To study the interaction of drugs of different properties, namely puerarin, borneol and catalpol in the process of in- clusion, in order to explore the inclusion regularity of multi-component and multi-property traditional Chinese medicine compound in- clusions. With HP-β-CD as the inclusion material, the freeze-drying method was used to prepare the inclusion. The inclusion between puerarin, borneol and catalpol was tested by measuring the inclusion concentration, DSC and X-ray diffraction. According to the find- ings, when insoluble drugs puerarin and borneol were included simultaneously, and puerarin was overdosed, puerarin included was almost equal to puerarin included, and borneol was not included. When puerarin was under-dosed, and HP-β-CD was overdosed, borne- ol was included, and the simultaneous inclusion was lower than the separate inclusion of borneol. When water-soluble drug catalpol was jointly included with puerarin or borneol, the simultaneous inclusion was almost the same with their separate inclusion, without charac- teristic peak of catalpol in DSC and X-ray diffraction patterns. There is a competition in the simultaneous inclusion between water-solu- ble drugs puerarin and borneol and a stronger competition in puerarin. The water-soluble drug catalpol could be included with HP-β-CD with no impact on the inclusion of puerarin or borneol.
2-Hydroxypropyl-beta-cyclodextrin ; Bornanes ; chemistry ; therapeutic use ; Brain Ischemia ; drug therapy ; Drug Compounding ; methods ; Freeze Drying ; Iridoid Glucosides ; chemistry ; therapeutic use ; Isoflavones ; chemistry ; therapeutic use ; Solubility ; beta-Cyclodextrins ; chemistry

OBJECTIVEPrader-Willi syndrome (PWS) is an example of a human genetic disorder that involves imprinting genes on the proximal long arm of chromosome 15 and SNRPN gene as a candidate gene for this syndrome. The purpose of this study was to show the molecular genetic defects and genomic imprinting basis in Chinese PWS patients and to evaluate the clinical applications of a differential diagnostic test for PWS.

METHODSFluorescence in situ hybridization (FISH) and methylation-specific PCR (MSPCR) techniques were applied for 4 clinically suspected PWS patients. Using three probes, including SNRPN probe for identification of the critical locus in PWS region, D15Z1 and PML control probes for identification of the 15p arm and 15q arm, the authors detected the deletions 15q in PWS. MSPCR was based on sodium bisulfite treatment of DNA and PCR primers specific for the maternal and paternal allele.

RESULTSWhen hybridized with mixed probes, it was found in 2 patients that the central specific signal was absent, but both the flanking control signals were retained, indicating SNRPN gene deletion of chromosome 15q11-13. Bisulfite-modified DNA from all PWS children amplified with methylated allele-specific primer pair showed only maternal 131bp PCR product, indicating the maternal uniparental disomy (UPD15).

CONCLUSIONGenomic imprinting plays an important role in the molecular pathogenesis of PWS that caused by paternal microdeletions of 15q11-q13 or maternal UPD of chromosome 15. The basic defect seemed to be an absence of function of PWS genes that are normally expressed only from the paternal chromosome 15. MSPCR is a rapid and simple PCR-based assay compared with other cyto-molecular tests and its results were consistent with the clinical diagnosis of PWS, so it seems to be a reliable diagnostic method for PWS patients who show abnormal methylation at SNRPN. The genetic differential tests for PWS are important in determining familial recurrence risk.

Adolescent ; Autoantigens ; Chromosome Deletion ; Chromosomes, Human, Pair 15 ; genetics ; Gene Deletion ; Genomic Imprinting ; genetics ; Humans ; In Situ Hybridization, Fluorescence ; Male ; Polymerase Chain Reaction ; methods ; Prader-Willi Syndrome ; genetics ; Ribonucleoproteins, Small Nuclear ; genetics ; snRNP Core Proteins

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

Objective To understand the periodicity of the incidence of hand, foot and mouth disease (HFMD) in representative provinces from different climatic zones in China, and to analyze the seasonality and the factors influencing the HFMD transmission rate, to provide a scientific reference for the prevention and treatment of HFMD. Methods Five climate-representative provinces including Hainan, Hunan, Shandong, Qinghai and Inner Mongolia were selected as research objects. Wavelet analysis was used to analyze the cyclic pattern of HFMD incidence. Time series susceptible infected recovered (TSIR) model was established to examine the HFMD transmission rate of the five provinces and of the entire country. The parameters in the TSIR model were estimated by markov chain monte carlo (MCMC). Linear regression model was used to analyze the effects of climate factors, school terms and the Spring Festival travel rush on the transmission rate of HFMD. Results (1) HFMD incidence in the provinces and the entire country exhibited annual or semi-annual cycles and the transmission rates in all provinces showed obvious seasonality with similar patterns. February to May was the peak period of HFMD transmission rate. (2) The transmission rate of HFMD was affected by the climate or the contact rate, depending on which factor was dominant. Conclusions The transmission rate of HFMD had obvious seasonality, which had increased significantly in February, and it was necessary to strengthen its prevention and control during the Spring Festival.

Multi-component traditional Chinese medicines are an innovative research mode for traditional Chinese medicines. Currently, there are many design methods for developing multi-component traditional Chinese medicines, but their common feature is the lack of effective connection of the traditional Chinese medicine theory. In this paper, the authors discussed the multi-component traditional Chinese medicine design methods based on medicinal property combination modes, provided the combination methods with the characteristics of traditional Chinese medicine for the prescription combinations, and proved its feasibly with hypertension cases.
Animals ; Antihypertensive Agents ; administration & dosage ; chemistry ; Blood Pressure ; drug effects ; Drug Combinations ; Drug Therapy ; Drugs, Chinese Herbal ; administration & dosage ; chemistry ; Humans ; Hypertension ; drug therapy ; physiopathology ; Medicine, Chinese Traditional ; Rats

OBJECTIVETo evaluate the clinical efficacy of combined treatment with lamivudine and famciclovir on chronic hepatitis B virus (HBV) infection.

METHODSNinety patients with chronic HBV infection were divided into 3 groups. Group one had 28 patients and was treated with combination of lamivudine (0.1 g/d, PO) and famciclovir (1.5 g/d,PO) for 24 weeks. Group two and three had 30 and 32 cases, respectively, and were treated with lamivudine 100 mg/day PO and famciclovir (1.5 g/d,PO) alone. All the patients had positive markers of HBsAg, HBeAg and anti-HBcAg in serum assayed by ELISA and of HBV DNA tested by PCR.

RESULTSThree strategies of treatment had no different effects on the change of patients' ALT levels. The serum HBV DNA became negative after treatment in 89.3% (25/28) of patients treated with combination of lamivudine and famciclovir, 66.7% (20/30) of patients treated with lamivudine, and 40.6% (13/32) of patients treated with famciclovir. The rate of serum HBeAg loss in 3 groups were 28.6% (8/28), 23.3% (7/30) and 21.9% (7/32), respectively.

CONCLUSIONSThe combination treatment of lamivudine and famciclovir for chronic HBV infection is safer than and superior to that of either drug alone.

2-Aminopurine ; analogs & derivatives ; therapeutic use ; Adolescent ; Adult ; Aged ; Antiviral Agents ; therapeutic use ; Child ; Drug Therapy, Combination ; Female ; Hepatitis B Antibodies ; blood ; Hepatitis B Core Antigens ; blood ; Hepatitis B Surface Antigens ; blood ; Hepatitis B e Antigens ; Hepatitis B virus ; immunology ; isolation & purification ; Hepatitis B, Chronic ; drug therapy ; Humans ; Lamivudine ; therapeutic use ; Male ; Middle Aged

Objective To construct a eukaryofic expression vector for A PP695 gene carrying green fluorescence protein (GFP) gene. Methods RT-PCR was used to amplify the full-length APP695 cDNA. The PCR products and the eukaryotic expression vector pIRES2-EGFP were digested by restriction endonueleases, and the digested APP695 gene was inserted into the digested eukaryotic expression vector. The positive recombinants were identified by PCR analysis, Nhe Ⅰ and Hind Ⅲ digestion and sequence analysis. Results The 2088-bp DNA fragment was amplified by PCR from the plasmid pCB6, and an identical DNA fragment was also amplified from the recombinants. The products of double restriction enzyme digestion were A PP695 gene with a 5.3-kb DNA fragment. Sequence analysis confirmed successful insertion of A PP695 gene into pIRES2-EGFP vector. Conclusion The eukaryotie expression vector pIRES2/APP695-EGFP has been successfully constructed.

OBJECTIVETo investigate the efficacy and safety of secreted interferon in treatment of chronic hepatitis B.

METHODSA multi-center randomized open-label controlled clinical trial was carried out. The patients of the study group were treated by secretory human interferon alpha-2a, and the patients of the control group were treated with an ordinary interferon.

RESULTSALT normalization rate in the secreted interferon group was 48.3% and it was higher at the end of treatment than that of the control group, but there was no difference between the two groups at the end of the follow-up. HBV DNA dropped more in the study drug group, but there was no difference in the normalization rate between the two groups. HBeAg seroconversions in secreted interferon group and in the control interferon group were 19.0% and 18.4% respectively. The safety of the two types of interferon was satisfactory.

CONCLUSIONSSecreted interferon was superior to ordinary interferon in ALT normalization and HBV DNA drop at the end of treatment in chronic hepatitis B patients, but there was no difference at the end of the follow-up. There was also no difference in HBeAg negative and HBeAg seroconversion between the two groups.

Adolescent ; Adult ; Antiviral Agents ; adverse effects ; therapeutic use ; DNA, Viral ; blood ; Follow-Up Studies ; Hepatitis B virus ; isolation & purification ; Hepatitis B, Chronic ; therapy ; Humans ; Interferon-alpha ; adverse effects ; therapeutic use ; Middle Aged ; Recombinant Proteins ; Treatment Outcome

This paper introduced an experimental study of the preparation of polylacticacid (PLA) nanoparticles of cucurbitacin (CuC) using a precipitation method. The residual acetone, ratio of CuC PLA precipitates, and the relationships between the ratios of two precipitates and drug incorporation rates were measured. It appeared that the nanoparticles with 60% of PLA incorporated with 5.5% of CuC were formed when acetone was injected into the aqueous phase. As the acetone gradually evaporated, drug incorporation/encapsulation continued, with most of CuC (about 70%) formed new crystalline cores and suspended in the form of microcrystals in the medium, resulting a suspension containing both nanoparticles and microcrystals. We also concluded that this system may not necessarily be suitable for all lipophilic drugs to be prepared to PLA nanoparticles with good incorporation rate. The drug incorporation depended on the interactions among drug, PLA, and organic solvents, in addition to the solubility of the drug.
Antineoplastic Agents, Phytogenic ; administration & dosage ; Chemical Precipitation ; Cucurbitaceae ; chemistry ; Cucurbitacins ; Delayed-Action Preparations ; Drug Compounding ; methods ; Drug Delivery Systems ; Lactic Acid ; Microspheres ; Nanotechnology ; Particle Size ; Plants, Medicinal ; chemistry ; Polyesters ; Polymers ; Triterpenes ; administration & dosage ; isolation & purification

OBJECTIVETo study the changes of peripheral plasmacytoid dendritic cells and lymphocyte subsets in patients with chronic hepatitis B (CHB) during consensus interferon (CIFN) treatment.

METHODSTwenty-three patients with CHB were treated with CIFN for 24 weeks and followed up for another 24 weeks. Peripheral plasmacytoid dendritic cells and lymphocyte subsets were measured throughout the treatment and follow-up periods.

RESULTSAfter CIFN treatment, 43.5% of the patients had virological and biochemical responses. The percentage and absolute number of peripheral plasmacytoid dendritic cells decreased significantly (P less than 0.05), the number of CD3+ cells, CD4+ T cells, B cells and the ratio of CD4+/CD8+ cells decreased also (P less than 0.05), but the number of CD8+ T cells and NK cells increased (P less than 0.05).

CONCLUSIONSConsistent virological and biochemical responses can be seen in some patients with CHB virus infection after CIFN treatment, and the percentage and number of their peripheral plasmacytoid dendritic cells greatly decreased, but the number of CD8+ T cells and NK cells increased.

Adult ; Antiviral Agents ; therapeutic use ; CD8-Positive T-Lymphocytes ; immunology ; Dendritic Cells ; immunology ; Female ; Hepatitis B, Chronic ; drug therapy ; immunology ; Humans ; Interferon-alpha ; therapeutic use ; Killer Cells, Natural ; immunology ; Male ; Young Adult