BACKGROUND: Recent studies have demonstrated that the size and shape of the hyperenhanced areas on contrast-enhanced magnetic resonance imaging (ceMRI) were nearly identical to areas of irreversible injury, as defined by histochemical staining. We compared the transmural extent of infarct (TEI), as defined by ceMRI, to the initial ECG findings for acute myocardial infarction (AMI), and we also assessed functional contractility according to TEI. METHODS: 12 patients who presented with their first myocardial infarction underwent cine and ceMRI 4 weeks later after their successful revascularization. TEI and wall thickening were determined by using a 30-segment model. RESULTS: Infarction was observed in 81 (23.9%) segments, of which 46 segments (56.8%) had abnormal wall motion and 35 segments (43.2%) had normal wall motion. Of the 35 segments, 33 (94.3%) had subendocardial infarction. 17 segments had infarct of less than 25% of the wall thickness, and all of them had normal wall motion. On the other hand, 11 segments had infarct of more than 75% of wall thickness, of which 11 (100%) had abnormal wall motion. None of segments with nearly transmural infarction were observed in non ST-elevation AMI. The majority of the segments with infarct had non-transmural infarction (87.5%), even if the segments were in ST-elevation AMI (76.1%). Infarct size, as defined by ceMRI, was strongly correlated with peak CK-MB and Troponin-T (r=0.96, p< 0.001, r=0.91, p< 0.001, respectively). CONCLUSION: TEI defined by ceMRI is inversely related to the contractility after revascularization in AMI. We were able to predict the future contractile function of segments with infarction using ceMRI before revascularization.
Contrast Media/administration & dosage ; Female ; Heterocyclic Compounds/administration & dosage ; Humans ; Magnetic Resonance Imaging, Cine/*methods ; Male ; Middle Aged ; *Myocardial Contraction ; Myocardial Infarction/pathology/*therapy ; *Myocardial Revascularization ; Myocardium/*pathology ; Necrosis ; Organometallic Compounds/administration & dosage

OBJECTIVE: To compare P792 (gadomelitol, a rapid clearance blood pool MR contrast agent) with gadolinium-tetraazacyclododecanetetraacetic acid (Gd-DOTA), a standard extracellular agent, for their suitability to diagnose a pulmonary embolism (PE) during a first-pass perfusion MRI and 3D contrast-enhanced (CE) MR angiography (MRA). MATERIALS AND METHODS: A perfusion MRI or CE-MRA was performed in a rabbit PE model following the intravenous injection of a single dose of contrast agent. The time course of the pulmonary vascular and parenchymal enhancement was assessed by measuring the signal in the aorta, pulmonary artery, and lung parenchyma as a function of time to determine whether there is a significant difference between the techniques. CE-MRA studies were evaluated by their ability to depict the pulmonary vasculature and following defects between 3 seconds and 15 minutes after a triple dose intravenous injection of the contrast agents. RESULTS: The P792 and Gd-DOTA were equivalent in their ability to demonstrate PE as perfusion defects on first pass imaging. The signal from P792 was significantly higher in vasculature than that from Gd-DOTA between the first and the tenth minutes after injection. The results suggest that a CE-MRA PE could be reliably diagnosed up to 15 minutes after injection. CONCLUSION: P792 is superior to Gd-DOTA for the MR diagnosis of PE.
Animals ; Contrast Media/administration & dosage ; Heterocyclic Compounds/administration & dosage/*diagnostic use ; Imaging, Three-Dimensional ; Injections, Intravenous ; Magnetic Resonance Angiography/*methods ; Magnetic Resonance Imaging/*methods ; Organometallic Compounds/administration & dosage/*diagnostic use ; Pulmonary Embolism/*diagnosis ; Rabbits

OBJECTIVE: To evaluate the utility of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) using macromolecular contrast agent (P792) for assessment of vascular disrupting drug effect in rabbit VX2 liver tumor models. MATERIALS AND METHODS: This study was approved by our Institutional Animal Care and Use Committee. DCE-MRI was performed with 3-T scanner in 13 VX2 liver tumor-bearing rabbits, before, 4 hours after, and 24 hours after administration of vascular disrupting agent (VDA), using gadomelitol (P792, n = 7) or low molecular weight contrast agent (gadoterate meglumine [Gd-DOTA], n = 6). P792 was injected at a of dose 0.05 mmol/kg, while that of Gd-DOTA was 0.2 mmol/kg. DCE-MRI parameters including volume transfer coefficient (K(trans)) and initial area under the gadolinium concentration-time curve until 60 seconds (iAUC) of tumors were compared between the 2 groups at each time point. DCE-MRI parameters were correlated with tumor histopathology. Reproducibility in measurement of DCE-MRI parameters and image quality of source MR were compared between groups. RESULTS: P792 group showed a more prominent decrease in K(trans) and iAUC at 4 hours and 24 hours, as compared to the Gd-DOTA group. Changes in DCE-MRI parameters showed a weak correlation with histologic parameters (necrotic fraction and microvessel density) in both groups. Reproducibility of DCE-MRI parameters and overall image quality was not significantly better in the P792 group, as compared to the Gd-DOTA group. CONCLUSION: Dynamic contrast-enhanced magnetic resonance imaging using a macromolecular contrast agent shows changes of hepatic perfusion more clearly after administration of the VDA. Gadolinium was required at smaller doses than a low molecular contrast agent.
Animals ; Antineoplastic Agents/therapeutic use ; Benzophenones/therapeutic use ; Disease Models, Animal ; Heterocyclic Compounds/administration & dosage/*chemistry ; Liver Neoplasms/drug therapy/pathology/*radiography ; *Magnetic Resonance Imaging ; Male ; Organometallic Compounds/administration & dosage/*chemistry ; Rabbits ; Reproducibility of Results ; Valine/analogs & derivatives/therapeutic use

A single dose of 3H-norcantharidin solution was intragastrically given, blood, tissues, urine and feces were collected as scheduled, and radioactivity in these samples was determined by tritium tracing method to investigate the pharmacokinetics, tissue distribution and excretion of norcantharidin in Kunming mice. The pharmacokinetic characteristics of norcantharidin were evaluated by DAS version 2.0. The blood concentration reached to maximum 0. 5 h after intragastric administration. The radioactivity in tissues was high in small intestine, gallbladder, stomach, adrenal gland, kidney, heart and uterus 15 minutes after administration, descending with time, and high in gallbladder, adrenal gland and uterus 3 hours post dosing. The 24 h accumulative excretion ratio of urine and feces were 65.40% and 1.33% respectively. 3H-norcantharidin was easily absorbed after orally given to mice, the radioactivity was high and existed for a long-time in gallbladder, adrenal gland and uterus, and low but also existed for a long-time in large intestine, thymus and fat tissue. 3H-norcantharidin was declined quickly in small intestine, stomach, kidney and heart, and occurred rarely in brain. Norcantharidin was excreted mainly by urinary route and seldom in feces, which may be the cause of the urinary stimulation side effects observed. Because the radioactivity measured were the sum of 3H labeled norcantharidin and its metabolites, further studies on the disposition of norcantharidin in mammal animals, on the separation or identification of metabolites and, if any, on their activities, are fairly needed.
Administration, Oral ; Animals ; Antineoplastic Agents ; administration & dosage ; chemistry ; pharmacokinetics ; urine ; Bridged Bicyclo Compounds, Heterocyclic ; administration & dosage ; chemistry ; pharmacokinetics ; urine ; Feces ; chemistry ; Female ; Male ; Mice ; Molecular Structure ; Random Allocation ; Tissue Distribution ; Tritium

Conventional combination therapies have not resulted in considerable progress in the treatment of acute myeloid leukemia (AML). Elderly patients with AML and poor risk factors have grave prognosis. Midostaurin has been recently approved for the treatment of FLT-3-mutated AML. Venetoclax, a BCL-2 inhibitor, has been approved for the treatment of relapsed and/or refractory chronic lymphoid leukemia. Clinical trials on applying venetoclax in combination with cytarabine and other agents to treat various hematological malignancies are currently underway. Here, we present a case of a male patient with poor performance status and who developed AML following allogeneic hematopoietic stem cell transplant for high-risk myelodysplasia. The patient with high risk AML achieved complete response to the combined treatment regimen of low-dose cytarabine and venetoclax. Furthermore, we reviewed current clinical trials on the use of venetoclax for hematological malignancies.
Aged ; Bridged Bicyclo Compounds, Heterocyclic ; administration & dosage ; Combined Modality Therapy ; Cytarabine ; administration & dosage ; Fatal Outcome ; Hematopoietic Stem Cell Transplantation ; Humans ; Leukemia, Myeloid, Acute ; drug therapy ; genetics ; Male ; Recurrence ; Remission Induction ; Sulfonamides ; administration & dosage

AIMTo prepare lipid microsphere of sodium norcantharidin (NCTD) and then study their characters and pharmacokinetic behavior.

METHODSDynamic Light Scattering, HPLC and retrodialysis technique were used to determine the in vitro characters of the NCTD loaded lipid microsphere (LM), such as the particle size, xi-potential, content, incorporation ratio, release profile and changes after dilute. And the plasma concentration was determined by HPLC-MS, compared with NCTD aqueous solution at the same time.

RESULTSEvery property showed that the LM was preferable. The average diameter was about 200 nm. The xi-potential was - 38 mV. The content was close to 100%. And the incorporation ratio exceeded 80%. After i. v. administration of single dose, the pharmacodynamic parameter of LM AUC was 111.28 microg x mL(-1) x h(-1). The data of plasma concentrations showed that the NCTD LM was of two compartment. There was no obvious difference between in vivo parameters of LM and reference solution.

CONCLUSIONThe NCTD LM was eligible and the character of it in vivo was not changed.

Animals ; Antineoplastic Agents ; administration & dosage ; blood ; pharmacokinetics ; Area Under Curve ; Bridged Bicyclo Compounds, Heterocyclic ; administration & dosage ; blood ; pharmacokinetics ; Chromatography, High Pressure Liquid ; Female ; Lipids ; Male ; Mass Spectrometry ; Microspheres ; Particle Size ; Rats ; Rats, Wistar

Influenza virus is a virus causing upper respiratory tract infection disease with high morbidity and mortality. China is considered as an area with high rate of influenza morbidity. Prevention and treatment of influenza currently rely on vaccines and antiviral agents in the world. In addition, traditional Chinese medicines also have been used in clinical for influenza therapy. In vitro anti-influenza virus activities of 10 traditional Chinese medicines were studied by cytopathic effect (CPE). Qingre Jiedu oral liquid (factory H) had strong antiviral activity against influenza virus A/Guangdong Luohu/219/2006 (H1N1); Yinhuang oral liquid had strong antiviral activity against influenza virus A/Hanfang/359/95 and A/Yuefang/243/72 (H3N2). Qingkailing oral liquid (factory G) had strong antiviral activity against influenza virus A/Jifang/15/90 (H3N2). Qingre Jiedu oral liquid (factory H) had strong antiviral activity against influenza virus A/Jifang/15/90, A/Yuefang/243/72 (H3N2) and virus B.
Administration, Oral ; Animals ; Antiviral Agents ; administration & dosage ; pharmacology ; Bridged Bicyclo Compounds, Heterocyclic ; administration & dosage ; pharmacology ; Cell Line ; Chlorogenic Acid ; administration & dosage ; pharmacology ; Cytopathogenic Effect, Viral ; drug effects ; Dogs ; Drugs, Chinese Herbal ; administration & dosage ; pharmacology ; Flavonoids ; administration & dosage ; pharmacology ; Indoles ; administration & dosage ; pharmacology ; Influenza A Virus, H1N1 Subtype ; drug effects ; Influenza A Virus, H3N2 Subtype ; drug effects ; Influenza B virus ; drug effects ; Iridoids ; administration & dosage ; pharmacology

This study is to elucidate the metabolic pathway of 1,2-[bis (1,2-benzisoselenazolone-3 (2H)-ketone)]-ethane (BBSKE) in rats. Rats were administrated with a single dose of BBSKE 200 mg x kg(-1). The metabolites in rat urine, feces, bile and plasma were identified by LC-MSn analysis. The characterization of fragment ions from LC-MSn chromatography and mass spectrometry was applied to the investigation of structures of metabolites. Three phase I metabolites were detected in rat urine and feces. Two of them were also found in plasma and one existed in bile. These products were derived from oxidized, methylated and S-methylated BBSKE, separately. One phase II glucuronide of BBSKE was also found in bile. Therefore, it is possible that BBSKE was metabolized by oxidization, methylation and glucuronidation.
Administration, Oral ; Animals ; Antineoplastic Agents ; administration & dosage ; blood ; metabolism ; urine ; Bile ; metabolism ; Bridged Bicyclo Compounds, Heterocyclic ; administration & dosage ; blood ; metabolism ; urine ; Chromatography, Liquid ; Feces ; chemistry ; Male ; Organoselenium Compounds ; administration & dosage ; blood ; metabolism ; urine ; Rats ; Rats, Sprague-Dawley ; Spectrometry, Mass, Electrospray Ionization

OBJECTIVETo evaluate the efficacy and safety of patient-controlled intravenous analgesia (PCIA) of dezocine combined with sufentanil in burn patients after escharectomy or tangential excision followed by autologous skin grafting.

METHODSSixty burn patients hospitalized in Department of Burns and Plastic Surgery of our hospital from February 2011 to December 2013, conforming to the study criteria and going to have escharectomy or tangential excision followed by autologous skin grafting, were divided into sufentanil group (S, n = 30) and dezocine+sufentanil group (DS, n = 30) according to the random number table. Patients in group S were given 150 mL normal saline containing 2.5 µg/kg sufentanil citrate and 6 mg tropisetron after skin grafting for 48 hours. Patients in group DS were given 150 mL normal saline containing 0.25 mg/kg dezocine, 1.5 µg/kg sufentanil citrate, and 6 mg tropisetron for 48 hours. Visual Analog Scale (VAS), Bruggrmann Comfort Scale (BCS), and Ramsay Sedation Scale were used to evaluate the sedative effect or analgesic effect, and their scores were recorded at administration hour (AH) 2, 6, 12, 24, and 48. The times of efficient injection and incidence of adverse effect within the 48 AH were recorded. Data were processed with analysis of variance for repeated measurement, t test, chi-square test, and Fisher's exact test.

RESULTSThere were no obvious differences in the scores of VAS and BCS between two groups at each time point (with t values from -0.426 to 0.864, P values above 0.05). The scores of Ramsay Sedation Scale in group S at AH 2, 6, 12, 24, and 48 were respectively (3.2 ± 0.6), (3.2 ± 0.5), (3.3 ± 0.7), (3.2 ± 0.4), and (3.3 ± 0.4) points, which were higher than those in group DS [(2.4 ± 0.6), (2.5 ± 0.5), (2.4 ± 0.6), (2.4 ± 0.4), and (2.4 ± 0.5) points, with t values from 5.302 to 8.391, P values below 0.001]. The times of efficient injection within the 48 AH was 6.8 ± 0.7 in group S and 6.5 ± 0.9 in group DS, showing no significantly statistical difference (t = 1.260, P > 0.05). Respiratory depression was not observed in both groups; the incidence of pruritus was the same, and that of urine retention was similar between the 2 groups within the 48 AH (with P values above 0.05). Within the 48 AH, the incidence of nausea and vomiting in group S was 26.7% (8/30), which was obviously higher than that in group DS (6.7%, 2/30, P < 0.05); the incidence of drowsiness in group S was 20.0% (6/30), which was significantly higher than that in group DS (no patient, P < 0.05).

CONCLUSIONSDezocine combined with sufentanil can provide effective postoperative analgesia with little adverse effect for PCIA in burn patients after escharectomy or tangential excision followed by autologous skin grafting, therefore it can be widely used.

Analgesia, Patient-Controlled ; adverse effects ; Analgesics, Opioid ; administration & dosage ; Bridged Bicyclo Compounds, Heterocyclic ; administration & dosage ; adverse effects ; Burns ; surgery ; Female ; Humans ; Hypnotics and Sedatives ; administration & dosage ; Infusions, Intravenous ; Male ; Pain, Postoperative ; drug therapy ; Reconstructive Surgical Procedures ; Skin Transplantation ; Sufentanil ; administration & dosage ; adverse effects ; Tetrahydronaphthalenes ; administration & dosage ; adverse effects ; Treatment Outcome

AIMTo study the morphology, particle size distribution and biological reliability of the norcantharindin (NCTD)-loaded microemulsion and pharmacokinetics of the W/O norcantharidin-loaded microemulsion in mice.

METHODSThe concentration of NCTD in plasma and tissues were determined by GC method. The data obtained were processed using 3P87 program.

RESULTSThe mean particle diameter of microemulsion was (44 +/- 9) nm. The concentration-time curve of NCTD-loaded microemulsion and NCTD injection was fitted to a two-compartment model. At the same dosage, the pharmacokinetic study for NCTD-loaded microemulsion showed the NCTD microemulsion had relatively longer circulating time in mice. Area under the curve of concentration versus time (AUC), mean residence time (MRT) and half life (T1/2) for microemulsion and injection were (29.7 +/- 0.9) mg x h x L(-1), (9.25 +/- 0.09) mg x h x L(-1), (110 +/- 11) h, (86.7 +/- 0.8) h, (103 +/- 12) h, (42 +/- 4) h, respectively. Targeting index of NCTD microemulsion in liver and kidney in mice were 0.43 and 0.12 after iv NCTD-loaded microemulsion. The effects of biological reliability was not significantly different between NCTD microemulsion and NCTD injection in vivo and in vitro.

CONCLUSIONThe liver targeting absorptive capability of NCTD-loaded microemulsion was enhanced and the release time was extended compared with NCTD injection. While the microemulsion vehicles could decrease the kidney distribution of NCTD.

Animals ; Antineoplastic Agents ; administration & dosage ; pharmacokinetics ; pharmacology ; Area Under Curve ; Bridged Bicyclo Compounds, Heterocyclic ; administration & dosage ; pharmacokinetics ; pharmacology ; Carcinoma, Hepatocellular ; pathology ; Cell Line, Tumor ; Cells, Cultured ; Drug Delivery Systems ; Emulsions ; Female ; Humans ; Injections, Intravenous ; Liver ; cytology ; metabolism ; Liver Neoplasms ; pathology ; Male ; Mice ; Particle Size ; Tissue Distribution