Objective To investigate the effects of berberine on basolateral calcium-activated potassium current I_K(Ca)and cAMP-activated potassium current I_K(cAMP)and its mechanism in treatment of secretory diarrhea.Methods The intact colonic crypt cells were isolated with EDTA solution.The effects of berberine(50,100,500?mol/L)on I_K(Ca)and I_K(cAMP)were detected by patch clamp technique under the conventional whole cell patch clamp mode.The solution of PSS was served as control.Results Berberine could significantly inhibite I_K(Ca)and I_K(cAMP)of rat colonic crypt cells(both P

OBJECTIVETo explore the changes in the mRNA expression of adiponectin (Adp), adiponectin receptors(AdpR), and leptin in different adipose tissues of Wannanhua pigs at different stages of development, and their sexual dimorphism.

METHODSFive Wannanhua boars and five Wannanhua gilts were sampled at birth, 30, 45, 90, and 180 days of age respectively. The delta delta Ct relative quantification real-time PCR was used to detect the transcription levels of Adp, AdpR1, AdpR2, and leptin mRNAs in subcutaneous (SC) and perirenal (PR) adipose tissues, and beta-actin were used as internal standards.

RESULTSThe expression level of Adp, AdpR1, AdpR2, and leptin mRNA in SC and PR adipose tissue were changed with age significantly (P < 0.01). In general, Adp mRNA expression in SC adipose tissue was significantly lower than that in PR adipose tissue (P < 0.05), while AdpR1, AdpR2, and leptin mRNA expression in SC adipose tissue were significantly higher than those in PR adipose tissue (P < 0.05 or P < 0.01). Although the sexual dimorphism were found in apart genes or apart days of age, Adp, AdpR1, AdpR2, and leptin mRNA expression both in SC adipose tissue and PR adipose tissue had no significant differences between Wannanhua gilts and boars in general. Significant positive correlation was found between Adp and AdpR1, AdpR2 (P < 0.05 or P < 0.01), and significant negative correlation was found between Adp and leptin (P < 0.05) in SC adipose tissue and PR adipose tissue respectively (P < 0.05).

CONCLUSIONThe expression of Adp, AdpR1, AdpR2, and leptin mRNA in adipose tissue of Wannanhua pigs followed specific developmental patterns and tissue specificity. Adp correlated with its receptors.

Actins ; metabolism ; Adiponectin ; metabolism ; Adipose Tissue ; growth & development ; metabolism ; Animals ; Female ; Leptin ; metabolism ; Male ; RNA, Messenger ; genetics ; Receptors, Adiponectin ; metabolism ; Swine

This study aimed to evaluate the effect of curcumin on brain hypoxicischemic(HI) damage in neonatal rats and whether the phosphoinositide 3-kinase(PI3K)/Akt/vascular endothelial growth factor (VEGF) signaling pathway is involved.Brain HI damage models were established in neonatal rats, which received the followingtreatments: curcumin by intraperitoneal injection before injury, insulin-likegrowth factor 1 (IGF-1) by subcutaneous injection after injury, and VEGF by intracerebroventricularinjection after injury. This was followed by neurological evaluation,hemodynamic measurements, histopathological assessment, TUNEL assay,flow cytometry, and western blotting to assess the expression of p-PI3K, PI3K, p-Akt,Akt, and VEGF. Compared with rats that underwent sham operation, rats with brainHI damage showed remarkably increased neurological deficits, reduced right bloodflow volume, elevated blood viscosity and haematocrit, and aggravated cell damageand apoptosis; these injuries were significantly improved by curcumin pretreatment.Meanwhile, brain HI damage induced the overexpression of p-PI3K, p-Akt, and VEGF,while curcumin pretreatment inhibited the expression of these proteins. In addition,IGF-1 treatment rescued the curcumin-induced down-regulated expression of p-PI3K, p-Akt, and VEGF, and VEGF overexpression counteracted the inhibitory effectof curcumin on brain HI damage. Overall, pretreatment with curcumin protectedagainst brain HI damage by targeting VEGF via the PI3K/Akt signaling pathway inneonatal rats.

This study aimed to evaluate the effect of curcumin on brain hypoxicischemic(HI) damage in neonatal rats and whether the phosphoinositide 3-kinase(PI3K)/Akt/vascular endothelial growth factor (VEGF) signaling pathway is involved.Brain HI damage models were established in neonatal rats, which received the followingtreatments: curcumin by intraperitoneal injection before injury, insulin-likegrowth factor 1 (IGF-1) by subcutaneous injection after injury, and VEGF by intracerebroventricularinjection after injury. This was followed by neurological evaluation,hemodynamic measurements, histopathological assessment, TUNEL assay,flow cytometry, and western blotting to assess the expression of p-PI3K, PI3K, p-Akt,Akt, and VEGF. Compared with rats that underwent sham operation, rats with brainHI damage showed remarkably increased neurological deficits, reduced right bloodflow volume, elevated blood viscosity and haematocrit, and aggravated cell damageand apoptosis; these injuries were significantly improved by curcumin pretreatment.Meanwhile, brain HI damage induced the overexpression of p-PI3K, p-Akt, and VEGF,while curcumin pretreatment inhibited the expression of these proteins. In addition,IGF-1 treatment rescued the curcumin-induced down-regulated expression of p-PI3K, p-Akt, and VEGF, and VEGF overexpression counteracted the inhibitory effectof curcumin on brain HI damage. Overall, pretreatment with curcumin protectedagainst brain HI damage by targeting VEGF via the PI3K/Akt signaling pathway inneonatal rats.

BACKGROUNDRenal sympathetic nerves are involved in the reflective activation of the sympathetic nervous system in circulatory control. Catheter-based renal denervation (RDN) ameliorated treatment-resistant hypertension safely, but 10%-20% of treated patients are nonresponders to radiofrequency denervation. The purpose of this study was to investigate the safety and efficiency of cryoablation for sympathetic denervation in a swine model and to explore a new way of RDN.

METHODSSeven swines randomly assigned to two groups: Renal cryoablation (CR) group and control group. The control group underwent renal angiogram only. The CR group underwent renal angiogram plus bilateral renal cryoablation. Renal angiograms via femoral were performed before denervation, after denervation and prior to the sacrifice to access the diameter of renal arterial and the pressure of aorta abdominalis. Euthanasia of the swine was performed on 28-day to access norepinephrine (NE) changes of the renal cortex and the changes of renal nerves.

RESULTSCryoablation did not induce severe complications at any time point. There was no significant change in diameter of renal artery. CR reduced systolic blood pressure (BP) from 145.50 ± 9.95 mmHg at baseline to 119.00 ± 14.09 mmHg. There was a slight but insignificant decrease in diastolic BP. The main nerve changes at 28-day consisted of necrosis with perineurial fibrosis at the site of CR exposure in conjunction with the nerve vacuolation. Compared with the control group, renal tissue NE of CR group decreased by 89.85%.

CONCLUSIONSPercutaneous catheter-based cryoablation of the renal artery is safe. CR could effectively reduce NE storing in the renal cortex, and the efficiency could be maintained 28-day at least.

Animals ; Cryosurgery ; methods ; Female ; Kidney ; innervation ; Male ; Swine ; Sympathectomy ; methods ; Treatment Outcome

OBJECTIVETo study the effects of insulin on the proteolysis of cultured rabbit skeletal muscular myotubes in vitro, and their possible mechanisms.

METHODSMuscles of lower limbs of juvenile rabbits were isolated for tissue-block culture. After passage, myoblasts were formed and fused into myotubes. Then the protein in myotubes was radiolabelled with L-[ 3,5-3H] tyrosine. The myotubes were cultured in DMEM medium containing 100 nmol/L insulin (n = 24, group B) , 100 nmol/L dexamethasone (n = 24, group C) , 100 nmol/L insulin and 100 nmol/L dexamethasone (n = 24, group D) , no insulin or dexamethasone (n =24, group A), respectively. Twenty-four hours after culture, the L-[3,5-3H] tyrosine content in culture medium and cells were determined, and the degradation rates of protein were calculated. The mRNA expressions of ubiquitin and protease C2 subunit were determined by Northern blot.

RESULTSThe degradation rates of myotube protein in group A(0. 38+/-0.04) was obviously lower than that in group C (0.50+/-0.03, P <0.01), but it was obviously higher than that in group B(0. 35+/-0.03, P <0.05). Though the degradation rates of myotube protein in group D (0.41+/-0. 03) was evidently lower than that in group C ( P < 0.01) , it was still higher than that in group A( P < 0.05 ). The mRNA expressions of ubiquitin and protease C2 subunit in group A ( the scale: 2. 4 kb ubiquitin was 0. 82+/-0. 15, 1. 2 kb ubiquitin was 0. 60+/-0. 10, C2 subunit was 0. 75+/-0. 16) was obviously lower than that in group C ( the scale: 2.4 kb ubiquitin was 2. 15+/-0. 23, 1.2 kb ubiquitin was 1.50+/-0. 14,C2 subunit was 1.50+/-0. 13 , P <0. 01) , but it in group D was lower than that in group C (the scale: 2. 4 kb ubiquitin was 1. 25+/-0. 17, 1. 2 kb ubiquitin was 0. 85+/-0. 09, C2 subunit was 0. 90+/-0. 15, P <0. 01) , and it was similar to that in group B (the scale: 2.4 kb ubiquitin was 0. 85+/-0.07, 1.2 kb ubiquitin was 0. 65+/- 0. 12, C2 subunit was 0. 76 +/-0. 09, P > 0. 05).

CONCLUSIONThe effects of insulin on the activity of ubiquitin-proteasome pathway and the proteolytic rate in normal myotubes were relatively weak. However, insulin can significantly inhibit the effects of dexamethasone on the gene expressions of ubiquitin system and the proteolytic rate in myotubes, but the mechanism needs further research.

Animals ; Cells, Cultured ; In Vitro Techniques ; Insulin ; pharmacology ; Male ; Muscle Fibers, Skeletal ; drug effects ; metabolism ; Muscle Proteins ; metabolism ; Rabbits ; Ubiquitin ; metabolism

BACKGROUNDCongestive heart failure (CHF) is associated with Cheyne-Stokes respiration (CSR), which may hasten CHF. Adaptive servoventilation (ASV) is a novel method of ventilatory support designed for removal of CSF in CHF patients. This study compares the efficacy of ASV in patients with CHF and CSR with the efficacy of oxygen therapy.

METHODSFourteen patients with CHF and CSR were recruited. During sleep, nasal oxygen therapy and ASV treatment were each performed for two weeks. Comparison before and after each treatment was made for the following items: a) parameters of sleep respiration, sleep structure and quality; b) left ventricle ejection fraction (LVEF) and 6-minute walk distance.

RESULTSCompared with the baseline levels of apnoea hypopnoea index of 34.5 +/- 6.1 before treatment, the apnoea hypopnoea index significantly decreased following oxygen therapy to 27.8 +/- 8.2, P < 0.05 and further reduced following ASV treatment to 6.5 +/- 0.8, P < 0.01. The minimal pulse oxygen saturation markedly increased following oxygen therapy from a baseline of (84.3 +/- 2.6)% to (88.6 +/- 3.7)%, P < 0.05 and further increased following ASV treatment (92.1 +/- 4.9)%, P < 0.01. Stages I + II sleep as percentage of total sleep time decreased from (81.9 +/- 7.1)% to (78.4 +/- 6.7)% following oxygen therapy and further to (72.4 +/- 5.0)% following ASV treatment. Stages III + IV sleep as percentage of total sleep time decreased from (8.4 +/- 5.5)% to (6.0 +/- 3.0)% following oxygen therapy and but increased to (11.9 +/- 5.4)% following ASV treatment. The arousal index of 30.4 +/- 8.1 before treatment significantly decreased following oxygen therapy to 25.6 +/- 5.7, P < 0.05 and further declined following ASV treatment to 18.2 +/- 6.1, P < 0.01. No significant difference was shown in above percentages between day 14 of oxygen therapy and before treatment (P > 0.05). LVEF was significantly higher on day 14 of ASV treatment (37.2 +/- 4.1)% than on day 14 of oxygen therapy (33.2 +/- 5.1)% and before treatment (30.2 +/- 4.6)% (all P < 0.05). Six-minute walk distance was the shortest before treatment (226 +/- 28) m, longer on day 14 of oxygen therapy (289 +/- 26) m, and the longest on day 14 of ASV treatment (341 +/- 27) m (all P < 0.01).

CONCLUSIONASV treatment is of better efficacy and greater clinical significance in improvement of CHF by eliminating CSR than oxygen therapy.

Adult ; Cheyne-Stokes Respiration ; physiopathology ; therapy ; Female ; Heart Failure ; complications ; physiopathology ; Humans ; Male ; Middle Aged ; Oxygen Inhalation Therapy ; Positive-Pressure Respiration ; methods ; Sleep ; physiology ; Stroke Volume ; Ventricular Function, Left

AIMTo develop a HPLC-ESI-MS assay for determination of eperisone hydrochloride in human plasma and investigate the pharmacokinetics and bioequivalence of two eperisone hydrochloride tablets in human.

METHODSBuflomedil hydrochloride was used as the internal standard. After alkalized with saturated sodium bicarbonate solution, plasma was extracted with diethylether-cyclohexane (1:1) and separated using HPLC on a reversed-phase C18 column with a mobile phase of 10 mmol x L(-1) ammonium acetate buffer solution (adjusted to pH 3.88 with acetic acid)-methanol (20:80). HPLC-ESI-MS was performed in the selected ion monitoring (SIM) mode using target ions at m/z 260 for eperisone and m/z 308 for the internal standard. A randomized crossover design was performed in 20 healthy volunteers. In the two study periods, a single 100 mg dose of each tablet was administered to each volunteer.

RESULTSCalibration curve was linear over the range of 0.02-20 microg x L(-1). The limit of quantification for eperisone hydrochloride in plasma was 0.02 microg x L(-1). The main pharmacokinetics parameters T1/2, Tmax and Cmax were (2.7 +/- 0.4) h, (1.1 +/- 0.5) h and (2.8 +/- 2.8) microg x L(-1) for the reference tablet; (2.8 +/- 0.5) h, (1.1 +/- 0.4) h and (3 +/- 4) microg x L(-1) for the test tablet, respectively. The relative bioavalability of the test tablet was (101 +/- 13)%.

CONCLUSIONThe assay was proved to be sensitive, accurate and convenient. The two formulations were bioequivalent.

Adult ; Chromatography, High Pressure Liquid ; Humans ; Male ; Propiophenones ; administration & dosage ; pharmacokinetics ; Spectrometry, Mass, Electrospray Ionization ; Tablets ; Therapeutic Equivalency

OBJECTIVE: To explore the feasibility of Diminished Criminal Responsibility Rating Scale(DCRRS) to schizophrenia offenders. METHODS: The DCRRS were used respectively to 325 cases of schizophrenia offender which were divided into three groups according to the degree of criminal responsibility. RESULTS: There were significant differences in rating score among three groups (mild group 21.16 +/- 4.17, moderate group 25.87 +/- 5.43, major group 29.35 +/- 4.60), and all items have good correlation with the total score of the scale. 6 factors were extracted by the factor analysis, and their cumulative squared loadings is 68.485%. CONCLUSION The diminished criminal responsibility in schizophrenia offenders could be divided into three grades.
Adolescent ; Adult ; Analysis of Variance ; Crime/psychology* ; Discriminant Analysis ; Female ; Forensic Psychiatry/methods* ; Humans ; Liability, Legal ; Male ; Mental Competency/psychology* ; Mentally Ill Persons/psychology* ; Middle Aged ; Psychiatric Status Rating Scales ; Schizophrenia ; Young Adult

BACKGROUND: Eccentric exercise displays many advantages over concentric and isometric contractions, and it has been applied in exercise training and rehabilitation. The existing researches focus on the underlying mechanisms at molecular and neural levels, and the specific adaptation after eccentric exercise may be related to the adaptive signaling pathway. OBJECTIVE: To review the unique physiological characteristics and mechanisms of eccentric exercise, thereby providing reference for in-depth understanding of eccentric exercise. METHODS: The relevant articles were searched in PubMed (1990-2017) and CNKI (2010-2017) with the keywords of "eccentric exercise, negative muscle work, eccentric exercise training, downhill run, concentric exercise, positive muscle work, concentric exercise training, and uphill running" in English and Chinese, respectively. Ultimately, the articles eligible for physiological characteristics, acute response and adaptive mechanism were enrolled. RESULTS AND CONCLUSION: Totally 98 articles were retrieved, and 54 pertinent papers were enrolled for analysis based on the inclusion and exclusion criteria. The mechanical, molecular and neural mechanisms of eccentric contractions differ from those of concentric and isometric contractions. Special metabolic and cardiorespiratory responses after eccentric exercise reflect the advantages in making programs of exercise training and rehabilitation. Particularly, compared with concentric exercise, fewer motor units are recruited during eccentric exercise and exert muscle a greater stimulation, which involves the process of exercise-induced muscle damage and the activation of satellite cells. The content of satellite cells after eccentric exercise is higher than that of concentric exercise, suggesting that satellite cells may play an important role in the muscle damage reconstruction caused by eccentric exercise. In conclusion, eccentric exercise is of great significance for exercise training and rehabilitation, while further study on the adaptive mechanism of eccentric exercise is necessary.