Objective To study the local irritation of repeated intrathecal injection of Ziconotide Acetate,and to provide reference for irritancy evaluation ofintrathecal injection.Methods Sixteen New Zealand rabbits were assigned into two groupsat random:Control group and Ziconotide Acetate group,eight animals each group.Totally 50 μL saline or Ziconotide Acetate (100 μg/mL) were administrated by repeated lumbar intrathecal injection once daily for 7 d.Animal behavior was observed every day,and four animals in each group were sacrificed 2 d later after the last injection,the lumbar spinal cord was removed for histopathological examination and irritancy evaluation.The remaining animals were sacrificed for initancy evaluation 14 d later after the last injection.Results Only one animal died after anesthesia on day three in saline group,while no obvious adverse reactions were observed in other rabbits during the entire study,and no intrathecal irritant reactions of histopathological examination were found in both groups.The reversible minor mechanical damage was observed at the injection point,2 d after the last administration.Conclusion For 7 d repeated lumbar intrathecal injection in rabbits,no intrathecal irritant reactions observed in Ziconotide group,and the New Zealand rabbit could be used as a local irritation evaluation model.

Objective To explore the possibility and safety of ~(32)P-colloidal chromic phosphate interstitial injection.Methods Ten Beagle dogs were randomly divided into 5 groups (n ＝ 2) according to different doses (185 and 370 MBq) ,different sites (gluteus maximus and liver) and cold colloid as a control group.At different time-points after surgery,the weights of dogs were measured,and the blood and blood biochemical inspections were examined.ECT imaging was performed and histomorphology was observed dynamically.The radioactive counts of body surface for 90 days,blood for 12 weeks and urine and feces for 30 days were measured continuously.Measured data were expressed by mean ±standard error ((x) ±s) and SPSS 13.0 software was used for statistical analysis.Results ECT imaging demonstrated that the whole liver imaging was obtained although the radioactive distribution was uneven in liver groups,and the radioactivity concentrated continuously in the area of injection,but no liver imaging in muscle groups.Dogs in group 4 lost weight progressively and reduced by 2.7 kg till 45 d after operation.While the mean weight increments in the other groups were 3.0,1.6,0.8 and 3.1 kg in order.In group 4,PLT and RBC reduced obviously.Dogs died at 23 or 45 d.AST and ALT were elevated sharply before death.In the other groups,blood and blood biochemistry inspection showed there were no significant statistical differences.The highest radioactive counts after operation were obtained from the injection spot,while the urinary bladder and the spleen were followed.The peak of blood cpm in liver groups presented at 5 min.Peak values were 0.5 × 10~7/min and 1.0 × 10~7/min,respectively.The blood cpm in the muscle groups was always maintained at 3 × l0~5/min.Histology study showed the hyperemia dropsy changes in muscle groups and 185 MBq liver group in 4 weeks,while after 8 weeks the organizational structure restored normally.There were partial liver cells necrosis in 4 weeks,and the massive liver cells balloon type changes in 6 weeks,as well as obvious hyperemia dropsy and the hepatic lobe structure unclear in 370 MBq liver group.For the radioactive counts of urine and excrement,the peak appeared at 13 and 12 d respectively,and the peak values were (42.0 ±3.3) × 10~4 and (29.6 ±4.5) ×10~4 /min in muscle groups,respectively ;while the peak appeared at 5 and 9 d,respectively and the peak values were (49.0 ± 10.2) × 10~4 and (28.5 ± 7.1) × 10~4 /min in liver groups,respectively.Cumulative excretion ratios in urine and excrement were 36.58% and 10.62% in muscle groups,respectively and 23.48% and 8.76% in liver groups till 30 d,respectively.The liver absorbed doses were 30.6 and 55.6 Gy in liver groups,while those were 2.3 and 6.5 Gy in muscle groups.The maximus absorbed doses of gluteus were 53.4 and 98.1 Gy in muscle groups.Conclusions When ~(32)P- colloidal chromic phosphate of 794.39 MBq/m~2 was injected into the liver of Beagle,the liver absorbed dose was 56 Gy,which could be lethal dose for its strong liver toxicity and systemic side effects.Injection of 463.98-772.93 MBq/m~2 in muscle of Beagle could be safe.~(32) P-colloidal chromic phosphate interstitial injection is secure to treat the solid tumors with poor and middle blood supply which could be reached by puncture.

OBJECTIVETo investigate the feasibility of using two- and three-dimensional (2D/3D) image registration for establishing a testing system of 3D kinematics of the spine in vivo.

METHODSCT data of the adult human lumbar spine were collected and the two orthogonal images of the same specimen were captured using an X-ray fluoroscope at two different positions. The 3D computer models of L3 and L4 vertebrae were reconstructed. A virtual fluoroscope was then created with solid modeling software to reproduce the relative positions of the orthogonal images. Two virtual cameras in the software were used to represent the X-ray sources. The 3D computer models of the L3 and L4 vertebrae were then introduced into the virtual fluoroscope respectively and projected onto the orthogonal images by the two virtual cameras. By matching the projections of the 3D model to the orthogonal images of L3 and L4 vertebrae, the 3D positions of L3 and L4 were obtained. After calculation, the relative displacement and angle of L3 were determined.

RESULTSAfter 2D/3D image registration, the relative displacement and angle were calculated. Compared with position I, the positional changes of L3 were represented with an extension of 5.86 degrees, left bending of 1.85 degrees and right rotation of 2.96 degrees.

CONCLUSION2D/3D image registration allows the simulation of 3D kinematics of the spine in vivo, but the efficiency and accuracy of this technique need further evaluation.

Adult ; Biomechanical Phenomena ; Feasibility Studies ; Fluoroscopy ; methods ; Humans ; Image Interpretation, Computer-Assisted ; methods ; Imaging, Three-Dimensional ; methods ; Lumbar Vertebrae ; diagnostic imaging ; physiology ; Range of Motion, Articular ; physiology ; Reproducibility of Results ; Tomography, Spiral Computed ; methods

OBJECTIVETo prepare the PrP specific monoclonal antibodies (mAbs) that can be used for the detection of mammalian prions and study of pathogenesis of prion diseases.

METHODSSeveral BALB/c mice were immunized with recombinant hamster prion protein (HaPrP). Three hybridoma cell lines designated as B7, B9, and B10, secreting monoclonal antibodies against HaPrP, were established by hybridoma technique. The mAbs reactivities were evaluated with ELISA, Western blot, and immunohistochemistry.

RESULTSThe mAbs produced by these cell lines reacted well with different recombinant hamster PrP proteins. Western blot analyses showed that mAbs B7 and B9 reacted with PrPSc from the scrapie-infected animals after proteinase K digestion with three glycosylated forms. The mAbs exhibited cross-reactivity with various PrPC from several other mammalian species, including humans and cattles. Immunohistochemistry assays confirmed that mAbs B7 and B9 could recognize not only extracellular but also intracellular PrPsSc.

CONCLUSIONThe mAbs of prion protein are successfully generated by hybridoma technique and can be applied for the diagnosis of prion associated diseases.

Animals ; Antibodies, Monoclonal ; immunology ; Blotting, Western ; Brain ; metabolism ; Cell Line, Tumor ; Cricetinae ; Enzyme-Linked Immunosorbent Assay ; Female ; Immunization ; Immunohistochemistry ; Mice ; Mice, Inbred BALB C ; PrPC Proteins ; genetics ; immunology ; PrPSc Proteins ; genetics ; immunology ; Recombinant Proteins ; immunology

BACKGROUNDDecreases in the bioavailability of rifampicin (RFP) can lead to the development of drug resistance and treatment failure. Therefore, we investigated the relative bioavailability of RFP from one four-drug fixed-dose combination (FDC; formulation A) and three two-drug FDCs (formulations B, C, and D) used in China, compared with RFP in free combinations of these drugs (reference), in healthy volunteers.

METHODSEighteen and twenty healthy Chinese male volunteers participated in two open-label, randomized two-period crossover (formulations A and C) or one three-period crossover (formulations B and D) study, respectively. The washout period between treatments was 7 days. Bioequivalence was assessed based on 90% confidence intervals, according to two one-sided t-tests. All analyses were done with DAS 3.1.5 (Mathematical Pharmacology Professional Committee of China, Shanghai, China).

RESULTSMean pharmacokinetic parameter values of RFP obtained for formulations A, B, C, and D products were 11.42 ± 3.41 μg/ml, 7.86 ± 5.78 μg/ml, 13.05 ± 6.80 μg/ml, and 16.18 ± 3.87 μg/ml, respectively, for peak plasma concentration (C max ), 91.43 ± 30.82 μg·h-1·ml-1 , 55.49 ± 37.58 μg·h-1·ml-1 , 96.50 ± 47.24 μg·h-1·ml-1 , 101.47 ± 33.07 μg·h-1·ml-1 , respectively, for area under the concentration-time curve (AUC 0-24 h ).

CONCLUSIONSAlthough the concentrations of RFP for formulations A, C, and D were within the reported acceptable therapeutic range, only formulation A was bioequivalent to the reference product. The three two-drug FDCs (formulations B, C and D) displayed inferior RFP bioavailability compared with the reference (Chinese Clinical Trials registration number: ChiCTR-TTRCC-12002451).

Adult ; Asian Continental Ancestry Group ; Biological Availability ; Drug Combinations ; Humans ; Male ; Rifampin ; administration & dosage ; pharmacokinetics ; therapeutic use ; Tuberculosis ; drug therapy ; Young Adult

BACKGROUNDTo analyze the genetic and antigenic characteristics of human H5N1 virus isolated from the mainland of China.

METHODSThe hemagglutinin (HA) gene of human H5N1 virus were sequenced and analyzed.

RESULTSThe results of HA gene sequencing showed that all the virus isolates belong to the same group because of the high similarity, but they were different from the virus isolated from Thailand and Vietnam. The sequence data also showed that the receptor specificity and the connecting peptide between HA1 and HA2 are still avian influenza origin.

CONCLUSIONThe virus isolates from mainland of China until now belong to the same group and are different from the virus isolated from Thailand and Vietnam, and there is no evidence showing the human-avian influenza reassortant and recombination.

Animals ; Chick Embryo ; China ; Hemagglutinin Glycoproteins, Influenza Virus ; genetics ; Humans ; Influenza A Virus, H5N1 Subtype ; classification ; genetics ; isolation & purification ; Influenza, Human ; virology ; Phylogeny ; Reverse Transcriptase Polymerase Chain Reaction ; Sequence Analysis, DNA

OBJECTIVETo understand the status of knowledge and behavior of drug use among urban and rural residents in 5 provinces in China to suggest priority intervention strategies and measures for drug use health education.

METHODSFrom March to May of 2011, 6159 urban and rural residents were selected from Beijing, Liaoning, Zhejiang, Yunnan, Shaanxi provinces by the multistage stratified sampling method and were investigated by the questionnaires on drug use knowledge and behavior.

RESULTSThe residents' average awareness rate for 11 pieces of basic drug use information was 48.3% (32,750/67,749). The residents' average awareness rate in the rural (40.3%, 9189/22 792) was lower than that in metropolitan (51.9%, 11 483/22 110) and small and middle-sized cities (52.9%, 12,078/22,847) and the differences had statistical significance (χ2=889.30, P<0.01). Overall, 77.0% (4742/6159) of residents purchased drug according to the doctors' prescription; 36.9% (2271/6159) of residents bought by their experiences; 33.3% (2049/6159) of residents did not know whether they had bought faked drugs; 32.7% (2016/6159) of residents did not read instructions carefully before using drug; 83.4% (5134/6159) of residents stored drugs in their house and only 29.2% (1798/6159) of residents would check up expired drugs regularly; 59.6% (3673/6159) of residents changed drug by themselves after suspected adverse reaction of drugs.

CONCLUSIONChinese urban and rural residents' knowledge level of drug use is inadequate and drug use behaviors are not optimistic. Drug use health education should be enhanced among urban and rural residents.

China ; Drug Therapy ; Health Education ; Health Knowledge, Attitudes, Practice ; Humans ; Prescription Drugs ; Surveys and Questionnaires

Objective To investigate the association between types of obesity and the 10-year-coronary heart disease risk in Tibet and Xinjiang of China.Methods Using the multi-stage random sampling method,7 631 participants aged 35 or older were examined under the International Standardized Examination process but with only 5 802 were eligible for analysis,in the 2015-2016 season.Results The prevalence rates of general obesity,central obesity,visceral obesity and compound obesity were 0.53％,12.62％,10.08％ and 42.35％,respectively.Out of all the compound obesity cases,58.65％ (1 441/2 457) of them appeared as having all types of obesity in our study.Risk related to the 10-year-coronary heart disease was higher in men than in women [(3.05 ± 4.14)％ vs.(1.42-2.37) ％,P＜0.000 1.Compound obesity (30.16％) showed the highest proportion on the risk of 10-year-coronary heart disease than central obesity (28.01％),visceral obesity (18.46％) or the general obesity (19.35％).After adjustment for confounding factors,results from the multivariate analysis showed the risk in compound obesity was higher than central obesity,visceral obesity or general obesity and was associated with the highest risk on the 10-year-coronary heart disease (OR=2.889,95％CI:2.525-3.305).People with anomalous BMI and WC seemed to have had the higher risk (OR=3.168,95％CI:2.730-3.677).Conclusions Obesity was popular in the residents of Tibet and Xinjiang areas of China.Men and people with compound obesity (especially both BMI and WC were abnormal) seemed to carry greater risk on the 10-year-coronary heart disease.

Objective To investigate the association between body fat percentage (BFP),visceral fat index (VFI) and Cardiometabolic Risk Factor Clustering (CRFC),among population aged 35 or older in Tibet and Xinjiang areas.Methods Using the stratified multi-stage random sampling method,7 571 residents aged 35 or above were examined with international standardized examination between 2015 and 2016.Of the eligible 5 643 participants,association of BFP and VFI with CRFC was defined as having two or more of the four risk factors:hypertension,diabetes mellitus,high TG and low HDL-C,at the same time.Logistic regression analysis and receiver operating characteristic (ROC) curve analysis were employed to further explore the relationships.Results The overall prevalence of CRFC among aged 35 and older population in Tibet and Xinjiang areas was 9.78％.BFP and VFI were divided into four groups by quartile.After adjustment for age,gender,race,cigarette smoking,alcohol consumption,education attainments,and altitude of residence,ORs of CRFC seemed to have increased with BFP and VFI.Compared with people having BFP of 5.0％-27.0％,the OR(95％CI) were 1.15(0.86-1.54),1.48(1.05-2.07) and 1.72(1.10-2.68) for the ones who presented 27.1％-31.7％,31.8％-36.6％ and 36.7％-50.0％ of BFP.Compared to people of having 1-6 of VFI,with OR (95％CI) as 1.20(0.81-1.79),1.91(1.30-2.80) and 3.91(2.64-5.77) for the ones having 7-9,10-13 and 14-30 of VFI.Areas under the curve (AUC) of CRFC appeared as 0.55 for BFP and 0.70 for VFI,respectively,with statistically significant difference (P＜0.01).Conclusion Both BFP and VFI levels were closely associated with CRFC while VFI seemed to have a better predictive value than the BFP.

OBJECTIVETo evaluate the safety of recombinant human interferon alpha-2b for nasal spray for the prevention of SARS and other upper respiratory viral infections.

METHODSField epidemiologic evaluation was conducted, the design was randomized and had a synchronously parallel control group. In the study, the drugs were given for five days and all subjects were followed up for ten days.

RESULTSDuring the period of using interferon, body temperature of the experimental group was normal compared to the control group. Experimental group had more influenza-like symptoms than the control group (P < 0.05), such as headache (4.83%-7.09%), dizziness (7.17%-11.63%), lassitude (8.55%-15.06%), muscular soreness (4.43%-7.09%), pharynx dryness (12.10%-17.85%), angina (6.25%-8.72%), abdominal pain (2.30%-5.50%) and diarrhea (2.45%-5.66%). Most of side effects reached their peak with in the first 3 days. Except for pharynx dryness, the incidences of all other side effects declined after completion of the use of the trial drug, and incidences of some symptoms in experimental group were lower than those of the control group. There were no significant differences in the symptoms of cough and expectoration between the experimental group and the control group. The incidence of exanthem in the control group was significantly higher than that in the experimental group. The side effect of bloody nasal mucus was not observed in experimental group, which had been reported by other authors in several volunteer studies.

CONCLUSIONUsing recombinant human interferon alpha-2b for nasal spray could lead to some influenza-like symptoms, however, all those symptoms were mild , reversible, and relieved after completion of the use of the trial drug. No serious side effects were found during the period of following up. The authors conclude that the drug is safe.

Abdominal Pain ; chemically induced ; Adolescent ; Adult ; Antiviral Agents ; administration & dosage ; adverse effects ; therapeutic use ; Dizziness ; chemically induced ; Female ; Follow-Up Studies ; Headache ; chemically induced ; Humans ; Interferon-alpha ; administration & dosage ; adverse effects ; therapeutic use ; Male ; Recombinant Proteins ; SARS Virus ; drug effects ; Severe Acute Respiratory Syndrome ; prevention & control ; virology ; Treatment Outcome ; Young Adult