarin against calcium overload.

METHODSFocal cerebral ischemia was induced by middle cerebral artery occlusion in rats. After cerebral ischemia, puerarin was administered in the rats at different time points. The volume of ischemic cerebral tissue was assessed by TTC staining, and the fluorescence intensity of Ca2+ in the cortex and corpora striata was determined under laser scanning confocal microscope.

RESULTSThe fluorescence intensity of Ca2+ in the infracted cortex and corpora striata begun to increase 2 h after the ischemia and was further enhanced with the prolongation of the ischemic time. No significance was found in the fluorescence intensity of Ca2+ between the cortex and corpora striata. The fluorescence intensity of Ca2+ in the infarcted corpora striata was obviously higher than that in the cortex after ischemia. Compared with that in the ischemic model group, the fluorescence intensity of Ca2+ in the infarcted cortex and corpora striata decreased significantly at 2 and 12 h following puerarin intervention (P<0.05).

CONCLUSIONPuerarin treatment can relieve calcium overload, reduce cerebral ischemic volume and play a neuroprotective role against focal cerebral ischemia. Twelve hours following cerebral ischemic injury may be the time window for administering puerarin intervention.

Animals ; Brain ; metabolism ; Brain Ischemia ; drug therapy ; metabolism ; Calcium ; metabolism ; Calcium-Transporting ATPases ; metabolism ; Infarction, Middle Cerebral Artery ; drug therapy ; metabolism ; Isoflavones ; pharmacology ; therapeutic use ; Male ; Neuroprotective Agents ; pharmacology ; therapeutic use ; Random Allocation ; Rats ; Rats, Sprague-Dawley

The objective of study was to investigate the expressions of CD80, CD86 and its ligand CD28 on peripheral lymphocytes in patients with idiopathic thrombocytopenic purpura (ITP), to explore the effect of interleukin 18 (IL-18) and its clinical significance in ITP. The expressions of co-stimulatory molecules (CD80, CD86 and its ligand CD28) on peripheral lymphocytes from 34 ITP patients and 34 normal humans were detected by immunofluorescence and flow cytometry. The IL-18 in the plasma was detected by using enzyme linked immunosorbent assay (ELISA). The results showed that the expressions of CD80 and CD86 on peripheral lymphocytes from ITP patients were higher than that of the normal control (4.21 +/- 2.27%, 7.19 +/- 5.16% vs 2.34 +/- 0.87%, 4.08 +/- 1.96%) (P < 0.01); the concentration of IL-18 in plasma of ITP patients was (538.31 +/- 111.33) pg/ml, but the concentration of IL-18 in plasma of controls was (489.44 +/- 49.07) pg/ml. The level of IL-18 negatively correlated with the platelet counts in peripheral blood (r = -0.395, P < 0.05). It is concluded that the CD28/CD80 and CD28/CD86 costimulatory molecules are overexpressed, when the IL-18 level in ITP patients is obviously higher than that in normal controls. When ITP occurred, and the co-stimulatory molecules CD80 and CD86 are closely associated with ITP, it seems that IL-18 may play an important role in ITP pathogenesis.
B7-1 Antigen ; metabolism ; B7-2 Antigen ; metabolism ; CD28 Antigens ; metabolism ; Humans ; Interleukin-18 ; blood ; Lymphocytes ; metabolism ; Purpura, Thrombocytopenic, Idiopathic ; blood ; immunology

objective To understand whether human metapneumovirus(hMPV)is one of the pathogens leading to the children's respiratory infections in Urumqi.Methods A total number of 209 samples were collected in the People's General Hospital of Xinjiang Uygur Autonomous Region from November 2006 to April 2007 with Some from the hospitalized children.while the others from outpatient clinic.Specimens included nasopharyngeal aspirates(NPA)and swabs were analyzed.Samples were all tested hMPV M gene by RT-PCR while the two positive PCR amplicons were sequenced and compared with other hMPV in GenBank by Blast and DNAstar.Results Of all the 209 samples.two positive ones were tested.The identities between them were 83.8%.Results from Phylogenetic analysis showed that they might belong to two different clusters.Conclusion hMPV was one of the pathogens leading to the children's respiratory tract infections in Urumqi.with two different hMPV groups existed in the same season.

BACKGROUNDHuman amniotic epithelial cells (HAECs), which have characteristics of both embryonic and pluripotent stem cells, are therefore a candidate in cell therapy without creating legal or ethical problems. In the present study, we aimed to investigate the effects of intracerebroventricular transplantation of HAECs on doubly transgenic mice of Alzheimer's disease (AD) coexpressing presenilin-1 (PS1) and mutant Sweden amyloid precursor protein (APPswe) genes.

METHODSThe offspring mice genotypes were detected using PCR identification of APPswe and PS1 gene. The doubly transgenic (TG) mice (n = 20) and wild-type (WT) mice (n = 20) were randomly divided into two groups respectively: the transplantation group treated with HAECs and the control group with phosphate buffered saline. Six radial arm water maze test was used to assess the spatial memory in the TG and WT mice. Amyloid plaques and neurofibrillary tangles were analyzed using congo red and acid-silver methenamine staining respectively. Immunofluorescence cytochemistry was used to track the survival of HAECs. Immunohistochemistry was used to determine the expression of octamer-binding protein 4 (Oct-4) and Nanog in the HAECs. High performance liquid chromatography was used to measure acetylcholine in hippocampus. The density of cholinergic neurons in basal forebrain and nerve fibers in hippocampus was measured using acetylcholinesterase staining.

RESULTSAmyloid deposition occurred in hippocampus and frontal cortex in the double TG mice aged 8 months, but not in WT mice. The results also showed that transplanted HAECs can survive for at least 8 weeks and migrate to the third ventricle without immune rejection. The graft HAECs can also express the specific marker Oct-4 and Nanog of stem cell. Compared with the control group, transplantation of HAECs can not only significantly improve the spatial memory of the TG mice, but also increase acetylcholine concentration and the number of hippocampal cholinergic neurites.

CONCLUSIONSThese results demonstrate that intracerebroventricular transplantation of HAECs can improve the spatial memory of the double TG mice. The higher content of acetylcholine in hippocampus released by more survived cholinergic neurites is one of the causes of this improvement.

Acetylcholine ; metabolism ; Alzheimer Disease ; genetics ; metabolism ; therapy ; Amnion ; cytology ; Amyloid beta-Protein Precursor ; genetics ; metabolism ; Animals ; Chromatography, High Pressure Liquid ; Epithelial Cells ; cytology ; transplantation ; Genotype ; Hippocampus ; metabolism ; Homeodomain Proteins ; genetics ; metabolism ; Humans ; Immunohistochemistry ; Memory Disorders ; genetics ; metabolism ; therapy ; Mice ; Mice, Transgenic ; Nanog Homeobox Protein ; Octamer Transcription Factor-3 ; genetics ; metabolism ; Polymerase Chain Reaction ; Presenilin-1 ; genetics ; metabolism

OBJECTIVEIt has been proposed that genetic polymorphisms in apoptosis-related genes might be associated with sensitivity of cancer cells to platinum-based chemotherapy. This study examined the relationship between p53 and p73 genetic polymorphisms and the response to platinum-based chemotherapy in patients with advanced non-small cell lung cancer (NSCLC).

METHODSA total of 165 patients with advanced NSCLC treated with platinum-based chemotherapy were genotyped for the p53 codon 72 Pro-->Arg and p73 exon 2 G4C14-->A4T14 polymorphisms using PCR-RFLP and ARMS-PCR assays. Clinical response to the chemotherapy was obtained after 2 to 3 cycles. The adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using unconditional logistic regression model. All statistical tests were two-sided.

RESULTSThe p53 Pro allele carriers had higher response rate than non-carriers (OR = 2.46; 95% CI = 1.11 - 5.45). A higher response rate was also observed for the p73 G4C14/A4T14 or A4T14/A4T14 genotype, compared with the G4C14/G4C14 genotype (OR = 2.22; 95% CI = 1.14 - 4.30). When these two polymorphisms were combined to be analyzed, it was found that the response rate in those carrying the wild-type genotypes at both genes was only 7.7%, whereas the response rates in patients carrying 1, 2, or more than 2 variant alleles of p53 and p73 were 34.8%, 42.2% and 40.7%, respectively.

CONCLUSIONThose results suggest that p53 and p73 polymorphisms may be associated with clinical responsiveness to platinum-based chemotherapy in advanced NSCLC.

Adult ; Aged ; Antineoplastic Agents ; therapeutic use ; Carboplatin ; administration & dosage ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; genetics ; pathology ; Cisplatin ; administration & dosage ; DNA-Binding Proteins ; genetics ; Exons ; Female ; Genotype ; Humans ; Lung Neoplasms ; drug therapy ; genetics ; pathology ; Male ; Middle Aged ; Neoplasm Staging ; Nuclear Proteins ; genetics ; Paclitaxel ; administration & dosage ; Polymorphism, Genetic ; Tumor Protein p73 ; Tumor Suppressor Protein p53 ; genetics ; Tumor Suppressor Proteins ; genetics