The Effect of Glycation Stress on Skeletal Muscle

Glycation stress (glycative stress) is a general concept of biological stress caused by a series of non-enzymatic glycation reactions, including advanced glycation end products (AGEs) formation, AGEs accumulation, glycation-associated dysfunction of proteins and cellular signaling, inflammation, oxidation, and/or tissue damage. There has been increasing evidence supporting a profound effect of AGEs on human diseases such as type 2 diabetes, cardiovascular disease, cancer, Alzheimer’s disease, osteoporosis, and dementia, as well as aging process itself. In addition, dietary AGEs intake has also been suggested to contribute to tissue dysfunction and development of the diseases. Skeletal muscle is the largest organ in the human body and important responsibility for maintaining our health as not only locomotor system but also metabolic and endocrine systems. Especially in past decades, numerous studies have suggested the contribution of glycation stress to skeletal muscle dysfunctions (e.g. muscle atrophy, reducing contractile property, and insulin resistance). In this chapter, we provide current evidence on the potential role of glycation stress in the impairment of skeletal muscle functions.

Characterization of α2-Adrenergic Receptors Mediated Vasoconstriction in ex vivo model

Introductionrat tail serves as a thermoregulatory organ by dilating or constricting tail blood vessels and rat tail lateral veins play a role in cutaneous circulation. However, this cutaneous vessel has never been examined and evaluated as a potential candidate ex vivo model to study peripheral vascular diseases. This study aims to investigate vascular tone mediated through α2-adenergic receptor on rat tail vein under different temperatures.MethodsVasoconstriction stimulated by α2-adrenergic receptor selective agonists UK14304, guanabenz was thoroughly examined in isolated rat tail lateral vein. Susceptibility of cutaneous vessel to temperature changes was investigated under 37 °C and 28 °C. Differentiated vascular reactivity exhibited at different temperature was further explored with different α2-adrenergic receptor selective agonists and validated with antagonism by α1-adrenergic receptor and α2-adrenergic receptor selective antagonist prazosin and RX821002, respectively.ResultsVascular tone of freshly isolated vein remained same compared with that of stored in pre-gassed physiologic buffer at 4 °C overnight. Presence of endothelium and repeated administration of UK14304 did not alter contractile property. Vessels away from torso (distal) showed significantly different contractile character compared with portion close to torso (proximal) at 28 °C but kept uniform at 37 °C. Enhanced vasoconstriction along with increased potency of α2-adrenergic receptor agonists UK14304 and guanabenz was consistently present at 28 °C, independent of temperature change orders. Potentiated vasoconstriction present at 28 °C was later proved via α2-adrenergic receptor alone.DiscussionHarvest and preparation of rat tail lateral vein was described in details. Contractile property of venous preparations stimulated by α2-adrenergic receptor selective agonists was first time examined. Differentiated vasoconstriction at moderate cooling temperature was described and confirmed to through α2-adrenergic receptor activation. Rat tail lateral vein is found valuable for studies of cutaneous circulation altered by temperature changes.

A rare case of hydatid cyst of the interventricular septum

A Hydatid disease or Echinococcosis is a zoonotic disease caused by the larvae (metacestode) of the cestode species of the genus Echinococcus. Humans are the accidental hosts of the diseases; they usually acquire it from canines; which are the definite host. It can present with systemic cyst, while cardiac manifestation of the disease is rare, due to contractile property of the heart’s muscle fiber which provide resistance. In this case report, the patient is diagnosed with hydatid cyst in the inter ventricular septum; it’s diagnosis and its successful treatment with surgery and albendazole. As, inter ventricular septum hydatid cyst occurs in only 0.5-2% cases, it’s a unique case and its successful treatment and diagnosis can help the physicians in the future to treat a similar case as this.

ATP2A2 rs3026468 does not associate with quadriceps contractile properties and acute muscle potentiation in humans

The ATP2A2 gene encodes the SERCA protein required for active calcium reuptake to the sarcoplasmic reticulum in cardiac and slow-twitch skeletal muscle. The ATP2A2 rs3026468 variant has been associated with voluntary strength phenotypes in humans but requires further validation. Here we investigated a homogenous cohort of 80 young, healthy, active Caucasian males who were assessed for maximal isometric strength, voluntary activation, stimulated contractile properties, and muscle potentiation in the quadriceps. A dynamometer was used to record knee extensions, and electrical stimulation was applied to the thigh to elicit a twitch response. DNA was isolated from cheek swabs, and the rs3026468 genotypes were assessed by TaqMan primer quantitative PCR. The results show no association between ATP2A2 rs3026468 variants and muscle strength measures. We conclude there is no effect of the rs3026468 variant in our cohort and that functional influences do not likely contribute to contractile property differences in young healthy men.

Effect of knee angle on quadriceps strength and activation after anterior cruciate ligament reconstruction

Quadriceps strength and activation deficits after anterior cruciate ligament (ACL) injury or surgery are typically evaluated at joint positions that are biomechanically advantageous to the quadriceps muscle. However, the effect of knee joint position and the associated changes in muscle length on strength and activation is currently unknown in this population. Here, we examined the effect of knee angle on quadriceps strength, activation, and electrically evoked torque in individuals with ACL reconstruction. Furthermore, we evaluated whether knee angle mediated the relationship between quadriceps weakness and functional performance after ACL reconstruction. Knee strength and activation were tested bilaterally at 90° and 45° of knee flexion in 11 subjects with ACL reconstruction using an interpolated triplet technique. The magnitude of electrically evoked torque at rest was used to quantify peripheral muscle contractile property changes, and the single-leg hop for distance test was used to evaluate functional performance. The results indicated that although quadriceps strength deficits were similar between knee angles, voluntary activation deficits were significantly higher in the reconstructed leg at 45° of knee flexion. On the contrary, the side-to-side evoked torque at rest ratio [i.e., (reconstructed/nonreconstructed) × 100] was significantly lower at 90° than at 45° of knee flexion. The association between quadriceps strength and functional performance was stronger at 45° of knee flexion. The results provide novel evidence that quadriceps activation is selectively affected at 45° of knee flexion and emphasize the importance of assessing quadriceps strength and activation at this position when feasible because it better captures activation deficits.

Abstract 662: Perivascular Adipose Tissue-derived Prostaglandins Constrict Vessel

Background: Perivascular adipose tissue (PVAT) is associated with reduced response to vasoconstricting agents in the murine vasculature and also in human small arteries, and this anti-contractile effect is reduced in subjects with metabolic syndrome. However, it was suggested that other vasoconstrictors released from PVAT such as leptin or Angiotensin II causes vasoconstriction, suggesting that PVAT has contractile properties as well. Here we show that prostaglandins and adrenalin signaling derived from PVAT contribute to contractile properties of PVAT. Results: The effect of donor PVAT on the vascular tone was evaluated in carotid, thoracic and mesenteric arteries using a myograph chamber in which the PVAT surrounding the tested vessel was completely removed. Fifteen mg of minced PVAT (size of ∼1 mm 3 ) from donor C57BL/6J mice into the myograph chamber results in mild vasoconstriction (1.52±0.6mN) on carotid artery rings. This contractile property of PVAT is effective on vessel rings obtained from the thoracic aorta and mesenteric artery as well. PVAT from leptin knockout mice used as a donor causes vasoconstriction similar to that of wild-type mice (1.55±0.5mN leptin knockout vs. 1.52±0.6mN C57BL/6J mice). Pre-incubation of vessel rings with increasing concentrations of nonspecific COX inhibitor (10 -9 M to 10 -6 M indomethacin) inhibits PVAT-induced constriction in a dose-dependent manner (1.55±0.7mN, 1.41±0.6mN, 1.23±0.5mN, 0.95±0.4mN, 0.56±0.6mN, respectively), suggesting that PVAT-derived prostaglandin are responsible for vascular constriction. Similarly, pre-incubation with alpha-adrenergic receptor antagonists blocks PVAT-dependent vasoconstriction. Carotid artery responses to a series of 10 -7 M phenylephrine (PE) addition/wash out (5x) experiments in the myograph chamber cause alpha-adrenergic desensitization. However, in the presence of donor PVAT, carotid arteries have preserved maximal contraction after 5 rounds of PE addition/wash out experiments. Conclusion: Our studies indicate that PVAT-derived prostaglandins rather than leptin or other adipokines cause vasoconstriction and reduce vascular alpha-adrenergic desensitization.