Physiological pharmacokinetic model of children and its application of modeling software / 药学学报

Developmental changes in children can affect drug disposition and clinical effects. A physiologically-based pharmacokinetic (PBPK) model is a mathematical model that can be used to predict blood drug concentrations in children and gain insight into age-dependent physiological differences in drug disposition impact. Pediatric PBPK (P-PBPK) models have attracted attention over the past decade. With the concerted efforts of academia, pharmaceutical companies, and regulatory agencies, there are more and more examples of pediatric clinical studies using PBPK models. Nevertheless, the number of P-PBPK models and their predictive performance still lag behind adult models. By referring to the literature, we study the process of children adapting to adult absorption, distribution, metabolism, and excretion (ADME) parameters and analyze the general principles of P-PBPK model establishment. In addition, we summarize the functions and application examples of commonly used P-PBPK modeling software to provide a basis for the rational application of modeling software.

Genetic Polymorphisms of 30 InDel Loci in Ewenki Ethnic Group from Inner Mongolia / 法医学杂志

OBJECTIVES@#To study the genetic polymorphisms of 30 insertion/deletion （InDel） loci and evaluate their forensic application in Ewenki ethnic group from Inner Mongolia.@*METHODS@#Peripheral blood samples were collected from 87 unrelated healthy individuals in Ewenki ethnic group. Genomic DNA were extracted, and 30 InDel loci of the samples were multiplex amplified and genotyped. Hardy-Weinberg balance tests were preformed for all loci and genetic parameters were calculated by modified PowerStats v1.2 software. The linkage disequilibrium between loci were tested by SNPAnalyzer v2.0 software. Based on the allele frequencies of 30 InDel loci, the genetic relationships between Ewenki ethnic group and other populations were evaluated by analysis of molecular variance, principal component analysis and phylogenetic reconstruction.@*RESULTS@#After correction, 30 InDel loci conformed to Hardy-Weinberg equilibrium. It was found that the pairwise InDel loci were in linkage equilibrium after Bonferroni correction. The results of population genetics indicated that Ewenki ethnic group had close genetic relationships with Henan Han and Beijing Han populations; whereas it was significantly different from several populations in Europe and Mexico.@*CONCLUSIONS@#There are relatively high genetic polymorphisms on 30 InDel loci of Ewenki ethnic group from Inner Mongolia, which can be used as a helpful supplement application for STR detection system.

Effects of pomegranate flowers polyphenols on liver PON expression of diabetes combining non-alcoholic fat liver diseases rats / 药学学报

To investigate the protective effects and possible mechanism of pomegranate flowers polyphenols (PFP) on liver function of rats with diabetes combining non-alcoholic fat liver diseases, diabetes combining nonalcoholic fat liver disease model rats were established with high calorie feeding and small dose intraperitoneal injection of streptozotocin (STZ). Model rats were randomly divided into: model group, metformin group, pomegranate flowers polyphenols low, medium and high dose group (75, 150 and 300 mg x kg(-1)). After four weeks treatment, the levels of FPG, blood fat profiles and serum insulin, ALT, AST levels, SOD and MDA in the liver and serum separately were analyzed with biochemical methods. Paraoxonase (PON1 and PON3) mRNA and protein expression in liver were checked by RT-PCR and immunohistochemical method. Pathological changes of the liver were observed. FPG, IRI, non-HDL-C and transaminase significantly reduced and HDL-C raised in the each PFP dose group; Furthermore, compared with model group, fat drops in liver cells significantly reduced, antioxidant ability enhanced, PON1 mRNA and protein expression level in liver increased significantly. The protective effects of PFP against diabetes combining non-alcoholic fat liver diseases rats might through the increase liver PON1 mRNA and protein expression further enhanced the body antioxidant capacity and reduced IRI so as to ameliorate the rat hepatic steatosis.

Effects of two different extracts of total saponins from Cicer arietinum on kidney of T2DM rats / 药学学报

Protective effects of two different extracts of TSCA (total saponins from Cicer arietinum) were studied on kidney of T2DM rats. The diabetic model group was established with high calorie feeding and small dose injection of streptozotocin (STZ, 45 mg x kg(-1)). DM rats were randomly assigned to model group (feed with propylene glycol 1 mL/100 g), TSCA high dose group (300 mg x kg(-1)), TSCA low dose group (100 mg x kg(-1)) and normal control group (feed with propylene glycol 1 mL/100 g). After four weeks treatment with TSCA I and II, the levels of FPG FIns, BUN, Scr, ATII, ET-1, TXB2 and 6-keto-PGF1alpha in blood and the activities of SOD, GSH-PX and MDA in kidney were analyzed by biochemical methods. After four weeks treatment with TSCA II, the levels of FPG FIns, BUN, Scr, ATII and ET-1 were reduced significantly; and the ratios of TXB2 to 6-keto-PGF1alpha and SOD were effectively alleviated in TSCA II group. While there is no significant change on FPG and BUN in comparison to the rats treated with TSCA I, Scr, ATII, ET-I, GSH-PX and SOD were alleviated. The results suggest that TSCA II could be used to reduce FPG and FIns. According to the result of vasoactive substances index, TSCA II is more effective than TSCA I on renal protection of DM rats.

Specificity effect of acupuncture at "Shuigou" (GV 26) on brain infarction area in MCAO rats and the influence of acupuncture parameter / 中国针灸

<p><b>OBJECTIVE</b>To investigate the specificity of the acupoints and related factors on acupuncture effects.</p><p><b>METHODS</b>The rat model of cerebral median artery occlusion (MCAO) was established with thread ligation according to Zea-Longa method. The acupoint group and the non-acupoint group were stimulated by acupuncture with 9 different parameters (marked group No. I - VI) combined by frequency (60 Hz, 120 Hz, 180 Hz) and time (5 s, 60 s, 180 s). The acupoint of "shuigou" (GV 26) was selected for the acupoint group, the fixed point which was at a distance of 10 mm from the iliac crest below the ribs in the affected side. The acupuncture effect was evaluated with the percentage of brain infarct area after TTC dyeing.</p><p><b>RESULTS</b>(1) Acupoint groups could obviously reduce the brain infarction area in MCAO rats. Under 9 intervention parameters, acupoint groups had much more effectiveness tendency than that of the non-acupoint groups. (2) Acupoint group VI was the most effective in reducing the brain infarction area among 9 acupuncture parameter groups.</p><p><b>CONCLUSION</b>(1) Acupoint has specificity effect on reduction of brain infarct area in MCAO rats. (2) Acupoint group VI (180 Hz; 5 s) could significantly reduce the percentage of cerebral infarction area by TTC dyeing.</p>

Experimental study on Shuigou (GV 26) of inhibiting effect for neuronal necrosis in rats: morphological evidence of the specificity of acupoint / 中国针灸

<p><b>OBJECTIVE</b>To investigate the effect of acupoint Shuigou (GV 26) and non-acupoint on inhibiting the neuronal necrosis induced by the middle cerebral artery obstruction (MCAO) in rats through the morphological observation.</p><p><b>METHODS</b>Forty two healthy adult male Wistar rats were randomly divided into a normal group, false-ope ration group, model control group, non-acupuncture group, Shuigou-acupuncture group and non-acupoint acupuncture group, 7 rats in each group. Besides the normal and false-operation groups, the experimental modal of MCAO was established in the other groups by using the Zea-Longa thread method. Acupoint Shuigou (GV 26) and non-acupoint (below the costal region) were selected respectively in the Shuigou-acupuncture group and non-acupoint acupuncture group for puncturing at 180 times/min for 5 seconds. Its effect was estimated by measuring the rate of the neuronal necrosis at the level of the light microscope and the degree of the neuronal necrosis at the level of the electron microscope.</p><p><b>RESULTS</b>(1) At the level of the light microscope, comparing with the model control group (0.66 +/- 0.18), of the neuronal necrosis there were no significant differences in the rate of neuronal necrosis in the non-acupuncture group (0.67 +/- 0.34) and non-acupoint acupuncture group (0.59 +/- 0.11) (both P > 0.05), while it was significantly decreased in the Shuigou-acupuncture group (0.200 +/- 12) (P < 0.05). It indicates that no intervention and wrong (non-acupoint) intervention could light the damage of the neurons, however, only right intervention (Shuigou, GV 26) can obviously decrease the rate of the neuronal necrosis, showing with the specificity of acupoint. (2) At the level of the electron microscope, the ultrastructure of the involved neurons in the non-acupuncture group and non-acupoint acupuncture group is similar to that of the model control group, showing with the serious edema and structure damage. In contrast, the ultrastructure of the involved neurons in the Shuigou-acupuncture group is similar to that of the normal group and false-operation group, showing with light neuronal damage.</p><p><b>CONCLUSION</b>Acupuncturing Shuigou (GV 26) could protect the involved neurons and inhibit the neuronal necrosis induced by the MCAO in rats, but acupuncturing the non-acupoint couldn't, which imply that there is the specificity of acupoint in the acupuncture.</p>

Effects of acupuncture at different acupoints on cerebral blood flow in cerebral ischemia model rats / 中国针灸

<p><b>OBJECTIVE</b>To probe into effective methods for treatment of ischemic cerebral infarction and specificity of acupoints in the acupuncture treatment.</p><p><b>METHODS</b>The rat model of middle cerebral artery occlusion (MCAO) was established with thread ligation according to Zea-Longa's method. They were divided into normal group, non-operation group, model control group, non-acupuncture group and acupuncture group, and the acupuncture group was divided into sham-acupuncture group and four Xingnao Kaiqiao groups (contain Shuigou group, Neiguan group, Chize group, Sanyinjiao group and Weizhong group). Then they were treated by acupuncture at "Shuigou" (GV 26), "Neiguan" (PC 6), "Chize" (LU 5), "Sanyinjiao" (SP 6), "Weizhong" (BL 40) and non-acupoints, 3 times/second, for 5 seconds. Cerebral blood blow (CBF) was used for assessment of the effect.</p><p><b>RESULTS</b>As compared with the model control group, in the non-acupuncture group CBF did not significantly change (P>0.05); compared with the non-acupuncture group, after acupuncture CBF was significantly increased in the Shuigou group and the Neiguan groups (all P<0.05), but did not significantly increased in the Chize group, Sanyinjiao group and Weizhong group (all P>0.05).</p><p><b>CONCLUSION</b>CBF has a tendency of spontaneous cure within 72 h after cerebral infarction in the MCAO rat; acupuncture can significantly improve CBF in the MCAO rat, so it is an effective method for treatment of ischemic stroke; among the acupoints in the "Xingnao Kaiqiao" needling method, "Shuigou" (GV 26) and "Neiguan" (PC 6) have obvious effect in improvement of CBF, indicating acupoint specificity of "Shuigou" (GV 26) and "Neiguan" (PC 6) in treatment of ischemic stroke.</p>

Study on optimum stimulation parameter for Shuigou (GV 26) in Xingnao Kaiqiao needling method / 中国针灸

<p><b>OBJECTIVE</b>to investigate the influence of acupuncture parameter on acupuncture effect and to probe the optimum stimulation parameter for Shuigou (GV 26) in Xingnao Kaiqiao needling method.</p><p><b>METHODS</b>The rat model of middle cerebral artery obstruction (MCAO) was replicated and "Shuigou" (GV 26) was stimulated by 9 acupuncture parameters combined by two factors at 3 levels, i. e. frequency 1, 2, 3 times/second, and needling duration 5 s, 60 s, 180 s. The effects of acupuncture at "Shuigou" (GV 26) with the 9 different acupuncture parameters on cerebral blood flow (CBF) in the MCAO rat were investigated by orthogonal test, factor analysis and one-way ANOVA.</p><p><b>RESULTS</b>Acupuncture effect was influenced by acupuncture frequency, acupuncture duration and their combination. Among them, the acupuncture duration was the most important factor. The best acupuncture effect could be attained by using as long acupuncture duration as possibly with the fastest acupuncture frequency.</p><p><b>CONCLUSION</b>In the Xingnao Kaiqiao needling method, acupuncture at "Shuigou" (GV 26) with fastest frequency and enough long duration can get the best acupuncture effect, which are the optimum stimulation parameters for "Shuigou" (GV 26).</p>