Objective To search for the methods preventing nephrotoxic injury of amikacin,Methods Case-control research was used in this study. There were 50 normal children in control group The urine routine, the ?2-microglobulin (?2 -M), mosmol and THP in urine and blood, the AIb, rGT and NAG in urine, the renal function and serum concentration of amikacin were determined respectively.The 43 patients with serious illness childten in study group, were divided into 2 groups (Group 1 and group 2 ). Group 1 (23 cases) was treated only with amikacin for 7 days, and group 2 (20 cases) was treated with vitaminC, vitamin E and amikacin for 7 days. Before treatment, the 3rd and 7th day during the treatment, all the items mentioncd above were examined in gtoup 1 and 2.Results The incidences of nephrotoxic injury of amikacin are 87 per cent (20/23)and 55 per cent (11/20) respectively in group 1 and 2. There is significant difference (P

Objective The aim of the study is to explore the sexual life situation of adult males with continuous ambulatory peritoneal dialysis (CAPD).Methods Data of experience about sexual life of 12 male CAPD patients was collected using in-depth interview and were analyzed with category approach.Results Five themes were sublimated:declined sexual desire,decreased self-confidence to get and to maintain an erection,restraint of sexual life,changes in sexual and marriage satisfaction,and urgent desire for sexual knowledge.Conclusions There are varying degrees of sexual dysfunction in adult male CAPD patients.Nurses should pay attention to and supply the education of sexual knowledge.

Treatment with the combination of Chinese herbs and cytotoxic chemotherapies showed a higher survival rate in clinical trials. In this report, the results demonstrated that the tanshinone II A, a key component of Salvia miltiorrhiza bunge, when it is combined with the cytotoxic drug cisplatin showed synergistic antitumor effects on human prostate cancer PC3 cells and LNCaP cells in vitro. Antiproliferative effects were detected with MTT assay. Cell cycle distribution and apoptosis were detected by flow cytometer. Protein expression was detected by Western blotting. The intracellular concentration of cisplatin was detected by high performance liquid chromatography. The results demonstrated that tanshinone II A significantly enhanced the antiproliferative effects of cisplatin on human prostate cancer PC3 cells and LNCaP cells with the increase of the intracellular concentration of cisplatin. These effects were correlated with cell cycle arrested at S phase and cell apoptosis. The apoptosis might be achieved through death receptor pathway and mitochondrial pathway. Furthermore, the Bcl-2 family members were also involved in this apoptotic process. Collectively, these results indicated that the combination of tanshinone II A and cisplatin had a better treatment effect in vitro not only on androgen-dependent LNCaP cells but also on androgen-independent PC3 cells.
Androgens ; metabolism ; Antineoplastic Agents ; pharmacology ; Antineoplastic Agents, Phytogenic ; isolation & purification ; pharmacology ; Apoptosis ; drug effects ; Cell Cycle ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Cisplatin ; pharmacology ; Diterpenes, Abietane ; isolation & purification ; pharmacology ; Drug Synergism ; Drugs, Chinese Herbal ; isolation & purification ; pharmacology ; Humans ; Male ; Plant Roots ; chemistry ; Plants, Medicinal ; chemistry ; Prostatic Neoplasms ; metabolism ; pathology ; Salvia miltiorrhiza ; chemistry

This study is to investigate the antitumor activity of ophiopogonin B (OP-B). MTT assay, flow cytometric analysis, acridine orange staining, Lyso-Tracker Red staining and HeLa-GFP-LC3 transfect cells assay were used to detect the proliferation activity, apoptosis and autophagy of HeLa cells. The results showed that OP-B exerted potent antiproliferative activity on HeLa cells, the cell growth inhibition effect of OP-B was not due to apoptosis and OP-B could induce autophagy of HeLa cells. OP-B also induced the protein expression up-regulation of Beclin-1 and promoted LC3 I transformation LC3 II, which were representative proteins of autophagy. Furthermore, 3-MA, an inhibitor of autophagy, not only inhibited OP-B-mediated autophagy but also almost completely reversed the antiproliferative effect of OP-B, suggesting that the growth inhibition effect of OP-B was autophagy dependent. Western blotting demonstrated that OP-B inhibited the phosphorylation of Akt and its' downstream vital protein, such as mTOR and p70S6K. In addition, OP-B also induced the protein expression up-regulation of PTEN, which is a negative regulation protein for Akt/mTOR signaling pathway. However, OP-B did not affect the protein expression of total Akt. Collectively, the antitumor effects of OP-B were autophagy-dependent via repression Akt/mTOR signaling pathway. Therefore, OP-B is a prospective inhibitor of Akt/mTOR and may be used as an alternative compound to treat cervical carcinoma.
Adenine ; analogs & derivatives ; pharmacology ; Antineoplastic Agents, Phytogenic ; pharmacology ; Apoptosis ; drug effects ; Apoptosis Regulatory Proteins ; metabolism ; Autophagy ; drug effects ; Beclin-1 ; Cell Proliferation ; drug effects ; Dose-Response Relationship, Drug ; HeLa Cells ; Humans ; Membrane Proteins ; metabolism ; Microtubule-Associated Proteins ; metabolism ; Ophiopogon ; chemistry ; PTEN Phosphohydrolase ; metabolism ; Phosphorylation ; Plants, Medicinal ; chemistry ; Proto-Oncogene Proteins c-akt ; metabolism ; Ribosomal Protein S6 Kinases, 70-kDa ; metabolism ; Saponins ; pharmacology ; Signal Transduction ; drug effects ; Spirostans ; pharmacology ; TOR Serine-Threonine Kinases ; metabolism ; Up-Regulation

OBJECTIVETo investigate the intervention effect of thalidomide on paraquat-induced acute lung injury in mice and its mechanism.

METHODSMale ICR mice were randomly allocated to negative control group (n = 30), thalidomide control group (n = 30), paraquat poisoning group (n = 30), 50 mg/kg thalidomide treatment group (n = 30), 100 mg/kg thalidomide treatment group (n = 30), and 150 mg/kg thalidomide treatment group (n = 30). The negative control group was intraperitoneally injected with the same volume of saline; the thalidomide control group was intraperitoneally injected with thalidomide (150 mg/kg); the paraquat poisoning group was intraperitoneally injected with diluted paraquat solution (22 mg/kg); each thalidomide treatment group was intraperitoneally injected with the same volume of paraquat solution (22 mg/kg) and was injected with thalidomide (50, 100, or 150 mg/kg) 1 h later. All mice were anesthetized and sacrificed at 1, 3, or 7 d after paraquat poisoning, and their lung tissue was collected. The levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 in lung tissue were measured by double-antibody sandwich ELISA; the mRNA expression of nuclear factor-kappa B (NF-κB) was measured by RT-PCR; the protein expression of nuclear NF-kgr;B p65 was measured by Western blot. The pathological changes of lung tissue were observed under light microscope; the wet/dry ratio of the lung was calculated.

RESULTSCompared with the negative control group, the paraquat poisoning group had significantly increased levels of TNF-α, IL-1β, IL-6, NF-κB mRNA, and nuclear NF-κB p65 and wet/dry ratio of the lung (P < 0.05). Compared with the paraquat poisoning group, the thalidomide treatment groups had significantly decreased levels of TNF-α, IL-1β, IL-6, NF-κB mRNA, and nuclear NF-κB p65 and wet/dry ratios of the lung (P < 0.05), and the 150 mg/kg thalidomide treatment group showed the most significant decrease in the levels of TNF-α, IL-1β, IL-6, NF-κB mRNA, and nuclear NF-κB p65. The observation of pathological changes showed that the paraquat poisoning group had the most marked lung tissue damage at 3 d after poisoning, and the lung tissue damage was lessened in the thalidomide treatment groups.

CONCLUSIONThalidomide can reduce paraquat-induced acute lung injury and lung edema. The mechanism may include inhibition of NF-κB activation and expression and downregulation of TNF-α, IL-1β, and IL-6.

Acute Lung Injury ; chemically induced ; drug therapy ; Animals ; Cytokines ; metabolism ; Disease Models, Animal ; Male ; Mice ; Mice, Inbred ICR ; NF-kappa B p50 Subunit ; metabolism ; Paraquat ; poisoning ; Thalidomide ; pharmacology ; Transcription Factor RelA ; metabolism

AIMTo study on synthesis and antibacterial activity evaluation of polyheterocycles.

METHODSThe condensation of 4-amino-3-pyridin-3-yl-4H-[1,2,4] triazole-5-thiol with 2-chloromethyl-5-substituted phenyl-[1,3,4] oxadiazoles gave the corresponding title heterocycle amines, and the in vitro antibacterial activity was primarily evaluated by the method of cup-plate diffusion solution.

RESULTSTwelve novel compounds were synthesized, and their structures were confirmed by IR, 1H NMR, MS and element analysis. Biological screening results demonstrated that most of the compounds prepared showed good antibacterial activity.

CONCLUSIONOxadiazoles incorporting pyridyl triazole ring may be a pharmacophor structure in the molecule for developing antibacterial candidate drugs.

Anti-Bacterial Agents ; chemical synthesis ; chemistry ; pharmacology ; Escherichia coli ; drug effects ; Oxadiazoles ; chemical synthesis ; chemistry ; pharmacology ; Proteus vulgaris ; drug effects ; Staphylococcus aureus ; drug effects ; Triazoles ; chemical synthesis ; chemistry ; pharmacology

Ulcerative colitis (UC) is associated with intestinal immune imbalance and inflammatory response. Because dehydrolovastatin (DLVT), a derivative of lovastatin, has been recently shown to inhibit inflammation and relieve immune arthritis induced by chemical stimuli, we studied its effect and possible mechanism on UC induced by dextran sulfate sodium. The BALB/c mice were classified into six groups: normal control group, model group, DLVT high dose group, DLVT low dose group, salazosulfapyridine (SASP) group and lovastatin (LVT) group. The disease activity indices of UC and pathological changes were investigated. The myeloperoxidase (MPO) activity in colon tissue and inflammatory factors such as IL-6, IL-10, IL-17, and TNF-α in the serum were analyzed by ELISA, while the expression of NF-κB p65 protein in colon tissue was detected by immunohistochemistry and western blot. DLVT relieved the disease activity indices and pathological damage of the UC mice. Furthermore, DLVT significantly decreased MPO activity and improved the imbalance of inflammatory cytokines through inhibiting the expression of NF-κB p65. Meanwhile, the positive drug of SASP has a similar effect to DLVT, but the effect of DLVT in both decreasing IL-17, TNF-α, and increasing IL-10 was significantly stronger than that of SASP. These results suggest that DLVT may ameliorates the symptoms of UC.

Ulcerative colitis (UC) is associated with intestinal immune imbalance and inflammatory response. Because dehydrolovastatin (DLVT), a derivative of lovastatin, has been recently shown to inhibit inflammation and relieve immune arthritis induced by chemical stimuli, we studied its effect and possible mechanism on UC induced by dextran sulfate sodium. The BALB/c mice were classified into six groups: normal control group, model group, DLVT high dose group, DLVT low dose group, salazosulfapyridine (SASP) group and lovastatin (LVT) group. The disease activity indices of UC and pathological changes were investigated. The myeloperoxidase (MPO) activity in colon tissue and inflammatory factors such as IL-6, IL-10, IL-17, and TNF-α in the serum were analyzed by ELISA, while the expression of NF-κB p65 protein in colon tissue was detected by immunohistochemistry and western blot. DLVT relieved the disease activity indices and pathological damage of the UC mice. Furthermore, DLVT significantly decreased MPO activity and improved the imbalance of inflammatory cytokines through inhibiting the expression of NF-κB p65. Meanwhile, the positive drug of SASP has a similar effect to DLVT, but the effect of DLVT in both decreasing IL-17, TNF-α, and increasing IL-10 was significantly stronger than that of SASP. These results suggest that DLVT may ameliorates the symptoms of UC.

This study was aimed to investigate the inducing-apoptosis effect of arsenic trioxide (ATO) on imatinib (IM)-resistant chronic myeloid leukemia (CML) cell line KBM5R with T315I point mutation. CML cell line KBM5R with T315I point mutation and wild-type cell line KBM5 were selected for study. Resistance of KBM5R cells to IM and proliferation of KBM5 and KBM5R cells treated with ATO were detected by MTT; apoptosis of KBM5 and KBM5R cells were quantified by flow cytometry; the expression of apoptosis-related protein caspase-3, -8, -9 was determined by Western blot. The results showed that (1) IC(50) of KBM5R and KBM5 cells treated with IM were 12.66 ± 0.565 µmol/L and 0.303 ± 0.031 µmol/L respectively, and significantly different from each other. (2) the proliferation of KBM5 and KBM5R cells treated with different concentrations of ATO was inhibited in dose- and time-dependent manners at 24, 48, 72, 96 hours, and inhibition of KBM5R cell proliferation was stronger than KBM5 in the same drug concentration and time. (3) the apoptosis rate of KBM5 and KBM5R cells treated with 2, 4, 8 µmol/L ATO for 48 hours increased in a concentration-dependent manner, and the apoptosis rate of KBM5R was higher than that of KBM5 cells in the same drug concentration. (4) the expression of cleaved caspase-3, -8, -9 protein in KBM5 and KBM5R cells treated with 4 µmol/L ATO for 24 hours significantly increased. It is concluded that KBM5R cells are significantly resistant to IM; ATO can inhibit the proliferation and induce the apoptosis of KBM5R and KBM5 cells. As compared with wild-type KBM5 cells, effect of ATO on inhibition of proliferation and induction of apoptosis in KBM5R cells are more stronger. ATO can induce the apoptosis of KBM5 and KBM5R cells through the activation of apoptosis-related caspase-3, -8, -9 protein.
Apoptosis ; drug effects ; Arsenicals ; pharmacology ; Benzamides ; Caspase 3 ; metabolism ; Caspase 8 ; metabolism ; Caspase 9 ; metabolism ; Cell Line, Tumor ; Drug Resistance, Neoplasm ; genetics ; Flow Cytometry ; Humans ; Imatinib Mesylate ; Oxides ; pharmacology ; Piperazines ; pharmacology ; Point Mutation ; Pyrimidines ; pharmacology

AIMStudies on synthesis and antibacterial activity of new heterocycles.

METHODSThe cyclocondensation of [(3-pyridyl)-1,3,4-oxadiazol-2-yl] thio acetic acid with various aroyl hydrazines in the presence of POCl3 and xylene gave the corresponding titled compounds, and the in vitro antibacterial activity was primarily evaluated by the method of cupplate diffusion solution.

RESULTSSixteen novel titled compounds were synthesized, their structures were confirmed by IR, 1HNMR, MS and elemental analysis. Biological screening results demonstrated that most of the compounds prepared displayed potential antibacterial activity.

CONCLUSIONOxadiazoles incorporting pyridyl oxadiazole ring may be usefully antibacterial candidate drugs.

Anti-Bacterial Agents ; chemical synthesis ; chemistry ; pharmacology ; Escherichia coli ; drug effects ; Oxadiazoles ; chemical synthesis ; chemistry ; pharmacology ; Proteus vulgaris ; drug effects ; Staphylococcus aureus ; drug effects