Insulin resistance in skeletal muscle, liver, beta-cells, fat cells, the gastrointestinal track, alpha-cells, kidneys, and brain represents the core defect in obesity or type 2 diabetes (T2D). Among them, skeletal muscle insulin resistance due to obesity or T2D is manifested by decreased glucose uptake because skeletal muscle comprises 40-50% of the total human body mass. Many previous reports indicate that T2D patients or obese insulin-resistant individuals have less mitochondria in their skeletal muscles than lean control subjects. Whether or not mitochondria in skeletal muscle play a causal role in insulin resistance has been debated. A large number of studies demonstrated that skeletal muscle insulin resistance is associated with mitochondrial deficiency including 1) reduced fatty acid oxidation and increased accumulation of lipid intermediates (e.g., FA-CoA, DAG, ceramide), 2) increased mitochondrial overload and incomplete fatty acid oxidation, and 3) increased mitochondrial oxidative stress (e.g., H2O2) in skeletal muscle. In contrast, some studies demonstrated that mitochondrial dysfunction in skeletal muscle is not responsible for insulin resistance, suggesting that 1) the development of insulin resistance in high-fat diet animals occurs with increased muscle mitochondria, and 2) fatty acid oxidation is higher in T2D patients and obese insulin-resistant individuals compared with lean control subjects. However, various types of exercises (acute vs chronic, aerobic vs resistance) are critical in the treatment and prevention of insulin resistance in obesity and T2D.
Adipocytes ; Animals ; Brain ; Diet, High-Fat ; Exercise ; Glucose ; Human Body ; Humans ; Insulin Resistance ; Kidney ; Liver ; Mitochondria ; Mitochondria, Muscle ; Muscle, Skeletal ; Obesity ; Oxidative Stress

PURPOSE: To determine evaluate the clinical effectiveness of low-dose erythromycin (EM) therapy in patients with diffuse panbronchiolitis (DPB), and to correlate the pulmonary function testing (PFT) changes seen at serial high-resolution CT (HRCT) withthe results of post-treatment. MATERIALS AND METHODS: We retrospectively evaluated 13 DPB patients [seven men and six women aged 23-68 (mean, 46.2) years] who had undergone PFT, HRCT, and transbronchial or open lung biopsy prior to long-term, low-dose EM therapy (250 mg twice daily for more than six months). The interval between initial and follow-up study ranged from 7 to 32 (mean, 16.6+/-8.0) months, and we compared the changes in HRCT findings and PFT parameters before and after treatment. RESULTS: At HRCT after EM therapy, the extent of centrilobular nodules (p=0.006), peripheral bronchiolar wall thickening (p=0.02), and areas of low attenuation (p=0.011) decreased significantly, while FVC and FEV1 showed significant increases: FVC, from 2.47+/-0.83 to 2.74+/-0.95 (p=0.028); and FEV1, from 1.66+/-0.75 to 1.95+/-0.87 (p=0.02). As the extent of peripheral bronchiolar wall thickening (r=-0.609, p=0.047) and areas of low attenuation (r=-0.687, p=0.041) decreased at serial HRCT, FVC and FEV1 increased significantly. CONCLUSION: Long-term follow-up HRCT findings showed that for DPB patients, lowdose EM provides effective treatment. In addition, HRCT appears to be valuable for the objective evaluation of responses to EM therapy.
Biopsy ; Bronchiolitis ; Erythromycin* ; Female ; Follow-Up Studies ; Humans ; Lung ; Male ; Respiratory Function Tests* ; Retrospective Studies

Extracellular vesicles (EVs) not only eliminate unwanted molecular components, but also carry molecular cargo essential for specific intercellular communication mechanisms. As the molecular characteristics and biogenetical mechanisms of heterogeneous EVs are different, many studies have attempted to purify and characterize EVs. In particular, exosomal molecules, including proteins, lipids, and nucleic acids, have been suggested as disease biomarkers or therapeutic targets in various diseases. However, several unresolved issues and challenges remain despite these promising results, including source variability before the isolation of exosomes from body fluids, the contamination of proteins during isolation, and methodological issues related to the purification of exosomes. This paper reviews the general characteristics of EVs, particularly microvesicles and exosomes, along with their physiological roles and contribution to the pathogenesis of major diseases, several widely used methods to isolate exosomes, and challenges in the development of disease biomarkers using the molecular contents of EVs isolated from body fluids.
Biomarkers* ; Body Fluids ; Exosomes ; Extracellular Vesicles* ; Nucleic Acids

BACKGROUND: It is known that long-term survival rate in patients underwent bronchial sleeve lobectomy for primary lung cancer is at least equal to that in patients underwent pneumonectomy, and bronchial sleeve lobectomy is performed in patients with suitable tumor location even in patients have adequate pulmonary function. Sleeve pneumonectomy is performed when carina was invaded by tumor or tumor location was near to the carina. We performed this study to know our results of sleeve resection for primary lung cancer. MATERIAL AND METHOD: We analyzed retrospectively the medical records of 45 patients who underwent sleeve lobectomy or sleeve pneumonectomy for primary lung cancer by one thoracic surgeon from May 1990 to July 2003 in Department of Thoracic & Cardiovascular Surgery, College of Medicine, Kyung Hee University. Follow-up loss was absent and last follow-up was performed in April 5, 2005. Kaplan-Meyer method and log-lank test were used to know long-term survival rate and p-value. RESULT: Mean age was 60 years old and male to female ratio 41:1. Histologic types were squamous cell carcinoma were 39, adenocarcinoma were 4, and others were 2 patients. Pathologic stages were I 14, II 14, and III 17 patients. Nodal stages were N0 23, N1 13, and N2 9 patients. Types of operation were sleeve lobectomy 40 and sleeve pneumonectomy 5 patients. Operative mortality was 3 patients and its cause was respiratory complications. Early complications were pneumonia 4, atelectasis 8, air leakage more than 7 days 6, and atrial fibrillation 4 patients. In 19 patients tumor was recurred. Local recurrence was 10 and systemic metastasis was 9 patients. Overall 5, 10-year survival rate were 54.2%, 42.5%. The 5, 10-year survival rates according to the pathologic stage were 83.9%, 67.1% in stage I, 55%, 47.1% in II, 33.3%, 25% in III, and significance difference was present between stage I and III. The 5, 10-year survival rate according to the lymph node involvement were 63.9%, 54.6% in N0, 53.8%, 46.5% in N1, 28.5%, 14.2% in N2, and significance difference was present between N0 and N2. CONCLUSION: Because bronchial sleeve lobectomy for primary lung cancer could be performed safely and shows acceptable long-term survival rate, it could be considered primary in case of suitable tumor location if complete resection is possible. Although sleeve pneumonectomy for primary lung cancer shows somewhat high operative mortality rate, it could be considered in view of curative treatment.
Adenocarcinoma ; Atrial Fibrillation ; Carcinoma, Squamous Cell ; Female ; Follow-Up Studies ; Humans ; Lung Neoplasms* ; Lung* ; Lymph Nodes ; Male ; Medical Records ; Middle Aged ; Mortality ; Neoplasm Metastasis ; Pneumonectomy ; Pneumonia ; Pulmonary Atelectasis ; Recurrence ; Retrospective Studies ; Survival Rate

Primary sternal osteomyelitis is a rare disease. Primary sternal osteomyelitis occurring during childhood is extremely rare; therefore, only eleven cases have been reported in the English language literatures. The predisposing factors of primary sternal osteomyelitis are malnutrition, immune deficiency, intravenous injection, blunt chest trauma, and sickle cell anemia. Drainage of pus with antibiotic therapy is the treatment of choice. We report a case of primary sternal osteomyelitis occurred in a 16-year old boy, who had no predisposing factors, with review of literatures.
Adolescent ; Anemia, Sickle Cell ; Causality ; Drainage ; Humans ; Injections, Intravenous ; Male ; Malnutrition ; Osteomyelitis* ; Rare Diseases ; Sternum ; Suppuration ; Thorax

PURPOSE: Exercise enhances memory function by increasing neurogenesis in the hippocampus, and circadian rhythms modulate synaptic plasticity in the hippocampus. The circadian rhythm-dependent effects of treadmill exercise on memory function in relation with neurogenesis were investigated using mice. METHODS: The step-down avoidance test was used to evaluate short-term memory, the 8-arm maze test was used to test spatial learning ability, and 5-bromo-2’-deoxyuridine immunofluorescence was used to assess neurogenesis. Western blotting was also performed to assess levels of synaptic plasticity-associated proteins, such as brain-derived neurotrophic factor, tyrosine kinase receptor B, phosphorylated cAMP response element-binding protein, early growth response protein 1, postsynaptic density protein 95, and growth-associated protein 43. The mice in the treadmill exercise at zeitgeber 1 group started exercising 1 hour after sunrise, the mice in the treadmill exercise at zeitgeber 6 group started exercising 6 hours after sunrise, and the mice in the treadmill exercise at zeitgeber 13 group started exercising 1 hour after sunset. The mice in the exercise groups were forced to run on a motorized treadmill for 30 minutes once a day for 7 weeks. RESULTS: Treadmill exercise improved short-term memory and spatial learning ability, and increased hippocampal neurogenesis and the expression of synaptic plasticity-associated proteins. These effects of treadmill exercise were stronger in mice that exercised during the day or in the evening than in mice that exercised at dawn. CONCLUSIONS: Treadmill exercise improved memory function by increasing neurogenesis and the expression of synaptic plasticity-associated proteins. These results suggest that the memory-enhancing effect of treadmill exercise may depend on circadian rhythm changes.
Animals ; Blotting, Western ; Brain-Derived Neurotrophic Factor ; Circadian Rhythm* ; Cyclic AMP Response Element-Binding Protein ; Early Growth Response Protein 1 ; Exercise Test ; Fluorescent Antibody Technique ; GAP-43 Protein ; Hippocampus ; Learning ; Memory* ; Memory, Short-Term ; Mice* ; Neurogenesis ; Neuronal Plasticity ; Post-Synaptic Density ; Protein-Tyrosine Kinases ; Spatial Learning

PURPOSE: Exercise enhances memory function by increasing neurogenesis in the hippocampus, and circadian rhythms modulate synaptic plasticity in the hippocampus. The circadian rhythm-dependent effects of treadmill exercise on memory function in relation with neurogenesis were investigated using mice. METHODS: The step-down avoidance test was used to evaluate short-term memory, the 8-arm maze test was used to test spatial learning ability, and 5-bromo-2’-deoxyuridine immunofluorescence was used to assess neurogenesis. Western blotting was also performed to assess levels of synaptic plasticity-associated proteins, such as brain-derived neurotrophic factor, tyrosine kinase receptor B, phosphorylated cAMP response element-binding protein, early growth response protein 1, postsynaptic density protein 95, and growth-associated protein 43. The mice in the treadmill exercise at zeitgeber 1 group started exercising 1 hour after sunrise, the mice in the treadmill exercise at zeitgeber 6 group started exercising 6 hours after sunrise, and the mice in the treadmill exercise at zeitgeber 13 group started exercising 1 hour after sunset. The mice in the exercise groups were forced to run on a motorized treadmill for 30 minutes once a day for 7 weeks. RESULTS: Treadmill exercise improved short-term memory and spatial learning ability, and increased hippocampal neurogenesis and the expression of synaptic plasticity-associated proteins. These effects of treadmill exercise were stronger in mice that exercised during the day or in the evening than in mice that exercised at dawn. CONCLUSIONS: Treadmill exercise improved memory function by increasing neurogenesis and the expression of synaptic plasticity-associated proteins. These results suggest that the memory-enhancing effect of treadmill exercise may depend on circadian rhythm changes.
Animals ; Blotting, Western ; Brain-Derived Neurotrophic Factor ; Circadian Rhythm* ; Cyclic AMP Response Element-Binding Protein ; Early Growth Response Protein 1 ; Exercise Test ; Fluorescent Antibody Technique ; GAP-43 Protein ; Hippocampus ; Learning ; Memory* ; Memory, Short-Term ; Mice* ; Neurogenesis ; Neuronal Plasticity ; Post-Synaptic Density ; Protein-Tyrosine Kinases ; Spatial Learning

The major cause of Sparganosis is ingestion of raw snake or frog. The most common clinical manifestation of Sparganosis is subcutaneous moving nodule in abdominal wall, chest wall, thigh, and scrotal area. The most accurate method of diagnosis and treatment for Sparganosis is surgical removal of the parasite. We experienced pleural sparganosis in a 70-years-old male patient, and report it with review of literatures.
Abdominal Wall ; Diagnosis ; Eating ; Humans ; Male ; Parasites ; Pleura ; Snakes ; Sparganosis* ; Thigh ; Thoracic Wall

Obesity is known to induce inhibition of glucose uptake, reduction of lipid metabolism, and progressive loss of skeletal muscle function, which are all associated with mitochondrial dysfunction in skeletal muscle. Mitochondria are dynamic organelles that regulate cellular metabolism and bioenergetics, including ATP production via oxidative phosphorylation. Due to these critical roles of mitochondria, mitochondrial dysfunction results in various diseases such as obesity and type 2 diabetes. Obesity is associated with impairment of mitochondrial function (e.g., decrease in O₂ respiration and increase in oxidative stress) in skeletal muscle. The balance between mitochondrial fusion and fission is critical to maintain mitochondrial homeostasis in skeletal muscle. Obesity impairs mitochondrial dynamics, leading to an unbalance between fusion and fission by favorably shifting fission or reducing fusion proteins. Mitophagy is the catabolic process of damaged or unnecessary mitochondria. Obesity reduces mitochondrial biogenesis in skeletal muscle and increases accumulation of dysfunctional cellular organelles, suggesting that mitophagy does not work properly in obesity. Mitochondrial dysfunction and oxidative stress are reported to trigger apoptosis, and mitochondrial apoptosis is induced by obesity in skeletal muscle. It is well known that exercise is the most effective intervention to protect against obesity. Although the cellular and molecular mechanisms by which exercise protects against obesity-induced mitochondrial dysfunction in skeletal muscle are not clearly elucidated, exercise training attenuates mitochondrial dysfunction, allows mitochondria to maintain the balance between mitochondrial dynamics and mitophagy, and reduces apoptotic signaling in obese skeletal muscle.
Adenosine Triphosphate ; Apoptosis ; Energy Metabolism ; Glucose ; Homeostasis ; Lipid Metabolism ; Metabolism ; Mitochondria ; Mitochondrial Degradation ; Mitochondrial Dynamics ; Muscle, Skeletal* ; Obesity ; Organelle Biogenesis ; Organelles ; Oxidative Phosphorylation ; Oxidative Stress ; Respiration

PURPOSE: Chemotherapy is associated with the side effects including damage to the mitochondrial DNA. Doxorubicin (DOX) serves as a chemotherapeutic agent for the patients with breast cancer or prostate cancer. DOX causes muscle weakness and fatigue. We investigated the effects of treadmill exercise on DOX-induced apoptosis and mitochondrial dysfunction in relation to central fatigue. For this study, we used the rat model of DOX-induced muscle damage. METHODS: DOX (2 mg/kg) was intraperitoneally injected 1 time per week for 4 weeks. Treadmill running continued 5 days per week for 4 weeks. Muscle strength and fatigue index in the gastrocnemius were measured. Immunohistochemistry for the expressions of tryptophan hydroxylase (TPH) and 5-hydroxytryptamine (5-HT) in the dorsal raphe was conducted. We used western blot analysis for the expressions of Bax, Bcl-2, and caspases-3 in the gastrocnemius. Mitochondrial function in the gastrocnemius was also evaluated. RESULTS: DOX treatment decreased muscle strength with increase of fatigue index in the gastrocnemius. Mitochondria function was deteriorated and apoptosis in the gastrocnemius was enhanced by DOX treatment. Expressions of TPH and 5-HT in the dorsal raphe were increased by DOX treatment. Treadmill exercise attenuated DOX-induced muscle fatigue and impairment of mitochondria function. Apoptosis in the gastrocnemius was inhibited and over-expression of TPH and 5-HT was suppressed by treadmill exercise. CONCLUSIONS Apoptosis was enhanced and mitochondria function was deteriorated by DOX treatment, resulting in muscle weakness and central fatigue. Treadmill exercise suppressed apoptosis and prevented deterioration of mitochondria function in muscle, resulting in alleviation of muscle weakness and central fatigue during DOX therapy.