Animals ; Dexamethasone ; administration & dosage ; metabolism ; pharmacokinetics ; Drug Administration Routes ; Ear, Middle ; Guinea Pigs ; Nanoparticles ; administration & dosage

Researches on MDR (multidrug resistance) of tumor presently focus on seeking chemosensitizers with more targets, high efficiency and low toxicity from traditional Chinese medicine. This paper reviews the research progress in the reversion of MDR of leukemia, hepatocarcinoma, breast carcinoma and oral epithelioid neoplasia by TDM compound, its extracts, its groups of active ingredients or its active ingredients.
ATP-Binding Cassette, Sub-Family B, Member 1 ; biosynthesis ; genetics ; Animals ; Breast Neoplasms ; metabolism ; Carcinoma, Hepatocellular ; metabolism ; DNA Topoisomerases, Type II ; metabolism ; Drug Combinations ; Drug Resistance, Multiple ; drug effects ; Drug Resistance, Neoplasm ; drug effects ; Drugs, Chinese Herbal ; isolation & purification ; pharmacology ; Genes, MDR ; Humans ; Leukemia ; metabolism ; Liver Neoplasms ; metabolism ; Medicine, Chinese Traditional ; Multidrug Resistance-Associated Proteins ; metabolism ; Plants, Medicinal ; chemistry ; RNA, Messenger ; biosynthesis ; genetics

Objective To investigate the effects of the overexpression of HO-1 induced by CoPP in the donor on the survival of transplanted allogeneic islets of rats and the mechanism.Methods (1) Brown Norway rats were randomly divided into control group, and CoPP-induced group receiving intraperitoneal injection of CoPP (2.5 mg/kg) at 3rd and 1st day prior to islet isolation.By using the cytoimmunofluorescenee and Western blot, the expression of HO-1 in isolated islets was detected.The insulin level in the supernatant of the cultured islets stimulated with glucose was determined by ELISA.(2) Lewis male rat diabetic models were established by a single intravenous injection of alloxan, and then randomly divided into CoPP group and control group.Islets were transplanted under the left kidney capsule of each diabetic recipient.The survival time after transplantation, and pathological changes following rejection of the islet grafts were analyzed.Results The HO-1 was highly expressed in the islets isolated from CoPP-treated rats by cytoimmunofluorescence and Western blot.After stimulation with 16.7 mmol/L glucose, the insulin concentration in Copp-treated and Copp-untreated groups was (46.60± 1.13) and (19.01 ± 1.49) mIU/L respectively (P<0.05).The insulin concentration in Copp-treated and Copp-untreated groups in islets stimulated with 5.6 mmol/L glucose was (15.65 ± 0.89) and (12.28 ± 0.89) mU/L respectively (P>0.05).The stimulated index in Copp-treated and Copp-untreated groups was (2.98 ± 0.10) and 1.55 + 0.01 respectively (P< 0.05).The survival time of islets allograft in Copp-treated and Copp-untreated groups was separately (12.20±5.67) and (5.60± 1.14) days respectively (P<0.05).Histological analysis revealed the presence of more islands of insulin-positive cells and considerably fewer lymphocytes or inflammatory infiltration than the controls.Conclusions CoPP could induce the HO-1 expression of islets, and improve their function.Over-expression of HO-1 in islets could prolong survival time of islets allograft.

OBJECTIVETo investigate the influence of drug properties on the encapsulation effiency (EE) and drug release of transfersomes for a proper transfersome preparation.

METHODTo prepare the transfersomes of colchicines (CLC), vincristine sulfate (VCR) and mitoxantrone hydrochloride (DHAD) with the same materials and methods, and then measure their EE. To find out the relationship between drug properties like solubility, molecular weight and charges, and EE. To performe the drug release experiments of various types of transfersomes in vitro, and compare their differences.

RESULTVCR and DHAD are lipophilic or hydrophilic, owing positive charges and large molecular weight, as a result, their EE are high, while CLC is amphipathic, neutral, and of small molecular weight, its EE is very low. As DHAD can insert into the membrane of transfersome, the drug release of DHAD-T in vitro is much slower than that of VCR-T.

CONCLUSIONTo prepare transfersomes with high EE, drugs that are lipophilic or hydrophilic, high molecular weight and opposite charges to the membrane should be chosen. Interaction between drugs and membrane will influnce the rate of drug release.

Antineoplastic Agents ; administration & dosage ; chemistry ; Antineoplastic Agents, Phytogenic ; administration & dosage ; chemistry ; Colchicine ; administration & dosage ; chemistry ; Deoxycholic Acid ; Drug Carriers ; Gout Suppressants ; administration & dosage ; chemistry ; Mitoxantrone ; administration & dosage ; chemistry ; Particle Size ; Phosphatidylcholines ; Solubility ; Technology, Pharmaceutical ; methods ; Vincristine ; administration & dosage ; chemistry

OBJECTIVETo study release mechanism of berberine hydrochloride (BH) from carboxymethyl konjac glucomannan pellets for colonic delivery.

METHODThe pellets were prepared by ionotropic gelation technique. The effects of the kinds of enzyme and enzyme concentration of dissolution media on the release of BH and the erosion properties of the pellets were studied.

RESULTCompared with the dissolution media without enzymes, the release of BH and the erosion of the pellets were increased obviously in the media with rat cecal and colonic content or beta-mannase, the degradation of the carrier material of pellets by enzymes was the main factor which result in the erosion of the pellets. With the increased of beta-mannase concentration, the release of BH and the erosion of the pellets increased, the amount relationships of the release of BH and the erosion of the pellets were approximately 1:1. The release of BH exhibit Peppas equation, the n value was more than 1.

CONCLUSIONThe release mechanism of BH from the pellets was enzymatic erosion-controlled, which indicates the potential of the pellets to serve as a colon-specific drug delivery system.

Animals ; Berberine ; administration & dosage ; pharmacokinetics ; Biological Transport ; drug effects ; Colon ; metabolism ; Drug Delivery Systems ; methods ; Mannans ; chemistry ; Rats ; Rats, Sprague-Dawley ; beta-Mannosidase ; pharmacology

OBJECTIVETo observe the absorption and concentration of berberine hydrochloride (BH) in gastric, entric, colonic tissue after intragastric administration of BH-containing carboxymethyl konjac glucomannan pellets for evaluating colon-specific drug delivery characteristics of the pellets.

METHODBH-containing carboxymethyl konjac glucomannan pellets (pellets group) and BH-containing carboxymethyl cellulose suspension (control group) were intragastric administrated to rats at the dose of 50 mg x kg(-1), respectively. A high performance liquid chromatography method determinated BH concentration in rat plasma and tissue. Drug delivery index (DDI) was calculated.

RESULTThe range of BH in plasma and tissue in rats were 0.025 2-2.52 mg x L(-1) (r = 0.999 2) and 0.126-25.22 mg x L(-1) (R > 0.99),respectively. The detection of BH in plasma and tissue were 10 microg x L(-1) and 8 microg x L(-1), respectively. The area under the curve (AUC(0 --> infinity)) in the plasma samples of pellets group was 0.477 times that of the control group; in the gastric, entric, colonic tissue, the AUC(0 --> infinity) of pellets group was as much as 0.187, 0.228, 2.00 times that of the control group, respectively. The DDI of the pellets was 0.392 4, 0.478 6, 4.193 in the gastric, entric, colonic tissue of the rat, respectively.

CONCLUSIONCarboxymethyl konjac glucomannan pellets may be a useful carrier of BH for colon-specific delivery.

Absorption ; Animals ; Berberine ; metabolism ; Calibration ; Chromatography, High Pressure Liquid ; Drug Implants ; Female ; Intestines ; metabolism ; Male ; Mannans ; administration & dosage ; pharmacokinetics ; Organ Specificity ; Rats ; Sensitivity and Specificity

OBJECTIVEIn vitro enzymatic degradation of carboxymethy konjac glucomannan (CMKGM) were studied to evaluate the feasibility of CMKGM used as carrier materials to prepare colon-specific drug delivery systems.

METHODThe solutions with rat gastrointestinal tract (GIT) contents or with commercial enzymes were chosen to stimulate in vivo GIT environment, respectively. Enzymatic degradation of CMKGM were studied by viscometic procedure. Degradation kinetics of CMKGM and konjac glucomannan (KGM) by enzymes, the effects of the degree of substitution (DS) of CMKGM and the pH of solution on its susceptibility to degradation were investigated.

RESULTCMKGM were degraded mainly in the simulated cecal and colonic media, but not in the simulated gastric and enteric media. Degradation of KGM and CMKGM by enzymes obeyed Michaelis-Menton kinetics. CMKGM with lower DS were more susceptible substrates. CMKGM were more susceptible substrates in solution with pH 6. 0-6. 8.

CONCLUSIONCMKGM had colon-specific enzymatic degradation characteristics and could be used as carrier materials to prepare colon-specific drug delivery systems.

Amorphophallus ; chemistry ; Animals ; Cecum ; enzymology ; Colon ; enzymology ; Drug Carriers ; chemistry ; Drug Delivery Systems ; Hydrogen-Ion Concentration ; Kinetics ; Mannans ; chemistry ; isolation & purification ; metabolism ; Plants, Medicinal ; chemistry ; Rats ; Rats, Sprague-Dawley ; beta-Mannosidase ; metabolism

OBJECTIVETo investigate the blood supply of the pedicle fat grafts with the third lumbar segmental artery and its clinical effects on reoperation for lumbar disc herniation.

METHODSTwelve sides of 6 adult cadaver examples were contributed to investigate the courser of lumbar segmental vessels and the distribution of hypodermic capillary net of the dorsal branch of the third lumbar segmental artery. From January 2000 to January 2007,49 patients needed reoperation to treat lumbar disc herniation,including 26 males and 23 females with an average age of 55.6 years (ranged from 39 to 70 years). Duration between two operations ranged from 8 months to 15 years with an average of 6.9 years. Reoperative reasons included recurrent lumbar disc protrusion(30 cases)postoperative epidural scar formation (17 cases), postoperative epidural cyst formation (2 cases). Of them,9 patients underwent posterior lumbar interbody fusion at the second operation. The pedicle fat grafts with the third lumbar segmental artery were covered on the sites of the laminectomy in these patients. After negative pressure drainage tube were pulled out, 2 ml Chitsan were injected to the sites of the laminectomy and around epidural nerve root through epidural catheter. VAS score and the Oswestry Disability Index (ODI) were used to assess clinical outcomes before and after operation.

RESULTSThe courser of third lumbar segmental vessels were invariant at the lateral face of the lumbar vertebral body. The dorsal branch of the third lumbar segmental artery penetrated thoracolumbar fascia and formed rich hypodermic capillary net in the region. All patients were followed up from 5 to 8 years with an average of 5.6 years. VAS score of low back pain and leg pain decreased respectively from preoperative 7.6 +/- 1.2, 8.9 +/- 0.9 to 3.6 +/- 0.5, 3.0 +/- 0.4 at final follow-up (P < 0.01); and ODI score decreased from preoperative 44.1 +/- 6.2 to 13.9 +/- 3.6 at final follow-up (P < 0.01). According to ODI score to evaluate the clinical outcomes, 29 cases got excellent results, 11 good, 7 fair, 2 poor.

CONCLUSIONThe pedicle fat grafts with the third lumbar segmental artery and Chitsan can reduce epidural scar formation and prevent peridural fibrosis and adhesion and improve clinical effects of reoperation for lumbar disc herniation.

Adipose Tissue ; pathology ; Adult ; Aged ; Arteries ; pathology ; physiopathology ; Female ; Follow-Up Studies ; Humans ; Intervertebral Disc Displacement ; pathology ; physiopathology ; surgery ; Lumbar Vertebrae ; blood supply ; pathology ; surgery ; Male ; Middle Aged ; Reoperation ; Transplantation ; Treatment Outcome

Objective To explore the different apoptotic gene expressions and apoptotic signaling transduction of human rhabdomyosarcoma (RD) cells infected by enterovirus 71 (EV71) in different stage.Methods The survival of EV71-infected RD cells was observed by trypan blue staining.The apoptotic morphology and rates of RD cells were surveyed and detected by Annexin V-FITC/PI staining and flow cytometry,respectively.PCR array was employed to analyze 88 apoptotic gene expressions from EV71-infected RD cells at 8 h and 20 h postinfection (p.i),respectively.Results After RD cells were infected with EV71 (MOI =5) at 8 h p.i,the viability was significantly decreased.Flow cytometry data demonstrated that the apoptotic rates of EV71-infected RD cells had increased to 18.0％ and 19.1％ at 20 h p.i in early and later stage respectively.RT-PCR array studies revealed significant variations in the expression of apoptotic genes.Among 88 genes,only the expression of IFN-β1 was upregulated 5.22 folds,whereas 47 genes including ACIN1,Akt,Apaf1,caspase and CIDEB were found to be downregulated that were lower than 2 folds at 8 h p.i.However,28 genes including FasL,CD40L,TNF,caspase-10 and caspase-3 were induced more than 2 folds after EV71 infection at 20 h.Conclusion The downregulation of apoptosis-related genes is associated with viral apoptosis-suppressing effect in RD cells in the early stage of EV71 infection.The death receptor signaling pathways including Fas/FasL and TNF/TNFR are activated to induce cell apoptosis in the late stage of EV71 infection.Moreover,host cell can also inhibit apoptosis by regulating signal pathway of CD40/CD40L,NF-κB/RelA and PI3K/Akt activation.

OBJECTIVETo study on the drug release characteristics and mechanism of gastrodin ion-activated nasal in situ gel in vitro.

METHODRegularity and mechanism of the drug release of gastrodin nasal in situ gel were studied by using the diffusion cell model and the membrane-less dissolution model, respectively. A novel kinesis diffusion cell model was designed according to the characteristics of release environment of nasal cavity. It was used to investigate the effect of adhesiveness on the release of the in situ gel.

RESULTDrug release of gastrodin nasal in situ gel followed the one order release model. Erosion rate of the gel was low and not linearly correlated with the release rate. Compared with gastrodin solution, the nasal in situ gel could increase release time and release amount.

CONCLUSIONGastrodin in the nasal in situ gel is released mainly by diffusion rather than erosion. Release amount of the in situ gel in nasal cavity may be obviously increased because of its adhesiveness.

Adhesiveness ; Benzyl Alcohols ; chemistry ; metabolism ; Calibration ; Diffusion ; Gels ; Glucosides ; chemistry ; metabolism ; Kinetics ; Models, Chemical ; Nose ; metabolism ; Solubility