The paper is aimed to investigate the effect of cyclosporine A (CyA) on the pharmacokinetics of ginkgolide B (GB) in rats, and to look for the mechanism of the changes in pharmacokinetic behaviors of GB. GB concentration in plasma, brain homogenate and urine samples of rats was determined by LC-MS. Effects of CyA on plasma levels, brain distributions as well as urinary excretions after intravenous administration of GB were evaluated. CyA co administrated intravenously at 10 mg kg(-1) or 20 mg kg(-1) significantly increased AUC(0-360 min) (P < 0.01) and decreased total CL of GB in rats. While co administrated CYP3A inhibitor itraconazole (ICZ) has no appreciable effect on the pharmacokinetic behavior of GB. CyA increased the brain uptake of GB in a dose-dependent manner. The brain distribution of GB was significantly increased at 5 min by different doses of CyA (P < 0.001), while at 20 and 60 min only high dose of CyA could significantly increase the levels of GB in the brain (P < 0.01 and P < 0.001). Different P-gp inhibitors CyA or verapamil (VER) or digoxin (DGX) decreased the urinary GB excretion, the urinary excretion of GB in 0-8 h were about 34.8% (P < 0.001), 59.4% (P < 0.001) and 79.7% (P < 0.05) of the control, separately. No appreciable effect of ICZ was observed on urinary excretion of GB. Coadministration of P-gp inhibitors CyA could significantly increase the plasma level, accelerate the brain distribution and decrease the urinary excretion of GB.
Animals ; Cyclosporine ; pharmacology ; Ginkgolides ; pharmacokinetics ; Herb-Drug Interactions ; Lactones ; pharmacokinetics ; Male ; Rats ; Rats, Sprague-Dawley ; Tissue Distribution

Adolescent ; Child ; Child, Preschool ; Factor IX ; administration & dosage ; therapeutic use ; Factor VIII ; administration & dosage ; therapeutic use ; Hemophilia A ; drug therapy ; prevention & control ; Hemophilia B ; drug therapy ; prevention & control ; Humans

OBJECTIVETo explore the biological effective markers, we investigated DNA strand breaks in peripheral lymphocytes from occupational population with broad ranges of soluble chromate exposure.

METHODSWe conducted a cross-sectional study in the chromate exposed workers employed at a chromate factory in a district of Jinan, Shandong Province. The studied population contained 114 workers from different processes of the chromate plants, in addition, 30 farmers in the countryside about one hundred kilometers away from the factory, without exposure to chromate were matched with the exposed subjects by age, gender and smoking status being identified as a control group. Personal information on age, chromate exposure, medical history (including acute infection and medicine usage), smoking habit and alcohol consumption was obtained by questionnaire. DNA strand breaks in lymphocytes were detected by single-cell gel electrophoresis assay (comet assay) and the DNA damaged degree was evaluated by the score weighted by comet type. The air concentration of chromate was determined by individual sampling for 8 hours per day as shift work and chromium was assayed by atomic absorption spectrometry. The chromium content in the erythrocytes from peripheral blood was determined by graphite furnace atomic absorption spectrometry. The data were analyzed by SPSS10.0 software for statistical significance.

RESULTS(1) The results showed that the score for DNA strand breaks in lymphocytes were 54.52 +/- 23.51 in the exposed group, which was significantly higher than those in the control group (24.70 +/- 11.84) (P < 0.01). (2) The degree of DNA strand breaks in lymphocytes was increased in a dose-dependent manner ranging from 0 microg/m(3) to 106.00 microg/m(3). (3) Correlation analysis showed that there was a significant positive correlation between airborne chromate concentration and the degree of DNA strand break in lymphocytes (P < 0.01). (4) By multiple regression analysis, it was found that the airborne concentrations, chromium contents in red blood cells and smoking habits were factors which might affect the degree of DNA breaks.

CONCLUSIONOur findings suggest that DNA strand break in lymphocytes should be an effective biomarker for occupational chromate-exposed population and be applied in biological monitoring and health risk assessment for occupational chromate-exposed population.

Adult ; Air Pollutants, Occupational ; analysis ; Causality ; Chromates ; analysis ; Chromium ; blood ; Comet Assay ; DNA Damage ; Female ; Humans ; Male ; Middle Aged ; Occupational Exposure ; Smoking ; Surveys and Questionnaires

OBJECTIVETo explore the CT criteria for evaluating lymph node (LN) metastasis and preoperative N-staging of gastric cancer through the comparison of CT signs and surgical pathology.

METHODSEighty-nine patients with gastric cancer underwent CT examinations before radical resections. A soft-reading method on PACS workstation was employed to evaluate the detection of LNs. The size and number of LNs were registered, and the accumulated size of LNs was calculated in every case. The pathological N-staging (pN(0-3)) was considered on the basis of pathological examination of excised specimens according to UICC TNM-staging system (6th edition, 2002). The relationships between LN metastases and CT findings were analyzed by SPSS using t test and one-way ANOVA analysis.

RESULTSThe distribution of maximal size, CT detection number and accumulated size were significantly different among different pN stages (P<0.01). All these 3 indicators were significantly different between LN metastasis group and non-metastasis group (P<0.01). There was no significant difference of maximal size among different pN stages in positive metastasis LNs (P>0.05), while significant difference could be found in CT detection number between pN1 and pN3 (P<0.01), pN2 and pN3 (P<0.01), and in accumulated size between pN1 and pN3 (P<0.01), pN1 and pN2 (P<0.01).

CONCLUSIONSThe involvement of LNs in gastric cancer and pN staging are associated with size, number, and accumulated size of CT detection. CT detection number is more valuable in the evaluation of N staging than LNs size. CT detection number combined with accumulated size of LNs can provide meaningful information for preoperative N-staging.

Adult ; Aged ; Female ; Humans ; Lymphatic Metastasis ; diagnostic imaging ; pathology ; Male ; Middle Aged ; Neoplasm Staging ; methods ; Stomach Neoplasms ; diagnostic imaging ; pathology ; Tomography, X-Ray Computed

OBJECTIVETo evaluate immunogenicity after primary vaccination by different sequential program of inactivated poliovirus vaccine (IPV) and oral poliovirus vaccine (OPV).

METHODSChildren of 2 months old (60-89 days) selected in Beijing were assigned to 4 groups, 1 dose IPV plus 2 doses OPV (I-O-O, 122 children), 2 doses IPV plus 1 dose OPV(I-I-O, 103 children), 3 doses IPV (I-I-I, 114 children), and 3 doses OPV (O-O-O, 106 children), and were vaccinated at the age of 2, 3, 4 months. Polio neutralizing antibody titers against poliovirus types 1, 2, and 3 were tested and protective rates were calculated before the 1st dose, after the last dose, and after the 1st and 2nd dose of IPV.

RESULTSAfter the primary immunization, geometric mean titers (GMT) of polio neutralizing antibody titers against poliovirus types 1, 2, and 3 were 788.32, 738.42 and 631.17 in O-O-O group, 212.02, 262.30 and 537.52 in I-I-I group, 940.35, 929.72 and 940.35 in I-O-O group and 901.09, 1102.68 and 1110.12 in I-I-O group (F values were 47.71, 53.84, and 9.81 respectively, all P values<0.01). The protective rate of three types among each group was 98.1% (104/106)-100.0% and the difference was not statistically significant (P>0.05). After the 1(st) dose of IPV, the GMT were 18.88, 37.77, 24.64 and the protective rate was 82.6% (122/138)-96.4% (133/138); after the 2nd dose of IPV, GMT were 177.03, 168.25, 321.86 and the protective rate was 99.1% (108/109)-100.0% (109/109) in antibody types 1, 2 and 3, respectively.

CONCLUSIONGMT of polio neutralizing antibody titers against poliovirus is higher after vaccination by sequential program of IPV and OPV than that by IPV or OPV 3-doses program. High level of protective rate after 2 doses of IPV in I-I-O group may lead to better protection from vaccine associated paralytic poliomyelitis (VAPP). Sequential program of IPV and OPV can be used to maintain high level of herd immunity and to prevent VAPP, and the I-I-O sequential program should be the first choice.

Humans ; Immunization Schedule ; Infant ; Poliovirus Vaccine, Inactivated ; administration & dosage ; immunology ; Poliovirus Vaccine, Oral ; administration & dosage ; immunology ; Vaccines, Attenuated ; immunology

OBJECTIVETo investigate the effects of three different ways of chronic caffeine administration on blast- induced memory dysfunction and to explore the underlying mechanisms.

METHODSAdult male C57BL/6 mice were used and randomly divided into five groups: control: without blast exposure, con-water: administrated with water continuously before and after blast-induced traumatic brain injury (bTBI), con-caffeine: administrated with caffeine continuously for 1 month before and after bTBI, pre-caffeine: chronically administrated with caffeine for 1 month before bTBI and withdrawal after bTBI, post-caffeine: chronically administrated with caffeine after bTBI. After being subjected to moderate intensity of blast injury, mice were recorded for learning and memory performance using Morris water maze (MWM) paradigms at 1, 4, and 8 weeks post-blast injury. Neurological deficit scoring, glutamate concentration, proinflammatory cytokines production, and neuropathological changes at 24 h, 1, 4, and 8 weeks post-bTBI were examined to evaluate the brain injury in early and prolonged stages. Adenosine A1 receptor expression was detected using qPCR.

RESULTSAll of the three ways of chronic caffeine exposure ameliorated blast-induced memory deficit, which is correlated with the neuroprotective effects against excitotoxicity, inflammation, astrogliosis and neuronal loss at different stages of injury. Continuous caffeine treatment played positive roles in both early and prolonged stages of bTBI; pre-bTBI and post-bTBI treatment of caffeine tended to exert neuroprotective effects at early and prolonged stages of bTBI respectively. Up-regulation of adenosine A1 receptor expression might contribute to the favorable effects of chronic caffeine consumption.

CONCLUSIONSince caffeinated beverages are widely consumed in both civilian and military personnel and are convenient to get, the results may provide a promising prophylactic strategy for blast-induced neurotrauma and the consequent cognitive impairment.

Animals ; Blast Injuries ; complications ; Brain Injuries, Traumatic ; complications ; Caffeine ; pharmacology ; Cerebral Cortex ; pathology ; Hippocampus ; pathology ; Male ; Memory Disorders ; etiology ; prevention & control ; Mice ; Mice, Inbred C57BL ; RNA, Messenger ; analysis ; Receptor, Adenosine A1 ; genetics

OBJECTIVETo investigate the prevalence and distributing feature of chronic heart failure (CHF) in adult population of Xinjiang.

METHODSFour-stage random sampling method was used to analyze the prevalence and distributing feature of self-reported congestive heart failure among different nationalities in adult (35 years and over) population of Xinjiang. Sampling was collected from 6 localities (Urumqi, Kelamayi, Fukang, Turfan Basin, Hetian, Yili Hazakh).

RESULTSA total of 8459 adults were surveyed. The prevalence of CHF was 1.26% in this cohort. The prevalence of CHF was 0.89%, 1.11% and 2.14%(*) in Han, Uygur and Hazakh population, respectively ((*)P < 0.05 vs. Han and Uygur). The risk of CHF was higher in the males than in the females (1.61% vs. 0.93%, u = 2.79, P < 0.05). The prevalence of CHF increased in proportion with aging and was 0.29%, 0.60%, 1.32%, 2.55% and 4.10% in 35 - 44, 45 - 54, 55 - 64, 65 - 74, 75 years and over age groups, respectively. Common complications of CHF were hypertension (63.55%), coronary heart disease (42.99%), diabetes (18.69%), valvular heart disease (5.61%) and atrial fibrillation (4.67%).

CONCLUSIONThe prevalence of CHF in Xinjiang was higher than the average level in China (0.9%) and was the highest in the Hazakh population.

Adult ; Aged ; Aged, 80 and over ; Asian Continental Ancestry Group ; China ; epidemiology ; Chronic Disease ; Female ; Heart Failure ; epidemiology ; Humans ; Male ; Middle Aged ; Prevalence

OBJECTIVETo summarize the management of pancreatic injuries after blunt abdominal trauma.

METHODSThe clinical data of 42 patients with blunt pancreatic injury admitted from January 2001 to December 2010 was analyzed retrospectively. There were 38 male and 4 female patients, aging from 13 to 65 years with a mean of 31 years. The organ injury scaling of Committee of the American Association for the Surgery of Trauma (AAST grade): grade I in 3 patients, grade II in 12 patients, grade III in 9 patients, grade IV in 13 patients and grade V in 5 patients. The mean injury severity score was 27 ± 21. Patients above AAST grade II underwent peritoneal drainage and "three neostomy" (gastrostomy, jejunostomy and gallbladder) according to damage control theory.

RESULTSThirty-eight patients got abdominal CT scanning with a positive rate of 79.9% (30/38). Forty patients underwent surgical procedures, and 2 patients with non-operative management. The surgical procedures include peritoneal drainage and "three neostomy" in 32 patients, pancreas suture or pancreatic tail resection in 6 patients, pancreatoduodenectomy or caudal pancreaticojejunostomy in 2 patients. Forty patients (95.2%) survived, 2 patients (4.8%) died and 16 patients (38.1%) had complications such as pancreatic fistula,pulmonary infection.

CONCLUSIONSAbdominal CT scanning will benefit the preoperative diagnosis of blunt pancreatic trauma. Although the survival rate of patients with blunt pancreatic trauma might be improved by using the damage control surgery, the management of damage control surgery also needs to be modified because of the high rate of complications.

Adolescent ; Adult ; Aged ; Drainage ; Female ; Humans ; Male ; Middle Aged ; Pancreas ; injuries ; surgery ; Retrospective Studies ; Wounds, Nonpenetrating ; surgery ; Young Adult

OBJECTIVETo evaluate safety of different sequential immunization schedules of inactivated poliovirus vaccine (IPV) and oral poliovirus vaccine (OPV) primary vaccination.

METHODSInfants of 2 months old (60-89 days) selected in Beijing, were assigned to four groups, 1 dose IPV plus 2 doses OPV (I-O-O), 2 doses IPV plus 1 dose OPV(I-I-O), 3 doses IPV (I-I-I), and 3 doses OPV (O-O-O), and were vaccinated at the age of 2, 3, 4 months, from 2009 to 2011. The frequencies of systemic as well as local injection site reactions after every dose were recorded and calculated. A total of 553 infants were enrolled in the study and 89 infants were quit, 1492 diseases were observed.

RESULTSThe incidence of adverse events in I-O-O, I-I-O, I-I-I, O-O-O were 22.9% (94/410), 18.4% (60/327), 22.0% (78/354) and 17.7% (71/401) with no statistical differences (χ(2) = 4.84, P = 0.184). Dose 1 (22.7% (32/141)-35.3% (54/153) ) was more frequently than dose 2 and dose 3. No serious adverse events (SAE) were reported during the study. The incidence of systemic adverse reactions in I-O-O, I-I-O, I-I-I, O-O-O were 21.5% (88/410), 17.7% (58/327) , 20.1% (71/354) and 17.7% (71/401) with no statistical differences (χ(2) = 2.53, P = 0.472). Abnormal crying were the most frequency reactions (7.2% (29/401)-11.3% (37/327) ) in 4 groups. Rarely severe reactions were observed of abnormal crying, somnolence, irritability and mild or medium reactions occurred in other symptoms. Local adverse reactions such as injection site pain, scleroma and swelling were reported by 2.2% (5/229)-5.6% (22/393) ,0-0.9% (2/229) and 0-1.0% (4/393) in I-O-O,I-I-O and I-I-I, and most reactions were mild.

CONCLUSIONThree IPV immunization and IPV/OPV sequential immunization as well as three OPV immunization demonstrated safe.

Humans ; Immunization Schedule ; Infant ; Poliovirus Vaccine, Inactivated ; administration & dosage ; adverse effects ; Vaccines, Attenuated ; administration & dosage ; adverse effects

Objective To investigate the relationship between stroke and ankle-brachial index (ABI), pulse wave velocity (PWV) in Han, Uighur, and Kazakh populations of Xinjiang. Methods Data was from the investigation of cardiovascular risk survey (CRS) program among different nationalities in Xinjiang from October 2007 to March 2010. A total of 14 618 samples aged over 35 with complete data dimension were surveyed. Results ( 1 ) There were 633 patients with stroke, including 258 Hans (4.48%), 247 Uighurs (5.18%), and 128 Kazakhs (3.13%). The incidence of stroke was significant different in the three ethnic groups (P＜0.001). (2)Compared to the Han population, the incidence of stroke was higher ( OR= 1.304) in Uighur but lower (OR=0.794) in Kazakh. (3) PWV was significant different between stroke and non-stroke patients. After adjustment for age, body mass index, systolic blood pressure, triglyceride, total cholesterol and other risk factors, the difference remained significant, indicating that PWV (OR=1.001, P＜0.001) might associate with the occurrence of stroke. Conclusion The results of this study showed that the incidence of stroke was significantly different in the three ethnic groups. PWV might associate with the occurrence of stroke.