ABSTRACT:The enzymic basis for intracellular reduction of N-hydroxylated amidines to their corresponding amidines, and hydroxylamines to their corresponding amines, is unknown. The hydroxylated amidines can be used as prodrug moieties, and an understanding of the enzyme system active in the reduction can contribute to more efficient drug development. In this study, we examined the properties of this enzyme system using benzamidoxime and N-hydroxymelagatran as substrates. In rats and humans, the hepatic enzyme system was localized in mitochondria as well as in microsomes, using preferably NADH as cofactor. Potassium cyanide, N-methylhydroxylamine, p-hydroxymercuribenzoate, and desferrioxamine were efficient inhibitors, whereas typical cytochrome P450 (P450) inhibitors were ineffective. In rats, the highest specific activity was found in liver, adipose tissue, and kidneys, whereas in humans, the specific activity in the preparations of adipose tissue examined was lower. A sex difference was observed in rat liver, where 4-fold higher activity was seen in microsomes from female rats. No gender differences were present in any other tissue investigated. Partial purification of the hepatic system was achieved using polyethylene glycol fractionation followed by Octyl Sepharose chromatography at low detergent concentrations, whereas the enzyme was denatured after complete solubilization. The unique appearance of the enzyme activity in adipose tissue, together with the cyanide sensitivity and the failure of typical P450 inhibitors to impede the reaction, indicates that the enzyme system active in reduction of benzamidoxime and N-hydroxymelagatran formation is not of cytochrome P450 origin, but likely consists of an NADH-dependent electron transfer chain with a cyanide-sensitive protein as the terminal component.
Established risk factors are of great importance for the prevalence of diabetes in the urban and rural Chinese populations and changes in these factors could explain the recent dramatic increase in diabetes prevalence, particularly in rural areas. Considering the high prevalence of obesity and physical inactivity, intervention is urgently required in China.
BackgroundThe Swedish Registry of Respiratory Failure (Swedevox) collects nationwide data on patients starting continuous positive airway pressure (CPAP) treatment, long-term mechanical ventilator (LTMV) and long-term oxygen therapy (LTOT). We validated key information in Swedevox against source data from medical records.MethodsThis was a retrospective validation study of patients starting CPAP (n=175), LTMV (n=177) or LTOT (n=175) across seven centres 2013–2017. Agreement with medical record data was analysed using differences in means (standard deviation) and proportion (%) of a selection of clinically relevant variables. Variables of interest included for CPAP: Apnea Hypopnea Index (AHI), height, weight, body mass index (BMI) and Epworth Sleepiness Scale (ESS) score; for LTMV: date of blood gas, PaCO2 (breathing air), weight and diagnosis group; and for LTOT: blood gases breathing air and oxygen, spirometry and main diagnosis.ResultsData on CPAP and LTOT had very high validity across all evaluated variables (all <5% discrepancy). For LTMV, variability was higher against source information for PaCO2 (>0.5 kPa in 25.9%), weight (>5 kg in 47.5%) and diagnosis group. Inconsistency was higher for patients starting LTMV acutely versus electively (PaCO2 –difference >0.5 kPa in 36% versus 21%, p<0.05, respectively). However, there were no signs of systematic bias (mean differences close to zero) across the evaluated variables.ConclusionValidity of Swedevox data, compared with medical records, was very high for CPAP, LTMV and LTOT. The large sample size and lack of systematic differences support that Swedevox data are valid for health care quality assessment and research.
Students with type 1 diabetes (T1D) need to take responsibility for their T1D and need professional support from school nurses. This study describes school nurses' experiences in supporting students with T1D in school. A qualitative approach was used. After purposive sampling, six school nurses were interviewed and data were analyzed with qualitative content analysis. For professional support, a network around the student was enabled constituting of a continuous dialogue and responsibility and preparedness. For professional support a mutual commitment from the student, parents, and the school nurse was needed which was built from initiating participation and security, the school nurse's ability to be present and available and on school nurse's perceived competence. The conclusion of the study, and its practical implication, is that school nurses' ability for professional support of students with T1D varied in relation to their perceived competence in nursing science as well as their ability to enable, strengthen and sustain teamwork and family-school team meetings.
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