Bt protein rhizosecreted from transgenic maize does not accumulate in soil

The persistence of CryIAb protein rhizosecreted in soil is important in the assessment of its environmental risk. Here we report that CryIAb protein from transgenic maize does not accumulate at high levels in soils. Levels of CryIAb protein rhizosecreted by three maize transgenic events (BT11, MON810 and 176) were studied in hydroponic cultures and found only in the MON810 and BT11 events but not in event 176 or control plants. Under field conditions, the cryIAb gene and a basal level of CryIAb protein was detected in soils from plots cultivated with transgenic and non-transgenic maize, possibly from Bacillus thuringiensis present in the soils

Cost effectiveness of zofenopril in patients with left ventricular systolic dysfunction after acute myocardial infarction: a post- hoc analysis of the smile-4 study.

BACKGROUND: In SMILE-4 (the Survival of Myocardial Infarction Long-term Evaluation 4 study), zofenopril + acetylsalicylic acid (ASA) was superior to ramipril + ASA in reducing the occurrence of major cardiovascular events in patients with left ventricular dysfunction following acute myocardial infarction. The present post hoc analysis was performed to compare the cost-effectiveness of zofenopril and ramipril. METHODS: In total, 771 patients with left ventricular dysfunction and acute myocardial infarction were randomized in a double-blind manner to receive zofenopril 60 mg/day (n = 389) or ramipril 10 mg/day (n = 382) + ASA 100 mg/day and were followed up for one year. The primary study endpoint was the one-year combined occurrence of death or hospitalization for cardiovascular causes. The economic analysis was based on evaluation of cost of medications and hospitalizations and was applied to the intention-to-treat population (n = 716). Cost data were drawn from the National Health Service databases of the European countries participating in the study. The incremental cost-effectiveness ratio was used to quantify the cost per event prevented with zofenopril versus ramipril. RESULTS: Zofenopril significantly (P = 0.028) reduced the risk of the primary study endpoint by 30% as compared with ramipril (95% confidence interval, 4%-49%). The number needed to treat to prevent a major cardiovascular event with zofenopril was 13 less than with ramipril. The cost of drug therapies was higher with zofenopril (328.78 Euros per patient per year, n = 365) than with ramipril (165.12 Euros per patient per year, n = 351). The cost related to the occurrence of major cardiovascular events requiring hospitalization averaged 4983.64 Euros for zofenopril and 4850.01 Euros for ramipril. The incremental cost-effectiveness ratio for zofenopril versus ramipril was 2125.45 Euros per event prevented (worst and best case scenario in the sensitivity analysis was 3590.09 and 3243.96 Euros, respectively). CONCLUSION: Zofenopril is a viable and cost-effective treatment for managing patients with left ventricular dysfunction after acute myocardial infarction

Administration route effect on the absorption kinetic of the ricobendazole in sheep

Se estudió el comportamiento farmacocinético del ricobendazole (RBZ) tras su administración intravenosa (i.v), intrarruminal (i.r) y subcutánea (s.c) en ovinos. El RBZ se administró como solución experimental al 10% por la vía i.v, como suspensión experimental al 10% por vía i.r y por vía s.c como solución comercial al 10% (Sintyotal-R®). En todos los casos la dosis administrada fue 5 mg.kg-1. Los datos de concentración plasmática fueron analizados mediante el método no compartimental y la discriminación del orden y la magnitud del proceso de absorción tras la administración i.r se realizó por construcción de curvas de cantidades acumulativas de fármaco ingresado a la circulación general mediante el método de Loo-Riegelman. Tras su administración i.r, el orden de absorción se asimiló a un proceso de orden cero, pero la fracción de la dosis biodisponible fue de alrededor del 30% mientras que tras su administración s.c el RBZ se absorbió rápidamente y casi en su totalidad. Estos resultados muestran un mejor comportamiento farmacocinético de la formulación inyectable con respecto a la clásica suspensión administrada por la vía i.r.The pharmacokinetic behavior of ricobendazole (RBZ) was studied after its intravenous (i.v), intrarruminal (i.r) and subcutaneous (s.c) administration in sheep. Ricobendazole was administered as experimental 10 % solution by i.v route, as experimental 10 % suspension by i.r route and by s.c route as 10% commercial solution (Sintyotal-R®). In all the cases the administered dose was 5 mg.kg-1. The plasma concentration profiles were analyzed by means non-compartmental methodology, and the discrimination of the rate and the order of absorption after i.r administration were performed by construction of cumulative curves of drug entered into the general circulation by means of the Loo-Riegelman method. After i.r administration the order of absorption was best explained as a zero order process, the bioavailability being around 30 %, while after s.c administration t RBZ absorption was fast and bioavailability almost complete. These results shown a best pharmacokinetic behavior of the injectable formulation in comparison with the classic suspension administered by i.r route.Facultad de Ciencias Veterinaria

Administration route effect on the absorption kinetic of the ricobendazole in sheep

Se estudió el comportamiento farmacocinético del ricobendazole (RBZ) tras su administración intravenosa (i.v), intrarruminal (i.r) y subcutánea (s.c) en ovinos. El RBZ se administró como solución experimental al 10% por la vía i.v, como suspensión experimental al 10% por vía i.r y por vía s.c como solución comercial al 10% (Sintyotal-R®). En todos los casos la dosis administrada fue 5 mg.kg-1. Los datos de concentración plasmática fueron analizados mediante el método no compartimental y la discriminación del orden y la magnitud del proceso de absorción tras la administración i.r se realizó por construcción de curvas de cantidades acumulativas de fármaco ingresado a la circulación general mediante el método de Loo-Riegelman. Tras su administración i.r, el orden de absorción se asimiló a un proceso de orden cero, pero la fracción de la dosis biodisponible fue de alrededor del 30% mientras que tras su administración s.c el RBZ se absorbió rápidamente y casi en su totalidad. Estos resultados muestran un mejor comportamiento farmacocinético de la formulación inyectable con respecto a la clásica suspensión administrada por la vía i.r.The pharmacokinetic behavior of ricobendazole (RBZ) was studied after its intravenous (i.v), intrarruminal (i.r) and subcutaneous (s.c) administration in sheep. Ricobendazole was administered as experimental 10 % solution by i.v route, as experimental 10 % suspension by i.r route and by s.c route as 10% commercial solution (Sintyotal-R®). In all the cases the administered dose was 5 mg.kg-1. The plasma concentration profiles were analyzed by means non-compartmental methodology, and the discrimination of the rate and the order of absorption after i.r administration were performed by construction of cumulative curves of drug entered into the general circulation by means of the Loo-Riegelman method. After i.r administration the order of absorption was best explained as a zero order process, the bioavailability being around 30 %, while after s.c administration t RBZ absorption was fast and bioavailability almost complete. These results shown a best pharmacokinetic behavior of the injectable formulation in comparison with the classic suspension administered by i.r route.Facultad de Ciencias Veterinaria

Learning from Conect4children: A Collaborative Approach towards Standardization of Disease-Specific Paediatric Research Data

The conect4children (c4c) initiative was established to facilitate the development of new drugs and other therapies for paediatric patients. It is widely recognized that there are not enough medicines tested in all relevant ages of the paediatric population. To overcome this, it is imperative that clinical data from different sources are interoperable and can be pooled for larger post-hoc studies. c4c has collaborated with the Clinical Data Interchange Standards Consortium (CDISC) to develop the cross-cutting data resources that build on existing CDISC standards, in an effort to standardize paediatric data. The natural next step was an extension to disease-specific data items. c4c brought together several existing initiatives and resources relevant to disease-specific data and to analyse their use for standardizing disease-specific data in clinical trials. Several case studies that combined disease-specific data from multiple trials have demonstrated the need for disease-specific data standardization. We identified three relevant initiatives. These include European Reference Networks, European Joint Programme on Rare Diseases, and Pistoia Alliance. Other resources reviewed were: National Cancer Institute Enterprise Vocabulary Services, CDISC standards, pharmaceutical company-specific data dictionaries, Human Phenotype Ontology, Phenopackets, Unified Registry for Inherited Metabolic Disorders, Orphacodes, Rare Disease Cures Accelerator-Data and Analytics Platform (RDCA-DAP) and Observational Medical Outcomes Partnership. The collaborative partners associated with these resources were also reviewed briefly. A plan of action focussed on collaboration was generated for standardizing disease-specific paediatric clinical trial data. A paediatric data standards multistakeholder and multi-project user group was established to guide the remaining actions– FAIRification of metadata, a Phenopackets pilot with RDCA-DAP, applying Orphacodes to case report forms of clinical trials, introducing CDISC standards into European Reference Networks, testing of the CDISC Pediatric User Guide using data from the mentioned resources and organization of further workshops and educational materials

Bt protein rhizosecreted from transgenic maize does not accumulate in soil

The persistence of CryIAb protein rhizosecreted in soil is important in the assessment of its environmental risk. Here we report that CryIAb protein from transgenic maize does not accumulate at high levels in soils. Levels of CryIAb protein rhizosecreted by three maize transgenic events (BT11, MON810 and 176) were studied in hydroponic cultures and found only in the MON810 and BT11 events but not in event 176 or control plants. Under field conditions, the cryIAb gene and a basal level of CryIAb protein was detected in soils from plots cultivated with transgenic and non-transgenic maize, possibly from Bacillus thuringiensis present in the soils

Late onset obesity in mice with targeted deletion of potassium inward rectifier Kir7.1 from cells expressing the melanocortinâ 4 receptor

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/147809/1/jne12670.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/147809/2/jne12670_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/147809/3/jne12670-sup-0001-FigS1-S4.pd