Permeability is a key factor in the bioavailability of oral drugs. Therefore, in the early stage of drug discovery, accurate and efficient evaluation of drug permeability is essential. The parallel artificial membrane permeability assay (PAMPA) with Caco-2 cells model was used by the industry as early evaluation methods. At present, the Ussing chamber rat model is also widely used. This review summarizes the human data for the in vivo single-pass perfusion technique (Loc-I-Gut) – the gold standard, and then focuses on the basic principles, experimental operation, and efficiency of the three in vitro methods, with correlation to the effective permeability coefficient (P_eff) and fractional absorbed (Fa) in man. We provide recommendations for the use of proper permeability methods at different stages in drug discovery and development.

OBJECTIVETo establish an experimental animal model of Alzheimer's disease (AD) with clinical and pathological specificity conformed to AD in human, and to observe the effect of Zhinao Capsule (ZNC) on learning, memory and patho-morphological parameters in the model.

METHODSThe experimental AD model of rats was improved and established by combined injection of beta-amyloid protein (beta-AP) to lateral ventricle and transforming growth factor beta 1 (TGF beta 1) to brain. The learning and memory function of the model rats were tested by step-through test and water-maze test, and the number and cross area of beta-AP deposited macula in cerebral cortex and CA1 region of hippocampus were estimated quantitatively using immunohistochemical method and image pattern analysis.

RESULTSThe improved AD animal model showed both the specificity of behavior (learning and memory impairments) and the typical pathological specificity (beta-AP deposited macula). ZNC could effectively improve the impairment of learning and memory and reduce the number and cross area of beta-AP deposited macula in cerebral cortex and hippocampus CA1 region in the AD model rats.

CONCLUSIONThe AD rat model induced by the combined injection of beta-AP and TGF beta 1 is a good animal model simulated to the clinical reality, which could be used to screen and evaluate the anti-dementia agents. ZNC could display anti-dementia effect of the AD model rats.

Alzheimer Disease ; drug therapy ; physiopathology ; Amyloid beta-Peptides ; Animals ; Disease Models, Animal ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Learning ; Male ; Memory ; drug effects ; Random Allocation ; Rats ; Rats, Wistar ; Transforming Growth Factor beta

Objective In order to explore the prevalence of chronic obstructive pulmonary disease (COPD)among residents aged over 40 in Yongjia County,and to provide basic data for the prevention and control strategies and measures of chronic obstructive pulmonary disease.Methods Residents were investigated by questionnaire investigation,body measurements, and pulmonary function tests.Questionnaire survey was including demographic information,chronic obstructive pulmonary disease knowledge awareness,personal and family history of the disease,respiratory symptoms,case management of respiratory diseases,risk factors.Body measurements were including height,body weight,waist circumference,blood pressure and heart rate.Pulmonary function tests was including one second forced expiratory volume (FEV1 ),forced expiratory volume (FEV6 ) and forced vital capacity (FVC ).Results A total of 585 residents were investigated, including 85 patients with chronic obstructive pulmonary disease,and the prevalence rate of 1 4. 53%.Male chronic obstructive pulmonary morbidity was higher than female (χ2 =44. 29,P=0. 001 ),and with age increased,the prevalence rate increased (χ2 =1 9. 56,P<0. 001 ).Single factor analysis showed that the main risk factors were male,age ≥40, often cough /expectoration,smoking,occupational exposure history.Multivariate logistic regression analysis showed that male (OR=1 . 962,95%CI:1 . 025 -3. 757),expectoration (OR=2. 346,95%CI:1 . 1 48 -4. 794)and age (in the age group of 50:OR=2. 561 ,95%CI:1 . 221 -5. 372;age≥60(OR=7. 438,95%CI:3. 601 -1 5. 361 )were the risk factors of chronic obstructive pulmonary disease (COPD).Conclusion Chronic obstructive pneumonia has become a public health problem that affects the health of the residents.We should take effective preventive measures against the risk factors.

Objective To explore the relationship between esophagus cancer patients and both environmental and genetic factors,through analyzing the data on birth orders from esophagus cancer patients of Shanxi province.Methods Both Greenwood and Haldane methods on birth order were used to study the 1101 cases with esophagus cancer from Shanxi province.All the patients had received surgery and were diagnosed,by pathological evidence.First certificates of the patients were confirmed through the standard genetic epidemiologic investigation.Birth order was investigated on probands of the 1101 cases with esophagus cancer and their 44 siblings.Results Results form the Greenwood method showed that there was a tendency for cases with esophagus cancer in birth orders First to Third.However,the Haldane method showed that the results were quite different between actual value and the average theory value of 6A (6A(actual value)=17 118,(X)6A(average theory value) =19 290,X=∣6A-(X)6A∣/√V6A =7.63,X ＞ 2) which suggested that the birth order had some effects on the occurrence of esophagus cancer.In addition,the actual value of 6A was lower than the theoretic average value,and the parents at younger productive age or baby at the first birth was easy to develop esophagus cancer.Conclusion Esophagus cancer was related with the birth order,especially at early order,which was not consistent with the national reports on esophagus cancer.Results from this study suggested that there were certain effects of environmental risk factors on esophagus cancer patients.

Objective To analyze the different risks of cardia neoplasms in the immediate relatives of the cardia cancer patients,through a case-control study.Methods A case-control study was adopted on 772 cases and 772 controls,and relative risk (RR) were measured to compare the results from patemal or matrilineal groups.Results (1)Risk of the 1st grade kinship to the male cardia-cancer-patient group was obviously higher than that of the control group with RR=2.61 (95％CI:1.44-4.73,P＜0.01).(2) The risks of both paternal (P＜0.05) and matrilineal (P＜0.05) in the male cardia-cancer-patients were obviously higher than that of the control groups while the risk of those male cardia-cancer-patients in the paternal was higher than that of the control group (P＜0.05),so as the case for female patients in the matrilineal group (P＜0.05).(3) Data from the 1st grade kinship of cardia-cancer-patient group showed that parents and siblings had a higher risk than the control group (P＜0.05).(4) No significant genetic differences were found between the patemal of either the cancer group or the control group (P＞ 0.05),but statistical difference was observed that the risk of someone being the matrilineal of the cancer group was higher than that of the control group (P＜0.05).Conclusion The risks of cardia-cancer were higher in the 1st grade kinship,which including parents,brothers,sisters,maternal grandmother,mother,and maternal aunt.It was suggested that prevention programs should be focused on both earlier detection and treatment of the patients.New strategy for cancer prevention also need to be further developed.

Objective To evaluate the feasibility,reliability,validity and responsiveness of a Chinese Menopause Rating Scale (CMRS).Methods Cross-sectional survey and convenience sampling were adopted. Participants:women with menopause syndrome and those in menopause but without menopause syndrome were recruited.All participants were asked to complete the CMRS,Kupperman Index,WHOQOL-BREF and MENQOL.The Self-control observation design was adopted when the responsiveness was evaluated.Patients were treated with TCM for weeks.MRSTCM was evaluated before and after the treatment.Results (1) Feasibility:3343 participants including 2320 patients and 1023 menopause women,were surveyed in 8 different settings.The recovery rate of CMRS was 100%,with a response rate as 99.7%.The completion of the CMRS took 10.30 minutes on average.(2)Reliability:Cronbach's alpha of CMRS,soma dimension,psychology dimension and community dimension of CMRS were 0.93,0.87,0.89 and 0.73 respectively,with the correlation coefficient of split half of the CMRS.Soma dimension,psychology dimension and community dimension were 0.92,0.89,0.86 and 0.73 respectively and the test-retest correlation coefficient of MRSTCM,the soma dimension,psychology dimension and community dimension were as 0.88,0.91,0.85 and 0.77 respectively.(3) Validity:CMRS was established on the basis of connotation of menopause syndrome,and a series of steps were adopted to modify the scale.CMRS was applicable for patients with menopause syndrome.CMRS seemed to have had good content-related validity.The result of exploratory factor analysis was accorded with the theory frame of CMRS by and large.The correlations between CMRS and KI,CMRS and WHOQOLBREF,CMRS and MENQOL seemed good.The CMRS was able to discriminate between groups of people with or without menopausal syndrome and bad good discriminative validity.(4) Responsibility:The CMRS was measured based on 174 patients with menopausal syndrome before and after the TCM therapy.Our result showed that the CMRS having the ability to measure the clinically important differences.Conclusion CMRS was suitable for outcome assessment of menopausal syndrome.This primary research proved that the CMRS had good feasibility,reliability,validity as well as responsiveness.

The aim of this study was to evaluate the application value of SPECT/PET (18)F-FDG imaging in patients with lymphoma and its significance in monitoring relapse of this disease. A retrospective analysis of 71 SPECT/PET examinations was performed in patients with lymphoma diagnosed by pathologic and immunohistochemistry means from 1998 to 2008 in Peking university first hospital. The results showed that 28 patients underwent SPECT/PET before initial therapy, the accuracy of SPECT/PET and CT were 100% and 81.7% respectively. The diagnostic sensitivity of SPECT/PET and CT for foci were 85.7% and 53.5% respectively, and there was significant difference between them (p = 0.003). The diagnostic sensitivity of SPECT/PET and CT for extranodal foci were 91.3% and 56.5% respectively, there was significant difference also between them (p = 0.007). 32 patients underwent 43 SPECT/PET for monitoring relapse during follow up. The positive predictive value and negative predictive value of SPECT/PET for relapse were 100% and 92.9% respectively. The relapse were found by SPECT/PET in 6 patients more early than appearance of clinical symptoms and physical signs as well as laboratory examination, imaging examination. In conclusion, SPECT/PET has significant value in diagnosing and monitoring relapse for patients with lymphoma.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Female ; Fluorodeoxyglucose F18 ; Humans ; Lymphoma ; diagnostic imaging ; pathology ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; diagnostic imaging ; prevention & control ; Retrospective Studies ; Tomography, Emission-Computed, Single-Photon ; methods ; Young Adult

The study was aimed to investigate the incidences and risk factors of acute and chronic graft-versus-host diseases (GVHD) and to clarify their effects on relapse and survival of recipients after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The clinical data of 100 cases of allo-HSCT were retrospectively analyzed. The incidences and risk factors of aGVHD and cGVHD, relapse and survival were studied. The results showed that 31 cases developed aGVHD of II - IV grade (34.4%) and 14 cases developed aGVHD of III - IV grade (17.7%). HLA matched or mismatched did not show significant difference in the development of aGVHD of II - IV grade (p > 0.05). Previous occurrence of aGVHD was the risk factor for cGVHD (HR = 2.303, p = 0.088). The female was a favorable factor for cGVHD (HR = 0.401, p = 0.055). The relapse rate was lower in patients who developed cGVHD. The development of aGVHD of II - IV grade was the risk factor for overall survival (p < 0.05). The mortality of patients with aGVHD of III - IV grade and mortality of patients with aGVHD of 0 - I grade were 81.0% and 35.7% respectively, there was very significant difference between them (p = 0.000). In conclusion, till now GVHD and graft-versus-leukemia (GVL) effect can not be separated. The positive effect of GVL could be counteracted by GVHD-related mortality. It is necessary to prevent and control the development of severe aGVHD. The development of local cGVHD may be beneficial to the long-term disease-free survival of patients after allo-HSCT.
Adolescent ; Adult ; Child ; Child, Preschool ; Disease-Free Survival ; Female ; Graft vs Host Disease ; etiology ; mortality ; Hematopoietic Stem Cell Transplantation ; adverse effects ; mortality ; Humans ; Incidence ; Male ; Middle Aged ; Recurrence ; Retrospective Studies ; Risk Factors ; Young Adult

OBJECTIVETo monitor blood cells EBV-DNA copies by quantitative Epstein-Barr virus (EBV) polymerase chain reaction after hematopoietic stem cell transplantation (HSCT) and to evaluate its implication.

METHODSEBV-DNA copies of peripheral blood mononucleated cells (PBMNCs) were detected by fluorescence quantitative PCR once a week since conditioning regimen from fifty one patients received HSCT. Correlation between development of lymphoproliferative disorders (LPD) and EBV-DNA copies and influence factors of EBV reactivation were analyzed.

RESULTSThe cumulative incidence of EBV viremia was 58.8%. EBV reactivation occurred (39.6 +/- 23.5) days after HSCT, later than that of cytomegalovirus (CMV) reactivation (25.0 +/- 15.1) days (P < 0.01). HLA mismatch (P < 0.01), use of antithymocyte globulin (ATG) (P < 0.01), age less than twenty (P < 0.001) were factors for EBV reactivation, (93.3% vs 48.1%, 92.3% vs 18.7%, and 100% vs 53.1%, respectively). EBV related post-transplant lymphoproliferative disorders (EBV-PTLD) occurred only in 4 out of 30 (13.3%) EBV reactivation patients, whose EBV DNA load maintained over 10(6) copies/ml for at least two weeks (4 out of 13 cases). The median survival time of EBV-PTLD patients was 19.5 (11 - 75) days.

CONCLUSIONSEBV reactivation occurs frequently after HSCT, especially in those received HLA mismatch grafts, used antithymocyte globulin or aged under twenty. Patients with EBV loads over 10(6) copies/ml, especially lasting over two weeks, appear to have an increased risk for PTLD, and pre-emptive therapy may be of clinical useful.

DNA, Viral ; blood ; Epstein-Barr Virus Infections ; Hematopoietic Stem Cell Transplantation ; Herpesvirus 4, Human ; genetics ; Humans ; Lymphoproliferative Disorders

BACKGROUNDAlthough severe acute respiratory syndrome (SARS) has been controlled, the subsequently emerging sporadic cases in 2004 emphasize the necessity of developing a rapid diagnostic method, which would be of great help in clinical diagnosis and also wild host screening. This study aims to establish an effective and rapid serological tool for the diagnosis of SARS-CoV by comparison among whole viral, N and N199 proteins by ELISA.

METHODSSARS-CoV N and N199 (a truncated nucleocapsid gene) genes were cloned, expressed, identified by Western blotting, and applied in screening of human and swine samples. Sera of SARS convalescent-phase patients, normal human sera, sera of patients with other respiratory diseases, and swine sera were screened by ELISA, with whole SARS-CoV F69, N and N199 proteins as antigens.

RESULTSThe sensitivity and specificity of N and N199 proteins in human sera diagnosis were approximate (P = 0.743), which was higher than whole viral protein but the difference was not significant (P = 0.234). The N199 protein proved to be more specific in swine sera screening than whole viral and N protein (P < 0.001).

CONCLUSIONN199 protein is feasible in both clinical diagnosis and SARS-CoV reservoir screening.

Amino Acid Sequence ; Animals ; Cloning, Molecular ; Enzyme-Linked Immunosorbent Assay ; methods ; Humans ; Molecular Sequence Data ; Nucleocapsid Proteins ; blood ; genetics ; Sensitivity and Specificity ; Severe Acute Respiratory Syndrome ; diagnosis ; Swine