ABSTRACT
Objective To establish the population pharmacokinetics(PPK)model of Lamotrigine(LTG)in children with epilepsy in China for promoting individualized dosage regimen. Methods The sparse data of LTG serum concentrations from 60 pediatric patients with epilepsy were collected. One hundred and fourteen serum concentration points were divided into LTG+valproic acid (VPA) group(n=56),LTG+enzymatic inducer(E1)group(n=26),LTG+EI+VPA group(n=16)and single LTG group(n=16).The serum drug concentrations were the clinical routinely tested steadv state concentrations.The LTG PPK parameters were calculated using the non-parametric expectation maximization(NPEM) Program of USC*PACK software,and then a PPK model was established. Based on this model,LTG serum concentrations were predicted with Bayesian fitting program of USC*PACK software.Mean prediction error(MPE)and mean squared prediction error(MSPE) were calculated to evaluate the accuracy and precision of the concentration prediction and to valid the PPK model.Results The greatest likelihood was-192.87.Optimum PPK parameters were:Ka=(1.97 1.66)h~(-1);Vs=(1.07±0.89)L/kg;Kel=(0.05±0.05)h~(-1).The linear regression function Y_(OBS)=-0.09+1.05 Y_(PRED)(R~2=0.98,P<0.001),and determination of coefficient was 0.98.MPE was-0.16 g/mL,and MSPE was 0.28(μg/mL)~2.Conclusion A PPK model of LTG in children with epilepsy in China can be successfully established using the USC*PACK software, based on which LTG serum concentrations can be predicted accurately with a Bayesian approach.
ABSTRACT
Lyophylized antler powder was hydrolyzed by pepsin and trypsin separately and also simultaneously to give hydrolysates with special physical activities. Complete hydrolysis peptides with MW lower than 1 x 10(3) were collected for assay of angiotensin I-converting enzyme (ACE) inhibitory activity, antioxidant activity and proliferative activity toward UMR-106 osteoblast cells. The results of the experiments revealed that all hydrolysates exhibited potent hydroxyl radical scavenging activity with an IC50 value less than 1 mg/ml which was much lower than the value of 5.5 g x L(-1) for vitamin C. The peptic and peptic tryptic hydrolysates demonstrated strong angiotensin I-converting enzyme (ACE) inhibitory activity. The tryptic hydrolysate increased the proliferation of the UMR-106 cells by 73.43%. The results verified the traditional use of antler in bone-strengthening, anti-aging. The exploratory studies on the ACE inhibitory activity of antler hydrolysates indicated that the hydrolysates might be potentially useful in prevention and treatment of hypertension. Further purification of peptides contributing to the antioxidant activity, angiotensin I-converting enzyme-inhibitory activity and proliferative activity toward osteoblasts from antler hydrolysates is warranted.
Subject(s)
Animals , Angiotensin-Converting Enzyme Inhibitors , Metabolism , Antioxidants , Metabolism , Antlers , Chemistry , Metabolism , Biphenyl Compounds , Metabolism , Cell Proliferation , Deer , Endopeptidases , Metabolism , Free Radical Scavengers , Hydrolysis , Hypertension , Pepsin A , Metabolism , Peptides , Pharmacology , Peptidyl-Dipeptidase A , Metabolism , Picrates , Metabolism , Trypsin , MetabolismABSTRACT
To explore the role of β-endorphin (β-EP) in the pathogenesis of the acute encephaledema, the levels of β-EP in both of plasma and CSF were determined by radioimmunoassay in 69 children with infection of central nervous system consisting of 39 cases with encephaledema and 30 cases without encephaledema, respectively. Another 19 cases without intracranial infection were as the control group. The results showed that the levels of plasma and CSF β-EP in the encephaledema group (50.74 ng/L±26.60ng/L，62.72ng/L±39.23ng/L) were significantly higher than those in without encephaledema group (32.78 ng/L±21.2ng/L，34.13ng/L±30.26ng/L)and the normal group (14.83ng/L±6.55ng/L，9.77ng/L±6.33ng/L)，respectively (P＜0.01).It is concluded that β-EP plays an important role in the occurrence and development of encephaledema in children with the infection of central nervous system.
ABSTRACT
Objective The lyophilized pilose antler water extract(PAE) was isolated,and their cell proliferation on PC12 cells was observed.Methods S-200 Size-exclusive gel and DEAE negative ion-exchange liquid chromatograph were employed to fractionate the PAE.SDS-PAGE was employed to analyze the proteins composition of PAE.The protein concentration was determined by Folin-Phenol assay.The proliferation rates of PC12 cells were measured by MTT assay.Results The proliferation rate of PAE on PC12 cells at 13.3 mg/mL was 47%(P