Abstract
Background
Recurrent hypoglycemia blunts counter-regulatory responses to subsequent hypoglycemic episodes, a syndrome known as hypoglycemia-associated autonomic failure (HAAF). Since ...adrenergic receptor blockade has been reported to prevent HAAF, we investigated whether the hypoglycemia-associated rise in plasma epinephrine contributes to pathophysiology and reported interindividual differences in susceptibility to HAAF.
Methods
To assess the role of hypoglycemia-associated epinephrine responses in the susceptibility to HAAF, 24 adult nondiabetic subjects underwent two 2-hour hyperinsulinemic hypoglycemic clamp studies (nadir 54 mg/dL; 0-2 hours and 4-6 hours) on Day 1, followed by a third identical clamp on Day 2. We challenged an additional 7 subjects with two 2-hour infusions of epinephrine (0.03 μg/kg/min; 0-2 hours and 4-6 hours) vs saline on Day 1 followed by a 200-minute stepped hypoglycemic clamp (90, 80, 70, and 60 mg/dL) on Day 2.
Results
Thirteen out of 24 subjects developed HAAF, defined by ≥20% reduction in average epinephrine levels during the final 30 minutes of the third compared with the first hypoglycemic episode (P < 0.001). Average epinephrine levels during the final 30 minutes of the first hypoglycemic episode were 2.3 times higher in subjects who developed HAAF compared with those who did not (P = 0.006).
Compared to saline, epinephrine infusion on Day 1 reduced the epinephrine responses by 27% at the 70 and 60 mg/dL glucose steps combined (P = 0.04), with a parallel reduction in hypoglycemic symptoms (P = 0.03) on Day 2.
Conclusions
Increases in plasma epinephrine reproduce key features of HAAF in nondiabetic subjects. Marked interindividual variability in epinephrine responses to hypoglycemia may explain an individual’s susceptibility to developing HAAF.
: Advanced glycation end products (AGEs) are a heterogeneous group of compounds that form continuously in the body. Their rate of endogenous formation is markedly increased in diabetes mellitus, a ...condition in which AGEs play a major pathological role. It is also known, however, that AGEs form during the cooking of foods, primarily as the result of the application of heat. This review focuses on the generation of AGEs during the cooking of food, the gastrointestinal absorption of these compounds, and their biological effects in vitro and in vivo. We also present preliminary evidence of a direct association between dietary AGE intake and markers of systemic inflammation such as C‐reactive protein in a large group of healthy subjects. Together with previous evidence from diabetics and renal failure patients, these data suggest that dietary AGEs may play an important role in the causation of chronic diseases associated with underlying inflammation.
The goals of a successful tympanoplasty type I are to reconstruct a vibrant, integer tympanic membrane. This type of surgery will change completely the life of patients with tympanic perforation. ...Prerequisite for tympanoplasty type I is that it exists intact ossicular chain. Several different types of grafts are used, such as temporalis fascia, cartilage and perichondrium. The aim of this study is to present social perspectives from 21 clinical cases with tympanic perforation and to determine prognostic factors that can influential the outcome of tympanoplasty type I. All the patients were treated in ENT Department “Sfanta Maria” Hospital, Bucharest. We present the clinical and paraclinical diagnostic algorithm for tympanic perforation used for the patients admitted in our Clinic from August 2013-November 2017. These patients underwent underlay myringoplasty type I, performed by junior surgeon. All patients’ undertakeclinical otologic examination and a pure tone audiogram preoperative and postoperative. At 1 month the postoperative otomicroscopy was performed and the hearing outcome assessed 2 months later. The presence of perforation was defined as surgical failure. The patients (7 men and 14women), were aged between 28-64 years old (mean age 47 years). 5 patients were diagnosed with anterior perforation, 4 patients had central perforations and 12 posterior perforation.Surgical success was obtained in 16 cases and 5 subjects presented with reperforation. Several prognostic factors have been identified as influential in tympanoplasty type I success such as the perforation size, the Eustachian tube function and middle ear pathological conditions.
Patients with end-stage renal disease (ESRD) undergoing hemodialysis are known to suffer cognitive deficits and stroke of unknown etiology. It has been suspected that the treatment itself may ...contribute to the syndrome by unknown mechanisms, which we investigated in this study. End-stage renal disease patients on hemodialysis (n = 19) or peritoneal dialysis (PD, n = 5) were compared with 14 healthy controls. Subjects participated in magnetic resonance imaging (MRI) measurements of cerebral atrophy, cerebral blood flow (CBF) arterial spin labeled-MRI (ASL-MRI), quantitative Doppler blood flow through the internal carotid artery, and cerebral oxymetry. The Doppler and oxymetry procedures were also performed at the beginning and end of a single hemodialysis session. End-stage renal disease patients on hemodialysis showed significant cerebral atrophy, associated with longer hemodialysis duration and cognitive deficits, including focal bilateral lesions in the caudate nucleus and midbrain. Cerebral oxygenation was extremely low before dialysis (rSO2 41 ± 13, compared with 70 ± 2 in controls, P < 0.02) and improved only slightly after dialysis. Carotid blood flow was also very low at the start of dialysis (115 ± 28mL/sec, versus 193 ± 56 in controls, P < 0.005) but normalized at the end of the session (181 mL/sec). The PD patients showed intermediate values, between the hemodialysis and controls. Notably, duration of hemodialysis treatment predicted global gray-matter volume (r = −0.74), change of blood flow during dialysis (r = −0.65), and baseline rSO2 (r = −0.65). The findings suggest that ESRD patients on hemodialysis suffer low CBF during the interdialytic cycle. Coupled with low cerebral oxygenation levels and atherosclerosis, this may contribute significantly to the etiology of the observed cerebral atrophy, cognitive deficits, and high stroke prevalence.
Insulin Resistance and Type 2 Diabetes in High-Fat–Fed Mice Are Linked to High Glycotoxin Intake
Oana Sandu 1 ,
Keying Song 1 ,
Weijing Cai 1 ,
Feng Zheng 1 ,
Jaime Uribarri 2 and
Helen Vlassara 1
1 ...The Brookdale Department of Geriatrics, Division of Experimental Diabetes and Aging, Mount Sinai School of Medicine, New York,
New York
2 Department of Medicine, Division of Nephrology, Mount Sinai School of Medicine, New York, New York
Address correspondence and reprint requests to Helen Vlassara, MD, Division of Experimental Diabetes and Aging, Mount Sinai
School of Medicine, One Gustave Levy Place, Box 1640, New York, NY 10029. E-mail: helen.vlassara{at}mssm.edu
Abstract
Dietary advanced glycosylation end products (AGEs) have been linked to insulin resistance in db/db (++) mice. To test whether dietary AGEs play a role in the progression of insulin resistance in normal mice fed high-fat diets,
normal C57/BL6 mice were randomly assigned to high-fat diets (35% g fat), either high (HAGE-HF group; 995.4 units/mg AGE)
or low (by 2.4-fold LAGE-HF group; 329.6 units/mg AGE) in AGE content for 6 months. Age-matched C57/BL6 and db/db (++) mice fed regular diet (5% g fat, 117.4 units/mg AGE) served as controls. After 6 months, 75% of HAGE-HF mice were diabetic
and exhibited higher body weight ( P < 0.001), fasting glucose ( P < 0.001), insulin ( P < 0.001), and serum AGEs ( P < 0.01) than control mice, while none of the LAGE-HF mice were diabetic despite a similar rise in body weight and plasma
lipids. The HAGE-HF group displayed markedly impaired glucose and insulin responses during glucose tolerance tests and euglycemic
and hyperglycemic clamps and altered pancreatic islet structure and function compared with those of LAGE-HF mice, in which
findings resembled those of control mice. The HAGE-HF group had more visceral fat (by two- and fourfold) and more AGE-modified
fat (by two- and fivefold) than LAGE-HF and control mice, respectively. In the HAGE-HF group, plasma 8-isoprostane was higher
( P < 0.01) and adiponectin lower ( P < 0.001) than control mice, while in the LAGE-HF group, these were more modestly affected ( P < 0.05). These results demonstrate that the development of insulin resistance and type 2 diabetes during prolonged high-fat
feeding are linked to the excess AGEs/advanced lipoxidation end products inherent in fatty diets.
AGE, advanced glycation end product
ALE, advanced lipoxidation end product
ELISA, enzyme-linked immunosorbent assay
Footnotes
Accepted May 6, 2005.
Received November 3, 2004.
DIABETES
Our societies are going through a process of continuous transformation. The challenges and opportunities of diversity and globalization can only be addressed if civic education and intercultural ...education are interrelated. More often than not, there is a lack of coherence between educational practices based on these approaches. Moreover, even if the principles and methods of civic and intercultural education are used for international as well as local development, very seldom their impact is measured through the means of scientific research. In this study, a methodology of civic and intercultural education was piloted, and its impact was measured regarding teachers’ and students’ attitudes toward Roma. We measured the acculturation orientations and stereotypes of teachers and students involved in a civic and intercultural program. The results show that there are changes in both teachers’ and students’ attitudes toward Roma.
Recent studies from our laboratory have shown that insulin stimulates myosin-bound phosphatase (MBP) in vascular smooth muscle cells (VSMCs) by decreasing site-specific phosphorylation of the ...myosin-bound subunit (MBS) of MBP via nitric oxide/cGMP-mediated Rho/Rho kinase inactivation. Here we tested potential interactions between Rho kinase and insulin signaling pathways. In control VSMCs, insulin inactivates ROK-α, the major Rho kinase isoform in VSMCs, and inhibits thrombin-induced increase in ROK-α association with the insulin receptor substrate-1 (IRS-1). Hypertension (in spontaneous hypertensive rats) or expression of an active RhoAV14up-regulates Rho kinase activity and increases ROK-α/IRS-1 association resulting in IRS-1 serine phosphorylation that leads to inhibition of both insulin-induced IRS-1 tyrosine phosphorylation and phosphatidylinositol 3-kinase (PI3-kinase) activation. In contrast, expression of dominant negative RhoA or cGMP-dependent protein kinase type Iα inactivates Rho kinase, abolishes ROK-α/IRS-1 association, and potentiates insulin-induced tyrosine phosphorylation and PI3-kinase activation leading to decreased MBST695 phosphorylation and decreased MBP inhibition. Collectively, these results suggest a novel function for ROK-α in insulin signal transduction at the level of IRS-1 and potential cross-talk between cGMP-dependent protein kinase type Iα, Rho/Rho kinase signaling, and insulin signaling at the level of IRS-1/PI3-kinase.
Thyroid hormones have a pivotal role in controlling metabolic processes, cardiovascular function, and autonomic nervous system activity. Hypothyroidism, a prevalent endocrine illness marked by ...inadequate production of thyroid hormone, has been linked to different cardiovascular abnormalities, including alterations in heart rate variability (HRV). The study included 110 patients with hypothyroid disorder. Participants underwent clinical assessments, including thyroid function tests and HRV analysis. HRV, a measure of the variation in time intervals between heartbeats, serves as an indicator of autonomic nervous system activity and cardiovascular health. The HRV values were acquired using continuous 24-h electrocardiogram (ECG) monitoring in individuals with hypothyroidism, as well as after a treatment period of 3 months. All patients exhibited cardiovascular symptoms like palpitations or fatigue but showed no discernible cardiac pathology or other conditions associated with cardiac disease. The findings of our study demonstrate associations between hypothyroidism and alterations in heart rate variability (HRV) parameters. These results illustrate the possible influence of thyroid dysfunction on the regulation of cardiac autonomic function.
From generation to generation, the theatre teacher stands in front of a new experience and that is why, each time, they have to approach the group of students by a different manner, trying to find ...common points, the binder that unites the team, to determine it to function flawlessly, united. Taking into account that each student comes with different life experiences, a different personality from the other actors, different visions and expectations, the teacher has the difficult task, in the first stage, to build a team, to make the students aware that everyone should “bring their contribution” on the construction of the show (or exam), to help, to listen, to be present and involved. The stage is not a personal fight, but a battle of ideas, which helps us to evolve, grow professionally and this is why the theatre performance cannot be made in a hostile, conflicting environment. This is how, precisely because of this need to unite a divided group made up of extremely talented students, but with totally different and powerful personalities, the acting teacher suggests as a study theme for the first semester ancient theatre, forcing the team to be together throughout the rehearsals and the show-examination on the stage, giving the choir’s soul and voice, to listen, to take over and to put, each of them, a brick in the construction of the main character, which, through the directorial vision, belonged to all and not to a single performer. This is how a merged, united team and a festival performance were built: Medea.
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