ABSTRACT
BACKGROUND: Respiratory rate (RR) is arguably the most important vital sign to detect clinical deterioration. Change in RR can also, for example, be associated with the onset of different diseases, opioid overdoses, intense workouts, or mood. However, unlike for most other vital parameters, an easy and accurate measuring method is lacking. OBJECTIVE: This study aims to validate the radar-based sleep monitor, Somnofy, for measuring RRs and investigate whether events affecting RR can be detected from personalized baselines calculated from nightly averages. METHODS: First, RRs from Somnofy for 37 healthy adults during full nights of sleep were extensively validated against respiratory inductance plethysmography. Then, the night-to-night consistency of a proposed filtered average RR was analyzed for 6 healthy participants in a pilot study in which they used Somnofy at home for 3 months. RESULTS: Somnofy measured RR 84% of the time, with mean absolute error of 0.18 (SD 0.05) respirations per minute, and Bland-Altman 95% limits of agreement adjusted for repeated measurements ranged from -0.99 to 0.85. The accuracy and coverage were substantially higher in deep and light sleep than in rapid eye movement sleep and wake. The results were independent of age, sex, and BMI, but dependent on supine sleeping position for some radar orientations. For nightly filtered averages, the 95% limits of agreement ranged from -0.07 to -0.04 respirations per minute. In the longitudinal part of the study, the nightly average was consistent from night to night, and all substantial deviations coincided with self-reported illnesses. CONCLUSIONS: RRs from Somnofy were more accurate than those from any other alternative method suitable for longitudinal measurements. Moreover, the nightly averages were consistent from night to night. Thus, several factors affecting RR should be detectable as anomalies from personalized baselines, enabling a range of applications. More studies are necessary to investigate its potential in children and older adults or in a clinical setting.
ABSTRACT
A commercial Rhodiola rosea (R. rosea) product has previously demonstrated CYP2C9 inhibition in humans. The purpose of this study was to provide in vitro inhibitory data for this particular interaction and to classify the mechanism of the interaction. Another aim was to examine the in vitro influence of ethanol on the CYP2C9 activity. Human CYP2C9 (wild type) isolated from a baculovirus-infected cell system was incubated with 0.8 µmol/L losartan for 20 min. Sulfaphenazole was used as a positive control. The commercial R. rosea product "Arctic Root" was used as test inhibitor. Formation of the CYP2C9-produced losartan metabolite EXP-3174 was determined by validated LC-MS/MS methodology. Possible mechanism-based (irreversible) inhibition was evaluated using time- and NADPH-dependent inhibition assays. Kinetic constants (Km , Vmax , and Ki ) were calculated from a Lineweaver-Burk plot. Mode of inhibition was determined. CYP2C9 was inhibited by "Arctic Root" with an IC50 (extract concentration yielding 50% reduction in enzyme activity) of 19.2 ± 2.7 µg/mL. Inhibitor concentrations of 20 µg/mL and 40 µg/mL yielded Ki values of 16.37 µg/mL and 5.59 µg/mL, respectively. The Lineweaver-Burk plot showed noncompetitive inhibition mode. No time- or NADPH-dependent inhibition was observed. The presence of ethanol inhibited CYP2C9 activity in a concentration-dependent manner. In conclusion, the commercial R. rosea product "Arctic Root" demonstrated noncompetitive inhibition of CYP2C9 in vitro. Further work identifying the constituents responsible for this inhibition is needed.
ABSTRACT
BACKGROUND: Bariatric surgery is a highly effective treatment of type 2 diabetes in patients with morbid obesity. The weight-loss independent improvement of glycemic control observed after these procedures has led to the discussion whether bariatric surgery can be introduced as treatment for type 2 diabetes in patients with a body mass index < 35 kg/m(2). We have studied the effects of two bariatric procedures on type 2 diabetes and on gastrointestinal hormone secretion in a lean diabetic animal model. METHODS: Male Goto-Kakizaki rats, 17-18 weeks old, were randomized into three groups: duodenojejunostomy (DJ), sleeve gastrectomy (SG), or sham operation. During 36 postoperative weeks we evaluated body weight, fasting blood glucose, glucose tolerance, insulin, HbA1c, glucagon-like peptide 1, cholesterol parameters, triglycerides, total ghrelin, and gastrin. RESULTS: Oral glucose tolerance was significantly improved for both DJ and SG at four weeks after surgery (p < 0.05). At the 34th postoperative week, SG had significantly lower area under the curve during oral glucose tolerance test compared to sham (p = 0.007). SG had significantly lower HbA1c compared to sham at 12 weeks; (mean ± SEM) 4.3 ± 0.1 % versus 5.2 ± 0.3 % (p < 0.05) and compared to both DJ and sham 34 weeks after surgery [median (75 %;25 %)] 5.2 (6.0; 4.3) % versus 7.0 (7.5; 6.7) % and 7.3 (7.6; 6.7) % (p = 0.009). Serum gastrin levels were markedly elevated for SG compared to DJ and sham; 188.0 (318.0; 121.0) versus 77.5 (114.0; 58.0) and 68.0 (90.0; 59.5) pmol/L (p = 0.004) at six weeks and 192.0 (587.8; 110.8) versus 65.5 (77.0; 59.0) and 69.5 (113.0; 55.5) (p = 0.001) 36 weeks after surgery. CONCLUSION: Sleeve gastrectomy induces hypergastrinemia, lowers HbA1c, and improves glycemic control in Goto-Kakizaki rats. Sleeve gastrectomy is superior to duodenojejunostomy as treatment of type 2 diabetes mellitus in this animal model.
