Comparative effect of ciprofloxacin and moxifloxacin on the modulation of bile acid profiles and gut microbiota in rats

Abstract Fluoroquinolones are an important class of antimicrobial agents to manage infectious diseases. However, knowledge about how host bile acids are modified by fluoroquinolones is limited. We investigated and compared the impact of fluoroquinolones on circulating bile acid profiles and gut microbiota from in vivo studies. We administered ciprofloxacin (100 mg/kg/day) or moxifloxacin (40 mg/kg/day) orally to male Wistar rats for seven days. Fifteen bile acids (BAs) from the serum and large intestine were quantified by HPLC-MS/MS. The diversity of gut microbiota after ciprofloxacin and moxifloxacin treatment was analyzed using high-throughput, next-generation sequencing technology. The two fluoroquinolone-treated groups had different BA profiles. Ciprofloxacin significantly reduced the hydrophobicity index of the BA pool, reduced secondary BAs, and increased taurine-conjugated primary BAs in both the serum and large intestine as compared with moxifloxacin. Besides, ciprofloxacin treatment altered intestinal microbiota with a remarkable increase in Firmicutes to Bacteroidetes ratio, while moxifloxacin exerted no effect. What we found suggests that different fluoroquinolones have a distinct effect on the host BAs metabolism and intestinal bacteria, and therefore provide guidance on the selection of fluoroquinolones to treat infectious diseases.

Acetoacetate extract of pleione bulbocodioides (franch. ) rolfe induces apoptosis of human leukemia thp-1cells through a mitochondria-regulated intrinsic apoptotic pathway / Extrato de acetoacetato de Pleione bulbocodioides (Franch. ) Rolfe induz a apoptose de células THP-1 de leucemia humana através de uma via apoptótica intrínseca regulada por mitocôndrias

The tubers of three orchidaceous plants, includingPleione bulbocodioides (Franch.) Rolfe, have been used as 'Shan-Ci-Gu' in traditional Chinese medicine for the treatment of bacterial infections and cancers for thousands of years. In this study, the effects of an acetoacetate (EtOAc) extract of P. bulbocodioides on the cell viability and apoptosis of THP-1 (human acute monocytic leukemia cell line) cells and its interaction with possible apoptotic pathways were investigated. THP-1 cells were treated with the EtOAc extract of P. bulbocodioides at different concentrations. The results showed that THP-1 cell viability was significantly inhibited by the EtOAc extract ofP. bulbocodioides with an IC50 of 51.37±2.68 µ g/ mL at 24 h. The examination of cytotoxic effects on healthy cells showed that the EtOAc extract of P. bulbocodioidesdid not show any effect on healthy Vero cells. Selectivity indexes were greater than 15.57, suggesting that the EtOAc extract of P. bulbocodioides had selective toxicity against THP-1 cells. The results of annexin V-FITC/PI and DAPI staining showed that the EtOAc extract of P. bulbocodioides induced cell apoptosis in a dose-dependent manner. The apoptotic rate was increased in the treatment groups compared with that in the control group (P<0.05). The distribution of cells in the G2 phase of the cell cycle increased along with typical cell apoptosis-induced morphological changes. The levels of the pro-apoptotic proteins Bax, cleaved PARP and cleaved caspase-3 increased with increasing concentration of acetoacetate extract of P. bulbocodioides, while the anti-apoptosis protein Bcl-2 was downregulated. Cyt c and AIF, which are characteristic proteins of the mitochondria-regulated intrinsic apoptosis pathway, also increased in the cytosol with increasing concentrations of the EtOAc extract of P. bulbocodioides. These results showed that the EtOAc extract of P. bulbocodioidessignificantly inhibits cell viability and induces cell apoptosis in the human leukemia cell line THP-1 through a mitochondria-regulated intrinsic apoptotic pathway

Os tubérculos de três plantas orquidáceas, incluindo Pleione bulbocodioides (Franch.) Rolfe, têm sido usados como "Shan-Ci-Gu" na medicina tradicional chinesa para o tratamento de infecções bacterianas e cânceres por milhares de anos. Neste estudo, os efeitos de um extrato de acetoacetato (EtOAc) de P. bulbocodioides na viabilidade celular e apoptose de células THP-1 (linhagem celular de leucemia monocítica aguda humana) e sua interação com possíveis vias apoptóticas foram investigados. As células THP-1 foram tratadas com o extrato EtOAc de P. bulbocodioides em diferentes concentrações. Os resultados mostraram que a viabilidade das células THP-1 foi significativamente inibida pelo extrato EtOAc de P. bulbocodioides com IC50 de 51,37 ± 2,68 µ g/mL às 24 h. O exame dos efeitos citotóxicos em células saudáveis mostrou que oextrato de EtOAc de P. bulbocodioides não mostrou nenhum efeito sobre células Vero saudáveis. Os índices de seletividade foram maiores que 15,57, sugerindo que o extrato de EtOAc de P. bulbocodioides teve toxicidade seletiva contra as células THP-1. Os resultados da coloração da anexina V-FITC/PI e DAPI mostraram que o extrato de EtOAc de P. bulbocodioides induziu a apoptose celular de maneira dose-dependente. A taxa de apoptose foi aumentada nos grupos de tratamento em comparação com o grupo controle (P <0,05). A distribuição de células na fase G2 do ciclo celular aumentou juntamente com alterações morfológicas típicas induzidas pela apoptose celular. Os níveis das proteínas pró-apoptóticas Bax, PARP clivada e caspase-3 clivada aumentaram com o aumento da concentração do extrato acetoacetato de P. bulbocodioides, enquanto a proteína anti-apoptose Bcl-2 foi regulada negativamente. Cyt c e AIF, que são proteínas características da via de apoptose intrínseca regulada por mitocôndrias, também aumentaram no citosol com concentrações crescentes do extrato de EtOAc de P. bulbocodioides. Estes resultados mostraram que o extrato de EtOAc de P. bulbocodioides inibe significativamente a viabilidade celular e induz a apoptose na linha celular de leucemia humana THP-1 através de uma via apoptótica intrínseca regulada por mitocôndrias.

Interaction between hydrogen sulfide and nitric oxide on cardiac protection in rats with metabolic syndrome / 中国医学科学院学报

<p><b>OBJECTIVE</b>To investigate the interaction between hydrogen sulfide (H2S)/cystathionine gamma-lyase (CSE) system and nitric oxide (NO)/nitric oxide synthase (NOS) system on cardiac protection in metabolic syndrome (MS) rats.</p><p><b>METHODS</b>Forty one male Sprague-Dawley rats were randomly divided into 6 groups: control group, MS group, H2S donor group, CSE inhibitor group, NOS inhibitor group, and NO donor group. The MS rat model was established by a high-fat diet of 16 weeks. Rats in control and MS groups were subjected to normal saline and the other four groups were respectively subjected to sodium hydrosulfide (NaHS, 56 μmol/kg), D,L-propargylglycine (PPG, 37.5 mg/kg), Nψ-nitro-L-arginine methyl ester (L-NAME, 18 mg/kg), L-Arginine (500 mg/kg) every day. Four weeks later, the obesity indices, blood sugar of oral glucose tolerance test in each time point (0,30,60, and 120 minutes) and blood lipids (cholesterol, triglyceride, high density lipoprotein, low density lipoprotein) were measured. The computer-based electrophysiological recorder system was used to measure the changes of the left ventricular systolic pressure (LVSP), the left ventricular end diastolic pressure (LVEDP), the maximal rate of pressure increase in the contraction phase (+dP/dtmax), and the maximal rate of pressure decrease in the diastole phase (-dP/dtmax). H2S and NO concentration in plasma and myocardium, as well as CSE, constitutive NOS (cNOS), and inducible NOS (iNOS) activities in myocardium were measured with colorimetric method. Reverse transcription-polymerase chain reaction was used to assess the gene expression of CSE and endothelial NOS (eNOS) mRNAs.</p><p><b>RESULTS</b>Compared with control group, the obesity indices, blood sugar at each time point, and blood lipids significantly increased in MS group (P<0.05). H2S and NO concentration in plasma and myocardium, CSE and cNOS activities in myocardium, the expressions of CSE mRNA and eNOS mRNA, and the myocardial function significantly decreased in MS group (P<0.05). Compared with MS group, NO concentration in plasma and myocardium, cNOS and iNOS activities in myocardium, and the expression of eNOS mRNA significantly increased in CSE inhibitor group (P<0.05). However, activities of cNOS and iNOS in myocardium and the expression of eNOS mRNA were significantly decreased in H2S donor group (P<0.01), while the myocardial function significantly increased (P<0.05). H2S concentration in plasma and myocardium, and the expression of CSE mRNA significantly increased in NOS inhibitor group (P<0.05). However, in NO donor group, the CSE activity in myocardium and the expression of CSE mRNA significantly decreased (P<0.05). And the myocardial function was improved significantly (P<0.05).</p><p><b>CONCLUSIONS</b>Both the H2S/CSE and NO/NOS systems appear to have a mutual down-regulation effect on myocardium in MS rats. Meanwhile, exogenous H2S and NO supplement is cardioprotective in rat model of MS.</p>

Surgical treatment and prognosis of cancer of hepatic flexure of colon invading the duodenum in 65 patients / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To discuss surgical treatment of right colon carcinoma of hepatic flexure invading the duodenum.</p><p><b>METHODS</b>Sixty-five patients with right colon carcinoma of hepatic flexure invading the duodenum, treated in our department from 1987 to 2007, were included in this study. Their clinicopathological data were retrospectively reviewed and analyzed. All the cases were divided into three types (local invasion, regional invasion, and cancer with internal fistula) according to duodenal defect, including local invasion (< 2.0 cm), wide invasion (> 2.0 cm) and the presence of internal fistula.</p><p><b>RESULTS</b>25 patients with local invasion underwent en bloc resection of the duodenal wall. Pedicled ileal flap was used to cover the large duodenal defect measuring 2.0 - 3.0 cm in 5 patients. Dudenojejunostomy was used to reconstruct the large defect measuring more than 5 cm in 3 patients. Conservative resection of right-sided colon was performed in 18 patients with wide invasion. 4 patients underwent pancreaticoduodenectomy combined with right hemicolectomy for colon cancer involving the pancreatic head. 10 underwent duodenal diverticularization. One patient with anastomotic leakage healed within 3 weeks. Other patients were cured without postoperative complications. The total 3-year and 5-year survival rates after surgery were 53.8% and 9.2%, respectively.</p><p><b>CONCLUSION</b>The surgical procedure to be performed is usually decided according to the cancer location, extent, and duodenal defect and invasion, which are important for prolonging life time, improving of quality of life and prognosis in these patients.</p>

Effects of Yuquan pills on pharmacokinetics of metformin hydrochloride in diabetic rats / 中国中药杂志

<p><b>OBJECTIVE</b>To study effects of Yuquan pills on the pharmacokinetics process of metformin hydrochloride in diabetic rats.</p><p><b>METHOD</b>After administration Yuquan pills 7 day to the diabetic rats, the metformin hydrochloride was orally administrated, then the blood samples were collected at different time. The concentrations of metformin hydrochloride in plasma were determined by HPLC method and the pharmacokinetic parameters were calculated.</p><p><b>RESULT</b>The pharmacokinetic parameter Cmax of the controlling group and the testing group were respectively, 18.95, 21.76 mg x L(-1); t1/2 were 1,069.8, 1,767.4 min, respectively; CL/F were 0.013, 0.008 L x min(-1) x kg(-1); AUC were 10,042.1, 10,712.2 mg z L(-1) x min(-1) respectively.</p><p><b>CONCLUSION</b>The pharmacokinetics process of metformin hydrochloride in diabetic rats fits one-compartment model. Yuquan pills has a significant effect on the pharmacokinetics of metformin hydrochloride in diabetic rats.</p>

Intractable constipation caused by adult dolichocolon / 中国普通外科杂志

Objective To summarize the diagnosis and surgical treatment for intractable constipation caused by adult dolichocolon.Methods Clinical data of 82 adult dolichocolon cases suffering from intractable constipation were analyzed retrospectively.Results Of the 82 patients,intractable constipation were found in 66 patients(80%),abdominalgia,abdominal distension in 28 patients(34%) and constipation alternatively with diarrhea in 16 patients(19%).Diagnosis was established in 74 patients by barium enema while 8 during the emergency operation.Dolichocolon was divided into 3 types as type Ⅰ in 35 cases,type Ⅱ in 19 and type Ⅲ in 28,in which there were 18 cases of total dolichocolon syndrome. Surgery performed including sigmoidectomy(32 patients),right hemicolectomy(3 patients),right hemicolon and transvers colon resection(4 patients),left side of transvers colon and splenic flexure colon resection(4 patients),descending colon and sigmoid colon resection(15 patients),transvers,descending and sigmoid colon resection(6 patients),pancolectomy with anastomosis of terminal ileum and upper rectum (18 patients).There were no severe postoperative complications such as anastomotic leakage and the recovery was uneventful in all 82 patients.The curative effect was graded as well and up in all 72 cases followed up from 3 months to 4 years,with a follow-up rate of 88%(72/82).Conclusion A history of intractable constipation and barium enema are the mainstay for the diagnosis of dolichocolon,and operation is the effective treatment for intractable constipation caused by adult dolichocolon.