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

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

AIMIn order to look for new active compounds, the structure of (+)-praeruptorin A is modified.

METHODS(+)-Praeruptorin A was isolated from the root of Peucedanum praeruptorum, basic hydrolysis of (+)-praeruptorin A and acyled reactions of hydrolysis product of (+)-praeruptorin A were carried out.

RESULTSEighteen compounds were semi-synthesized from (+)-praeruptorin A.

CONCLUSIONFourteen compounds (5-18) among them are new compounds. Preliminary bioactivity assay indicated that the new compounds show calcium antagonist activity, but they are not as strong as (+)-praeruptorin A.

Animals ; Aorta, Thoracic ; drug effects ; Apiaceae ; chemistry ; Calcium Channel Blockers ; chemical synthesis ; isolation & purification ; pharmacology ; Coumarins ; chemical synthesis ; isolation & purification ; pharmacology ; Drugs, Chinese Herbal ; chemical synthesis ; isolation & purification ; pharmacology ; Molecular Structure ; Muscle Contraction ; drug effects ; Muscle, Smooth, Vascular ; drug effects ; Plants, Medicinal ; chemistry ; Rats

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

OBJECTIVE: It was reported lately that to obtain consistent liver T1rho measurement, at 3T MRI using six spin-lock times (SLTs), is feasible. In this study, the feasibility of using three or two SLT points to measure liver T1rho relaxation time was explored. MATERIALS AND METHODS: Seventeen healthy volunteers underwent 36 examinations. Three representative axial slices were selected to cut through the upper, middle, and lower liver. A rotary echo spin-lock pulse was implemented in a 2D fast field echo sequence. Spin-lock frequency was 500 Hz and the spin-lock times of 1, 10, 20, 30, 40, and 50 milliseconds (ms) were used for T1rho mapping. T1rho maps were constructed by using all 6 SLT points, three SLT points of 1, 20, and 50 ms, or two SLTs of 1 and 50 ms, respectively. Intra-class correlation coefficient (ICC) and Bland and Altman plot were used to assess the measurement agreement. RESULTS: Two examinations were excluded, due to motion artifact at the SLT of 50 ms. With the remaining 34 examinations, the ICC for 6-SLT vs. 3-SLT T1rho measurements was 0.922, while the ICC for 6-SLT vs. 2-SLT T1rho measurement was 0.756. The Bland and Altman analysis showed a mean difference of 0.19 (95% limits of agreement: -1.34, 1.73) for 6-SLT vs. 3-SLT T1rho measurement, and the mean difference of 0.89 (95% limits of agreement: -1.67, 3.45) for 6-SLT vs. 2-SLT T1rho measurement. The scan re-scan reproducibility ICC (n = 11 subjects) was 0.755, 0.727, and 0.528 for 6-SLT measurement, 3-SLT measurement, and 2-SLT measurement, respectively. CONCLUSION: Adopting 3 SLTs of 1, 20, and 50 ms can be an acceptable alternative for the liver T1rho measurement, while 2 SLTs of 1 and 50 ms do not provide reliable measurement.
Adult ; Eating ; Echo-Planar Imaging/*methods ; Fasting ; Female ; Humans ; Liver/*anatomy & histology ; Magnetic Resonance Imaging/*methods ; Male ; Young Adult

OBJECTIVETo investigate sex hormone deficiency related osteoporosis and efficacy of different therapies.

METHODSOrchiectomized and ovariectomized rat models are used to investigate sex hormone deficiency related osteoporosis and efficacy of different therapies. A rat vertebral body can be longitudinally divided into central portion, which contain more trabecular bone, and para-endplate portions which contain more compact bone. In matured male and female Wistar and Sprague-Dawley rat lumbar spines, we investigated baseline bone mineral density (BMD) characteristics and the differential segmental responses in bone loss within the lumbar vertebral body post gonadal surgery with clinical multidetector computed tomography.

RESULTSPara-endplate sections had a higher BMD than central sections. The cephalad para-endplate sections had a higher BMD than the caudad para-endplate sections. Eight weeks after gonadal removal, there was more bone loss in central sections than para-endplate sections. The relative difference of bone loss between para-endplate and central sections was more apparent in male rats than in female rats. There was more bone loss in caudad sections than cephalad sections; this lead to a further increase of BMD difference between caudad para-endplate sections and cephalad para-endplate sections post gonadal surgery.

CONCLUSIONThe approach described in this study provided a consistent way to study BMD change within predominantly compact bone portion and trabecular bone portion of the vertebral body.

Animals ; Bone Density ; drug effects ; Female ; Gonadal Steroid Hormones ; deficiency ; metabolism ; Lumbar Vertebrae ; physiology ; Male ; Orchiectomy ; Ovariectomy ; Rats ; Sex Factors

OBJECTIVE: Bilateral oophorectomy leads to reduced bone mineral density (BMD), and reduced BMD is associated with increased marrow fat and reduced marrow perfusion. Purpose of this study was to investigate how soon these changes occur following surgical oophorectomy. MATERIALS AND METHODS: Six patients who underwent hysterectomy and bilateral salpingo-oophorectomy were studied. At baseline, mean patient age was 49.5 years (range: 45-54 years). Third lumbar vertebral body BMD measurement using quantitative CT, marrow fat fraction (FF) using MR spectroscopy and marrow perfusion using dynamic contrast enhanced MRI were conducted immediately prior to surgery and at 3, 9, and 21 months after surgery. RESULTS: Reduced BMD, increased marrow FF, and reduced marrow perfusion occurred synchronously post-oophorectomy. There was a sharp decrease of 12.5 +/- 7.2% in BMD (n = 6), a sharp increase of 92.2 +/- 46.3% (n = 6) in FF, a sharp decrease of 23.6 +/- 3.9% in maximum contrast enhancement (n = 5), and of 45.4 +/- 7.7% for enhancement slope (n = 5) during the initial 3 months post surgery. BMD and marrow perfusion continued to decrease, and marrow FF continued to increase at a slower rate during the following 18 months. Friedman test showed a significant trend for these changes (p < 0.05). CONCLUSION: Bilateral oophorectomy leads to a rapid decrease in lumbar BMD, an increase in marrow fat content, and a decrease in marrow blood perfusion.
Body Mass Index ; Bone Density ; Bone Marrow/*metabolism ; Contrast Media/diagnostic use ; Female ; Humans ; Hysterectomy ; Lipids/analysis ; Longitudinal Studies ; Lumbar Vertebrae/*radiography ; *Magnetic Resonance Imaging ; Middle Aged ; Ovariectomy ; Prospective Studies

PURPOSE: Cefodizime is a new third-generation cephalosporin which has a structure and immunomodutation properties similar to cefotaxime. Various studies on cefodizime have demonstrated the direct eradication of bacteria in cooperation with the host defense mechanism, particularly with phagocytosis. We evaluated the effects of cefodizime on the phagocytosis of COS-1 cells transfected with FcgammaRI/gammagamma or FcgammaRIIA cDNA. METHODS: Phagocytosis was measured using the in vitro COS-1 cell modeling system according to Schreiber's method. COS-1 cells, which lack endogenoous Fcgammareceptors but have phagocytic potential, were transfected with either FcgammaRI/gammagammaor FcgammaRIIA cDNA. COS-1 cells, as target cells, were treated with antibiotics for 1 or 24 hours and incubated for 30 min with IgG coated sheep RBCs. Adhered IgG coated sheep RBCs were removed after brief exposure to hypotonic phosphate buffered saline. Phagocytosis index (PI) was calculated as the number of ingested RBCs per 100 phagocytic cells after wright-Giemsa staining. RESULTS: COS-1 cells tranfected with FcgammaR (either FcgammaRI/gammagamma or FcgammaRIIA cDNA) showed the phagocytic activity against IgG coated sheep RBC, while untransfected COS-1 cells did not. After treatment with cefodizime, phagocytic activity of FcgammaRI/gammagammacDNA transfected COS-1 cells was significantly increased, while that of FcgammaRIIA cDNA transfected COS-1 cells did not. Marked enhancement of phagocytosis of COS-1 cells was observed after treatment with cefodizime, but was not observed with ceftriaxone or moxalactam. CONCLUSION: Cefodizime showed marked enhancement of phagocytic activity of FcgammaR transfected COS-1 cells. FcgammaRI seems to play an important role in the enhancement of phagocytosis. Further studies will be required.
Animals ; Anti-Bacterial Agents ; Bacteria ; Cefotaxime ; Ceftriaxone ; COS Cells ; DNA, Complementary ; Immunoglobulin G ; Moxalactam ; Phagocytes ; Phagocytosis* ; Sheep

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