Re-188 is useful candidate for therapeutic radionuclide because it has a physical half life of 17 hours, contains beta ernissions suitable for therapy(maximum energy 2.12MeV) and emits a garnma ray that is suitable for quantitative diagnostic scanning(155keV). To use He-188 as a radionuclide compound of angioplasty balloon radiotherapy, we investigated the labelling method and biodistribution of Re-188- DTPA. We postulated that labeled Re-188-DTPA is preferable because it would be excreted via urinary system more easily than other compounds. To label Re-188 with DTI'A, 1ml of 222MBqI(6mCi) of Re-188 was added to DTPA solution(DTPA 20mg, SnC4 2HsO 10mg, pH 3.5) and boiled at 100C for 120min in water bath. pH was adjuted to 5 with 2.3Fo sodium acetate. I.abeling efficiency was measured using TLC-SG(acetone, saline). We evaluated biodistribution of Re-188-DTPA in sacrificed mice at 10 and 60 minutes after injection. We acquired images of kidneys, and drew tirne-activity r.urves in normal dogs and rats and calculated Trnax and Tl/2 in rats. The labelling efficiency was 95.7Yo on average. Labelling of Re-188-DTPA was stable(90% after 5hours) in vitro at room temperature. According to time-activity curves of dogs and rats, it took 15 to 20 minutes after injection for Re-188-DTPA to be washed out through kidneys. In conclusion, Re-188-DTPA was successfully labeled, Re-188-DTPA was stable in vitro and was excreted early via kidneys in animals. We could recornmend Re-188-DTPA as radionuclide of potential use in angioplasty balloon radiotherapy.
Angioplasty ; Animals ; Baths ; Dogs ; Half-Life ; Hydrogen-Ion Concentration ; Kidney ; Mice ; Pentetic Acid ; Radiotherapy ; Rats ; Sodium Acetate ; Water

A simple, rapid and selective liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) is developed and validated for quantification of venlafaxine in human plasma with simple liquid-liquid extraction step consisted of extraction with ether and dichloromethane for 10 min and mixing with 1 M sodium acetate in human plasma using fluoxetine as an internal standard (IS). The analyte are separated using an isocratic mobile phase consisted of acetonitrile and 5 mM ammonium formate (4/3, v/v) on a isocratic YMC hydrosphere C18 (2.0x50.0 mm, 3.0 microm) column and analyzed by MS/MS in the multiple reaction monitoring (MRM) mode using the transitions of respective [M+H](+) ions, m/z 278.2-->260.3 and m/z 310.1-->148.1 for quantification of venlafaxine and IS, respectively. The standard calibration curves showed good linearity within the range of 1.0-200.0 ng/mL (r2=0.9986, 1/chi2 weighting). The lower limit of quantification (LLOQ) was 1.0 ng/mL. The retention times of venlafaxine and IS were 0.6 min and 0.7 min that means the potential for the high-throughput potential of the proposed method. In addition, no significant metabolic compounds were found to interfere with the analysis. Acceptable precision and accuracy were obtained for the concentrations over the standard curve range. The validated method was successfully applied to bioequivalence study after 75-mg of venlafaxine sustained-release (SR) capsule in 24 healthy Korean subjects.
Ammonium Compounds ; Calibration ; Chromatography, Liquid ; Ether ; Fluoxetine ; Humans ; Ions ; Liquid-Liquid Extraction ; Methylene Chloride ; Pharmacokinetics ; Plasma* ; Sodium Acetate ; Tandem Mass Spectrometry ; Therapeutic Equivalency* ; Venlafaxine Hydrochloride

OBJECTIVE: To evaluate the efficacy of volume therapy with sodium acetate Ringer solution during the perioperative period in children with cyanotic congenital heart disease (CHD). METHODS: The children who underwent elective surgery for cyanotic CHD admitted to Shanghai Children's Medical Center Affiliated to the Medical School of Shanghai Jiaotong University from September to December 2018 were divided into three groups according to random number table with the informed consent of their legal representatives. All of the children received volume therapy with infusion of sodium acetate Ringer solution intravenously upon anesthesia induction. The volume of infusion was calculated according to the "4-2-1" formula (group A, the rehydration volume was 4 mL×kg^-1×h^-1 for the first 10 kg body weight, 2 mL×kg^-1×h^-1 for the second 10 kg, and 1 mL×kg^-1×h^-1 for the third 10 kg and above), and the volume was increased by 50% or 100% in groups B and C, respectively. The intravenous infusion lasted for 30 minutes in all the three groups. Arterial blood gas analysis was performed before and 30 minutes after infusion to observe the acid-base status and electrolyte level. Pulse oxygen saturation (SpO₂), heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP) before and 10, 20, 30 minutes after infusion, central venous pressure (CVP) at 30 minutes after infusion were recorded, as well as adverse events occurred after infusion. RESULTS: Twenty-six children with cyanotic CHD, 17 male and 9 female, aged from 1 to 36 months, body weight 3.6 to 16.0 kg, and America Society of Anesthesiologists (ASA) level of III or IV, were enrolled in the study. The pH value in group B at 30 minutes after infusion was significantly higher than that before infusion (7.35±0.05 vs. 7.32±0.06, P < 0.05), while no significant changes were found before and after infusion in the other two groups. The hematocrits (Hct) after infusion in three groups were significantly lower than those before infusion (0.433±0.141 vs. 0.473±0.146 in group A, 0.324±0.054 vs. 0.372±0.063 in group B, 0.363±0.097 vs. 0.418±0.111 in group C, all P < 0.01), indicating that all the children in the three groups achieved effective hemodilution. However, there was no significant difference in blood gas analysis before and after infusion among the three groups. The level of blood lactic acid (Lac) in all CHD children was decreased from (1.33±0.63) mmol/L to (0.98±0.36) mmol/L after infusion of sodium acetate Ringer solution, the serum Ca²⁺ concentration was decreased from (1.22±0.06) mmol/L to (1.19±0.06) mmol/L, and the serum Cl^- concentration was increased from (108.74±2.70) mmol/L to (109.77±2.54) mmol/L with the statistically significant differences (all P < 0.01). However, no significant difference was found in Lac or electrolyte levels before and after infusion among the three groups. There was no significant difference in vital signs before and after infusion among the three groups, but the period of infusion had an effect on SpO₂ (F = 5.998, P < 0.01), HR (F = 34.279, P < 0.01) and SBP (F = 4.345, P < 0.05). HR in groups A and C were significantly lower than those before infusion, and SBP in group A was decreased gradually with the prolongation of infusion time. The CVP value at 30 minutes after infusion in group B was higher than that in group A. No adverse reactions such as rash or anaphylactic shock occurred after infusion of sodium acetate Ringer solution in all children. CONCLUSIONS The perioperative volume therapy with sodium acetate Ringer solution in children with cyanotic CHD can effectively prevent the increase in Lac level and does not aggravate metabolic acidosis. The volume of infusion was well tolerated by all the children without disturbing the hemodynamic parameters.
Child, Preschool ; China ; Cyanosis/therapy* ; Female ; Fluid Therapy ; Heart Defects, Congenital/therapy* ; Humans ; Infant ; Infant, Newborn ; Infusions, Intravenous ; Male ; Perioperative Care ; Sodium Acetate/administration & dosage* ; Treatment Outcome

BACKGROUND: Recent studies suggest that the cardioprotective effect of ischemic preconditioning (IPC) is related to intracellular glycogen content in rat hearts, however, controversies still remain. METHODS: To test this hypothesis, isolated Langendorff-perfused rabbit hearts were subjected to 45 min global ischemia followed by 120 min reperfusion with IPC (n=0) or without IPC (ischemic control, n=). IPC was induced by one cycle of 5 min global ischemia and 10 min reperfusion. In the glucose (G)-free preconditioned group (n=0), G depletion-repletion was induced by perfusion with G-free Tyrode solution for 5 min and then G-containing Tyrode solution for 10 min followed by 45 min ischemia and 120 min reperfusion. For glycogen depletion or loading, hearts were treated with sodium acetate (NA, 5 mM, n=) or insulin (Ins, 1 unit/L, n=) for 15 min before 45 min ischemia. Left ventricular function and coronary flow (CF) were continuously recorded during experiments. Myocardial cytosolic and membrane protein kinase C (PKC) activities were measured by 32P-gamma-ATP incorporation into PKC-specific pepetide; glycogen content in the cardiac myocytes was determined by spectrophotometry with amyloglucosidase; expression of PKC isozymes was determined by Western blot with monoclonal antibodies. Infarct size was determined by staining with tetrazolium salt and planimetry. Data were analyzed by ANOVA and Tukey's post-hoc test. RESULTS: IPC or G-free preconditioning enhanced LV functional recovery; NA did not influence on functional recovery but Ins depressed it. Infarct size was significantly reduced by IPC, G-free preconditioning, and NA treatment (35.3+/-2.1% in the ischemic control, 18.7+/-1.2% in the IPC, 22.1+/-1.2% in the G-free preconditioned, 16.3+/-1.2% in the NA-treated group, and 32.8+/-1.6% in the Ins-treated group, p<0.05). Membrane PKC activities significantly increased by IPC, IPC and 45 min ischemia, G-free preconditioning, and G-free preconditioning and 45 min ischemia; especially, expression of membrane PKC-epsilon increased by IPC and G-free preconditioning. Glycogen content decreased by 45 min ischemia, IPC, G-free preconditioning, and by NA treatment, but increased by Ins treatment. CONCLUSION: These results suggest that in rabbit heart, intracellular glycogen may not significantly be related with the cardioprotective effect of IPC; G-free preconditioning could not improve post-ischemic contractile dysfunction but it has an infarct size-limiting effect; this cardioprotective effect may be related in part to activation of PKC, especially epsilon isozyme.
Animals ; Antibodies, Monoclonal ; Blotting, Western ; Cytosol ; Glucan 1,4-alpha-Glucosidase ; Glucose ; Glycogen* ; Heart ; Insulin ; Ischemia ; Ischemic Preconditioning* ; Isoenzymes ; Membrane Proteins ; Membranes ; Myocytes, Cardiac ; Perfusion ; Phosphotransferases ; Protein Kinase C* ; Protein Kinases* ; Rats ; Reperfusion ; Sodium Acetate ; Spectrophotometry ; Ventricular Function, Left

OBJECTIVETo investigate whether brain reactive oxygen species mediate sympathoexcitation and arterial pressure elevation in DOCA-salt hypertensive rats.

METHODSDOCA-salt hypertensive model was established in male SD rats by subcutaneous injection of DOCA after uninephrectomy and drinking 1% NaCl solution for 4 weeks. The baseline mean arterial pressure (MAP), heart rate (HR) and renal sympathetic nerve activity (RSNA) were recorded in the rats under mild anesthesia, and MAP changes following intravenous hexamethonium injection were observed. The responses of MAP, HR and RSNA to intracerebroventricular administration of tempol (20 µmol/L in 10 µl) were evaluated; plasma NE level was measured with ELISA, and ROS level and NAD(P)H oxidase activity in the hypothalamus were detected using chemiluminescence assay.

RESULTSMAP and plasma NE levels were significantly increased in DOCA-salt rats as compared with those in the control group (P<0.01). In DOCA-salt hypertensive rats, intravenous hexamethonium injection induced a blood pressure reduction 240% of that in control rats, and significantly increased the levels of superoxide anion and NAD(P)H oxidase activity in the hypothalamus. Intracerebroventricular microinjection of tempol also resulted in more significant changes of MAP, HR and RSNA in DOCA-salt rats than in the control group (P<0.01).

CONCLUSIONSympathoexcitation due to increased NAD(P)H oxidase-derived ROS levels in the hypothalamus may mediate arterial pressure elevation in DOCA-salt hypertensive rats.

Animals ; Antioxidants ; Arterial Pressure ; Blood Pressure ; Brain ; metabolism ; Cyclic N-Oxides ; pharmacology ; Desoxycorticosterone ; Desoxycorticosterone Acetate ; Disease Models, Animal ; Heart Rate ; Hypertension ; Kidney ; innervation ; Male ; NADPH Oxidases ; metabolism ; Rats ; Rats, Sprague-Dawley ; Reactive Oxygen Species ; metabolism ; Sodium Chloride ; Spin Labels ; Superoxides ; metabolism ; Sympathetic Nervous System

CG200745 is a novel inhibitor of histone deacetylases (HDACs), initially developed for treatment of various hematological and solid cancers. Because it is water-soluble, it can be administered orally. We hypothesized that the HDAC inhibitor, CG200745, attenuates cardiac hypertrophy and fibrosis in deoxycorticosterone acetate (DOCA)-induced hypertensive rats. For establishment of hypertension, 40 mg/kg of DOCA was subcutaneously injected four times weekly into Sprague-Dawley rats. All the rats used in this study including those in the sham group had been unilaterally nephrectomized and allowed free access to drinking water containing 1% NaCl. Systolic blood pressure was measured by the tail-cuff method. Blood chemistry including sodium, potassium, glucose, triglyceride, and cholesterol levels was analyzed. Sections of the heart were visualized after trichrome and hematoxylin and eosin stain. The expression of hypertrophic genes such as atrial natriuretic peptide A (Nppa) and atrial natriuretic peptide B (Nppb) in addition to fibrotic genes such as Collagen-1, Collagen-3, connective tissue growth factor (Ctgf), and Fibronectin were measured by quantitative real-time PCR (qRT-PCR). Injection of DOCA increased systolic blood pressure, heart weight, and cardiac fibrosis, which was attenuated by CG200745. Neither DOCA nor CG200745 affected body weight, vascular contraction and relaxation responses, and blood chemistry. Injection of DOCA increased expression of both hypertrophic and fibrotic genes, which was abrogated by CG200745. These results indicate that CG200745 attenuates cardiac hypertrophy and fibrosis in DOCA-induced hypertensive rats.
Animals ; Blood Pressure ; Body Weight ; Cardiomegaly* ; Chemistry ; Cholesterol ; Connective Tissue Growth Factor ; Desoxycorticosterone ; Desoxycorticosterone Acetate ; Drinking Water ; Eosine Yellowish-(YS) ; Fibronectins ; Fibrosis* ; Glucose ; Heart ; Hematoxylin ; Histone Deacetylase Inhibitors* ; Histone Deacetylases* ; Histones* ; Hypertension ; Methods ; Potassium ; Rats* ; Rats, Sprague-Dawley ; Real-Time Polymerase Chain Reaction ; Relaxation ; Sodium ; Triglycerides