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

Objective: . To investigate the impact of the amendment of the Korean National Health Insurance (KNHI) reimbursement criteria for anti-tumor necrosis factor-α (TNF-α) agents based on from conventional clinical and laboratory measurements to disease activity score of 28 joints (DAS28) on treatment pattern, clinical response, and persistence rate in patients with rheumatoid arthritis (RA). Methods: . This multicenter retrospective cohort study evaluated 148 RA patients eligible for the initiation of anti- TNF-α agents as the first-line biologics by either the past (n=95) or current (n=53) KNHI reimbursement criteria. Persistence was defined as the duration between the initiation and discontinuation of anti-TNFα agents. Results: . In total, 106 (71.6%), 35 (23.6%), and 7 (4.7%) RA patients started treatment with adalimumab, etanercept, and infliximab, respectively. RA patients who received anti-TNF-α agents under the current reimbursement criteria had a significantly lower mean DAS28-erythrocyte sedimentation rate (ESR) (6.02 vs. 6.95, p＜0.001) and daily prednisolone-equivalent glucocorticoid dose (4.51 vs. 6.17 mg, p＜0.001) than those who received anti-TNF-α agents under the past reimbursement criteria. No significant differences in the 1-year remission rate defined by DAS28-ESR＜2.6 (17.9% vs. 30.2%, p=0.085) and the persistence rate (p=0.703) between the past and current reimbursement criteria was observed. Conclusion . Our data suggest that less active RA patients can receive reimbursement for anti-TNF-α agents under the current criteria, and the amendment of the KNHI reimbursement criteria may improve access to anti-TNF-α agents without affecting the treatment response and persistence rate.

PURPOSE: The numbers of male nurse were steadily increased. This study was to examine the effects of gender stereotypes (GS) on academic and employment stress among male and female nursing students. METHODS: Total 414 nursing students (109 male and 305 female) were sampled from two nursing college in Gwangju. Data collected from March 5th to 17th 2015 by self-reported questionnaires. Descriptive analyses, t-tests, one-way ANOVA, correlation analyses and multiple linear regression analyses were conducted to reveal the association between GS and academic and employment stress. RESULTS: Overall GS score was 2.4±0.47. And GS scores of male students (2.6±0.48) were significantly higher than the score of female students (2.4±0.45). The average scores of academic stress were similar between male student (2.1±0.46) and female students (2.2±0.47). The average score of employment stress was similar between female students (2.4±0.49) and male students (2.3±0.52). In multiple linear regression analysis, domestic GS were positively associated with academic stress in male nursing students (β=0.125, p=.009). In the case of female students, total GS (β=0.122, p=.014) and occupational GS (β=0.145, p=.017) were positively associated with academic stress. And occupational GS were positively associated with employment stress in male students (β=0.206, p=.048). In the case of female students, social GS (β=0.147, p=.012) were positively associated with employment stress. CONCLUSIONS: GS were significantly associated with academic and employment stress in both male and female students. And the association GS and stress were varied by subcategory of GS and sex. Assessment and appropriate management of GS might be helpful to decrease of stress in nursing students.
Employment* ; Female* ; Gwangju ; Humans ; Linear Models ; Male* ; Nurses, Male ; Nursing* ; Students, Nursing*

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

A ~20 kDa heat-labile toxin (BFT) produced by enterotoxigenic B. fragilis induces chemokine responses that are associated with mucosal inflammation. In the present study, we assessed whether the activation of mitogen-activated protein kinase (MAPK) affects the levels of IL-8 and MCP-1 produced by BFT stimulation in human epithelial HT-29 cells. Human intestinal epithelial HT-29 cell lines were incubated with purified BFT. MAPK and AP-1 in HT-29 cells were measured by Western blot and luciferase assay, respectively. The expression of chemokines such as IL-8 and MCP-1 were determined by quantitative RT-PCR, ELISA, and luciferase assay. BFT stimulation activated MAPK such as ERK1/2 and p38 in HT-29 cells. Treatment with MAPK inhibitors attenuated BFT-induced expression of IL-8 and MCP-1. Transfection with mutant genes for Ras or c-Jun did not only suppressed AP-1 reporter genes, but also inhibited BFT-induced expression of IL-8 and MCP-1 reporter genes. These results suggest that Ras and MAPK cascade may act as the upstream signaling for the activation of AP-1, which induce chemokine expression in BFT-stimulated intestinal epithelial cells.
Bacteroides fragilis* ; Bacteroides* ; Blotting, Western ; Chemokines ; Enterotoxins* ; Enzyme-Linked Immunosorbent Assay ; Epithelial Cells* ; Genes, Reporter ; HT29 Cells ; Humans* ; Inflammation ; Interleukin-8 ; Luciferases ; Phosphotransferases* ; Protein Kinases ; Transcription Factor AP-1 ; Transfection

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

Malakoplakia is a characteristic inflammatory condition, which is usually seen in the urogenital tract, and less frequently in the gastrointestinal tract. We present a case of colonic malakoplakia in an immunocompromised patient. A 55-year-old female visited the outpatient clinic for routine cancer surveillance. Her past medical history was significant for kidney transplantation 11 years ago, and she had been taking immunosuppressants. A colonoscopy revealed several depressed flat lesions and elevated polyps, which were 0.3 to 0.4 cm in size and accompanied by whitish exudates. A biopsy revealed an infiltration of histiocytes with ample granular eosinophilic cytoplasm, with some lymphocytes and plasma cells. Many histiocytes had the characteristic morphology, described as Michaelis-Gutmann bodies: one or several round basophilic structures of approximately 1 to 10 microm in size with some being laminated, some appearing homogeneous, and others having a dense central core with a targetoid appearance. These Michaelis-Gutmann bodies were positively stained on von Kossa stain, and were diagnostic for malakoplakia.
Ambulatory Care Facilities ; Basophils ; Biopsy ; Colon ; Colonoscopy ; Cytoplasm ; Eosinophils ; Exudates and Transudates ; Female ; Gastrointestinal Tract ; Histiocytes ; Humans ; Immunocompromised Host ; Immunosuppressive Agents ; Kidney ; Kidney Transplantation ; Lymphocytes ; Malacoplakia ; Plasma Cells ; Polyps ; Transplants

Raynaud syndrome is a medical condition that causes pain, numbness, and changes in skin color at the distal extremities. Raynaud syndrome can be subdivided into primary Raynaud's and secondary Raynaud's. The former is diagnosed when the cause is unknown and the latter is caused by an underlying condition, such as connective tissue diseases, injury, smoking, or certain medications. Both cancer chemotherapy and β-blockers are relatively common causes of Raynaud syndrome but there are no reports of its association with methimazole administration. The authors encountered a 43-year old woman with hyperthyroidism who developed digital ulcers associated with Raynaud syndrome after a methimazole treatment. Her digital ulcers and Raynaud syndrome were improved after methimazole was replaced with propylthiouracil and conventional therapy. This paper reports this case along with a review of the relevant literature.
Connective Tissue Diseases ; Drug Therapy ; Extremities ; Female ; Humans ; Hyperthyroidism ; Hypesthesia ; Methimazole* ; Propylthiouracil ; Skin Pigmentation ; Smoke ; Smoking ; Ulcer