Background: Enavogliflozin is a novel sodium-glucose cotransporter-2 inhibitor currently under clinical development. This study evaluated the efficacy and safety of enavogliflozin as an add-on to metformin in Korean patients with type 2 diabetes mellitus (T2DM) against dapagliflozin. Methods: In this multicenter, double-blind, randomized, phase 3 study, 200 patients were randomized to receive enavogliflozin 0.3 mg/day (n=101) or dapagliflozin 10 mg/day (n=99) in addition to ongoing metformin therapy for 24 weeks. The primary objective of the study was to prove the non-inferiority of enavogliflozin to dapagliflozin in glycosylated hemoglobin (HbA1c) change at week 24 (non-inferiority margin of 0.35%) (Clinical trial registration number: NCT04634500). Results: Adjusted mean change of HbA1c at week 24 was –0.80% with enavogliflozin and –0.75% with dapagliflozin (difference, –0.04%; 95% confidence interval, –0.21% to 0.12%). Percentages of patients achieving HbA1c <7.0% were 61% and 62%, respectively. Adjusted mean change of fasting plasma glucose at week 24 was –32.53 and –29.14 mg/dL. An increase in urine glucose-creatinine ratio (60.48 vs. 44.94, P<0.0001) and decrease in homeostasis model assessment of insulin resistance (–1.85 vs. –1.31, P=0.0041) were significantly greater with enavogliflozin than dapagliflozin at week 24. Beneficial effects of enavogliflozin on body weight (–3.77 kg vs. –3.58 kg) and blood pressure (systolic/diastolic, –5.93/–5.41 mm Hg vs. –6.57/–4.26 mm Hg) were comparable with those of dapagliflozin, and both drugs were safe and well-tolerated. Conclusion Enavogliflozin added to metformin significantly improved glycemic control in patients with T2DM and was non-inferior to dapagliflozin 10 mg, suggesting enavogliflozin as a viable treatment option for patients with inadequate glycemic control on metformin alone.

Background: This study evaluated the efficacy and safety of add-on gemigliptin in patients with type 2 diabetes mellitus (T2DM) who had inadequate glycemic control with metformin and dapagliflozin. Methods: In this randomized, placebo-controlled, parallel-group, double-blind, phase III study, 315 patients were randomized to receive either gemigliptin 50 mg (n=159) or placebo (n=156) with metformin and dapagliflozin for 24 weeks. After the 24-week treatment, patients who received the placebo were switched to gemigliptin, and all patients were treated with gemigliptin for an additional 28 weeks. Results: The baseline characteristics were similar between the two groups, except for body mass index. At week 24, the least squares mean difference (standard error) in hemoglobin A1c (HbA1c) changes was –0.66% (0.07) with a 95% confidence interval of –0.80% to –0.52%, demonstrating superior HbA1c reduction in the gemigliptin group. After week 24, the HbA1c level significantly decreased in the placebo group as gemigliptin was administered, whereas the efficacy of HbA1c reduction was maintained up to week 52 in the gemigliptin group. The safety profiles were similar: the incidence rates of treatment-emergent adverse events up to week 24 were 27.67% and 29.22% in the gemigliptin and placebo groups, respectively. The safety profiles after week 24 were similar to those up to week 24 in both groups, and no new safety findings, including hypoglycemia, were noted. Conclusion Add-on gemigliptin was well tolerated, providing comparable safety profiles and superior efficacy in glycemic control over placebo for long-term use in patients with T2DM who had poor glycemic control with metformin and dapagliflozin.

Vestibular compensation is a recovery process from vestibular symptoms over time after unilateral loss of peripheral vestibular end organs. The aim of the present study was to observe time-dependent changes in long-term potentiation (LTP) at Schaffer collateral-CA1 synapses in the CA1 area of the hippocampus during vestibular compensation. The input-output (I/O) relationships of fEPSP amplitudes and LTP induced by theta burst stimulation to Schaffer's collateral commissural fibers were evaluated from the CA1 area of hippocampal slices at 1 day, 1 week, and 1 month after unilateral labyrinthectomy (UL). The I/O relationships of fEPSPs in the CA1 area was significantly reduced within 1 week post-op and then showed a non-significant reduction at 1 month after UL. Compared with sham-operated animals, there was a significant reduction of LTP induction in the hippocampus at 1 day and 1 week after UL. However, LTP induction levels in the CA1 area of the hippocampus also returned to those of sham-operated animals 1 month following UL. These data suggest that unilateral injury of the peripheral vestibular end organs results in a transient deficit in synaptic plasticity in the CA1 hippocampal area at acute stages of vestibular compensation.
Animals ; Compensation and Redress* ; Hippocampus* ; Long-Term Potentiation* ; Neuronal Plasticity ; Rats* ; Synapses*

PURPOSE: This study was conducted to test the effect of Image Making Programs on image making efficacy, positive thinking, self-esteem, and nursing professionalism in nursing students. METHODS: A non-equivalent control group pretest-posttest design was used. Participants were 124 nursing students at two universities, and were assigned to the treatment group (n=62) or the comparison group (n=62). The treatment was the Image Making Program, which was held twice over 2 days for 120 minutes per session. Data were collected from August to September 2012, and were analyzed using descriptive statistics, Kolmogorov-Smironov test, chi2-test, independent t-test, Mann-Whitney U test, one-tailed Mann-Whitney U test, independent one-tailed t-test with the SPSS/WIN 21.0 program. RESULTS: Nursing students in the treatment group showed statistically significantly higher levels of image making efficacy, positive thinking, and nursing professionalism than those in the comparison group. CONCLUSION: The results indicate that the Image Making Program is an effective intervention for increasing image making efficacy, positive thinking, and nursing professionalism in nursing students. However, further research and practices are needed in this area.
Humans ; Nursing* ; Self Concept ; Students, Nursing* ; Thinking*

OBJECTIVE: The vestibular system contributes control of blood pressure during postural changes through the vestibulosympathetic reflex. In the vestibulosympathetic reflex, afferent signals from the peripheral vestibular receptors are transmitted to the vestibular nuclei, rostral ventrolateral medullary nuclei, and then to the intermediolateral cell column of the thoracolumbar spinal cord. Physiological characteristics of the vestibulosympathetic reflex in terms of neurogenic and humoral control of blood pressure were investigated in this study. METHODS: Conscious rats with sinoaortic denervation were used for removal of baroreceptors in reflex control of blood pressure, and hypotension was induced by intravenous infusion of sodium nitroprusside (SNP). Expression of c-Fos protein was measured in the medial vestibular nuclei (MVN), rostral vestrolateral medullary nuclei(RVLM), and intermediolateral cell column (IMC) in T4-7, and levels of blood epinephrine were measured following SNP-induced hypotension. RESULTS: SNP-induced hypotension significantly increased expression of c-Fos protein in the MVN, RVLM, and IMC, also significantly increased level of blood epinephrine compared to normotensive control animals. CONCLUSION: These results suggest that the vestibulosympathetic reflex regulates blood pressure through neurogenic control including MVN, RVLM, and IMC, also through humoral control including epinephrine secretion by the adrenal medulla following SNP-induced hypotension. The physiological characteristics of the reflex may contribute to basic treatment of impairment of blood pressure control during postural changes.
Adrenal Medulla ; Animals ; Blood Pressure ; Denervation ; Epinephrine ; Hypotension ; Infusions, Intravenous ; Nitroprusside ; Pressoreceptors ; Rats ; Reflex ; Spinal Cord ; Vestibular Nuclei

BACKGROUND: Hypertension and type 2 diabetes mellitus are major risk factors for cardiovascular disease. This study analyzed the changes in central aortic waveforms and pulse wave velocity as well as related parameters after treatment with valsartan, an angiotensin II type 1 receptor blocker, in patients with type 2 diabetes and hypertension. METHODS: We used pulse wave analysis to measure central aortic waveform in a total of 98 subjects. In 47 of these patients, pulse wave velocity measurements were obtained before and after 12 weeks of treatment with valsartan. RESULTS: In the central aortic waveform analysis, the aortic pulse pressure and augmentation index were significantly decreased after valsartan treatment, as was the aortic pulse wave velocity. Factors contributing to the improvement in pulse wave velocity were the fasting blood glucose and haemoglobin A1c levels. CONCLUSION: Short-term treatment with valsartan improves arterial stiffness in patients with type 2 diabetes and hypertension, and the glucose status at baseline was associated with this effect.
Angiotensins ; Arterial Pressure ; Blood Glucose ; Cardiovascular Diseases ; Diabetes Mellitus ; Diabetes Mellitus, Type 2 ; Fasting ; Glucose ; Humans ; Hypertension ; Pulse Wave Analysis ; Receptor, Angiotensin, Type 1 ; Risk Factors ; Tetrazoles ; Valine ; Vascular Stiffness ; Valsartan

No abstract available.
Angiotensins ; Diabetes Mellitus, Type 2 ; Humans ; Hypertension ; Vascular Stiffness

The purpose of this study was to investigate effects of combined treatment with high intensity exercise and (-) epigallocatechin-3 gallate (EGCG), a potent free radical scavenger on a transcriptional level of hemoxygenase-1 gene in the large intestine. Sprague-Dawley rats were randomly divided into control group (CON, n=7), high intensity exercise group (HIE, n=7), EGCG group (EGCG, n=7), and EGCG plus high intensity exercise group (HIE + EGCG, n=7). Animals were given an intraperitoneal injection of EGCG with 50 mg of dosage per kg for four weeks 30 minutes before exercise. In order to induce HIE animals were allowed to ran on a treadmill with 0 degree of slope at speed of 28 m/min for 30 minutes. The exercise was performed four times a week for four week. The results of this study were as following; The expression level of hemoxygenase-1 mRNA of the high intensity exercise group was 15.21 times higher than that of the control group. The EGCG plus high intensity exercise group showed 5.98 times increased expression level of hemoxygenase-1 mRNA than control group. These results suggest that treatment of EGCG decrease the expression level of HO-1 mRNA through the removal of oxygen radicals produced by a high intensity exercise.
Animals ; Catechin ; Heme ; Heme Oxygenase-1 ; Injections, Intraperitoneal ; Intestine, Large ; Rats ; Rats, Sprague-Dawley ; Reactive Oxygen Species ; RNA, Messenger ; Tea

The vestibular end-organs generate very sophisticated gravity sensory information about head movement by sensing head acceleration in three-dimensional space. Vestibular information is crucial for higher brain functions such as cognition of spatial orientation, spatial memory, and perception of self-motion. The term "vestibular cortex" represents cortical area where vestibular information is processed, converged with other sensory inputs to maintain cortical functions. The vestibular cortex gives rise to commend signals that control the vestibulosomatic reflex through the modulation of vestibular nuclear activity in the brainstem. The vestibular cortex includes such different cortical regions as the premotor region of the frontal cortex, parietal areas, temporal areas, and a central core region called parietoinsular vestibular cortex. This paper summarizes systemically animal and clinical research data concerned with the vestibular cortex in order to understand anatomy and functions of the vestibular cortex and to provide a basic literature for further study.
Acceleration ; Animals ; Brain ; Brain Stem ; Cognition ; Gravitation ; Head ; Head Movements ; Memory ; Orientation ; Reflex ; Thalamic Nuclei

No abstract available.