The purpose of the present study is to use beta-cyclodextrin polymers (beta-CDP) with different cross-linked degree (CLD) to form inclusion complexes with ibuprofen and examine the effects of structural and compositional factors of beta-CDP on its drug loading and release behaviors. A series of beta-CDP with different CLD were synthesized and characterized by Fourier Transform Infrared Spectroscopy (FT-IR) and 13C NMR spectrum. The beta-CDP was systemically characterized for the relation between the CLD of beta-CDP and the drug loading and release as well. The results of FT-IR and 13C NMR showed that similar peak-shaped vibration of beta-CDP and beta-CD implies that the polymer keeps the original characteristic structure of beta-CD. The CLD of the beta-CDP played a critical role in the drug loading and release, increasing the CLD resulted in reduction of drug loading, but increase in drug release.
Carbon Isotopes ; Cross-Linking Reagents ; chemistry ; Delayed-Action Preparations ; Drug Carriers ; Drug Compounding ; Drug Delivery Systems ; Ibuprofen ; administration & dosage ; chemistry ; Magnetic Resonance Spectroscopy ; Pharmaceutical Preparations ; administration & dosage ; chemistry ; Polymers ; chemistry ; Solubility ; Spectroscopy, Fourier Transform Infrared ; beta-Cyclodextrins ; chemistry

The inclusion complex of isotretinoin was prepared by sealed-control temperature method and amylose was used as carrier. The formation of inclusion complex was confirmed by powder X-ray diffraction and DSC. The equation of enzymatically-controlled drug release was established by kinetic theory, and the release characteristic of drug was confirmed by using the kinetic equation. The results show that the drug release was attributed to first order reaction without alpha-amylase. However, with alpha-amylase, the drug release was an acceleration process by the effect of both dissociation and enzymatic hydrolysis simultaneously. The research indicates that drug release from the inclusion complex was modulated by the addition of alpha-amylase.
Amylose ; chemistry ; Calorimetry, Differential Scanning ; Dermatologic Agents ; chemistry ; Drug Carriers ; chemistry ; Hydrolysis ; Isotretinoin ; chemistry ; Kinetics ; Temperature ; X-Ray Diffraction ; alpha-Amylases ; chemistry

This paper described the preparation and liver targeting traits of new solid lipid nanoparticles (SLN) containing floxuridinyl dibutyrate (FUDRB) modified with beta-D-galactosides (G2). FUDRB-SLN and FUDRB-G2SLN were prepared by thin layer ultrasonic technique. Transmission electron microscopy micrograph analysis demonstrated that the particle sizes of FUDRB-SLN and FUDRB-G2SLN were (137.5 +/- 11.1) nm and (95.0 +/- 10.7) nm. Drug loading were 9.64% and 8.56%, and entrapment efficiency were 99.81% and 96.23%, respectively. The concentrations of floxuridine (FUDR) in serum and some organs (liver, kidney and lung) were determined by RP-HPLC after iv administration of SLN. FUDR release was confirmed, and a significant enrichment of SLN modified with G2 was observed in liver with G2 complex (targeting rates of SLN-G2 was 8.28 for liver) in comparison with FUDR-sol (targeting rate was 2.56). FUDR could be detected in liver in mice at 480 min after iv administration of FUDRB-G2SLN. These results suggested that incorporation of G2 (4%-5%, g/g) into SLN enhanced the liver targeting-ability of FUDRB. SLN containing G2 could be a useful drug carrier system for liver targeting.
Animals ; Antimetabolites, Antineoplastic ; administration & dosage ; pharmacokinetics ; Area Under Curve ; Drug Carriers ; Drug Compounding ; Drug Delivery Systems ; Female ; Floxuridine ; administration & dosage ; blood ; pharmacokinetics ; Galactosides ; chemistry ; Lipids ; chemistry ; Liver ; metabolism ; Male ; Mice ; Nanoparticles ; Particle Size ; Tissue Distribution

OBJECTIVETo study the technological parameters of the purification process for effective part from Polygonum cuspidatum.

METHODUsing adsorption capacities and desorption rates of polydatin, resveratrol,emodin,physcion and total anthraquinone as the primary screening indexes, six resins were surveyed,and the optimized conditions of adsorption and desorption of the effective ingredients were studied.

RESULTResin D101 gave good separation performance and was selected to purify the effective part in Polygonum cuspidatum. The optimum parameters were established as the following: 1 BV (bed volume) sample extract was passed through the column with a flow rate of 2.4 BV x h(-1), 30 min later,the column was washed with 2 BV water, 2 BV 20% ethanol, 5 BV 50% ethanol, 2 BV 70% ethanol and 5 BV 95% ethanol, respectively. The combined 50% and 95% ethanolic elutes were concentrated to yield the purified effctive part.

CONCLUSIONThe purity of the total effective ingredients in the product was up to 36. 87%. Macroporous resin D101 could be well used in separating and purifying the effective part from Polygonum cuspidatum.

Adsorption ; Anthraquinones ; chemistry ; isolation & purification ; Drugs, Chinese Herbal ; chemistry ; isolation & purification ; Emodin ; analogs & derivatives ; isolation & purification ; Fallopia japonica ; chemistry ; Glucosides ; isolation & purification ; Plants, Medicinal ; chemistry ; Resins, Synthetic ; chemistry ; Stilbenes ; isolation & purification ; Technology, Pharmaceutical ; methods ; Temperature

OBJECTIVETo explore germline mutations of MLH1 in hereditary nonpolyposis colorectal cancer (HNPCC), and to investigate the pathobiology of novel detectable mutations of MLH1.

METHODRNA was extracted from the peripheral blood of 12 patients from 12 different families fulfilling the Amsterdam II Criteria of HNPCC. Germline mutations of MLH1 were determined by RT-PCR with gene specific primers, heat-resistance reverse transcriptase and long-template PCR polymerase, followed by cDNA sequencing analysis. PCR-Genescan analysis was used to further investigate microsatellite instability with a panel of 5 microsatellite markers (BAT26, BAT25, D5S346, D2S123 and Mfd15), along with immunohistochemistry staining to detect the expression of MLH1 protein in the tumor tissues.

RESULTSFour germline mutations were found in 4 patients, 2 of which were previously reported GTT-->GAT mutation at codon 384 of exon 12, and the other two were novel mutations: CGC-->TGC at codon 217 of exon 8 and CCG-->CTG at codon 581 of exon 16. Two tumors with the novel mutations had high frequency microsatellite instability showing more than 2 instable loci (RER + phenotype), and both tumors lost their MLH1 protein expression.

CONCLUSIONThe two novel germline mutations of MLH1 identified in this study, i.e. CGC-->TGC at codon 217 of exon 8 and CCG-->CTG at codon 581 of exon 16, are very likely to have pathological significance.

Adaptor Proteins, Signal Transducing ; Carrier Proteins ; genetics ; metabolism ; Codon ; Colorectal Neoplasms, Hereditary Nonpolyposis ; genetics ; metabolism ; DNA Mutational Analysis ; DNA, Neoplasm ; genetics ; Exons ; Female ; Germ-Line Mutation ; Humans ; Male ; Microsatellite Instability ; Middle Aged ; MutL Protein Homolog 1 ; Nuclear Proteins ; genetics ; metabolism ; Phylogeny

OBJECTIVETo analyze systematically the characteristics of occupational hazards in the foundry, and provide precise data for epidemiology studies and control of occupational hazards in the foundry.

METHODSData of airborne dust, chemical occupational hazards and physical occupational agents in environment in the foundry from 1978 to 2008 were dynamically collected. Mean concentration and intensity (geometric mean) of occupational hazards were calculated by job in different years.

RESULTSMain occupational hazards in the foundry were silica, metal fume, noise and heat stress. Silica existed in all of main jobs. The mean concentration of silica before 1986 was an extremely high level of 8.6 mg/m(3), and then remarkably dropped after 1986, with the level of 2.4 mg/m(3) from 1986 to 1989, 2.7 mg/m(3) from 1990 to 2002 and 2.7 mg/m(3) from 2003 to 2008. The trend of silica concentrations by job was consistent with that in general. Silica concentrations among jobs were significantly different, with highest level in melting (4.4 mg/m(3)), followed by cast shakeout and finishing (3.4 mg/m(3)), pouring (3.4 mg/m(3)), sand preparation (2.4 mg/m(3)), moulding (2.1 mg/m(3)) and core-making (1.7 mg/m(3)). Concentration of respirable dust in pouring was highest (2.76 mg/m(3)), followed by cast shakeout and finishing (1.14 mg/m(3)). Mean concentration of asbestos dust in melting was a relative high level of 2.0 mg/m(3). In core-making and sand preparation, there existed emission production of adhesive, with mean concentrations as followed, ammonia (5.84 mg/m(3)), formaldehyde (0.60 mg/m(3)), phenol (1.73 mg/m(3)) and phenol formaldehyde resin (1.3 mg/m(3)) also existed. Benzene and its homologues existed in cast shakeout and finishing, and the level of benzene, toluene, xylene was 0.2 mg/m(3), 0.1 mg/m(3) and 1.3 mg/m(3), respectively. In pouring and melting, there existed chemical occupational hazards, including benzo(a) pyrene, metal fume (lead, cadmium, manganese, nickel, chromium) and gas(hydrogen sulfide, phosphine, sulfur dioxide, carbon monoxide). Mean concentration of benzo(a) pyrene was a low level of 1.80 x 10(-4) microg/m(3). Physical occupational agents in the foundry were noise, heat stress and vibration. Intensity of heat stress was high in melting, pouring and cast shakeout and finishing, with the level of 30 degrees C, 29 degrees C and 26 degrees C, respectively. Noise was high in cast shakeout and finishing and core-making, with the level of 93.1 dB(A) and 89.5 dB(A), respectively. Vibration existed in core-making and cast shakeout and finishing. Compulsory postures included long standing, seating and bowing.

CONCLUSIONOccupational hazards in environment of the foundry are diversified and their concentrations exceed permissible exposure limits stipulated by the national occupational hygienic standards. High-concentrations of dust, metal fume, low-concentrations of variety of chemicals, high-intensity of noise and vibration, heat stress, and harmful compulsory posture, and so on all co-exist in the foundry. Control and protective measures should be strengthened.

Dust ; analysis ; Hazardous Substances ; analysis ; Metallurgy ; Occupational Exposure

OBJECTIVETo analyze the association of variants of hepatocyte nuclear factor-1alpha (HNF-1alpha) gene with type 2 diabetes in Chinese population.

METHODSIn 152 unrelated type 2 diabetes patients and 93 unrelated controls, eleven single nucleotide polymorphisms (SNPs) were identified and genotyped. Statistical analyses were performed to investigate whether these SNPs were associated with diabetes status in our samples.

RESULTSIn the individual SNP study, no SNP differed significantly in frequency between type 2 diabetes patients and controls. In the haplotype analysis, two haplotype blocks were identified. In haplotype block 1, no evidence was found between common HNF-1alpha haplotypes and type 2 diabetes. However, in haplotype block 2, a common haplotype GCGC formed by four tagging SNPs (tSNPs) was found to be associated with decreased risk of type 2 diabetes (odds ratio [OR] 0.6011, 95% confidence interval [CI] 0.4138-0.8732, P = 0.0073, empirical P = 0.0511, permutation test). A similar trend was also observed in the diplotype analysis, indicating that the increasing copy number of the haplotype GCGC was associated with the decreased frequency of diabetes (P = 0.0193).

CONCLUSIONThe results of this study provide evidence that the haplotype of HNF-1alpha decreases the risk of type 2 diabetes in Chinese individuals.

Adult ; Aged ; Case-Control Studies ; China ; epidemiology ; Diabetes Mellitus, Type 2 ; epidemiology ; genetics ; Genetic Predisposition to Disease ; Haplotypes ; Hepatocyte Nuclear Factor 1-alpha ; genetics ; Humans ; Middle Aged ; Polymorphism, Single Nucleotide

OBJECTIVETo investigate how F261S mutation identified from Chinese obese patients affects the function of melanocortin 4 receptor (MC4R) and to analyze the obesity-related phenotypes in subjects carrying the F261S mutation.

METHODSF261S mutant of MC4R was generated by site-directed mutagenesis. Plasmids encoding wild-type or F261S mutant of MC4R were transfected into HEK293 and COS-7 cells to examine their functional characteristics. Signaling properties of F261S MC4R were assessed by measuring intracellular cAMP levels in response to alpha-MSH stimulation. Cell surface expression of F261S MC4R was compared with that of wild-type MC4R. Clinical examinations were performed in subjects carrying F261S mutation and in non-mutated controls.

RESULTSThe alpha-MSH-stimulated reporter gene activity was significantly reduced in cells expressing F261S MC4R, with a maximal response equal to 57% of wild-type MC4R. The F261S mutation also led to a significant change in the Es50 value compared with the wild-type receptor (P<0.01). Immunofluorescent assay revealed a marked reduction in plasma membrane localization of the MC4R in cells expressing the F261S mutant receptor. The resting metabolic rate and fat composition of the mutant carriers were not significantly different from those of the non-mutated obese controls.

CONCLUSIONSThe decreased response to alpha-MSH due to the intracellular retention of MC4R may cause early-onset obesity in the F261S pedigree of Chinese.

Adult ; Age of Onset ; Aged ; Animals ; COS Cells ; Cercopithecus aethiops ; Child ; China ; Female ; Humans ; Male ; Middle Aged ; Mutation ; Obesity ; epidemiology ; metabolism ; Pedigree ; Receptor, Melanocortin, Type 4 ; genetics ; metabolism

OBJECTIVETo investigate the prevalence of mutations of hepatocyte nuclear factor (HNF)-1 alpha gene in Chinese families with early-onset and/or multiplex diabetes mellitus.

METHODSThe studied population consisted of 247 unrelated Chinese residents in Shanghai, including 93 healthy controls and 154 probands of early-onset and/or multiplex diabetes pedigrees. The ten exons, flanking introns and minimal promoter region of HNF-1 alpha gene were screened using polymerase chain reaction-single strand conformation polymorphism and DNA sequencing.

RESULTSFourteen substitutions were identified in 154 probands. Three variants were not observed in 93 healthy controls. Two of them (nt-128T-->G IVS2 nt+21G-->A) were not reported previously and all co-segregated with diabetes. The genotype and allele frequencies of the other eleven variants in the diabetic patients were not significantly different from those in the healthy controls. There were no significant relationships between the eleven variants of HNF-1 alpha gene and clinical variables (plasma glucose, insulin, C-peptide and fasting lipid profile).

CONCLUSIONHNF-1 alpha gene is not a major cause of early-onset or multiplex diabetes pedigrees in this Chinese population in Shanghai.

Asian Continental Ancestry Group ; genetics ; Base Sequence ; Blood Glucose ; metabolism ; China ; Cholesterol ; blood ; Cholesterol, HDL ; blood ; Cholesterol, LDL ; blood ; Diabetes Mellitus, Type 2 ; blood ; ethnology ; genetics ; Female ; Hepatocyte Nuclear Factor 1-alpha ; genetics ; Humans ; Insulin ; blood ; Male ; Molecular Sequence Data ; Mutation ; Pedigree ; Peptides ; blood ; Polymerase Chain Reaction ; Polymorphism, Single-Stranded Conformational

OBJECTIVETo study the method for synthesis of 2-hydroxyl-5- butyramidobenzoic acid and test its effect on acetic acid-induced colitis in rats.

METHODS2-hydroxyl-5-butyramidobenzoic acid was synthesized from 5-aminosalicylic acid and butyric acid by amidation, esterification and hydrolization. The effect of 2-hydroxyl-5-butyramidobenzoic acid on acetic acid enema-induced colitis in rats was investigated.

RESULTSThe structure of 2-hydroxyl-5-butyramidobenzoic acid was identified by IR and 1H-NMR. After treatment with acetic acid, the colon mucosal damage index (CMDI), fecal occult blood (OB) test, and activity of myelperoxidase (MPO) increased significantly in the rats as compared to the control levels. 2-hydroxyl-5- butyramidobenzoic acid obviously reduced the CMDI and OB, and reduced the level of MPO in the rats with colitis.

CONCLUSIONThe synthesis of 2-hydroxyl-5-butyramidobenzoic acid requires only mild conditions with simple procedures, and the synthesized 2-hydroxyl-5-butyramidobenzoic acid shows obvious therapeutic effects on mucosal damage of in rats with acetic acid-induced colitis.

Acetic Acid ; Aminobenzoates ; chemical synthesis ; chemistry ; pharmacology ; therapeutic use ; Animals ; Colitis, Ulcerative ; chemically induced ; drug therapy ; Male ; Protective Agents ; chemical synthesis ; pharmacology ; therapeutic use ; Rats ; Rats, Sprague-Dawley ; Salicylates