The association rate constant and dissociation rate constant are important parameters of the drug-cyclodextrin supermolecule systems, which determine the dissociation of drugs from the complex and the further in vivo absorption of drugs. However, the current studies of drug-cyclodextrin interactions mostly focus on the thermodynamic parameter of equilibrium constants (K). In this paper, a method based on quantitative high performance affinity chromatography coupled with mass spectrometry was developed to determine the apparent dissociation rate constant (k(off,app)) of drug-cyclodextrin supermolecule systems. This method was employed to measure the k(off,app) of meloxicam and acetaminophen. Firstly, chromatographic peaks of drugs and non-retained solute (uracil) on β-cyclodextrin column at different flow rates were acquired, and the retention time and variance values were obtained via the fitting the peaks. Then, the plate heights of drugs (H(R)) and uracil (H(M,C)) were calculated. The plate height of theoretical non-retained solute (H(M,T)) was calculated based on the differences of diffusion coefficient and the stagnant mobile phase mass transfer between drugs and uracil. Finally, the k(off,app) was calculated from the slope of the regression equation between (H(R)-H(M,T)) and uk/(1+k)2, (0.13 ± 0.00) s(-1) and (4.83 ± 0.10) s(-1) for meloxicam and acetaminophen (control drug), respectively. In addition, the apparent association rate constant (k(on,app)) was also calculated through the product of K (12.53 L x mol(-1)) and k(off,app). In summary, it has been proved that the method established in our study was simple, efficiently fast and reproducible for investigation on the kinetics of drug-cyclodextrin interactions.
Acetaminophen ; chemistry ; Chromatography, Affinity ; Drug Interactions ; Kinetics ; Mass Spectrometry ; Thermodynamics ; Thiazines ; chemistry ; Thiazoles ; chemistry ; beta-Cyclodextrins ; chemistry

The release behavior of single pellet was investigated by LC/MS/MS method with tamsulosin hydrochloride (TSH) as the model drug of the research and then the pellets were divided into four groups according to the drug loading. Comparison of dissolution profiles of each group and capsule were performed using f1 and f2 factor methods to study the difference and similarity. The release profiles of single pellet, each group and capsule were analyzed using principle component analysis (PCA). The particle system was built through Matlab to get the target release profile. The result of this research demonstrated the release behavior of single pellet correlated well with the drug loading. While the dissolution profile of capsule as a reference, the similarity factor of dissolution profiles of the lower drug loading groups were 62.2, 67.1, 53.9, respectively and, 43.3 for highest drug loading group. The particle systems with different pellet distribution and same release profiles were built through release behavior of single pellet. It is of significance to investigate the release behavior of single pellets for studying the release regularity of multiple-unit drug delivery system.
Capsules ; Chemistry, Pharmaceutical ; Chromatography, Liquid ; Delayed-Action Preparations ; Drug Delivery Systems ; Drug Liberation ; Principal Component Analysis ; Sulfonamides ; administration & dosage ; chemistry ; Tandem Mass Spectrometry ; Technology, Pharmaceutical

OBJECTIVE: In order to determine the major species of sarcosaphagous flies and their regular activity on carcass in Hohhot district. METHODS: Six rabbits were killed and placed outdoors at different time from July to October in Hohhot district. Some species of sarcosaphagous flies that appeared the cadavers were observed and identified. RESULTS: It showed that there are 10 main spieces belonging to 3 families and 8 genera were from Diptera, including Musa domestica domestica Linnaeus, Musa domestica vicina Maequart, Ophyra capensis (Wiedemann), Hydrotaea armipes (Fall.), Muscina stabulans (Fall.) from Museidae; Lucilia sericata (Meigen), Chrysomya megacephala (Fabricius), Lucilia cuprina (Wiedemann) from Calliphoridae; Boettcherisca peregrina (Robineau-Desvoiy), Parascarcophaga crassipalpis (Maequart) from Sacrophagidae. Besides, it showed obvious regulations that different species of sarcosaphagous flies appeared on carcass at different postmortem interval and the first part of carcass that sarcosaphagous flies appeared on. CONCLUSION It may be useful for estimating postmortem interval in Hohhot district.
Animals ; China ; Diptera/physiology* ; Larva/growth & development* ; Postmortem Changes ; Rabbits ; Seasons ; Species Specificity ; Time Factors

Acquired Immunodeficiency Syndrome ; epidemiology ; virology ; Adolescent ; Adult ; Aged ; Aged, 80 and over ; China ; epidemiology ; Female ; Humans ; Male ; Middle Aged ; Young Adult

OBJECTIVE: To analyze the causes of medical malpractice in patients with tumor, to determine the medical responsibility, and to recommend the related preventions. METHODS: Seventy four medical malpractice cases, which were involved in tumor and collected from 2000 to 2009 in medicolegal expertise center of west China, were analyzed retrospectively. RESULTS: The medical malpractice cases in the patients with tumor showed an increasing tendency in recent years. The main causes are missed diagnosis, misdiagnosis, improper chemotherapy and neglect of complications. The causes of medical malpractice were different in the different levels of medical services. The occurrence of medical malpractice in surgery and OB-GYN showed more frequent than the others. CONCLUSION Forensic pathology autopsy is important to resolve medical malpractice of tumor patients by finding out the cause of death and clarifying the medical responsibility. The occurrence of medical malpractice could be reduced by the clinical doctors through improving serve consciousness, obtaining the patients' trust, improving the medical treatment, following related laws and rules, fulfiling duty of medical careness.
Adult ; Age Distribution ; Expert Testimony ; Female ; Forensic Pathology ; Hospital Administration ; Humans ; Liability, Legal ; Male ; Malpractice/statistics & numerical data* ; Medical Errors/statistics & numerical data* ; Middle Aged ; Neoplasms/therapy* ; Retrospective Studies ; Sex Distribution

OBJECTIVESepsis and septic shock remain a common problem that results in significant mortality and morbidity in pediatric intensive care units (PICU). According to literature, the use of more physiologic steroid replacement therapy is associated with hemodynamic and survival benefits in adult patients with relative adrenal insufficiency (RAI) and catecholamine-resistant septic shock. But little information is available in children. The aim of the current prospective study was to determine the prevalence of adrenal insufficiency in children with sepsis and septic shock using a low-dose adrenocorticotropic hormone (ACTH) stimulation test (1 microg/1.73 m2) in children.

METHODSThe authors performed cortisol estimation at baseline and after low-dose (1 microg/1.73 m2) ACTH stimulation at 30 mins in children during the first 24 hours in patients with sepsis or septic shock admitted to our PICU. Adrenal insufficiency was defined as a response < or = 90 microg/L. Absolute adrenal insufficiency (AAI) was further defined as baseline cortisol (T0) < 200 microg/L and RAI insufficiency by T0 > or = 200 microg/L.

RESULTSSixty-two consecutive cases with sepsis and septic shock admitted to PICU of Shanghai Jiaotong University Affiliated Children's Hospital from April, 2006 to March, 2007. The median age was 37.6 months (range, 2 - 168 months), and their gender distribution was 42 (67.7%) males and 20 (32.3%) females, 53 cases had sepsis (85.5%) and 9 had septic shock (14.5%). The mean pediatric critical illness score (PCIS) was 79.3 +/- 9.2 and median pediatric risk of mortality score (PRMSIII) 11.3 (5 - 19), respectively. Overall mortality of sepsis and septic shock was 27.42%. The evaluation of adrenal insufficiency was conducted as follows. (1) The mean cortisol levels at baseline (T0) and 30 mins after ACTH stimulation (T1) were (318.6 +/- 230.4) microg/L, (452.3 +/- 230.7) microg/L and (454.7 +/- 212.7) microg/L, (579.3 +/- 231.9) microg/L in patients with severe sepsis and septic shock group, respectively. There were no significant difference between the two groups (P > 0.05). (2) The proportion of patients with adrenal insufficiency in the study population was 40.3% as defined by a response < or = 90 microg/L post test. The proportion of patients with adrenal insufficiency in sepsis and septic shock were 39.6% and 44.4%, respectively (chi2) = 0.073, P > 0.05). (3) The serum T0 and T1 levels were (320.5 +/- 223.9) microg/L, (462.3 +/- 212.0) microg/L and (384.3 +/- 258.3) microg/L, (500.7 +/- 470.6) microg/L, respectively, and the proportion of patients with adrenal insufficiency were 37.8% and 47.1% in the survivors and the dead (P > 0.05). The levels of T0 and T1 were related to the PCIS (P < 0.05). The morbidity of adrenal insufficiency was not related to the PCIS, PRISMIII, and number of organ that developed functional insufficiency (P > 0.05).

CONCLUSIONSAdrenal insufficiency may occur in patients with sepsis and septic shock in children. ACTH stimulation test may be helpful to determine whether corticosteroid therapy has a survival benefit in patients with relative adrenal insufficiency. A low-dose ACTH stimulation test can be used to evaluate the adrenal function status of severe sepsis and septic shock in children.

Adolescent ; Adrenal Insufficiency ; diagnosis ; etiology ; Adrenocorticotropic Hormone ; metabolism ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Intensive Care Units, Pediatric ; Male ; Prospective Studies ; Sepsis ; physiopathology ; Shock, Septic ; physiopathology ; Systemic Inflammatory Response Syndrome ; physiopathology

The study was purposed to explore the efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) combined with Imatinib for treatment of Philadelphia chromosome positive acute lymphoblastic leukemia (Ph(+)ALL) patients. From 2007 to 2008, 3 patients with Ph(+)ALL were treated with allogeneic hematopoietic stem cell transplantation and Imatinib, and the follow-up ended at Oct 21(st) 2009. 1 patient received HSCT from matched sibling donor and 2 patients from haploidentical related donors. All 3 patients achieved complete remission before transplantation and were treated with Imatinib for distinct time at different periods before and/or after transplantation. The level of bcr/abl mRNA was monitored using real-time PCR. The results showed that all 3 patients achieved stable engraftments without severe transplantation related complications. The level of bcr/abl mRNA declined and achieved zero level finally. In conclusion, the allo-HSCT combined with Imatinib is an effective therapy regimen for Ph(+)ALL patients.
Adolescent ; Adult ; Benzamides ; Combined Modality Therapy ; Hematopoietic Stem Cell Transplantation ; Humans ; Imatinib Mesylate ; Male ; Piperazines ; therapeutic use ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; therapy ; Pyrimidines ; therapeutic use ; Transplantation, Homologous ; Treatment Outcome

OBJECTIVETo analyze the etiological and epidemiological characteristics of hand-foot-and-mouth disease (HFMD) seen in Jiangsu province from 2008 to 2010, and provide evidence for its prevention and control.

METHODSBased on the requirement of supervision program of HFMD, surveillance and report were done according to National Disease Supervision Information Management System. Descriptive epidemiological method, performed between 2008 and 2010, was used to analyze the time, region and population distribution and results of etiologic analysis of HFMD. Nucleic acid of enterovirus (EV) genome was detected by real-time RT-PCR.

RESULTSThe average incidence rate of HFMD was 86.70 per million between 2008 and 2010, the peak incidence occurred in April to July. There were significant differences among the incidence in different districts (P<0.05), and the highest incidence was seen in the densely inhabited southern areas of Jiangsu province. Most of the cases were infants and children aged less than 5 years. The number of male cases (2008: 17,008, 2009: 48 768, 2010: 50,231) was much larger than that of the female cases 2008: 9662, 2009: 29 151, 2010: 30,655. The HFMD cases with mild symptoms were caused mainly by enterovirus 71 (EV71) and coxsackievirus A16 (Cox A16) and there was difference among different years. The severe HFMD cases and deaths were mainly caused by EV71 infection.

CONCLUSIONSThe epidemiologic characteristics of HFMD in Jiangsu province from 2008 to 2010 had close relationship with season, population and region. The mild cases of HFMD were mainly infected with EV71 and Cox A16. However, EV71 illness seemed to be more severe and had significantly greater frequency of serious complications and fatality than the illness caused by Cox A16.

Child, Preschool ; China ; epidemiology ; Disease Outbreaks ; Enterovirus A, Human ; pathogenicity ; Female ; Hand, Foot and Mouth Disease ; epidemiology ; virology ; Humans ; Infant ; Male

This research was performed to establish the HPLC fingerprint of Sabia parviflora. HPLC method was carried out on a Thermo Accucore-C18(4. 6 mm×150 mm,2. 6 μm) column by 30% tetrahydrofuran in methyl alcohol-acetonitrile-0. 1% phosphate solution as mobile phase at a flow rate of 1. 0 m L·min-1,the column temperature was 30 ℃ and the detection wavelength was 360 nm. The fingerprints were further evaluated by chemometrics methods including similarity analysis,hierarchical clustering analysis,and principal component analysis. In HPLC fingerprint,15 common peaks were selected as the common peaks,and 6 contents of them were identified. The similarity degrees of 38 batches of the samples was more than 0. 710,and the samples were divided into 6 clusters by their quality difference. The method was precision,repeatable,stable,simple and reliable,which could be used for quality control and evaluation of S. parviflora.
Chromatography, High Pressure Liquid ; Cluster Analysis ; Drugs, Chinese Herbal ; Principal Component Analysis ; Quality Control

Methotrexate (MTX) injection has a short half-life and significant toxic side effects. In order to overcome the demerits of MTX injection, MTX@COF was prepared for subcutaneous injection by loading MTX in crosslinked cyclodextrin metal-organic framework (COF) in this study. The cationic lipid material (2, 3-dioleoyl-propyl)-trimethylamine (DOTAP) was then coated on the MTX@COF surface by solvent evaporation. Different surface charge characteristics were observed in the coated MTX@COF@DOTAP with no significant change in particle morphology. The in vitro release behaviors of sustained-release particles were investigated in water and phosphate buffer (pH 7.4), and the in vivo release characteristics were evaluated for pharmacokinetics in rats. The in vitro release results showed that the cumulative release of MTX, MTX@COF and MTX@COF@DOTAP within 6 h was 92.70%, 36.31% and 18.19% in water, respectively; the cumulative release of MTX, MTX@COF and MTX@COF@DOTAP within 4 h was 90.82%, 79.37% and 58.30% in phosphate buffer, respectively; the results showed that MTX@COF can significantly delay the release of MTX, the modification to MTX@COF by DOTAP can further delay the release of MTX. Pharmacokinetic studies in rats showed that the mean retention time [MRT_(0-t)] and the time to peak (T_max) of the subcutaneous injection of MTX@COF@DOTAP group were significantly prolonged compared with the MTX@COF group and the MTX group. The area under the concentration-time curve [AUC_(0-t)] of the MTX@COF@DOTAP subcutaneous injection group was 1.8 times high as that of the MTX group. In this study, MTX@COF@DOTAP particles had a certain sustained-release effect, and could prolong the bioavailability of MTX by subcutaneous injection, which provided a new idea for the development of new MTX dosage forms.