Bexarotene is a synthetic analogue of retinoic acid and exerts protective effects on the nervous system. However, low bioavailability and poor solubility of the crystal type I form severely limits the application of bexarotene in the clinic. A co-amorphous sample of bexarotene-PVP-K30 was prepared and the structure was characterized by X-ray diffraction and infrared spectroscopy. To determine the pharmacokinetics and tissue distribution of bexarotene, an LC-MS method was established to profile and quantify bexarotene in plasma and tissues of SD rats. In vitro dissolution indicated that the co-amorphous form improved the dissolution of bexarotene in pure water 4.17-fold. After rats were orally administered bexarotene or bexarotene-PVP-K30 co-amorphous (equivalent to 30 mg·kg^-1 bexarotene) the AUC of bexarotene was 7 034.89 and 10 174.03 μg·L^-1·h respectively, the peak time was advanced from 7.33 h to 0.9 h with the amorphous form, and C_max was enhanced from 627.76 to 3 011.88 μg·L^-1. The co-amorphous form yielded higher concentrations of bexarotene in various tissues, especially brain, liver and kidney. Animal welfare and experimental procedures complied with the rules of the Animal Ethics Committee of the Institute of Materia Medica, Chinese Academy of Medical Sciences. The results indicate that bexarotene-PVP-K30 co-amorphous improves the pharmacokinetic characteristics of bexarotene and provides preclinical data in support of bexarotene-PVP-K30 for the treatment of brain diseases.

Parasitic diseases are common infectious diseases closely related to poverty,which are mainly endemic in the trop-ical and subtropical regions.Africa is the major epidemic area of parasitic diseases,and the global burden of malaria and schisto-somiasis is over 85% in Africa.This paper reviews the disease burden,regional distribution and control strategies of the main parasitic diseases in Africa,in order to promote the prevention and control of parasitic diseases in this area.

Adjuvants, Immunologic ; adverse effects ; Adult ; Aminoquinolines ; adverse effects ; Female ; Humans ; Lichen Planus ; chemically induced ; Male ; Vitiligo ; chemically induced

OBJECTIVETo analyze immunophenotypes and gene mutations of colorectal precancerous lesions and adenocarcinoma, and to compare the difference of carcinogenetic mechanisms between the two precancerous lesions.

METHODSFifty-three cases of colorectal serrated lesions including 30 hyperplastic polyps, 20 sessile serrated adenomas (SSA) and 3 mixed polyps were collected from January 2006 to June 2012.Forty-five cases of traditional adenomas and 50 cases of colorectal adenocarcinomas were also recruited. Thirty hyperplastic polyps, 20 cases of SSA, 3 mixed polyps and 45 traditional adenomas were investigated by immunohistochemistry for the expression of DNA mismatch repair (MMR) proteins (MLH1, MSH2 and MSH6) and DNA methyltransferase MGMT. Mutations of KRAS, BRAF and PIK3CA genes in 10 cases of SSAs, 10 traditional adenomas, 1 mixed polyps and 50 colorectal adenocarcinomas were analyzed by PCR followed by direct Sanger sequencing.

RESULTS(1) Only 3 cases of hyperplastic polyps lost MLH1 expression, and none of SSAs or traditional adenomas showed loss of MLH1. The negative expression rates of MSH2, MSH6 and MGMT in hyperplastic polyps and SSA were significantly higher than those of traditional adenomas. (2) KRAS mutation was found in 5/10 cases of SSAs, 5/10 traditional adenomas and 1/1 mixed polyps. (3) Colorectal adenocarcinomas harbored the mutations of KRAS (48%, 24/50), BRAF (6%, 3/50) and PIK3CA (4%, 2/50).

CONCLUSIONSImmunophenotypic and gene mutation profiles are different between colorectal serrated lesion and traditional adenoma. Alterations of MMR and MGMT expression play important roles in the pathogenesis of "serrated neoplasm". KRAS mutation is a significant genetic change in the early phase of colorectal carcinogenesis.

Adaptor Proteins, Signal Transducing ; metabolism ; Adenocarcinoma ; genetics ; metabolism ; Adenoma ; genetics ; metabolism ; Aged ; Class I Phosphatidylinositol 3-Kinases ; Colonic Polyps ; genetics ; metabolism ; Colorectal Neoplasms ; genetics ; metabolism ; DNA Mismatch Repair ; DNA Modification Methylases ; metabolism ; DNA Repair Enzymes ; metabolism ; DNA, Neoplasm ; metabolism ; DNA-Binding Proteins ; metabolism ; Female ; Humans ; Hyperplasia ; Immunophenotyping ; Male ; Middle Aged ; MutL Protein Homolog 1 ; MutS Homolog 2 Protein ; metabolism ; Nuclear Proteins ; metabolism ; Phosphatidylinositol 3-Kinases ; genetics ; Point Mutation ; Precancerous Conditions ; genetics ; metabolism ; Proto-Oncogene Proteins ; genetics ; Proto-Oncogene Proteins B-raf ; genetics ; Proto-Oncogene Proteins p21(ras) ; Sequence Analysis, DNA ; Tumor Suppressor Proteins ; metabolism ; ras Proteins ; genetics

BACKGROUND: Previous studies demonstrated that construction of eoexpression plasmid containing multiple genes on the same vector could improve transfection and expression rates.OBJECTIVE: To construct eukaryotic expression plasmid pcDNA3.1 (+)-MUC1 -GM-CSF by human polymorphic epithclial mucin (MUC 1) and granulocyte macrophage colony stimulating factor.(GM-CSF) and to observe expression of recombinant plasmid in COS-7 cells.DESIGN,TIME AND SETTING: Gene recombination design,which was carried out in the Animal Central Laboratory,the Fourth Military University of Chinese PLA from September 2005 to December 2006.MATERIALS: Eukaryotic expression vector pcDNA3.1 (+) was presented by Pro.Taylor-Papadimitriou;pGEM-3zf()-GM-CSF plasmid,COS-7 cells,pUCI 8 vector,and E.coli DH5α were made in the center; female BALB/c mice were provided by Experimental Animal Center of the Fourth Military University of Chinese PLA.METHODS: Signal peptide was synthesized with encoded MUCI gene sections to obtain repeated sequence coneatemer after renaturation.Next,the accepted concatemer was cloned with GM-CSF following enzyme identification and sequencing analysis,and then they were put in eukaryotic expression vector pcDNA3.1(+) to construct eukaryotic coexpression plasmid pcDNA3.1 (+)-MUCI -GM-CSF in order to transform COS-7 cells.MAIN OUTCOME MEASURES: Gene expression was detected by indirect immunofluorescence and enzyme linked immunosorbent assay (ELISA).RESULTS: Enzyme identification and sequencing analysis showed that recombinant plasmid contained a fusion gene encompassing human MUC1 repeated sequence concatemer and GM-CSF; moreover,MUC1 expression was detected in COS-7 cells,while recombinant plasmid could induce the production of anti-GM-CSF antibody.CONCLUSION: The recombination between human MUC1 repeated sequence concatemer and GM-CSF gene successfully constructs eukaryotic coexpression plasmid.

OBJECTIVETo study the effect of liposuction on insulin resistance and lipid metabolism.

METHODSThe levels of serum triglyceride (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), and insulin sensitivity were measured pre-and 2-4 months postoperatively in 20 consecutive patients undergoing liposuction.

RESULTSCompared with preoperative, the insulin sensitivity increased significantly, the levels of TC and LDL-C decreased after the liposuction procedure.

CONCLUSIONSLiposuction may improve the insulin resistance and lipid metabolism.

Adult ; Blood Glucose ; metabolism ; Cholesterol ; blood ; Cholesterol, HDL ; blood ; Cholesterol, LDL ; blood ; Female ; Humans ; Insulin Resistance ; Lipectomy ; Lipid Metabolism ; Middle Aged ; Triglycerides ; blood ; Young Adult

BACKGROUNDHuman group O red blood cells have great benefit in specialized transfusion areas such as armed conflict and natural calamity. The group B antigen differs structurally from group O antigen only by the addition of one terminal alpha-linked galactose residue. In this study we aimed to remove the terminal galactose from group B red blood cell to get group O red blood cell.

METHODSalpha-galactosidase cDNA was cloned by RT-PCR from Catimor coffee beans grown on Hainan Island of China. The vector for alpha-galactosidase cDNA expression was constructed and transferred into Pichia pastoris cells by electroporation. The transgenic cells were cloned by fermentation and the recombinant alpha-galactosidase was purified by ion exchange chromatography. After studying the biochemical characters of alpha-galactosidase, we have used it in converting human erythrocytes from group B to group O.

RESULTSThe purity of recombinant alpha-galactosidase was higher than 96%, which was thought to be suitable for the use of blood conversion. Enzymatically converted human group O red blood cells (ECHORBC) exhibited membrane integrity, metabolic integrity, normal cell deformation and morphology. There were no coagulation between ECHORBC and any group of human blood. The ECHORBC will keep normal structure and function for a period of 21 days at 4 degrees C in monoammoniumphosphate nutrient solution. Experiments with Rhesus monkeys and gibbons showed that transfusion of enzymatically converted erythrocytes was safe.

CONCLUSIONECHORBC can be easily obtained from group B red blood cell by alpha-galactosidase digestion. This study suggests that ECHORBC could be transfused to patients safely and efficiently.

ABO Blood-Group System ; classification ; metabolism ; Animals ; Blood Transfusion ; Cloning, Molecular ; Coffee ; enzymology ; Erythrocytes ; metabolism ; Humans ; Macaca mulatta ; Quality Control ; Recombinant Proteins ; isolation & purification ; pharmacology ; alpha-Galactosidase ; immunology ; isolation & purification ; pharmacology ; toxicity

OBJECTIVETo establish a simple, reproducible, and practical mechanical injury model of hippocampal neurons of Sprague-Dawley rats in vitro.

METHODSHippocampal neurons isolated from 1-2-day old rats were cultured in vitro. Mild, moderate and severe mechanical injuries were delivered to the neurons by syringe needle tearing, respectively. The control neurons were treated identically with the exception of trauma. Cell damage was assessed by measuring the Propidium Iodide (PI) uptaking at different time points (0.5, 1, 6, 12 and 24 hours) after injury. The concentration of neuron specific enolase was also measured at some time points.

RESULTSPathological examination showed that degeneration, degradation and necrosis occurred in the injured cultured neurons. Compared with the control group, the ratio of PI-positive cells in the injured groups increased significantly after 30 minutes of injury (P<0.05). More severe the damage was, more PI-positive neurons were detected. Compared with the control group, the concentration of neuron specific enolase in the injured culture increased significantly after 1 hour of injury (P<0.05).

CONCLUSIONSThe established model of hippocampal neuron injury in vitro can be repeated easily and can simulate the damage mechanism of traumatic brain injury, which can be used in the future research of traumatic brain injury.

Analysis of Variance ; Animals ; Brain Injuries ; enzymology ; pathology ; Equipment Design ; Hippocampus ; enzymology ; injuries ; In Vitro Techniques ; Neurons ; enzymology ; pathology ; Phosphopyruvate Hydratase ; biosynthesis ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Reproducibility of Results

OBJECTIVETo study the correlation between brain edema, elevated intracranial pressure (ICP) and cell apoptosis in traumatic brain injury (TBI).

METHODSIn this study, totally 42 rabbits in 7 groups were studied. Six of the animals were identified as a control group, and the remaining 36 animals were equally divided into 6 TBI groups. TBI models were produced by the modified method of Feeney. After the impact, ICP of each subject was recorded continuously by an ICP monitor until the animal was sacrificed at scheduled time. The apoptotic brain cells were detected by an terminal deoxynucleotide-transferase-mediated dUTP-digoxigenin nick end labeling (TUNEL) assay. Cerebral water content (CWC) was measured with a drying method and calculated according to the Elliott formula. Then, an analysis was conducted to determine the correlation between the count of apoptotic cells and the clinical pathological changes of the brain.

RESULTSApoptotic cell count began to increase 2 h after the impact, and reached its maximum about 3 days after the impact. The peak value of CWC and ICP appeared 1 day and 3 days after the impact, respectively. Apoptotic cell count had a positive correlation with CWC and ICP.

CONCLUSIONSIn TBI, occurrence of brain edema and ICP increase might lead to apoptosis of brain cells. Any therapy which can relieve brain edema and/or decrease ICP would be able to reduce neuron apoptosis, thereby to attenuate the secondary brain damage.

Animals ; Apoptosis ; Brain Edema ; etiology ; metabolism ; pathology ; Brain Injuries ; complications ; pathology ; physiopathology ; Cell Count ; Disease Models, Animal ; In Situ Nick-End Labeling ; Intracranial Hypertension ; etiology ; pathology ; physiopathology ; Male ; Necrosis ; genetics ; pathology ; Rabbits ; Reference Values ; Telencephalon ; metabolism ; Water ; metabolism

OBJECTIVETo investigate the knowledge and attitudes of healthcare professionals (doctors, nurses and administrators) to adverse drug reactions (ADR) in Wuhan city and to identify the reasons for under-reporting.

METHODSStructured interviews were carried out in Wuhan, Hubei province. Questionnaire survey to approximately 15% of the medical practitioners selected from 16 hospitals, was conducted during the period from February to March 2003.

RESULTSOnly 2.7% of the interviewees knew the definition of adverse drug reactions. 61.7% of the doctors, 62.7% of the nurses and 61.1% of the administrators had ever encountered an ADR during their practices, but did not report to the national monitoring center or other centers. The major reasons for not reporting included: ignorant about the requirement and the reporting process of ADR (71.4%); address of the reporting agency and Forms unavailable (67.9%, 60.4%); unaware of the existence of a national ADR reporting system (52.2%); needless to report as the ADR being too well known (44.1%). They mainly reported an ADR to the hospital pharmacy or other departments, or to the pharmaceutical administration. Education, training and developing new institutions were ways to improve the reporting system.

CONCLUSIONSOur results showed that healthcare professionals had little knowledge on the basic ADR knowledge. The main reasons for underreporting were related to factors on reporting process, address of related centers and unavailable of the Forms. Education and training to doctors and nurses to enhance the awareness of administrators were the ways to improve the reporting system.

Adverse Drug Reaction Reporting Systems ; Attitude of Health Personnel ; China ; Drug-Related Side Effects and Adverse Reactions ; Female ; Health Knowledge, Attitudes, Practice ; Humans ; Male ; Practice Patterns, Physicians' ; Surveys and Questionnaires