A physiologically-based pharmacokinetic model adequately predicted the human pharmacokinetic profiles of ZSP1601, a novel pan-phosphodiesterase inhibitor / 药学学报

ZSP1601, a novel pan-phosphodiesterase inhibitor is in development for the treatment of nonalcoholic steatohepatitis. A physiologically-based pharmacokinetic (PBPK) model was developed to predict the pharmacokinetics of ZSP1601 in human. The PBPK model following intravenous and oral dose of ZSP1601 in rats and dogs was firstly built using preclinical in vitro and in vivo data. The PBPK model in human was then built based on models in animal. The in vitro-in vivo extrapolation (IVIVE) method and some allometric scaling methods were used to predict the clearance in human, respectively. The PBPK models using IVIVE and allometry of unbound CL plus the rule of exponents methods predicted the pharmacokinetics of ZSP1601 in healthy Chinese subjects successfully. The predicted parameters Cmax and AUC following single oral dose administration were within 0.5-2 folds of the observed data. The model was optimized and the final model was used to predict the pharmacokinetics of ZSP1601 in North European Caucasian, Geriatrics, Obese and Morbidly Obese, respectively. Animal studies were approved by the Animal Management and Use Committee of Suzhou AppTec Inc., and the approved No. is SZ20140916.

Change in serum intestinal fatty acid binding protein and its significance in children with pneumonia and gastrointestinal injury / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To study the change in serum intestinal fatty acid binding protein (IFABP) in children with pneumonia and its correlation with gastrointestinal injury.</p><p><b>METHODS</b>A total of 82 children with community-acquired pneumonia who were treated from January to October, 2015 were enrolled, among whom 34 had mild pneumonia and 48 had severe pneumonia. According to pediatric critical illness score (PCIS), the children with severe pneumonia were further divided into non-critical group (25 patients) and critical group (23 patients). Thirty healthy children who underwent physical examination at outpatient service were enrolled as the control group. ELISA was used to measure serum IFABP level, and the acute gastrointestinal injury (AGI) grade was determined for children with severe pneumonia. Serum IFABP level was compared between groups, and the correlations of IFABP with AGI grade and PCIS were analyzed.</p><p><b>RESULTS</b>The severe pneumonia group showed a significantly higher serum IFABP level than the control group and the mild pneumonia group (P<0.01), and the mild pneumonia group also showed a significantly higher serum IFABP level than the control group (P<0.01). The critical group showed a significantly higher serum IFABP level than the non-critical group (P<0.01). The patients with grade I-IV AGI had significantly higher serum IFABP levels than the control group (P<0.01), and the serum IFABP level increased significantly with the increasing AGI grade (P<0.01). Serum IFABP level was positively correlated with AGI grade (P<0.01) but negatively correlated with PCIS (P<0.01).</p><p><b>CONCLUSIONS</b>Children with pneumonia experience an increased serum IFABP level which can be used as a sensitive indicator for the early diagnosis of gastrointestinal injury and the evaluation of conditions in children with pneumonia.</p>

Inhibitory effects of Zengshengping fractions on DMBA-induced buccal pouch carcinogenesis in hamsters / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Zengshengping (ZSP) tablets had inhibitory effects on oral precancerous lesions by reducing the incidence of oral cancer. However, the severe liver toxicity caused by systemic administration of ZSP limits the long-term use of this anti-cancer drug. The purpose of this study was to evaluate the tumor inhibitory effects due to the topical application of extracts from ZSP, a Chinese herbal drug, on 7, 12-dimethlbenz(a)anthracene (DMBA) induced oral tumors in hamsters. The study also investigated the anti-cancer mechanisms of the ZSP extracts on oral carcinogenesis.</p><p><b>METHODS</b>DMBA (0.5%) was applied topically to the buccal pouches of Syrian golden hamsters (6 - 8 weeks old) three times per week for six weeks in order to induce the development of oral tumors. Different fractions of ZSP were either applied topically to the oral tumor lesions or fed orally at varying dosages to animals with oral tumors for 18 weeks. Tumor volume was measured by histopathological examination. Tumor cell proliferation was evaluated by counting BrdU labeled cells and by Western blotting for mitogen-activated protein kinase (MAPK) protein levels. The protein levels of apoptosis marker Caspase-3 and regulator Bcl-2 protein were also measured by Western blotting.</p><p><b>RESULTS</b>Topical application of DMBA to the left pouch of hamsters induced oral tumor formation. Animals treated with DMBA showed a loss in body weight while animals treated with ZSP maintained normal body weights. Both the ZSP n-butanol fraction and water fraction significantly reduced tumor volume by 32.6% (P < 0.01) and 22.9% (P < 0.01) respectively. Topical application of ZSP also markedly decreased the BrdU-positive cell numbers in oral tumor lesions and reduced the expression level of MAPK. In addition, ZSP promoted tumor cell apoptosis by increasing Caspase-3 expression but decreasing Bcl-2 protein production.</p><p><b>CONCLUSION</b>The n-butanol and water fractions of ZSP are effective at inhibiting tumor cell proliferation and stimulating apoptosis in oral cancer suggesting that these fractions have chemopreventive effects on DMBA induced oral carcinogenesis.</p>

Preparation and evaluation of puerarin self-microemulsifying drug delivery system / 中草药

Objective: To study the formulation of puerarin (PUE) self-microemulsifying drug delivery system (SMEDDS). Methods: The optimum formulation of PUE SMEDDS was screened by test of solubility, compatibility of oil and surfactant, and pseudo-ternary phase diagram, and the prescription of PUE SMEDDS was optimized by particle size, self-microemulsifying time, and drug loading; The physicochemical characteristics and stability were also determined. Results: The optimum SMEDDS composed of Miglyol 812N (19.0%), oleic acid (19.0%), polysorbate 80 (19.0%), EL-35 (19.0%), 1, 2-propanediol (19.0%), and puerarin (5.0%). The particle size was (17.28 ± 0.24) nm, and self- microemulsifying time was less than 120 s; The appearance, content of PUE, particle size, and self-microemulsifying time had no obvious changes under room temperature storage for six months. Conclusion: The acquired PUE SMEDDS is stable with small particle size, which meets the needs of good SMEDDS formulation.

Analysis of 262 Cases of Seizures Detected with Video-Electroencephalogram / 实用儿科临床杂志

Objective To evaluate the clinical significance of video-electroencephalogram(VEEG) in the diagnosis of paroxysmal events in children.Methods The VEEG and routine electroencephalogram(EEG) were used to inspect 262 cases of seizures respectively collected of outpatient clinic and admission department from Apr.2006 to Dec.2007,and VEEG monitoring results were analyzed and compared with primary diagnoses retrospectively.According to the characteristics of EEG and clinical observation to decide whether it be epilepsy or not and compare the difference between the results of EEG and VEEG to evaluate the application value of the 2 examination methods in children with NES.SPSS 13.0 software was used to analyze the data.Results Of all 262 cases,113 cases of clinical outbreak were recorded,meanwhile the diagnose of 4 patients of epileptic seizures(ES) group were changed to non-epileptic seizures(NES) and 3 patients of NES were rediagnosed to ES,69 cases couldn′t be confirmed according to VEEG or EEG and there was no outbreak recorded in the other 149 cases.In the period onset,79 children′s characteristics of EEG were captured which included 76 children in ES group,and 3 children in NES group.Thirty-six children′s characteristics of EEG were not captured which included 4 children in ES group and 30 children in NES group.The differences of the ratio of total detect and abnormity between EEG and VEEG were significant,improving the diagniosis rate and the control rate of symptom.VEEG had a clinical significance in differential diagnosis of ES and NES.Conclusions Compared with EEG,VEEG will be more helpful in diagnosing and differentiating seizures diseases,improving the diagnosis rate and the control rate of symptom.VEEG has a clinical in diffe-rential diagnosis for ES and NES.