Oligosaccharide Sensing in Aqueous Media Using Porphyrin-Curdlan Conjugates: An Allosteric Signal-Amplification System.

A series of porphyrin-curdlan conjugates 1-5 of varying degree of substitution (DS) were synthesized to examine their morphological features, chiroptical properties, and oligosaccharide sensing in aqueous media, particularly for tetrasaccharide acarbose, which is a drug to treat type-2 diabetes. The random coil state of compounds 1-5 in DMSO becomes the globule curdlan-saccharide coaggregate upon interaction of acarbose in aqueous DMSO solution to induce various circular dichroism (CD) responses. The high cooperativity and positive homotropic allosterism were observed in the acarbose recognition, enabling the allosteric signal-amplification sensing, for which the DS, stacking character, and microenvironmental polarity changes of the tethered porphyrin reporters are likely to be responsible.

Oligosaccharide Sensing in Aqueous Media by Porphyrin-Curdlan Conjugates: A Prêt-á-Porter Rather Than Haute-Couture Approach.

Saccharide sensing in aqueous media is an intriguing but challenging goal in current chemistry. Herein we report the oligosaccharide-sensing behavior of newly synthesized porphyrin-curdlan conjugates, which are random coils in DMSO but become globules in aqueous solutions to induce circular dichroism (ICD) in the biologically accessible spectral region due to the conformational fixation of porphyrin reporters. The magnitude of ICD was significantly varied specifically in the presence of acarbose, a drug for type-2 diabetes, enabling us to detect the aminosaccharide at concentrations down to 200 µm. This result demonstrates that the prêt-á-porter approach, using less-defined reporter-curdlan conjugates, is more advantageous than the traditional haute-couture approach with highly sophisticated hosts in particular in oligosaccharide sensing.

Primary aldosteronism in patients with acute stroke: prevalence and diagnosis during initial hospitalization.

BACKGROUND: Hypertension is the prime risk factor for stroke, and primary aldosteronism (PA) is the most common cause of secondary hypertension. The prevalence of PA in stroke patients has never been reported. The aim of this study was to elucidate the prevalence of PA. METHODS: A total of 427 consecutive patients with acute stroke were prospectively enrolled for this study. The screening tests were performed at the initial visit and a week after admission by measuring plasma aldosterone concentration and plasma renin activity. The rapid adrenocorticotropic hormone (ACTH) test was performed as the confirmatory test when both screening tests were positive. The primary endpoint was a final diagnosis of PA. RESULTS: The sensitivity of the dual screening system for the diagnosis of PA was 88.2 %, and PA was finally diagnosed in 4.0 % of acute stroke patients and in 4.9 % of stroke patients with a history of hypertension. Patients with PA were less likely to be male and have diabetes, and they had higher blood pressure at the initial visit, lower potassium concentration, and more intracerebral hemorrhage. The rapid ACTH test was performed safely even in acute stroke patients. CONCLUSIONS: The prevalence of PA is not low among acute stroke patients. Efficient screening of PA should be performed particularly for patients with risk factors. TRIAL REGISTRATION: UMIN-CTR; UMIN000011021 . Trial registration date: June 23, 2013 (retrospectively registered).

Exploring sleep heart rate variability: linear, nonlinear, and circadian rhythm perspectives.

Background: Heart rate variability (HRV) is believed to possess the potential for disease detection. However, early identification of heart disease remains challenging, as HRV analysis in dogs primarily reflects the advanced stages of the disease. Hypothesis/objective: The aim of this study is to compare 24-h HRV with sleep HRV to assess the potential utility of sleep HRV analysis. Animals: Thirty healthy dogs with no echocardiographic abnormalities were included in the study, comprising 23 females and 7 males ranging in age from 2 months to 8 years (mean [standard deviation], 1.4 [1.6]). Methods: This study employed a cross-sectional study. 24-h HRV and sleep HRV were measured from 48-h Holter recordings. Both linear analysis, a traditional method of heart rate variability analysis, and nonlinear analysis, a novel approach, were conducted. Additionally, circadian rhythm parameters were assessed. Results: In frequency analysis of linear analysis, the parasympathetic index nHF was significantly higher during sleep compared to the mean 24-h period (mean sleep HRV [standard deviation] vs. mean 24 h [standard deviation], 95% confidence interval, p value, r-family: 0.24 [0.057] vs. 0.23 [0.045], 0.006-0.031, p = 0.005, r = 0.49). Regarding time domain analysis, the parasympathetic indices SDNN and RMSSD were also significantly higher during sleep (SDNN: 179.7 [66.9] vs. 156.6 [53.2], 14.5-31.7, p < 0.001, r = 0.71 RMSSD: 187.0 [74.0] vs. 165.4 [62.2], 13.2-30.0, p < 0.001, r = 0.70). In a geometric method of nonlinear analysis, the parasympathetic indices SD1 and SD2 showed significantly higher values during sleep (SD1: 132.4 [52.4] vs. 117.1 [44.0], 9.3-21.1, p < 0.001, r = 0.70 SD2: 215.0 [80.5] vs. 185.9 [62.0], 17.6-40.6, p < 0.001, r = 0.69). Furthermore, the circadian rhythm items of the parasympathetic indices SDNN, RMSSD, SD1, and SD2 exhibited positive peaks during sleep. Conclusion: The findings suggest that focusing on HRV during sleep can provide a more accurate representation of parasympathetic activity, as it captures the peak circadian rhythm items.

The Effects of Bazedoxifene on Bone, Glucose, and Lipid Metabolism in Postmenopausal Women With Type 2 Diabetes: An Exploratory Pilot Study.

BACKGROUND: Selective estrogen receptor modulators (SERMs) decrease homocysteine and cross-linking of pentosidine and reduce low-density lipoprotein cholesterol (LDL-C), and they are expected to improve bone quality and atherosclerosis. Therefore, the potential effects of bazedoxifene on bone (bone resorption, bone formation, and bone quality), as well as on glucose and lipid metabolism markers, were examined in Japanese postmenopausal women with type 2 diabetes mellitus (T2DM). METHODS: Eligible patients received 20 mg of bazedoxifene tablets once daily and were followed up for 12 weeks. Bone resorption markers including tartrate-resistant acid phosphatase 5b (TRACP-5b), bone formation markers and bone quality markers such as homocysteine and serum pentosidine, total cholesterol (TC), LDL-C, high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), and HbA1c were all measured. RESULTS: Twenty patients completed this study. All bone resorption markers decreased significantly 4 weeks after bazedoxifene treatment. In particular, TRACP-5b decreased significantly at 12 weeks (median percent change: -20.6%), and the minimum significant change (MSC) achievement rate of TRACP-5b was 65%. Bazedoxifene also decreased bone formation markers. However, bazedoxifene did not improve bone quality markers. LDL-C, HDL-C, and non-HDL-C were decreased, but TG was unchanged. Glucose metabolism was not changed after bazedoxifene treatment. In a subgroup analysis, the group of patients in whom the percent change in TRACP-5b exceeded the MSC had no change in pentosidine levels at 12 weeks. However, in the group of patients in whom the percent change in TRACP-5b did not exceed the MSC, pentosidine levels tended to increase. CONCLUSIONS: Bazedoxifene may improve bone resorption markers and LDL-C without affecting glucose metabolism in Japanese postmenopausal women with T2DM.

Effects of ezetimibe on atherogenic lipoproteins and glucose metabolism in patients with diabetes and glucose intolerance.

AIM: To evaluate the effects of ezetimibe on atherogenic lipoproteins and glucose metabolism in patients with diabetes and glucose intolerance. METHODS: Seventy-six patients with diabetes and glucose intolerance were enrolled in this study. At baseline and 12 weeks after treatment with ezetimibe 10mg/day, we measured the levels of lipid and glucose parameters. RESULTS: Ezetimibe reduced the mean levels of low-density lipoprotein cholesterol (LDL-C) (-20%, P<0.001), remnant-like particle cholesterol (-22%, P<0.001), small dense-LDL (-19%, P<0.001), apolipoprotein B-48 (-2%, P<0.01), malondialdehyde modified-LDL (-15%, P<0.001), and serum immunoreactive insulin (IRI) (-4%, P<0.01). In the insulin resistance subgroup, ezetimibe reduced the abdominal circumference (-1%, P<0.05) and mean levels of fasting plasma glucose (-7%, P<0.05), IRI (-36%, P<0.01), s-CPR (-27%, P<0.01), HOMA-IR (-39%, P<0.01) and HbA1c tended to decrease (-2%, P=0.06). CONCLUSIONS: Ezetimibe reduced atherogenic lipoproteins in patients with diabetes and glucose intolerance; besides, it improved glucose metabolism in patients with insulin resistance.