Physiologically based pharmacokinetic model (PBPK), a mechanistic mathematic model, which can simulate the absorption, distribution, metabolism and excretion of drugs, is being more widely used in pharmaceutical research and development areas. This article reviews primarily the recent advances in the procedure of establishing a PBPK model, including specifying of the PBPK model structure, specification of the tissue model, writing of equations, set of model parameters, simulation and evaluation. Application significance, major challenges and future developments of PBPK model in pharmaceutical areas are also discussed.
Animals ; Biological Transport ; Computer Simulation ; Humans ; Models, Biological ; Pharmaceutical Preparations ; chemistry ; metabolism ; Pharmacokinetics ; Software ; Tissue Distribution

Objective To explore changes of local renin-angiotensin system(RAS)in renal tissue of rat during short-and mid-term tail suspension,as well as their relations with humoral regulation and renal function induced by real or simulated weightlessness.Methods 1-and 4-week(wk)tail-suspended rat model were used to simulate short-and mid-term weightlessness,respectively.Reverse transcriptase polymerase chain reaction(RT-PCR)was carried out to examine the mRNA expression of components of local RAS in renal tissue.Results Except for angiotensin Ⅱ receptor type 2(AT2),all of the other components of local RAS,including angiotensinogen(AGT),renin,angiotensin converting enzyme(ACE),angiotensin Ⅱ receptor type 1a(AT1a)and angiotensin Ⅱ receptor type 1b(AT1b),were found their expression in renal tissue of Sprague-Dawley rats.After 1 wk of tail suspension,mRNA expression of renin in renal tissue increased significantly(P

Objective To evaluate the effect of transnasal optic nerve decompression for traumatic optic neuropathy in different surgery time. Methods The databases of the Cochrane library, Embase, PubMed, Wanfang Database, China Journal Full-text Database (CNKI), Weipu Database(VIP) were searched for retrospective studies and clinical controlled trials. The search words included traumatic optic neuropathy, TON, eye traumas, transnasal endoscopicoptic decompression, TEOND, decompression of optic canal and endoscopy. According to the inclusion and exclusion criteria, the data were extracted. The RevMan 5.3 was used to analyze the data. Results All of 1 087 studies were detected. Sixteen eligible studies were enrolled, including 803 eyes. Meta analysis showed that the recovery degree of visual acuity, curative effect in operation group within 7 d of trauma was obviously superior to the operation group 7 d after trauma (OR=2.78;95%CI:2.02-3.82;P<0.01). Conclusions Transnasal endoscopic optic nerve decompression in treatment of traumatic optic neuropathy should be operated as soon as possible, and it is better to operate within 7 d.

To state the importance of scientific research capability and general practitioners training for the poor scientific innovation conditions of general practitioner standardization training by the analysis of several ways to improve the scientific research capacity and the probe of the impact on strengthening the consciousness of scientific research to help general practitioner to better work in the areas of primary care and public health.

Objective To understand the current situation and the main influencing factors of hospital staffs' scientific research work in a affiliated hospital of Xinjiang,so as to provide the basis for improving awareness and level of scientific research of hospital staffs.Methods Survey using stratified random sampling method,using self-questionnaire research capacity factors questionnaire, to investigate the status of project leaders' research capacity in a affiliated hospital of Xinjiang.Using frequencies and relative number described ability to research,using x2 to compare research level among the various metrics.Scientific research levels' multivariate analysis using Ordinal Logistic Regression Analysis.Results regarding of scientific research,low level of 14 people,accounting for 4.9％,the middle level of 158 people,accounting for 55％,a high level of 115 people,accounting for 40.1％.Univariate analysis showed that age,length of service,education level,job title,whether master instructor it is,the research team,the situation of foreign training and learning opportunities,foreign academic session (times),support from leadership and family,non-working time for research,the total research funding (ten thousands yuan),discipline level have impact on the level of scientific research work.Ordinal Logistic regression analysis showed that age,length of service,educational level,whether master instructor it is,the total research funding (ten thousands yuan),discipline level are the main factors on level of scientific research work.Conclusions The scientific research level needs to be further improved,the level of scientific research is affected by many factors.

OBJECTIVE:To investigate the permeability of lomefloxacin through blood-pancreatic barrier in rats.METHO-DS:Lomefloxacin(20mg/kg body weight) was injected through caudal vein.At the given time points,the samples were collected.The concentrations of lomefloxacin in the serum,pancreatic tissue and liver tissue were measured by HPLC.RESULTS:The concentration-time profiles of lomefloxacin could be described as two-compartment model in rats.The peak concentrations in serum,pancreatic tissue and liver tissue were 65.550?g/ml,48.801?g/g and 84.121?g/g at 5 min post-injection respectively.Then the concentrations decreased quickly in all of them.Concentrations in pancreatic tissue were higher than those in serum at 10 min and even at 480 min post-injection.The permeation ratio (PR) through blood-pancreatic barrier was 0.744 at 5 min and rose to 3.817 at 480min.CONCLUSION:After intravenous injection,lomefloxacin can permeate blood-pancreatic barrier satisfactory,therefore it is worthy of being recommended for prevention and treatment of pancreatic infections.

OBJECTIVETo analyze the clinical characteristics of elderly patients with spinal tuberculosis and explore its clinical effects with anti-TB drugs alone.

METHODSFrom January 2008 to July 2010, the data of 36 patients with spinal tuberculosis underwent conservative treatment of anti-TB drugs alone were analyzed. There were 19 males and 17 females with an average age of 73.5 years (ranged, 60 to 85). All patients were in the active phase with high ESR and CRP levels and were treated with 3HRZE/6-9HRE (course from 9 to 12 months). According to clinical symptoms, chemical examination, radiological image to adjust drug and depending on VAS score to evaluate pain.

RESULTSAll the patients were followed up from 8 to 24 months with an average of 15 months. Tuberculose of 31 patients healed after chemotherapy from 9 to 12 months and ESR and CRP recovered normally. Levofloxacin and para-amino salicylic acid were used in 4 cases because of 4 cases occurred drug fast for RFP or INH, after 15 months, their obtained healing. Symptom of 1 case got worse during chemotherapy, and surgical treatment were performed, after 3 months, ESR and CRP recovered normally, X-ray and CT showed spinal osteosclerosis and fusion without significant kyphosis and internal fixation loosening. Cobb angle was respectively(17.6+/-2.3) degrees, (18.1+/-2.7) degrees before treatment and last follow-up (P>0.05). MRI showed abscess was absorbed and spinal inflammation subsidised. VAS score was respectively 6.5+/-1.7, 1.4+/-0.5 before treatment and last follow-up (P<0.05). Seven patients had complications relating with drug adverse reaction,after discontinuation and treated with clinical symptom,the patients recovered normally.

CONCLUSIONAnti-TB drugs alone can obtain satisfactory effects in treating early senile spinal tuberculosis, but strict supervision and individual administration should not be disregardful.

Aged ; Aged, 80 and over ; Antitubercular Agents ; therapeutic use ; Female ; Humans ; Male ; Middle Aged ; Tuberculosis, Spinal ; diagnosis ; drug therapy

Objective To evaluate the potential association of CD4+CD25+ T cells with alopecia areata.Methods Totally,this study enrolled 23 patients with progressive alopecia areata,25 patients with stable alopecia areata,and 25 healthy controls.Peripheral blood was isolated from these subjects followed by isolation of CD4+ CD25+ regulatory T cells,which were then cuhured with the presence of anti-CD3 and-CD28 monoclonal antibodies for four days.Subsequently,enzyme-linked immunosorbent assay was performed to measure the levels of interleukin (IL)-10 and transforming growth factor (TGF)-β1 in the culture supematant of these T cells.Results The levels of IL-10 and TGF-β1 were (31.68 ± 6.78) pg/ml and (32.29 ± 6.8) pg/ml respectively in the culture supernatant of CD4+CD25+ regulatory T cells from patients with progressive alopecia areata,significantly lower than those from the healthy controls ((57.34 ± 14.15) pg/ml and (57.43 ± 15.16) pg/ml,both P ＜ 0.05) and patients with stable alopecia areata ((52.56 ± 13.02) pg/ml and (61.75 ± 14.10) pg/ml,both P ＜ 0.05).However,no significant difference was observed in the supernatant levels of IL-10 or TGF-β1 between the healthy controls and patients with stable alopecia areata.Conclusions The secretion of IL-10 and TGF-β1 by CD4+CD25+ T cells is decreased in patients with progressive alopecia areata,which may contribute to the pathogenesis of alopecia areata.

Bilirubin ; Child ; Duodenogastric Reflux ; diagnosis ; Esophageal Diseases ; diagnosis ; Esophagus ; metabolism ; Gastroesophageal Reflux ; diagnosis ; Humans

Objective To determine the level of interleukin (IL)-10 in sera and culture supernatants of CD4+CD25+T cells from children with atopic dermatitis (AD),and to evaluate its relationship with clinical course and severity of AD.Methods Totally,46 children with AD and 31 healthy controls were included in the study.All the patients were divided into 3 groups,i.e.,mild (n =10),moderate (n =16) and severe (n =20) group,according to severity scoring of atopic dermatitis (SCORAD) score.Venous blood samples were obtained from the patients and healthy controls.CD4+CD25+ regulatory T cells were separated from the blood samples by magnetic cell sorting (MACS) system in two steps and cultured in vitro.Enzyme linked immunosorbent assay (ELISA) was conducted to quantify the level of IL-10 in sera and culture supernatants of CD4+CD25 + T cells from these subjects.Analysis of variance was carried out to compare the level of supematant and serum IL-10 between the patients and controls,and Pearson correlation analysis to assess the relationship between the level of IL-10 and SCORAD score.Results The patients with mild,moderate and severe AD showed a similar serum IL-10 level compared with the healthy controls ((43.10 ± 25.07) pg/ml,(68.40 ± 36.65) pg/ml and (55.55 ± 41.97) pg/ml vs.(58.27 ± 36.84) pg/ml,all P ＞ 0.05).The level of supernatant IL-10 secreted by CD4+CD25+ T cells from the controls was significantly higher than that from the patients with severe AD ((55.15 ± 11.15) pg/ml vs.(27.25 ± 7.01) pg/ml,P ＜ 0.05),but similar to that from the patients with mild and moderate AD ((52.96 ± 11.69) pg/ml and (49.86 ± 9.18) pg/ml,respectively,both P ＞ 0.05).The level of secreted IL-10 was negatively correlated with SCORAD score (r =－0.757,P ＜ 0.01),whereas the serum level of IL-10 showed no statistical correlation with SCORAD score.Conclusion CD4+CD25+ T cells and IL-10 may be implicated in the development of AD.