Thienorphine is a chemically-new opioid developed in Beijing Institute of Pharmacology and Toxicology. To elucidate the chemical basis for the unique pharmacological effects of thienorphine, 15 derivatives were synthesized according to combinatorial chemistry and the structure-activity relationships of these compounds were studied. It is demonstrated that thienorphine is a potent long-acting partial agonist. N-Cyclopropylmethyl is responsible for the antagonist effect of thienorphine. More importantly, thiophene at the end of side chain is most likely the pharmacophore accounts for the long-lasting effect of thienorphine. Change of the connection of thiophene and the side chain does not result in changes in the antinociceptive activity.
Animals ; Buprenorphine ; analogs & derivatives ; pharmacokinetics ; pharmacology ; Combinatorial Chemistry Techniques ; Dose-Response Relationship, Drug ; Female ; Male ; Mice ; Mice, Inbred Strains ; Morphine ; pharmacology ; Rats ; Rats, Wistar ; Receptors, Opioid ; agonists ; Structure-Activity Relationship

The total RNA was extracted from ginseng leaves of Panax ginseng. The Cu/Zn-SOD gene was amplified via RT-PCR and the pET-28(a)-Cu/Zn-SOD expression vector was constructed. The pET-28 (a)-Cu/Zn-SOD recombinant plasmid was transformed into Escherichia coli BL21 (DE3) competent cells and was induced by IPTG in order to select optimal induction of expression conditions. The target protein was purified by the nickel ions (Ni ) affinity chromatography and the target protein enzyme activity was determinated by the xanthine oxidase method. The similarity of the Cu/Zn-SOD gene sequences and the Cu/Zn-SOD gene sequences of Korean ginseng in NCBI was 99. 00%. The target protein expression level was about 44.42%, and the molecular weight was 16.30 kDa after the pET-28(a)-Cu/Zn-SOD recombinants were induced by IPTG. The purified Cu/Zn-SOD protease activity reached 10,596.69 U x mg(-1). The P. ginseng pET-28(a)-Cu/Zn-SOD prokaryotic expression vector was built by the method of molecular biology, which provided the foundation for studying the Cu/Zn-SOD biology function.
Cloning, Molecular ; Escherichia coli ; genetics ; Gene Expression ; Genetic Engineering ; methods ; Genetic Vectors ; genetics ; Panax ; enzymology ; genetics ; Sequence Analysis ; Superoxide Dismutase ; genetics ; isolation & purification ; metabolism

OBJECTIVETo investigate the late results of using posterior restoration and three-column fixation to treat lumbar spondylolisthesis.

METHODSOne hundred and eighty-four patients with lumbar spondylolisthesis were collected from March 1999 to May 2007, they were treated by posterior restoration and fixation with single nail-grooved tail steel plate and fixed with cage (WDFC). Among these cases, 87 cases were fixed with one WDFC, 97 cases were used two WDFCs.

RESULTSAll patients were followed up for 8 to 69 months(averaged 23 months). According to Nakai standard, the results was excellent in 142 cases, good in 34, fair in 8, the excellent and good rates were 95.6%. Seventy-nine vertebraes with I degree spondylolisthesis were reduced after surgery. Eighty-seven vertebraes with II degree spondylolisthesis were reduced except 9 with I degree spondylolisthesis left. Twenty-one with III degree spondylolisthesis were reduced except 5 with I degree spondylolisthesis left; In 2 with IV degree spondylolisthesis, one with I degree spondylolisthesis left and the other with II degree spondylolisthesis left. The follow-up results showed that there was no statistical significance in the height of intervertebral space between preoperation and post-operation, and no recurrence was observed and no single nail-grooved tail steel plate and WDFC were loose or crashed.

CONCLUSIONPosterior restoration and three-column fixation is a positive modus operandi to treat lumbar spondylolisthesis,which can reduce excellently,keep the height of intervertebral space and stabilization of segment, obtain high rate of fusion, and cut down complication.

Adolescent ; Adult ; Aged ; Bone Plates ; Female ; Follow-Up Studies ; Fracture Fixation, Internal ; methods ; Humans ; Lumbar Vertebrae ; surgery ; Male ; Middle Aged ; Spinal Fusion ; instrumentation ; Spondylolisthesis ; surgery

OBJECTIVETo evaluate the neuroprotective effect of tetramethylpyrazine (TMP) against focal cerebral ischemic injury in rats with diffusion-weighted magnetic resonance imaging (DWMRI).

METHODSRat models of focal cerebral ischemic injury were established in 16 male SD rats. They were randomly divided into the TMP group and the control group, eight in each group, and pretreated with TMP and normal saline respectively before modeling. Change of infarcted cerebral focus was observed with DWMRI at 1, 2, 6, 12 and 24 hrs after infarction, and the infarction volume (IV) at 24 hrs after modeling was estimated by triphenyltetrazolium chloride (TTC) stain.

RESULTSThe IV in all time points observed in the TMP group with DWMRI was significantly smaller than that in the control group (P<0.01). Compared with that at 1 hr after infarction, in the control group at 2, 6, 12 and 24 hrs after modeling, the IV enlarged by 13.3%, 29.7%, 50.3% and 57.3% respectively, while that in the TMP group 9.9%, 21.3%, 37.1% and 40.5% respectively. The cerebral IV estimated by TTC stain 24 hrs after modeling was larger than that estimated by DWMRI.

CONCLUSIONTMP pretreatment before modeling was effective in protecting brain against cerebral ischemic damage in rats. DWMRI dynamic scanning observation has important significance in observing the cerebral ischemic developing process and evaluating the effectiveness of brain protective measures.

Animals ; Diffusion Magnetic Resonance Imaging ; Infarction, Middle Cerebral Artery ; drug therapy ; pathology ; Male ; Neuroprotective Agents ; pharmacology ; therapeutic use ; Phytotherapy ; Pyrazines ; pharmacology ; therapeutic use ; Random Allocation ; Rats ; Rats, Sprague-Dawley

Low birth weight (LBW) and preterm birth (PB) are associated with newborn mortality and diseases in adulthood.We explored factors related to LBW and PB by conducting a population-based case-control study from January 2011 to December 2013 in Wuhan,China.A total of 337 LBW newborn babies,472 PB babies,and 708 babies with normal birth weights and born from term pregnancies were included in this study.Information of newborns and their parents was collected by trained investigators using questionnaires and referring to medical records.Univariate and logistic regression analyses with the stepwise selection method were used to determine the associations of related factors with LBW and PB.Results showed that maternal hypertension (OR=6.78,95％ CI:2.27-20.29,P=0.001),maternal high-risk pregnancy (OR=1.53,95％ CI:1.06-2.21,P=0.022),and maternal fruit intake ≥300 g per day during the first trimester (OR=1.70,95％ CI:1.17-2.45,P=0.005) were associated with LBW.BMI ≥24 kg/m2 of mother prior to delivery (OR=0.48,95％ CI:0.32-0.74,P=0.001) and gestation ≥37 weeks (OR=0.01,95％ CI:0.00-0.02,P＜0.034) were protective factors for LBW.Maternal hypertension (OR=3.36,95％ CI:1.26-8.98,P=0.016),maternal high-risk pregnancy (OR=4.38,95％ CI:3.26-5.88,P＜0.001),maternal meal intake of only twice per day (OR=1.88,95％ CI:1.10-3.20,P=0.021),and mother liking food with lots of aginomoto and salt (OR=1.60,95％ CI:1.02-2.51,P=0.040) were risk factors for PB.BMI ≥24 kg/m2 of mother prior to delivery (OR=0.66,95％ CI:0.47-0.93,P=0.018),distance of house from road ≥36 meters (OR=0.72,95％ CI:0.53-0.97,P=0.028),and living in rural area (OR=0.60,95％ CI:0.37-0.99,P=0.047) were protective factors for PB.Our study demonstrated some risk factors and protective factors for LBW and PB,and provided valuable information for the prevention of the conditions among newborns.

BACKGROUNDBroad-spectrum antibiotic administration promotes intestinal colonization of exogenous fungal pathogens in healthy animals and has been recognized as one of the risk factors of invasive fungal infection in clinical settings. It is unclear whether broad-spectrum antibiotic treatment would change the intestinal mycobiota without exogenous fungal challenge in the context of sepsis.

METHODSWe established a rat model of double-hit sepsis using burn injury and endotoxin challenge. Rats with burn injury or double-hit sepsis received imipenem treatment for 3 days or 9 days, and their colon contents were sampled for selective fungal culture and isolation counts.

RESULTSImipenem treatment promoted the overgrowth of the commensal fungus Geotrichum capitatum in rats with burn injury. Imipenem treatment also promoted colon colonization by exogenous fungi in rats with burn injury and double-hit sepsis, including Trichosporon cutaneum, Candida albicans, Candida krusei, and Candida glabrata. A longer duration of imipenem treatment had a stronger impact on colon colonization by exogenous fungi.

CONCLUSIONImipenem treatment facilitates the overgrowth of commensal fungi and colonization by exogenous, potentially pathogenic fungi in the colons of rats with burn injury or double-hit sepsis.

Animals ; Anti-Bacterial Agents ; therapeutic use ; Burns ; complications ; microbiology ; Candida ; pathogenicity ; Colon ; microbiology ; Imipenem ; therapeutic use ; Male ; Rats ; Rats, Sprague-Dawley ; Sepsis ; drug therapy ; microbiology ; Trichosporon ; pathogenicity

The pharmacokinetics of 6beta-naltrexol (6beta-NOL) following single intramuscular administration and multiple intramuscular injection once per day for seven days was studied in 4 Beagle dogs. Plasma concentration of 6beta-NOL in dogs was analyzed by a combination of high performance liquid chromatography (HPLC) and electrochemical detection with naloxone (NLX) as internal standard. After single intramuscular injection of 0.2 mg x kg(-1) 6beta-NOL, the plasma concentration-time curve of the drug was found to fit to a two compartment model with first-order absorption. The main parameters of single dosing were as follows: t1/2alpha was (0.26 +/- 0.23) h, t1/2beta was (4.77 +/- 1.65) h, C(max) was (81.65 +/- 5.61) ng x mL(-1), t(peak) was (0.27 +/- 0.07) h, CL(s) was (1.20 +/- 0.06) L x kg(-1) x h(-1), V/F(c) was (1.94 +/- 0.15) L x kg(-1), and AUC(0-t) was (166.82 +/- 7.68) ng x h x mL(-1), separately. After multiple intramuscular injection of 0.2 mg x kg(-1) 6beta-NOL once per day for seven days, the plasma concentration-time curve of the drug fitted to a two compartment model with first-order absorption too. The main parameters of the last dosing were as follows: t1/2alpha was (0.19 +/- 0.18) h, t1/2beta was (5.79 +/- 1.50) h, C(max) was (79.82 +/- 10.5) ng x mL(-1), t(peak) was (0.18 +/- 0.08) h, CL(s) was (1.12 +/- 0.07) L x kg(-1) x h(-1), V/F(c) was (2.10 +/- 0.27) L x kg(-1), and AUC(0-t) was (173.23 +/- 9.49) ng x h x mL(-1), separately. The difference of the parameters between the first and the last dosing was not significant, showing that the plasma kinetics of 6beta-naltrexol was not changed after multiple administrations. In the course of multiple administration, the peak and valley concentration of plasma 6beta-naltrexol were (79.03 +/- 10.3) and (1.50 +/- 0.93) ng x mL(-1), respectively. No clear adverse events were noted during this study. These results showed that plasma 6beta-naltrexol fits to a two compartment model with first-order absorption in dog after intramuscular administration and their pharmacokinetic parameters were reported. There was no remarkable change on plasma pharmacokinetics of 6beta-naltrexol after multiple intramuscular administrations.
Animals ; Chromatography, High Pressure Liquid ; Dogs ; Half-Life ; Injections, Intramuscular ; Male ; Naltrexone ; administration & dosage ; analogs & derivatives ; pharmacokinetics

OBJECTIVETo evaluate the relation of dose intensity and efficacy, toxicity in advanced breast cancer treated with paclitaxel as a single agent.

METHODSSeventy-one patients with advanced breast cancer received paclitaxel as a single agent with different dose intensities. According to the phase I or phase II trial, the standard dose intensity of paclitaxel was defined as 58.3 mg.(m(2))(-1).week(-1). The dose of paclitaxel was 175 mg/m(2) given every three weeks, ranging 33.3 - 70.3 mg.(m(2))(-1).week(-1) [median delivered dose intensity 58.82 mg.(m(2))(-1).week(-1)]. Efficacy and toxicity was evaluated.

RESULTSThe overall response rate in this group of advanced breast cancer was 40.8%. Responses were seen in lungs, soft tissue, bone and liver, with the response rates of 52.0%, 38.0%, 12.5%, 7.7%, respectively. When the relative dose intensity (RDI) was > 1.0, 0.9 - 1.0, < 0.9, the response rates were 44.2%, 47.6%, 0, respectively. The difference between the group (RDI >/= 0.9% - 1.0%) in 7 patients and the group (RDI < 0.9) was significant (P < 0.05). Toxicity was well tolerated, with the efficacy decreased as soon as the RDI had been reduced without embarrassing the toxicity.

CONCLUSIONPaclitaxel as a single agent therapy with standard dose intensity is effective and well tolerated by patients with advanced breast cancer.

Adult ; Aged ; Antineoplastic Agents, Phytogenic ; administration & dosage ; adverse effects ; Bone Neoplasms ; drug therapy ; secondary ; Breast Neoplasms ; drug therapy ; pathology ; Dose-Response Relationship, Drug ; Female ; Humans ; Leukopenia ; chemically induced ; Liver Neoplasms ; drug therapy ; secondary ; Middle Aged ; Neoplasm Staging ; Paclitaxel ; administration & dosage ; adverse effects ; Remission Induction

OBJECTIVETo compare the efficacy of endocrine therapy with chemotherapy for bone metastasis of breast cancer.

METHODSA total of 138 breast cancer patients with bone metastasis, but without visceral metastasis as retrospectively reviewed.

RESULTSThe response rates of endocrine therapy and chemotherapy as the first-line therapy were 35.4% and 31.7% (P = 0.687), and the total response rates were 27.1% and 25.0% (P = 0.690). The clinical benefit rates of endocrine therapy and chemotherapy as first-line were 43.9% and 36.6% (P = 0.437), as second-line were 47.8% and 24.2% (P = 0.033), in total treatments were 47.5% and 27.7% (P = 0.001). The median interval to treatment failure (TTF) was 5 months and 2 months (P < 0.001), and that to progression (TTP) was 5 and 2.5 months (P < 0.001) in endocrine therapy and chemotherapy group, respectively.

CONCLUSIONEndocrine therapy is superior to chemotherapy for bone metastasis of breast cancer.

Antineoplastic Agents ; therapeutic use ; Bone Neoplasms ; secondary ; therapy ; Breast Neoplasms ; mortality ; therapy ; Female ; Humans ; Prognosis ; Retrospective Studies ; Survival Rate ; Treatment Failure

OBJECTIVETo investigate the predictive value of HER-2 and ER expression for chemosensitivity of taxane in the treatment of advanced breast cancer.

METHODSOf 268 advanced breast cancer patients treated: 71 were by paclitaxel alone, 32 by docetaxel alone, 110 by paclitaxel combined with anthracylines or gemcitabine or platins and 55 by docetaxel-based combinations. HER-2 and ER expression of all patients treated by taxane underwent immunohistochemical (IHC) assay.

RESULTSUnivariate analysis showed: the response rate (RR) in HER-2 overexpression group was 56.7%, and in HER-2 weak expression group 33.3% (P = 0.003). The response rate in ER positive group and ER negative group was 33.3% and 48.9%, respectively, with a significant difference (P = 0.015). The RR was 67.6% in ER negative but HER-2 overexpression group. However, in ER positive but HER-2 weak expression group and the other groups, the RR were around 35% (P < 0. 01). Multivariate analysis showed that overexpression of HER-2 was the only significant factor to predict the chemosensitivity of taxane (P = 0. 007), but the ER, Karnofsky performance score (KPS), anthracylines, metastatic sites were not the statistically significant chemo-sensitivity predictive factors for taxane.

CONCLUSIONER negative and/or HER-2 overexpression, especially latter, may be associated with good response in advanced breast cancers treated by taxane.

Antineoplastic Agents, Phytogenic ; therapeutic use ; Breast Neoplasms ; drug therapy ; metabolism ; pathology ; Female ; Humans ; Immunohistochemistry ; Multivariate Analysis ; Neoplasm Staging ; Paclitaxel ; therapeutic use ; Predictive Value of Tests ; Prognosis ; Receptor, ErbB-2 ; metabolism ; Receptors, Estrogen ; metabolism ; Remission Induction ; Retrospective Studies ; Taxoids ; therapeutic use