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.
INTRODUCTIONThe littoral/sublittoral hoplonemertean (phylum Nemertea) species Oerstedia dorsalis (Abildgaard, 1806) is described as polymorphic in external characters (Örsted, 1844; Burger, 1895; Brunberg, 1964). Sundberg (1984) grouped specimens in three classes based on external morphology and asked, using multivariate morphometrics, if there was a consistent correlation between external and internal characters. Such a correlation would have indicated a restricted gene flow between the externally different morphs, and thus the possibility of a group of species instead of one, polymorphic, species.One of the forms in Sundberg (1984) appeared to be different from the other two morphs but the morphometric analysis was inconclusive. Later, Sundberg & Janson (1988) established by enzyme electrophoresis that this form was genetically different and it was later described as Oerstedia striata (Sundberg, 1988). A problem both in Sundberg (1984), and Sundberg & Janson (1988) was that one of the groupings (class ‘C’ in both studies) of specimens subsumed a number of morphs, all speckled or dotted but to varying degrees. These morphs may in fact represent different species, which would have been concealed in the electrophoretic and morphometric analysis as merely increased intraspecific variation. One of the ‘C’ morphs in Sundberg (1984) and Sundberg & Janson (1988) is light brown with numerous small dark brown/black dorsal spots. Based on one specimen from Anglesey, North Wales, Gibson (1988) described Oerstedia (Paroerstedia) nigrimaculata which is externally similar to this variety. Envall & Sundberg (1993) could not find any differences in internal characters between the type specimen of O. nigrimaculata and the brown form of O. dorsalis but hesitated to conclude that O. nigrimaculata is a variety of O. dorsalis.
ObjectiveTo investigate gender differences in the association between self-rated health (SRH) and impaired glucose tolerance (IGT) in subjects unaware of their glucose tolerance.DesignA cross-sectional population-based study.SettingThe two municipalities of Vara and Skövde in south-western Sweden.SubjectsA total of 2502 participants (1301 women and 1201 men), aged 30–75, were randomly selected from the population.Main outcome measuresIGT was regarded as the outcome measure and SRH as the main risk factor.ResultsThe prevalence of IGT was significantly higher in women (11.9%) than in men (10.1%), (p = 0.029), as was the prevalence of low SRH (women: 35.4%; men: 22.1%, p = 0.006). Both men and women with low SRH had a poorer risk factor profile than those with high SRH, and a statistically significant crude association between SRH and IGT was found in both men (OR = 2.8, 95% CI 1.8–4.4) and women (OR = 1.5, 95% CI 1.0–2.2, p = 0.033). However, after controlling for several lifestyle factors and biomedical variables, the association was attenuated and remained statistically significant solely in men (OR = 2.3, 95% CI 1.2–4.3).ConclusionThe gender-specific associations found between SRH and IGT suggest that SRH may be a better indicator of IGT in men than in women. Future studies should evaluate the utility of SRH in comparison with objective health measures as a potential aid to health practitioners when deciding whether to screen for IGT and T2DM.
The aim of the study was to identify symptoms in people with impaired glucose tolerance (IGT) and describe their experiences of living with the symptoms which they related to their condition. Twenty-one participants, from a cross-sectional population-based study, diagnosed as having IGT, were invited for an interview. The interviews were analyzed in two phases by means of a manifest and latent content analysis. The narratives included seven categories of symptoms (and more than 25 different symptoms) presented by the respondents. This study shows that symptoms such as the patient's own interpretation of different perceptions in the body must be considered, as well as signs and/or objective observations. Symptoms ought to be seen as complementary components in the health encounter and health conversation. The results of this study indicate that health professionals should increase their awareness of the balance between the implicit and the explicit bodily sensations that individuals communicate. Further studies are needed.
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