No abstract available.
Sertoli-Leydig Cell Tumor*

Patients of choriocarcinoma with brain metastases are considered to have a very poor prognosis due to chemo-refractoriness and recurrence. So, selection and individualization of patients then followed by multimodality therapy are very important. We present a case of a patient who experienced twice of craniotomies due to intracranial hemorrhage and an emergent explorative laparotomy due to intestinal perforation of the metastatic sites of choriocarcinoma. She was treated with 12 cycles of high-dose MTX/EMA-CO, intrathecal MTX and WBRT. Eventually she has obtained a complete remission that ongoing for 2 years. So, we report this case with a brief review of the literatures.
Brain* ; Choriocarcinoma* ; Craniotomy ; Female ; Humans ; Intestinal Perforation ; Intracranial Hemorrhages ; Laparotomy ; Neoplasm Metastasis* ; Pregnancy ; Prognosis ; Recurrence

OBJECTIVE: The purpose of this study is to evaluate and compare the usefulness of the serum levels of tissue polypeptide specific antigen (TPS) and CA 125 for the diagnosis of epithelial ovarian cancer. MATERIALS AND METHODS: A total of 93 patients were included in this study. Of theses 51 proposed with epithelial ovarian cancer including 27 borderline malignant tumor, while 42 suffered from benign ovarian tumor. The levels of serum CA 125 and TPS was measured retrospectively in all patients using sera collected before surgery. RESULTS: Elevated levels of TPS were detected in 56.9% (29/51) of patients with epithelial ovarian cancer and borderline malignancy and in 35.7% (15/42) of patients with benign ovarian tumor. Elevated levels of CA 125 were detected in 45.1% (23/51) of patients with epithelial ovarian cancer and borderline malignancy and in 14.3% (6/42) of patients with benign ovarian tumor. The detection rate for serous cancer was 81.0% (17/21) with TPS, and 71.4% (15/21) with CA 125. In mucinous cancer, the detection rate was 37.5% (9/24) with TPS, and 25.0% (6/24) with CA 125. CONCLUSION: Determination of the level of TPS is useful for detection of epithelial cancer and borderline malignancy especially in mucinous tumor.
Diagnosis* ; Humans ; Mucins ; Ovarian Neoplasms* ; Retrospective Studies

This study describes the development of an analytical method to determine radotinib levels in human plasma using high performance liquid chromatography (HPLC) coupled with triple quadrupole tandem mass spectrometry (MS/MS) for pharmacokinetic application. Plasma samples were sequentially processed by liquid-liquid extraction using methyl tert-butyl ether, evaporation, and reconstitution. Analytes were separated and analyzed using HPLC-MS/MS in selected reaction monitoring mode, monitoring the specific transitions of m/z 531 to 290 for radotinib and m/z 409 to 238 for amlodipine (internal standard). The HPLC-MS/MS analytical method was validated with respect to selectivity, linearity, sensitivity, accuracy, precision, recovery, and stability. Calibration curves were linear over a concentration range 5–3,000 ng/mL with correlation coefficients (r) > 0.998. The lower limit of quantification for radotinib in plasma was 5 ng/mL. The accuracy and precision of the analytical method were acceptable within 15% at all quality control levels. This method was suitable to determine radotinib levels in human plasma because of its simplicity, selectivity, precision, and accuracy.
Amlodipine ; Calibration ; Chromatography, Liquid ; Ether ; Humans* ; Liquid-Liquid Extraction ; Mass Spectrometry* ; Methods* ; Plasma* ; Quality Control ; Tandem Mass Spectrometry

BACKGROUND: Both aspirin and simvastatin are prescribed as treatments or prevention of cardiovascular diseases. The aim of this study was to investigate the influence of simvastatin on pharmacokinetics and pharmacodynamics of aspirin after oral co-administration in healthy subjects. METHODS: Subjects were orally administered aspirin 100 mg for 7 days followed by co-administration of aspirin 100 mg and simvastatin 40 mg for 7 days once daily. A series of blood samples were collected before and till 24hours after drug administration on Day 1 (single-dose of aspirin), Day 7 (multiple-dose of aspirin) and Day 14 (multiple-dose of aspirin and simvastatin). The effects of simvastatin on pharmacokinetics of acetylsalicylic acid and salicylic acid were assessed with the 90 % confidence intervals (CIs) of thegeometric mean ratios (GMRs) of Day 14 over Day 7 for maximum plasma concentration (Cmax) and the area under the concentration-time curve (AUC0-24). Pharmacodynamics was assessed with maximal changes of platelet aggregation from baseline. RESULTS: Twenty-fourhealthy men aged 20 to 36 years were enrolled and 23 of them completed the study. GMRs (90 % CIs) of Cmax and AUC0-24 for acetylsalicylic acid were 1.21 (1.04 - 1.42) and 1.28 (1.19 - 1.38), respectively. For salicylic acid, GMRs of Cmax and AUC0-24 were 0.96 (0.91 - 1.00) and 1.00 (0.97 - 1.04), respectively. Maximal changes of platelet aggregation on Day 7 and Day 14 from baseline were not significantly different (p=0.41); 87.5 +/- 8.8 % and 87.3 +/- 9.2 %, respectively. CONCLUSION: Coadministration of simvastatin slightly increased the systemic exposure of acetylsalicylic acid with no changes of systemic exposure of salicylic acid or inhibition of platelet aggregation.
Aged ; Aspirin ; Cardiovascular Diseases ; Drug Interactions ; Humans ; Male ; Plasma ; Platelet Aggregation ; Salicylic Acid ; Simvastatin

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.

PURPOSE: This study aimed to investigate the effects of single-bout exercise on mitochondrial function, dynamics (fusion, fission), and mitophagy in cardiac and skeletal muscles. METHODS: Fischer 344 rats (4 months old) were randomly divided into the control (CON) or acute exercise (EX) group (n=10 each). The rats performed a single bout of treadmill exercise for 60 minutes. Mitochondrial function (e.g., O₂ respiration, H₂O₂ emission, Ca²⁺ retention capacity), mitochondrial fusion (e.g., Mfn1, Mfn2, Opa1), mitochondrial fission (e.g., Drp1, Fis1), and mitophagy (e.g., Parkin, Pink1, LC3II, Bnip3) were measured in permeabilized cardiac (e.g., left ventricle) and skeletal (e.g., soleus, white gastrocnemius) muscles. RESULTS: Mitochondrial O₂ respiration and Ca²⁺ retention capacity were significantly increased in all tissues of the EX group compared with the CON group. Mitochondrial H₂O₂ emissions showed tissue-specific results; the emissions showed no significant differences in the left ventricle or soleus (type I fibers) but was significantly increased in the white gastrocnemius (type II fibers) after acute exercise. Mitochondrial fusion and fission were not altered in any tissues of the EX group. Mitophagy showed tissue-specific differences: It was not changed in the left ventricle or white gastrocnemius, whereas Parkin and LC3II were significantly elevated in the soleus muscle. CONCLUSIONS A single bout of aerobic exercise may improve mitochondrial function (e.g., O₂ respiration and Ca²⁺ retention capacity) in the heart and skeletal muscles without changes in mitochondrial dynamics or mitophagy.

Neuroinflammation is a central pathological feature of several acute and chronic brain diseases, including Alzheimer disease (AD), Parkinson disease (PD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS). It induces microglia activation, mitochondrial dysfunction, the production of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), pro-inflammatory cytokines, and reactive oxygen species. Exercise, which plays an important role in maintaining and improving brain health, might be a highly effective intervention for preventing neuroinflammation-related diseases. Thus, since exercise can improve the neuroimmune response, we hypothesized that exercise would attenuate neuroinflammation-related diseases. In this review, we will highlight (1) the biological mechanisms that underlie AD, PD, ALS, and MS, including the neuroinflammation pathways associated with microglia activation, NF-κB, pro-inflammatory cytokines, mitochondrial dysfunction, and reactive oxygen species, and (2) the role of exercise in neuroinflammation-related neurodegenerative diseases.

Purpose: The effects of aerobic exercise training on soleus muscle morphology, mitochondria-mediated apoptotic signaling, and atrophy/hypertrophy signaling in ovariectomized rat skeletal muscle were investigated. Methods: Female Sprague-Dawley rats were divided into control (CON), ovariectomy (OVX), and ovariectomy plus exercise (OVX+EX) groups. After ovarian excision, exercise training was performed using a rat treadmill at 20 m/min, 50 min/day, 5 days/week for 12 weeks. Protein levels of mitochondria-mediated apoptotic signaling and atrophy/hypertrophy signaling in the skeletal muscle (soleus) were examined through western immunoblot analysis. Results: The number of myocytes and myocyte cross-sectional area (CSA) were increased and the extramyocyte space was decreased in the OVX group compared to those in the CON group. However, aerobic exercise training significantly increased myocyte CSA and decreased extramyocyte space in the OVX+EX group compared to those in the OVX group. The protein levels of proapoptotic signaling and muscle atrophy signaling were significantly increased, whereas the protein levels of muscle hypertrophy signaling were significantly decreased in the OVX group compared to that in the CON group. Aerobic exercise training significantly decreased the protein levels of proapoptotic signaling and increased the protein level of antiapoptotic protein in the OVX+EX group compared to that in the OVX group. Aerobic exercise training significantly increased the protein levels of hypertrophy signaling and decreased protein levels of atrophy signaling in the OVX+EX group compared to those in the OVX group. Conclusions Treadmill exercise improved estrogen deficiency-induced impairment in skeletal muscle remodeling, mitochondria-mediated apoptotic signaling, and atrophy/hypertrophy signaling in skeletal muscle.

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