Absorption and excretion of CT-707 in healthy male subjects studied by radioisotope tracer method / 中国临床药理学与治疗学

AIM: To study the absorption and excretion of CT-707 in healthy male subjects. METHODS: Six healthy male subjects received a single 300 mg (120 μCi) oral dose of radio-labeled CT-707 as a suspension in a fasted state. Blood, urine and feces were collected. Radioactivity concentrations were measured by liquid scintillation counting (LSC). The pharmacokinetic parameters of total radioactivity in plasma were calculated by WinNonlin (Pharsight version 8.1) software according to the non-compartment model. The recovery rate of total radioactivity in urine and feces was calculated according to the weight and radioactivity concentration of urine and feces collected at each time interval. RESULTS: After a single 300 mg oral of radio-labeled CT-707 552 h (23 d) as a suspension in a fasted state, the mean AUC

The prediction of disease progression by 18Fluorodeoxyglucose-positron emission computed tomography/CT in patients with dermatomyositis and interstitial lung disease / 中华内科杂志

To investigate the predictive value of [ 18F]fluorodeoxyglucose-positron emission computed tomography(PET)/CT for disease progression in patients with dermatomyositis (DM) and interstitial lung diseases (ILD). Sixty-seven DM patients who underwent [ 18F] FDG-PET/CT imaging were retrospectively analyzed from January 2012 to September 2017 at PLA General Hospital. Their clinical manifestations and imaging characteristics were recorded. Compared with those chronically progressed (C-ILD), patients with rapid progression (RP-ILD) had significantly higher erythrocyte sedimentation rate (ESR) and standardized uptake value (SUV) in lungs ( P<0.05). In patients with RP-ILD, SUV in lungs was positively correlated with age, disease course, and ESR. Receiver operating characteristic curve analysis suggested that when lung SUV cut off value was 2.25, the sensitivity and specificity to predict disease progression was 77.8% and 72.8%, respectively. Old age, longer disease course, low creatine kinase level, higher ESR, and high SUV are prognostic factors for DM-associated ILD.

Advances in molecular chaperones regulating yeast prion [ PSI+] propagation / 军事医学

The finding and research on yeast prion are of great values for biology and medical sciences.Research advances in molecular chaperones, especially in Hsp104p, Hsp70p and Hsp40p, regulating yeast prion [PSI+] propaga-tion,are reviewed.

Influences of sulfated polysaccharide from pine (Pinus massoniana) pollen on the regulation of [ Ca2+] i in T lymphocytes / 中国药理学通报

Aim Tostudytheinfluencesofsulfated polysaccharides ( SPPM60-D) on the regulation of free calcium concentration ( [ Ca2+] i ) of T lymphocytes of mice in vitro and explore the mechanisms involved. Methods Polysaccharides(PPM60)wereextracted from masson pine pollen with hot water and 60% etha-nol. PPM60-D was separated and purified from PPM60 with Sephacryl S-400HR. Sulfated polysaccharides ( SPPM60-D ) were derivated by chlorosulfonic acid-pyridine method and the [ Ca2+] i of T lymphocytes were measured by fluorescence spectrophotometer. IL-2 and IL-4 were measured by ELISA kits. Results ConAandSPPM60-Dcouldincrease[Ca2+]iinT lymphocytes by 211. 5% and 201. 8% respectively ( P<0. 01). 2-APB, LY294002, U73122 and verapamil rather than TAK-242 could significantly inhibit the in-crease of [ Ca2+] i induced by SPPM60-D. SPPM60-D could significantly increase the level of IL-2 and IL-4 in supernatant ( P <0. 01 ) . 2-APB rather than TAK-242 could significantly inhibit the increase of cyto-kines.Conclusion ItisspeculatedthatSPPM60-D could increase [ Ca2+ ] i via TCR/CD3-PI3K-PLC-IP3 R-Ca2+ signal pathway through TCD/CD3 receptor in T lymphocytes so that it could improve the level of IL-2 and IL-4 in supernatant in T lymphocytes.

A preliminary study of serum-deprivation-induced release of S100A13 and flbroblast growth factor 1 from thyroid cancer TT cell / 中华内分泌代谢杂志

Objective To investigate the effect of serum-deprivation on the changes of [ Ca2+ ] i and the protein release of S100A13 and fibroblast growth factor 1 ( FGF-1 ) in thyroid cancer TT cell,and to reveal the role of Ca2+in the protein release of S100Al3 and FGF-1.Methods The protein expressions of FGF-1 and S100A13 in TT cells under serum-deprivation were detected by Western blot.The released FGF-1 protein from TT cells in the supernatant fluid was detected by ELISA.Realtime dynamic examinations on the change of 1 h [ Ca2+ ] i in TT cells under serum-deprivation were detected by confocal laser scanning microscopy.Then,the effect of EGTA( 2.5 mmol/ L),BAPTA-AM (2.5 μmol/L)on distributions of the fluorescence of S100AI 3 and FGF-1 in TT cells under serumdeprivation for6 h were detected by indirect immunofluorescence.Results The expressions of FGF-1 and S100A13 in TT cells after serum-deprivation for4 h and 6 h were reduced( P＜0.05 or P＜0.01 ),but the released FGF-1 protein from TT cells in the supernatant fluid was elevated ( P＜0.05 or P＜0.01).Confocal laser scanning of Ca2+ imaging indicated that [ Ca2+ ] i of serum-deprivation TT cells maintained the relative stabilization within 23 win,but the rapid rise of [ Ca2+ ] i achieved peak value 1.6 μmol/L after 30 min,and remained stable for about 17 win,and thereafter 40 win slowly dropped to a low level From 40 win to 60 win the [ Ca2+ ] i was about 0.3-0.6 μ mol/L.The average [ Ca2+ ] i was higher than that in normal group,EGTA group,and BAPTA-AM group within 1 h.The protein expressions of S100A13 and FGF-1 did not drop obviously in EGTA group and BAPTA-AM group.Conlusion The release of S100A13 and FGF-1 from TT cell under serum-deprivation is possibly related with the change of [ Ca2+ ]i.Both Ca2+-chelating agents EGTA and BA PTA-AM are able to inhibit the rise of [ Ca2+ ] i and release of S100A 13 and FGF-1 from TT cells under serum-deprivation.

Oxcarbazepine for refractory epilepsy: systematic review of the literature / Oxcarbazepina para epilepsia refratária: revisão sistemática da literatura

CONTEXT AND OBJECTIVE: It has been estimated that 50 million people worldwide suffer from epilepsy and around 30 percent will not achieve adequate control over the disease. The aim was to evaluate the effectiveness of oxcarbazepine for refractory partial or generalized epilepsy. METHODS: Systematic review. A search was conducted in the PubMed, Lilacs, EMBASE and CENTRAL databases. Studies were analyzed using the Cochrane Collaboration methodology. RESULTS: Four randomized clinical trials of medium to poor methodological quality were included. Among the adult patients, the chances that they would obtain a 50 percent reduction in seizure frequency were greater after using oxcarbazepine at doses of 600 mg (relative risk, RR 2.11; 95 percent confidence interval, CI 1.32 to 3.35), 1,200 mg (RR 3.24; 95 percent CI 2.11 to 4.98) and 2,400 mg (RR 3.83; 95 percent CI 2.59 to 5.97). Among the children, the response in the group using oxcarbazepine was also greater (RR 2.11; 95 percent CI 1.32 to 3.35). The oxcarbazepine doses of 1,200 mg (RR 17.59; 95 percent CI 2.37 to 130.35) and 2,400 mg (RR 25.41; 95 percent CI 6.26 to 103.10) were effective for keeping patients probably free from seizures, but the dose of 600 mg was not. There was no significant difference between oxcarbazepine and carbamazepine for controlling the crises. CONCLUSIONS: There is moderate evidence indicating that oxcarbazepine is effective as an alternative treatment for partial or generalized epilepsy in children and adults who were refractory to previous treatment

CONTEXTO E OBJETIVO: Estima-se que 50 milhões de pessoas no mundo sofrem de epilepsia e cerca de 30 por cento não obterão controle adequado da doença. O objetivo foi de avaliar a efetividade de oxcarbazepina na epilepsia parcial ou generalizada refratária. MÉTODOS: Revisão sistemática. A busca foi nas bases de dados PubMed, Lilacs, EMBASE e CENTRAL. Os estudos foram analisados segundo a metodologia da Cochrane Colaboration. RESULTADOS: Foram incluídos quatro ensaios clínicos aleatórios de média a má qualidade. Entre os pacientes adultos as chances de obterem redução de 50 por cento na frequência de convulsões foram maiores após uso de oxcarbazepina na dose de 600 mg (risco relativo, RR 2.11; intervalo de confiança, IC 95 por cento 1,32 a 3,35; na dose de 1.200 mg (RR 3,24; IC 95 por cento 2,11 a 4,98) e na dose de 2.400 mg (RR 3,83; IC 95 por cento 2,59 a 5,97). Entre as crianças a resposta no grupo usando oxcarbazepina também foi significativamente maior (RR 2,11; IC 95 por cento 1,32 a 3,35). Oxcarbazepina mostrou probabilidade dos pacientes ficarem livre de convulsões, ser eficaz nas doses de 1.200 mg (RR 17,59; IC 95 por cento 2.37 a 130,35) e 2.400 mg (RR 25,41; IC 95 por cento 6,26 a 103,10) não foi eficaz na dose de 600 mg. Não houve diferença estatística significante entre oxcarbazepina e carbamazepina no controle das crises. CONCLUSÕES: Há evidências moderada de que a oxcarbazepina é um tratamento eficaz como alternativa para os casos de epilepsia parcial ou generalizada em crianças e adultos que tenham sido refratários a tratamento prévio.

Effects of Gingko biloba extract on glutamate-induced [ Ca2+ ]i changes in cultured cortical astrocytes after hypoxia/reoxygenation, H2O2 or L-glutamate injury / 药学学报

Aim To investigate glutamate-induced [ Ca2 + ] i changes in cultured rat neonatal cortical astrocytes after hypoxia/reoxygenation, H2O2 or high concentration of L-glutamate injury. In the meantime, the effects of Gingko biloba extract (GbE) were examined. Methods [ Ca2+ ]i changes in astrocytes were monitored by laser scanning confocal microscopy with the Ca2+ sensitive fluorescent probe [ Ca2 + ] i, but decrease by ( 3.3 ± 1.6) %, (81 ± 11 ) % and ( 81 ± 7 ) %, respectively. Pretreatment with H2O2 or high concentration of L-glutamate injury were ( 135 ± 98 ) %, ( 117 ± 93 ) % and ( 89 ± 36) %,different injury. Conclusion Hypoxia/reoxygenation, H2O2 and high concentration of L-glutamate impaired astrocytes' response to exogenous L-glutamate, and then bidirectional communication between astrocytes and neurons could not take place. GbE could improve the abnormal responses and maintain the normal function of astroglical network. These effects support that GbE has potential beneficial actions against brain injury.

Effects of iptakalim hydrochloride on the association and dissociation kinetic processes of [~3H] glibenclamide binding with ATP-sensitive potassium channels in artery smooth muscles and its crosstalk with nucleotides / 中国药理学通报

AIM To investigate the effects of iptakalim hydrochloride(Ipt) on the association and dissociation kinetic processes of [ 3H]glibenclamide(Gli) binding with sulfonylurea receptor(SUR 2B ) of ATP sensitive potassium channel (K ATP ) in vascular smooth muscles derived from Wistar rats,and to compare the properties of Ipt with those of nucleotides. The interactions between Ipt and nucleotides were also determined. METHODS The experiments of the association and dissociation kinetic processes of K ATP blocker[ 3H]Gli binding with endothelium denuded aorta smooth muscles were used. RESRLTS (1)The specific bindings of[ 3H]Gli with SUR 2B were not displaced by Ipt at the concentrations of 10 pmol?L -1 ～ 0 5 mmol?L 1 . Ipt 100 ?mol?L -1 retarded the association kinetic process and accelerated the dissociation kinetic process of [ 3H]Gli binding with SUR 2B . (2)Opposite to Ipt, ATP 1 mmol?L -1 accelerated the association kinetic process and retarded the dissociation kinetic process of [ 3H]Gli binding with SUR 2B There was an interaction between ATP and Ipt in the modulation of [ 3H]Gli binding with SUR 2B . (3) Similar with Ipt, ADP 1 mmol?L -1 retarded the association kinetic process and accelerated the dissociation kinetic process of [ 3H]Gli binding with SUR 2B , there was an interaction between ADP and Ipt in the modulation of [ 3H]Gli binding with SUR 2B . (4)Different from ATP and ADP, UDP had no effect on the association and dissociation kinetic process of [ 3H]Gli binding with SUR 2B . And there was not interaction between UDP and Ipt. CONCLUSION Ipt had no affinity with the binding sites of K ATP blocker in SUR 2B , but had negative allosterical modulation on it. The modulatory properties of Ipt were opposite to those of ATP, similar with those of ADP and different from those of UDP. There were interactions between ATP, ADP and Ipt in the modulation of [ 3H]Gli binding with SUR 2B , but there was not interaction between UDP and Ipt.