Animals ; Chronic Disease ; Heart Failure ; drug therapy ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; adverse effects ; therapeutic use

Adult ; Altitude ; Female ; Heart ; physiology ; Humans ; Male ; Occupational Health ; Railroads ; Tibet

Objective To examine the caregivers' burden and quality of life (QOL) of main caregivers of patients with Parkinson's disease by analyzing caregiver and patient-related factors. Methods A total of 53 cases with Parkinson's disease seen from October 2012 to December 2013 in Yantaishan hospital of Yantai City were selected. Assessments: (a) EuroQol-5 questionnaires, including: EQ-5 dimensions (EQ -5d) and visual analogue scale (VAS). (b) Unified Parkinson's Disease Rating Scale. (c) Hoehn-Yahr(H-Y) stage; (d) Parkinson's disease sleep scale (PDSS), 15 items; (e) Hamilton Anxiety Rating Scale (HAMD-14), Hamilton Depression Rating Scale (HAMA-24); (f) Chinese version of Zarit caregiver burden interview. Results Spearman correlation analysis showed that the EQ-5D index and EQ-VAS negatively correlated with HAMD-14 of caregivers of Parkinson diseasepatients (r=- 0.318, - 0.046) (P<0.05), and negatively correlated with H-Y staging (r=-0.592, -0.531), UPDRSI (r=-0.434, -0.316) , UPDRS Ⅱ (r=0.521, 0.513) , UPDRS Ⅲ (r=0.520, 0.534), UPDRS Ⅳ (r=0.564, 0.509), PDSS in patients with Parkinson's disease (r=0.547, 0.490), HAMD-14 (r=0.315, 0.350), HAMA-24 (r=0.413, 0.401) of Parkinson's disease patients (P<0.05). Caregiver burden was related with HAMD-14 (r=0.496), HAMA-24 (r=0.551),H-Y stage (r=0.697), PDSS (r=0.659), UPDRS Ⅰ-Ⅳ (r=0.538, 0.668, 0.696, 0.600), EQ-5D index of Parkinson disease patients (r=0.682), EQ-VAS of Parkinson disease patients (r=0.670) (P<0.05); and positively related with anxiety of caregivers (r=0.275) , and a negative correlation with the caregivers' quality of lives (r=0.665) (P<0.05). Bivariate analyses showed significant correlations between caregiver burden and patients' sleep, scores of Parkinson's motor symptoms, and caregivers' depression. Based on multiple regression analysis, Zarit score proved to be the main predictor of caregivers' QOL. Caregivers' age, total numbers of caregivers and H-Y stage also proved to be a relevant factor. Conclusion Improvement of patient's sleep, motor symptoms anddepression might alleviate caregivers' strain. There is a correlation between caregivers' burden and QOL. QOL of caregivers can be improved through reducing their care-burden.

AIMTo evaluate the effects of beta3-adrenergic receptors (ARs) agonist (BRL-37344) on beating rate and cAMP levels and investigate the influence on the chronotropic action of beta3-ARs in cultured cardiomyocyte of rats.

METHODSCultured neonatal rat cardiomyocytes were divided randomly into eight groups, control group, ISO group, Nadolol + ISO group, BRL group, PIX + BRL group, L-NAME + BRL group, Nadolol + BRL group and Bupranolol + BRL group. Beating rate of culture neonatal rat cardiomyocytes was observed and cAMP measured by enzyme immunoassay kit. Expression levels of beta3-ARs mRNA in cardiomyocytes was evaluated by reverse transcription-polymerase chain reaction (RT-PCR).

RESULTSISO, nonspecific beta-ARs agonist increased beating rate and intracellular cAMP production, antagonized by Nadolol, beta1, beta2-ARs antagonist. BRL37344 decreased beating rate and intracellular cAMP levels. FPTX, Gi protein inhibitor and Bupranolol, nonspecific beta-ARs antagonist totally blocked the effect and L-NAME, nitric oxide synthase (NOS) inhibitor partly blocked the effect, but Nadolol did not. There was the expression of beta3-AR mRNA in cardiomyocytes by RT-PCR.

CONCLUSIONSBeta3-ARs showed in cardiomyocytes and produced negative chronotropic effects. beta1, beta2-ARs antagonist did not affect it. It suggested beta3-ARs signal transduction was related with G1 protein. The negative inotropic effect of beta3-ARs stimulation was mediated by activation of the NOS pathway.

Adrenergic beta-Agonists ; pharmacology ; Animals ; Animals, Newborn ; Cells, Cultured ; Cyclic AMP ; metabolism ; Ethanolamines ; pharmacology ; Myocytes, Cardiac ; drug effects ; metabolism ; RNA, Messenger ; genetics ; Rats ; Rats, Wistar ; Receptors, Adrenergic, beta-3 ; metabolism

OBJECTIVETo compare the intervention effects of four traditional Chinese medicines (TCMs) with typical cold or hot property on body temperature and temperature-sensitive transient receptor potential ion channel proteins (TRPs) of rats with yeast-induced fever.

METHODThe pyrexia model was induced by injecting yeast suspension subcutaneously. Totally 108 male SD rats were randomly divided into the normal group, the model group, the Rhei Radix et Rhizoma treated group, the Coptidis Rhizoma treated group, the Euodiae Fructus treated group, and the Alpiniae Officinarum Rhizoma treated group, with 18 rats in each group. At the 4 h, 8 h and 12 h after injection of yeast, the rats were sacrificed to collect their hypothalamus and dorsal root ganglion. The expressions of TRPV1 and TRPM8 were detected by immunohistochemistry and Western blot method.

RESULTCompared with the normal group, after injection of yeast, the temperature of rats in the model group notably increased, and reached the peak at 8 h (P < 0.01). The TRPV1 level in hypothalamus and dorsal root ganglia (DRG) of the model group significantly increased, whereas the TRPM8 level significantly reduced. Compared with the model group, the Rhei Radix et Rhizoma group and the Coptidis Rhizoma group showed significant decrease in the high body temperature of rats caused by yeast, down-regulation in the expression of TRPV1, and up-regulation in the expression of TRPM8 (P < 0.05 or P < 0.01). Euodiae Fructus and Alpiniae Officinarum Rhizoma had no significant effect on either temperature or TRPs of fever rats.

CONCLUSIONRhei Radix et Rhizoma and Coptidis Rhizoma, both are TCMs with cold property, can reduce the temperature of fever rats induced by yeast, which may be related to their effective regulation of TRPV1 and TRPM8 in hypothalamus and DRG, while Euodiae Fructus and Alpiniae Officinarum Rhizoma had no relevant effect.

Animals ; Antipyretics ; administration & dosage ; chemistry ; Body Temperature Regulation ; drug effects ; Drugs, Chinese Herbal ; administration & dosage ; chemistry ; Fever ; drug therapy ; immunology ; microbiology ; physiopathology ; Gene Expression Regulation ; drug effects ; Humans ; Male ; Rats ; Rats, Sprague-Dawley ; Saccharomyces cerevisiae ; immunology ; TRPM Cation Channels ; genetics ; immunology ; TRPV Cation Channels ; genetics ; immunology

Objective To understand the role of NOD-like receptor pyrin domain containing 3 (NLRP3)-dependent activation of cysteinyl aspartate specific proteinase 1 (caspase-1) in mediating the neuroinflammatory response in mice with MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine)-induced Parkinson's disease(PD) and to investigate the underlying mechanism. Methods Male C57BL/6 mice were randomly divided into two groups:experimental and control groups. MPTP solution (30 mg·kg-1·d-1) was given to mice through intraperitoneal injection to prepare the PD model and equal amount of saline was used to set up the control group. Changes in mouse behavior were observed through pole climbing and suspension experiment. Expression of inflammasome in the midbrain of mice was detected by Western blot. SH-SY5Y cells,a human neuroblastoma cell line,were cultured in vitro and randomly divided into five groups including control,nonsense,siRNA-NLRP3,MPP+(1-methyl-4-phenylpyridinium) and siRNA+MPP+groups. siRNA-NLRP3 was transfected into SH-SY5Y cells using Lipofectamine 2000 to silence the expression of NLRP3 gene. Then the transfected cells were incubated with MPP+for 48 h to observe the protective effect of NLRP3 on nerve cells. MTT assay and flow cytometry were performed to measure the viability and the apoptosis rate of SH-SY5Y cells,respectively. Western blot was used to detect the levels of NLRP3,B-cell lymphoma 2 (Bcl-2),Bcl-2-associated X protein (Bax) and cleaved caspase-3. Results Compared with the control group,the mice in the experimental group spent more time climbing from the top to the bottom of the pole (P<0. 05),got a lower score on suspension experiment (P<0. 05) and showed enhanced expression of NLRP3, IL-1β,Pro-IL-1β and caspase-1 in the substantia nigra (P<0. 05). Compared with the MPP+group,the siR-NA+MPP+group showed significantly inhibited expression of NLRP3, cleaved caspase-3 and Bax ( P<0. 05),enhanced cell viability (P<0. 05),suppressed cell apoptosis (P<0. 05) and promoted expression of Bcl-2 ( P<0. 05). Conclusion NLRP3-dependent activation of caspase-1 plays an important role in the nerve injury in PD. Inhibition of NLRP3 expression in vitro can significantly enhance the vitality and inhibit the apoptosis of SH-SY5Y cells,which may have a protective effect on nerve cells through regulating mito-chondrial apoptosis signaling pathway and provide a new drug target for the treatment of PD.

OBJECTIVETo study the effect of a microRNA-132 antagonist on lithium-pilocarpine-induced status epilepticus (SE) in young Sprague-Dawley (SD) rats.

METHODSForty-five 3-week-old SD rats were randomly and equally divided into epilepticus model group, microRNA-132 antagonist group, and microRNA-132 antagonist negative control group. The young SD rat model of SE was established using lithium-pilocarpine. For the microRNA-132 antagonist group and the negative control group, pretreatment was performed 24 hours before the model establishment. Behavioral observation was performed to assess the latency of SE and success rate of induction of SE. The scale of Lado was used to evaluate the seizure severity. Electroencephalography (EEG) was used to assess the frequency and amplitude of epileptiform discharges. The mortality rate was calculated in each group.

RESULTSThere was no significant difference in the success rate of induction of SE between the three groups (P>0.05). Compared with the microRNA-132 negative control group and the epilepticus model group, the microRNA-132 antagonist group had significantly prolonged SE latency after model establishment (P<0.05), a significantly lower Lado score of seizure (P<0.05), significantly lower frequency and amplitude of epileptiform discharges on EEG (P<0.05), and a slightly reduced mortality rate.

CONCLUSIONSThe treatment with the microRNA-132 antagonist shows an inhibitory effect on the development and progression of lithium-pilocarpine-induced SE in young SD rats. The inhibition of microRNA-132 is likely to be a potential target or direction for drug treatment of SE.

Animals ; Electroencephalography ; Male ; MicroRNAs ; antagonists & inhibitors ; Pilocarpine ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Status Epilepticus ; chemically induced ; drug therapy

OBJECTIVETo observe the effects of beta3-adrenergic receptor(beta3-AR) antagonist on myocardial uncoupling protein 2 (UCP2) expression and energy metabolism in chronic heart failure rats.

METHODSSeven weight-matched normal adult rats (control group), 18 isoproterenol (ISO) induced heat failure (HR) rats (ISO group) and 21 ISO induced heart failure rats but received specific beta3-AR inhibitor SR59230A (ISO+ SR59230A group) for 6 weeks were included in this research. At the end of the study, echocardiography was performed, the ratio of left ventricular weight and body weight (LVW/BW) was calculated. The expression of beta3-AR ad UCP2 mRNA in myocardium were detected by reverse transcription-polymerase chain reaction (RT-PCR), the UCP2 protein in myocardium were detected by Western blot. The myocardial contents of creatine phosphate (PCr) and adenosine triphosphate (ATP) were measured by high performance liquid chromatography (HPLC).

RESULTSCompared with control group, the cardiac function was significantly reduced and myocardial beta3-AR mRNA significantly increased, UCP2 mRNA and protein were also significantly increased in ISO group, this change could be attenuated by the treatment with SR59230A, and the expression of myocardial UCP2 protein negatively correlated with the ratio of PCr/ATP.

CONCLUSIONIn the chronic stage of HF, the expression of UCP2 increases, which causes myocardial energy shortage, SR59230A improves myocardia energy efficiency and cardiac function by means of suppressing the expression of UCP2.

Adrenergic Antagonists ; pharmacology ; Animals ; Energy Metabolism ; Heart Failure ; metabolism ; Ion Channels ; metabolism ; Male ; Mitochondrial Proteins ; metabolism ; Myocardium ; metabolism ; Rats ; Rats, Wistar ; Receptors, Adrenergic, beta-3 ; metabolism ; Uncoupling Protein 2

Three cyclotides were isolated from the whole plant of Viola yedoensis in this study. The two, vary peptide E and cycloviolacin Y5, were previously reported, and a novel cycloviolacin VY1 was characterized according to the interpretation of MS/MS fragmentation of peptides which were produced from the reduced and alkylated parent peptide with the digestion of Endo Lys-C, trypsin and chymotrypsin, separately. The stability of remarkable resistance to proteolytic degradation by trypsin and chymotrypsin, and that of thermal denaturation was confirmed again. Besides, the IC50 value of cycloviolacin VY1 against influenza A H1N1 virus was (2.27 +/- 0.20) microg x mL(-1). It is the first cyclotide reported with anti-influenza A H1N1 virus activity in vitro assay.
Antiviral Agents ; isolation & purification ; pharmacology ; Cyclotides ; pharmacology ; Influenza A Virus, H1N1 Subtype ; drug effects ; Tandem Mass Spectrometry ; Viola ; chemistry

OBJECTIVETo evaluate the effects of different doses of N(G)-nitro-L-arginine methyl ester (L-NAME) on hemodynamics, cyclic guanosine monophosphate (cGMP) production and the level of beta-adrenergic receptors (beta-ARs) mRNA in a heart failure rat model after BRL-37344 (beta(3)-ARs agonist) injection. Meanwhile, to investigate the influence of beta(3)-ARs and L-NAME on signal transduction in failing heart.

METHODSThe rats were randomly divided into six groups, control group (group I), Iso (isoproterenol) group (group II), Iso + BRL group (group III), Iso + BRL + low dose of L-NAME group (5 mg/kg, group IV), Iso + BRL + moderate dose of L-NAME group (50 mg/kg, group V), Iso + BRL + high dose of L-NAME group (100 mg/kg, group VI). The hemodynamics [left ventricular end systolic pressure (LVESP), +/- dp/dt, left ventricular end diastolic pressure (LVEDP)], cardiac cGMP and the levels of beta(1)-, beta(2)-, and beta(3)-ARs mRNA were measured.

RESULTS(1) LVESP, +/- dp/dt values in group II were significantly lower, and LVEDP was significantly higher than that in group I (except -dp/dt P < 0.05, the rest were P < 0.01). Comparing with group II, group III had lower -dp/dt value and LVESP, higher LVEDP (P < 0.05). The level of +dp/dt had a trend to be lower but lacked statistical significance between two groups. The value of +/- dp/dt got higher and LVEDP got lower along with higher dose of L-NAME, but a large dose of L-NAME had more deteriorated cardiac functions. (2) The cardiac cGMP in group I, II and III had a higher tendency (P < 0.01). The tendency of cardiac cGMP in group IV, V and VI was inversed with the dose of L-NAME. After a large dose of L-NAME was applied, cGMP returned to the same level as Group I. (3) Among groups I, II and III, the level of beta(1)-AR mRNA was the highest in group I and the lowest in group III (P < 0.01). The levels of beta(2)-AR mRNA were also tended to be lower among three groups but with no significance. While the level of beta(3)-AR mRNA was the highest in group III. The levels of beta-AR mRNA were all the same in group VI, V and VI.

CONCLUSIONSThe negative inotropic effect of beta(3)-ARs stimulation was mediated by activation of the NOS pathway. L-NAME blocked beta(3)-ARs agonist negative chronotropic effect on failing heart partly and improved hemodynamics, but a large dose of L-NAME had more deteriorated cardiac functions.

Adrenergic Agonists ; therapeutic use ; Animals ; Cyclic GMP ; metabolism ; Heart Failure ; drug therapy ; metabolism ; physiopathology ; Male ; NG-Nitroarginine Methyl Ester ; administration & dosage ; pharmacology ; RNA, Messenger ; metabolism ; Rats ; Rats, Wistar ; Receptors, Adrenergic, beta-3 ; metabolism