Isolated rat thoracic aorta which is pharmacologically precontracted by phenylephrine induces photorelaxation when exposed to long wave length UV-light. The aim of the present study was to characterize the mechanism of UV-light induced by photorelaxation in the rat aorta. 1. UV light relaxed both endothelium-intact and -denuded rat aortic rings contracted by phenylephrine. The magnitude of relaxation on UV light was dependent on the exposure time and slightly greatly in endothelium-denuded rings than in endothelium-intact preparations. 2. L-NAME (10 nM-100 uM) but not D-NAME completely inhibited the photorelaxation in a concentration dependent manner. 3. The UV-induced relaxation was inhibited by methylene blue (1 -100 uM), and verapamil (100 nM), and removal of extracellular Ca2+. In contrast, UV-light induced photorelaxation was potentiated by N(w)-nitro-Larginine (L-NOARG) treatment. 4. In immunocytochemical analysis of UV-light induced iNOS and eNOS expression in rat aortas, at which expression levels were increased in a time-dependent manner on UV-irradiation in aortic endothelium and smooth muscle, respectively. These results suggest that UV light-induced photorelaxation may be due to nitric oxide from exogenously administered L-arginine as well as endogenous nitric oxide donors such as amino acid and arginine derivatives. Additional suggestion is that UV light stimulates the expression of nitric oxide synthases, and its activity for nitric oxide generation is dependent on cytosolic Ca2+ originated from extracellular space.
Acetylcholine/pharmacology ; Animals ; Aorta, Thoracic/drug effects/*physiology/radiation effects ; Calcium Channel Blockers/pharmacology ; Cholinergic Agents/pharmacology ; Endothelium, Vascular/drug effects/physiology/radiation effects ; Enzyme Inhibitors/pharmacology ; Female ; Male ; Methylene Blue/pharmacology ; NG-Nitroarginine Methyl Ester/pharmacology ; Nitric Oxide Synthase/antagonists & inhibitors/metabolism ; Phenylephrine/pharmacology ; Rats ; Rats, Sprague-Dawley ; *Ultraviolet Rays ; Vasoconstrictor Agents/pharmacology ; Vasodilation/drug effects/*radiation effects ; Vasodilator Agents/pharmacology ; Verapamil/pharmacology

Diabetes mellitus is a major predictor of heart failure, although the mechanisms by which the disease causes cardiomyopathy are not well understood. The purpose of this study was to determine whether prolonged exposure of cardiomyocytes to high glucose concentrations induces autophagy and contributes to cardiomyopathy. Interestingly, there were no differences in the autophagic activation produced by different glucose concentrations. However, cell viability was decreased by high glucose. In the diabetic rats, we found a higher level of microtubule-associated protein light chain 3 (LC3) expression and a reduction in the size of the left ventricle (LV) (P<0.05) caused by growth retardation, suggesting activated autophagy. Our in vitro findings indicate that hyperglycemic oxidative stress induces autophagy, and our in vivo studies reveal that autophagy is involved in the progression of pathophysiological remodeling of the heart. Taken together, the studies suggest that autophagy may play a role in the pathogenesis of juvenile diabetic cardiomyopathy.
Animals ; Autophagy ; Cardiomyopathies ; Cell Survival ; Diabetes Mellitus ; Diabetic Cardiomyopathies ; Glucose ; Heart ; Heart Failure ; Heart Ventricles ; Hyperglycemia ; Light ; Myocytes, Cardiac ; Oxidative Stress ; Rats

Diabetes decreases skeletal muscle mass and induces atrophy. However, the mechanisms by which hyperglycemia and insulin deficiency modify muscle mass are not well defined. In this study, we evaluated the effects of swimming exercise on muscle mass and intracellular protein degradation in diabetic rats, and proposed that autophagy inhibition induced by swimming exercise serves as a hypercatabolic mechanism in the skeletal muscles of diabetic rats, supporting a notion that swimming exercise could efficiently reverse the reduced skeletal muscle mass caused by diabetes. Adult male Sprague-Dawley rats were injected intraperitoneally with streptozotocin (60 mg/kg body weight) to induce diabetes and then submitted to 1 hr per day of forced swimming exercise, 5 days per week for 4 weeks. We conducted an intraperitoneal glucose tolerance test on the animals and measured body weight, skeletal muscle mass, and protein degradation and examined the level of autophagy in the isolated extensor digitorum longus, plantaris, and soleus muscles. Body weight and muscle tissue mass were higher in the exercising diabetic rats than in control diabetic rats that remained sedentary. Compared to control rats, exercising diabetic rats had lower blood glucose levels, increased intracellular contractile protein expression, and decreased autophagic protein expression. We conclude that swimming exercise improves muscle mass in diabetes-induced skeletal muscle atrophy, suggesting the activation of autophagy in diabetes contributes to muscle atrophy through hypercatabolic metabolism and that aerobic exercise, by suppressing autophagy, may modify or reverse skeletal muscle wasting in diabetic patients.
Adult ; Animals ; Atrophy ; Autophagy ; Blood Glucose ; Body Weight ; Exercise ; Glucose Tolerance Test ; Humans ; Hyperglycemia ; Insulin ; Male ; Muscle, Skeletal ; Muscles ; Muscular Atrophy ; Proteolysis ; Rats ; Rats, Sprague-Dawley ; Streptozocin ; Swimming

Exercise training can improve strength and lead to adaptations in the skeletal muscle and nervous systems. Skeletal muscles can develop into two types: fast and slow, depending on the expression pattern of myosin heavy chain (MHC) isoforms. Previous studies reported that exercise altered the distribution of muscle fiber types. It is not currently known what changes in the expression of caveolins and types of muscle fiber occur in response to the intensity of exercise. This study determined the changes in expression of caveolins and MHC type after forced exercise in muscular and non-muscular tissues in rats. A control (Con) group to which forced exercise was not applied and an exercise (Ex) group to which forced exercise was applied. Forced exercise, using a treadmill, was introduced at a speed of 25 m/min for 30 min, 3 times/day (07:00, 15:00, 23:00). Homogenized tissues were applied to extract of total RNA for further gene analysis. The expression of caveolin-3 and MHC2a in the gastrocnemius muscle of female rats significantly increased in the Ex group compared with the Con group (P<0.05). Furthermore, in the gastrocnemius muscle of male rats, the expression of MHC2x was significantly different between the two groups (P<0.05). There was an increased expression in caveolin-3 and a slightly decreased expression in TGFbeta-1 in muscular tissues implicating caveolin-3 influences the expression of MHC isoforms and TGFbeta-1 expression. Eventually, it implicates that caveolin-3 has positive regulatory function in muscle atrophy induced by neural dysfunction with spinal cord injury or stroke.
Animals ; Caveolin 3 ; Caveolins ; Female ; Humans ; Male ; Muscle, Skeletal ; Muscles ; Muscular Atrophy ; Myosin Heavy Chains ; Myosins ; Nervous System ; Protein Isoforms ; Rats ; RNA ; Spinal Cord Injuries ; Stroke

OBJECTIVES: To find evidence that sleep is necessary for normal brain function, thus indicating that declines in both sleep quality and quantity are related to worse performance of many daily tasks and deteriorated physical functions. The present study investigates the relationships of balance control and reaction time with sleep quality. METHODS: 58 healthy (male 20, female 38) volunteers with informed consent participated in this study. The Self-reported Pittsburgh Sleep Quality Index (PSQI) was used to evaluate sleep quality and relevant factors, and the subjects were divided into groups A (PSQI < 5) and B (PSQI ≥ 5) based on this index. Static balance control and reaction time to visual stimuli were conducted to assess their relationship with sleep quality. RESULTS: Group B exhibited excessive daytime sleepiness significantly more often compared to group A. Static balance control did not markedly change relative to sleep quality, but reaction time and error to visual stimuli were significantly increased in group B compared to group A. CONCLUSION: These findings indicate that a decline in sleep quality can result in delayed reactions, as well as decreased accuracy of these reactions. They also suggest that low sleep quality may be associated with changes in physical functions, including balance control through reduced selective attention.
Brain ; Female ; Humans ; Informed Consent ; Physical Phenomena ; Reaction Time* ; Volunteers

Preclinical ischemic stroke studies extensively utilize the intraluminal suture method of middle cerebral artery occlusion (MCAo). General anesthesia administration is an essential step for MCAo, but anesthetic agents can lead to adverse effects causing death and making a considerable impact on inducing cerebral ischemia. The purpose of this study was to comparatively assess the effect of isoflurane and xylazine on transient cerebral ischemia in a mouse model of MCAo. Twenty animals were randomly divided into four groups: sham group (no MCAo), control group (MCAo under isoflurane, no agent till reperfusion), isoflurane group (MCAo under isoflurane continued till reperfusion), xylazine group (MCAo under isoflurane, and administration of xylazine till reperfusion). The survival rate, brain infarct volume, and neurologic deficits were studied to assess the effect of isoflurane and xylazine on the stroke model. Our results showed that the body weight showed statistically significant change before and 24 h after surgery in the control and Isoflurane groups, but no difference in the Xylazine group. Also, the survival rate, brain infarct volume, and neurologic deficits were slightly reduced in the isoflurane group at 24 h after reperfusion injury. However, the xylazine and control groups showed similar BIV and neurologic deficits. Interestingly, a high survival rate was observed in the xylazine group. Our results indicate that the modified method of inhalation anesthetics com‑ bined with xylazine can reduce the risk of mortality and develop a reproducible MCAo model with predictable brain ischemia. In addition, extended isoflurane anesthesia after MCAo is associated with the risk of mortality.

Muscle atrophy is the result of two opposing conditions that can be found in pathological or diseased muscles: an imbalance in protein synthesis and degradation mechanisms. Thus, we investigated whether exogenous melatonin could regulate muscle components in stroke-induced muscle atrophy in rats. Comparing muscle phenotypes, we found that long-term melatonin administration could influence muscle mass. Muscle atrophy-related genes, including muscle atrophy F-box (MAFbx) and muscle ring finger 1 (MuRF1) were significantly down-regulated in melatonin-administered rats in the gastrocnemius. However, only MAFbx at the mRNA level was attenuated in the soleus of melatonin-administered rats. Insulin-like growth factor-1 receptor (IGF-1R) was significantly over-expressed in melatonin-administered rats in both the gastrocnemius and soleus muscles. Comparing myosin heavy chain (MHC) components, in the gastrocnemius, expression of both slow- and fast-type isoforms were significantly enhanced in melatonin-administered rats. These results suggest that long-term exogenous melatonin-administration may have a prophylactic effect on muscle atrophy through the MuRF1/MAFbx signaling pathway, as well as a potential therapeutic effect on muscle atrophy through the IGF-1-mediated hypertrophic signaling pathway in a stroke animal model.
Animals ; Fingers ; Melatonin ; Models, Animal ; Muscles ; Muscular Atrophy ; Myosin Heavy Chains ; Phenotype ; Protein Isoforms ; Rats ; RNA, Messenger ; Stroke

We conducted a systematic review and meta-analysis to examine the protective effects of botulinum toxin-A (Botox-A) on spasticity and nociceptive pain in individuals with spinal cord injuries (SCIs). PubMed, Embase, and Cochrane Library databases were searched from inception to July 2023. The primary outcome of interest was spasticity and nociceptive pain. We pooled the available data using the generic inverse variance method, and we used a fixed-effect/random-effects model. We then calculated standardized mean difference (SMD) and 95% confidence intervals (95% CIs) to estimate the effect size. A total of fourteen studies meeting the inclusion criteria comprised two randomized controlled trials, five pre-post studies, and seven case reports. Across the various study designs, the majority of trials were assessed to have fair to high quality. The meta-analysis shows that Botox-A significantly decreased spasticity (SMD, -1.73; 95% CI, -2.51 to -0.95; p<0.0001, I2=48%) and nociceptive pain (SMD, -1.79; 95% CI, -2.67 to -0.91; p<0.0001, I2=0%) in SCI patients. Furthermore, Botox-A intervention improved motor function, activities of daily living (ADL), and quality of life. Our study suggests that Botox-A may alleviate spasticity and nociceptive pain in SCI patients. Moreover, the observed improvements in motor function, ADL, and overall quality of life following Botox-A intervention underscore its pivotal role in enhancing patient outcomes.