Domperidone with ORT in the treatment of pediatric acute gastroenteritis in Japan: a multicenter, randomized controlled trial.

Domperidone is an antiemetic that is often prescribed for children with acute gastroenteritis in Japan. In this study, the authors assessed the efficacy of domperidone prescription in combination with oral rehydration treatment (ORT) in the treatment of vomiting during acute gastroenteritis in children during the early period. They performed a prospective multicenter randomized trial in Japan. Patients received either ORT or ORT and domperidone prescription. The primary outcome was the proportion of patients who had vomiting during the first 2 hours after randomization. A total of 56 children were eligible; 24 received ORT alone, and 32 received ORT and prescribed domperidone suppository. Results showed that 27.3% of children in the ORT group vomited as compared with 20.7% of children in the ORT and domperidone group (P = .41). In this study, it appears that domperidone in combination with ORT in the treatment of acute gastroenteritis does not reduce vomiting in the early period.

[Left ventriculoplasty in a patient with suspected takotsubo cardiomyopathy followed by a left ventricular aneurysm].

A 42-year-old woman was admitted with chest pain. Coronary angiography did not reveal any significant stenosis, but left ventriculography showed akinesis and ballooning of the apex with a hyperkinetic basal segment indicating Takotsubo cardiomyopathy. Cerebral embolism occurred after one and a half years because of a left ventricular thrombus. The apical akinesis had worsened to a left ventricular aneurysm (maximum diameter 43 mm). The left ventricle was reconstructed to avoid repeated thrombus formation and cerebral infarction despite anticoagulant therapy. A pathological assessment revealed a fibrotic myocardium, but the cause of the cardiac aneurysm remained unknown. Although the outcome of Takotsubo cardiomyopathy is relatively good, careful observation and appropriate treatment are needed considering the possibility of aggravation.

Design, synthesis, and biological evaluation of novel transrepression-selective liver X receptor (LXR) ligands with 5,11-dihydro-5-methyl-11-methylene-6H-dibenz[b,e]azepin-6-one skeleton.

To obtain novel transrepression-selective liver X receptor (LXR) ligands, we adopted a strategy of reducing the transactivational agonistic activity of the 5,11-dihydro-5-methyl-11-methylene-6H-dibenz[b,e]azepin-6-one derivative 10, which exhibits LXR-mediated transrepressional and transactivational activity. Structural modification of 10 based on the reported X-ray crystal structure of the LXR ligand-binding domain led to a series of compounds, of which almost all exhibited transrepressional activity at 1 or 10 µM but showed no transactivational activity even at 30 µM. Among the compounds obtained, 18 and 22 were confirmed to have LXR-dependent transrepressional activity by using peritoneal macrophages from wild-type and LXR-null mice. A newly developed fluorescence polarization assay indicated that they bind directly to LXRα. Next, further structural modification was performed with the guidance of docking simulations with LXRα, focusing on enhancing the binding of the ligands with LXRα through the introduction of substituents or heteroatom(s). Among the compounds synthesized, compound 48, bearing a hydroxyl group, showed potent, selective, and dose-dependent transrepressional activity.

Design and synthesis of phthalimide-based fluorescent liver x receptor antagonists.

Based on our structure-activity relationship study of liver X receptor (LXR) ligands, we designed and synthesized fluorescent LXR antagonists containing an unsubstituted or substituted amino group on a phthalimide unit.

Survey of severe respiratory syncytial virus infection in Kyoto Prefecture from 2003 to 2007.

BACKGROUND: Respiratory syncytial virus (RSV) infection in infants can develop into a severe condition. METHODS: A survey of patients with severe RSV infection in hospitals in Kyoto Prefecture was performed from 2003 to 2007. Patients requiring intubation and those with cardiopulmonary arrest on arrival (CPAOA) were considered to have severe RSV infection. RESULTS: Twenty-five patients with severe infection were identified and detailed data were available for 21 patients, of whom 18 required intubation and three had CPAOA. The male/female ratio was 12/9 and age ranged from 8 days to 19 years (average, 5.2 months; median: 2 months). At admission white blood cell count, lactate dehydrogenase (P < 0.05), and blood glucose (P < 0.01) were higher and Na was lower (P < 0.01) in the 18 patients with severe infection (excluding the CPAOA cases) compared to 18 sex- and age-matched patients with mild RSV infection. The incidence of bacterial infection was also higher in severe cases (P < 0.05). The outcome was death in four patients (19.0%, including two sudden deaths), aftereffects in two (9.5%), hospital discharge with improvement in 14 (66.7%), and an unclear outcome in one patient. Excluding the two sudden death cases, 14 of 19 patients (73.7%) were extubated within 2 weeks. The period of intubation was longer in older patients (P < 0.05). CONCLUSION: Because severe RSV infection led to sudden death in two cases, detection of RSV is important at admission for an infant with CPAOA. Fourteen patients (66.7%), however, had good outcomes and most patients were extubated within 2 weeks.

A contact investigation of the transmission of Mycobacterium tuberculosis from a nurse working in a newborn nursery and maternity ward.

A nurse working in a newborn nursery and maternity ward developed 3+ smear-positive lung tuberculosis. The hospital infection control committee, in collaboration with the local public health and welfare center, conducted a contact investigation. The infection period was defined as April to August 2006. The investigation included 109 infant and mother pairs, 28 children aged under 10 years and their guardians, 62 coworkers, and 63 household visitors to the ward. Tuberculosis infection in infants and children aged under 5 years was primarily determined by tuberculin skin test (TST), while subjects aged 5 years or more were tested using QuantiFERON-TB Gold (QFT). The first investigation, in August 2006, was conducted in all subjects, and the second investigation, in October 2006, targeted selected subjects. No infants were TST-positive. Two children aged 1 year or under, vaccinated with bacillus Calmette-Guérin, were positive for TST, as determined by the criteria of the Japan Anti-Tuberculosis Association; however, other tests for tuberculosis were negative. Of the 13 QFT-positive adult subjects, 1 mother and 2 coworkers could have become infected with Mycobacterium tuberculosis through exposure to the index nurse. Fifty-four infants and 6 children underwent "window-period" prophylaxis, and 4 adults completed 6-month prophylactic treatment with isoniazid. To date, no secondary cases of tuberculosis disease have occurred.

Implantation of mesenchymal stem cells overexpressing endothelial nitric oxide synthase improves right ventricular impairments caused by pulmonary hypertension.

BACKGROUND: Pulmonary hypertension (PH) is a life-threatening disease. Bone marrow cell transplantation is reported to reduce the development of PH by increasing vascular beds in pulmonary circulation. However, adenoviral overexpression of endothelial nitric oxide synthase (eNOS) in the lung is also known to reduce PH. Because mesenchymal stem cells (MSCs) are potential cell sources for neovascularization, the implantation of MSCs overexpressing eNOS (MSCs/eNOS) may further improve the surgical results. We evaluated the efficacy of MSCs/eNOS implantation in monocrotaline (MCT)-induced PH rats. METHODS AND RESULTS: MSCs were isolated from rat bone marrow. PH was induced in rats by subcutaneous injection of MCT. One week after MCT administration, the rats received 3 different treatments: MSCs (MSC group), MSCs/eNOS (MSC/eNOS group), or nontreatment (PH group). As the negative control, rats received saline instead of MCT (control group). Right ventricular (RV) hypertrophy and the elevation of RV systolic pressure (RVSP) were evaluated 3 weeks after MCT administration. Moreover, the effects of MSCs/eNOS on survival were investigated in PH induced by MCT 3 weeks earlier. RVSP in both the MSC and MSC/eNOS groups was significantly lower than the PH group. RVSP in the MSC/eNOS group was significantly lower than the MSC group. The RV weight to body weight ratio was significantly lower in the MSC and MSC/eNOS groups than the PH group. The survival time of rats receiving MSCs/eNOS was significantly longer than the nontreatment rats. CONCLUSIONS: Intravenous implantation of MSCs/eNOS may offer ameliorating effects on PH-related RV impairment and survival time.

Synthetic vascular prosthesis impregnated with mesenchymal stem cells overexpressing endothelial nitric oxide synthase.

BACKGROUND: Endothelial dysfunction is known to exaggerate coronary artery disease, sometimes leading to irreversible myocardial damage. In such cases, repetitive coronary revascularization including coronary artery bypass grafting is needed, which may cause a shortage of graft conduits. On the other hand, endothelial nitric oxide synthase (eNOS) is an attractive target of cardiovascular gene therapy. The vascular prostheses, of which the inner surfaces are covered with mesenchymal stem cells (MSCs) overexpressing eNOS, are expected to offer feasible effects of NO and angiogenic effects of MSCs on the native coronary arterial beds, as well as improvement of self-patency. Herein, we attempted to develop small caliber vascular prostheses generating the bioactive proteins. Also, we attempted to transduce eNOS cDNA into MSCs. METHODS AND RESULTS: The MSCs were isolated from rat bone marrow and transduced with each adenovirus harboring rat eNOS cDNA and beta-galactosidase (beta-gal) (eNOS/MSCs and beta-gal/MSCs). The beta-gal/MSCs were impregnated into vascular prostheses, then the expressions of beta-gal on the inner surfaces of them were evaluated by 5-bromo-4-chloro-3-indolyl beta-D-galactoside staining. The NOS activity of eNOS/MSCs was assayed by monitoring the conversion of 3H-arginine to 3H-citrulline. The inner surfaces of the vascular prostheses were covered with MSCs expressing beta-gal. The amount of the 3H-citrulline increased, and eNOS/MSCs were determined to generate enzymatic activity of eNOS. This activity was completely inhibited by N(G)-nitro-L-arginine methyl ester. CONCLUSIONS: The inner surface of expanded polytetrafluoroethylene vascular prostheses seeded with lacZ gene-transduced MSCs exhibited recombinant proteins. Development of eNOS/MSC-seeded vascular prostheses would promise much longer graft patency and vasculoprotective effects.

Landiolol enhances effect of ischemic preconditioning in isolated rabbit hearts.

The effect of the ultra-short-acting beta blocker, landiolol, on ischemic preconditioning was examined in isolated rabbit hearts. Ischemic preconditioned hearts received 2 episodes of 5 min each of global ischemia and reperfusion. The left anterior descending coronary artery was occluded for 1 hour and reperfused for 1 hour. Left ventricular end-systolic and end-diastolic pressures and infarct size were measured. Seven control hearts had no drug infused. Four groups of 6 hearts each were pretreated with 1 or 3 microM of landiolol or a combination of 1 or 3 microM landiolol and ischemic preconditioning. A further group of 6 hearts had ischemic preconditioning without landiolol. Ischemic preconditioning significantly reduced left ventricular end-diastolic pressure and infarct size compared to the controls. Landiolol alone did not change left ventricular end-diastolic pressure or infarct size, but landiolol 3 microM and ischemic preconditioning decreased left ventricular end-diastolic pressure more than preconditioning alone. These data suggest that pre-ischemic landiolol infusion may enhance the cardioprotective effect of ischemic preconditioning.

Activation of beta2-adrenergic receptor plays a pivotal role in generating the protective effect of ischemic preconditioning in rat hearts.

BACKGROUND: Ischemic preconditioning (IPC) protects hearts against ischemia by reducing infarct size. However, IPC does not preserve cardiac function, such as left ventricular peak developed pressure (LVPDP). Moreover, IPC fails to protect the post-myocardial infarct (MI) heart. DESIGN: Rat hearts were transfected with beta2-adrenergic receptor (B2AR) cDNA by the hemagglutinating virus of Japan-liposome method. After the gene transfer, the hearts were perfused in a Langendorff mode and preconditioned with two cycles of 5 min of ischemia and reperfusion. After 20 min of global ischemia, the hearts were reperfused under aerobic conditions for 90 min. LVPDP was measured as an indicator of the cardiac function. RESULTS: LVPDP of ischemic hearts was well preserved by the combination treatment of IPC and gene transfer of B2AR, but not IPC or gene transfer of B2AR alone. Moreover, the treatment was beneficial to even the post-MI heart. On the contrary, gene transfer of beta-adrenergic receptor kinase 1 (BARK1) reduced the protective effect of IPC. We also found that the mRNA ratio of B2AR and BARK1 was well correlated with the preservation of the LVPDP. CONCLUSIONS: The combination treatment of IPC and gene transfer of B2AR protects cardiac function against ischemia and it shows the beneficial effect also in post-MI hearts.

Synthetic vascular prosthesis impregnated with genetically modified bone marrow cells produced recombinant proteins.

The aim of this study is to develop an experimental model of small caliber expanded polytetrafluoroethylene (ePTFE) vascular prostheses that produce recombinant proteins by seeding genetically modified bone marrow mesenchymal stem cells (MSC). Beta-galactosidase (beta-gal) cDNA was transduced into rat MSC mediated by an adenovirus vector. The cells were impregnated into the ePTFE vascular prostheses measuring 2 mm in internal diameter and 90 microm in fibril length, followed by 48 h of incubation. The expressions of beta-gal were determined by X-gal staining. The luminal surface of the ePTFE vascular prostheses was covered with the MSC expressing beta-gal. Most of the gene-transduced MSC spread along the fibers forming colonies. These results suggest that small caliber vascular prostheses, in which the inner surface was seeded by genetically modified MSC, produced recombinant proteins. This may be a preliminary model to autocrine functioning vascular prostheses.