Objective Increasing evidence shows that excitatory amino acids (EAAS) play an important role in the development of brain ischemia/reperfusion damage EAAS accumulation in ischemic tissues induces a sequence of biochemical reactions and eventually leads to cell death The aim of this study was to investigate the effects of propofol ,midazolam and thiopental on amino acid accumulation in ischemic areas in rats subjected to focal cerebral ischemia Methods Male SD rats weighing 240 260g were anesthetized with 10% chloral hydrate 350mg/kg and middle cerebral artery (MCA) occlusion was performed according to the method of Longa The animals were divided into 5 groups of 6 7animals each: group A (ischemia group) received 3 h MCA occlusion without reperfusion and medication; group B (ischemia/reperfusion group) received 3 h MCA occlusion followed by 3 h reperfusion without medication; group C,D and E received propofol or midazolam or thiopental 50mg/kg intrapentoneally after MCA occlusion but before reperfusion Commom carotid artery(CCA),external carotid artery (ECA) and internal carotid artery(ICA) were exposed through a longitudinal incision in the neck A 4 0 nylon thread with rounded tip was inserted into ICA through ECA and threaded cranially until slight resistance was felt The distance from the bifurcation of CCA to the tip of the nylon thread was about 22 cm In this way MCA was occluded After 3 h MCA occlusion the nylon thread was withdrawn to allow reperfusion After 3 h reperfusion the animals were sacrificed with lethal dose of chloral hydrate Brain was removed immediately Hemispheres of both sides were weighed separately and kept at -75℃ Concentrations of various amino acids (aspartate,glutamate,glycine,taurine and GABA) of each hemisphere were measured with high performance liquid chromatography Results Propofol and midazolam significantly reduced aspartate and glutamate accumulation in ischemic areas during reperfusion Propofol augmented but midazolam diminished GABA accumulation Thiopental had no significant effect Conclusions Propofol and midazolam may provide neuroprotection through acceleretion of excitatory amino acid elimination during reperfusion but thiopental does not

Objective To investigate the long-term effects of xanthine oxidase inhibitor,oxypurinol on myocardial contractility of post-ischemic heart failure in mice,and explore the underlying mechanism. Methods One hundred and twenty SV120 mice were randomly assigned into myocardial infarction control group,sham operation group and Oxy treatment group.Post-ischemic heart failure were induced by left anterior descending coronary artery ligation in myocardial infarction control group and Oxy treatment group,and mice in Oxy treatment group and sham operation group were orally administered with 0.5 mmol/L Oxy each day.Nine to eleven months after treatment,echocardiography was performed in all groups.Trabeculae from the right ventricle of mice were dissected for assessment of changes in excitation-contraction coupling.Sarcomere length was measured by laser diffraction.Intracellular free Ca~(2+) concentration([Ca~(2+)]_I)was detected with fluorescent dye Fura-2,which was microinjected iontophoretically into cells. Steady-state force-[Ca~(2+)]_I was achieved by addition of ryanodine and increasing the stimulus frequency to induce tetanization,and the relationship between myocardial contractility and intracellular Ca~(2+) transients was analysed.Besides,Western blotting was performed to determine the oxidation of myofilament proteins. Results Long-term oral administration of oxypurinol significantly improved myocardial contraction function and reduced ventricular wall thickness.Programming of excitation-contraction coupling was significantly improved,and maximal Ca~(2+) activated force(F_(max))in steady-state wag also significantly increased.Western blotting revealed the oxidative modification of actin in mice of Oxy treatment group was significantly inhibited compared with that of myocardial infarction control group. Conclusion Long-term treatment with Oxy improves the cardiac contraction function and boosts the cardiac force dramatically in post-ischemia heart failure.The increase in contraction is the result of increased myofilament Ca~(2+) responsiveness.Thus,antioxidant oxypurinol,by preventing oxidative damage to contractile proteins,can augment contraction with little changes in[Ca~(2+)]_I,represents new class of inotropic agents with advantages of reducing Ca~(2+) overload,and offers new promises in management of heart failure in the future.

OBJECTIVETo investigate the differences in body composition between Crohn's disease(CD) patients and healthy subjects as well as the characteristics of human body composition in various types of CD.

METHODSA total of 57 CD patients were prospectively selected from the Sixth Affiliated Hospital of Sun Yat-sen University as the study group, while 51 healthy subjects as the control group. Protein content, mineral content, fat content, lean body mass, waist circumference, and hip circumference in the two groups were measured by body composition analyzer. Characteristics of CD at different location and different disease activity index were investigated as well.

RESULTSIntracellular fluid, extracellular fluid, weight, protein content, fat content, lean body mass, muscle weight, body fat ratio, waist hip ratio, body weight ratio, arm muscle circumference, arm circumference, quality of cells, BMI and basal metabolic rate in CD patients were significantly lower than those in control group(all P<0.05). Proportion of protein-deficiency patients and fat-deficiency patients were 66.7% and 47.4% respectively. Protein content, fat content, and lean body mass in ileocolic CD patients were lower than those with small bowel and colonic CD(all P<0.05). Protein content, fat content, lean body mass in patients with high disease activity index were lower than those in patients with low and medium index, but higher basal metablic rate was found in the former group(all P<0.05).

CONCLUSIONSThe human body composition in patients with CD are different from healthy people. Disease location and disease activity index have an impact on protein content, fat content, and lean body mass.

Adipose Tissue ; Body Composition ; Body Weight ; Crohn Disease ; physiopathology ; Humans

BACKGROUND: Colorectal carcinogenesis and progression are related to the gut microbiota and the tumor immune microenvironment. Our previous clinical trial demonstrated that berberine (BBR) hydrochloride might reduce the recurrence and canceration of colorectal adenoma (CRA). The present study aimed to further explore the mechanism of BBR in preventing colorectal cancer (CRC). METHODS: We performed metagenomics sequencing on fecal specimens obtained from the BBR intervention trial, and the differential bacteria before and after medication were validated using quantitative polymerase chain reaction. We further performed ApcMin/+ animal intervention tests, RNA sequencing, flow cytometry, immunohistochemistry, and enzyme-linked immunosorbent assays. RESULTS: The abundance of fecal Veillonella parvula ( V . parvula ) decreased significantly after BBR administration ( P = 0.0016) and increased through the development from CRA to CRC. Patients with CRC with a higher V. parvula abundance had worse tumor staging and a higher lymph node metastasis rate. The intestinal immune pathway of Immunoglobulin A production was activated, and the expression of TNFSF13B (Tumor necrosis factor superfamily 13b, encoding B lymphocyte stimulator [BLyS]), the representative gene of this pathway, and the genes encoding its receptors (interleukin-10 and transforming growth factor beta) were significantly upregulated. Animal experiments revealed that V. parvula promoted colorectal carcinogenesis and increased BLyS levels, while BBR reversed this effect. CONCLUSION: BBR might inhibit V. parvula and further weaken the immunomodulatory effect of B cells induced by V. parvula , thereby blocking the development of colorectal tumors. TRIAL REGISTRAION ClinicalTrials.gov, No. NCT02226185.
Animals ; Humans ; Berberine/therapeutic use* ; Carcinogenesis ; Veillonella ; Colorectal Neoplasms/genetics* ; Tumor Microenvironment