Ochratoxin A is a natural contaminant of mouldy food and feed, which is produced by Penicillium and Aspergillus, and is suspected of being one of the etiological agents responsible for Balkan endemic nephropathy and the associated urinary tract tumors. For evaluation of the mutagenicity of ochratoxin A, we performed in vitro chromosome aberration tests using Chinese hamster lung fibroblast cells (CHL cells) and monkey kidney cells (VERO cells), in vivo micronueleus tests using ddY mouse bone marrow cells and somatic mutation and recombination tests (SMART) using Drosophila melanogaster. The results of chromosome aberration tests in CHL cells showed no incidence of increased structural and numerical aberrations regardless of metabolic activation, while in VERO cells treated with 2.0, 1.0, 0.5, 0.3 ug/ml of ochratoxin A showed significant increase of structural aberrations without metabolic activation. Aspartame and-phenylalanine, structural analogs of ochratoxin A, didn't affect the chromosome aberrations induced by ochratoxin A. The in vivo induction of micronucleated polychromatic erythrocytes were measured in bone marrows of ddY mice treated with 10.0, 5.0, 2.5mg/kg/10ml of ochratoxin A through intraperitoneal route once. At 24 and 48 hours after treatment, ochratoxin A didn't induce micronuclei in bone marrows of ddY mice. And at the concentration of 40, 20, 10 ug/ml of ochratoxin A, which was administered by feeding to larvae of Drosophila melanogaster, showed no incidence of increased multiple wing hairs and flares. Summarizing all results, we concluded that ochratoxin A is a kidney cell specific direct genotoxicant.
Animals ; Asian Continental Ancestry Group* ; Aspartame ; Aspergillus ; Balkan Nephropathy ; Biotransformation ; Bone Marrow ; Bone Marrow Cells ; Chromosome Aberrations ; Cricetinae ; Cricetulus* ; Drosophila melanogaster* ; Drosophila* ; Erythrocytes ; Fibroblasts ; Hair ; Haplorhini ; Humans ; Incidence ; Kidney ; Larva ; Lung* ; Mice* ; Penicillium ; Recombination, Genetic ; Urinary Tract ; Vero Cells*

BACKGROUND AND PURPOSE: Middle East respiratory syndrome (MERS) has a high mortality rate and pandemic potential. However, the neurological manifestations of MERS have rarely been reported since it first emerged in 2012. METHODS: We evaluated four patients with laboratory-confirmed MERS coronavirus (CoV) infections who showed neurological complications during MERS treatment. These 4 patients were from a cohort of 23 patients who were treated at a single designated hospital during the 2015 outbreak in the Republic of Korea. The clinical presentations, laboratory findings, and prognoses are described. RESULTS: Four of the 23 admitted MERS patients reported neurological symptoms during or after MERS-CoV treatment. The potential diagnoses in these four cases included Bickerstaff's encephalitis overlapping with Guillain-Barré syndrome, intensive-care-unit-acquired weakness, or other toxic or infectious neuropathies. Neurological complications did not appear concomitantly with respiratory symptoms, instead being delayed by 2–3 weeks. CONCLUSIONS: Neuromuscular complications are not rare during MERS treatment, and they may have previously been underdiagnosed. Understanding the neurological manifestations is important in an infectious disease such as MERS, because these symptoms are rarely evaluated thoroughly during treatment, and they may interfere with the prognosis or require treatment modification.
Cohort Studies ; Communicable Diseases ; Coronavirus ; Coronavirus Infections* ; Diagnosis ; Encephalitis ; Guillain-Barre Syndrome ; Humans ; Middle East Respiratory Syndrome Coronavirus ; Middle East* ; Mortality ; Neurologic Manifestations ; Pandemics ; Peripheral Nervous System Diseases ; Prognosis ; Republic of Korea

Prostate cancer is the most frequently diagnosed malignancy and the second leading cause of cancer mortality among men in the United States. Accumulating evidence suggests that lysophosphatidic acid (LPA) serves as an autocrine/paracrine mediator to affect initiation, progression and metastasis of prostate cancer. In the current study, we demonstrate that LPA stimulates migration and proliferation of highly metastatic human prostate cancer, PC-3M-luc-C6 cells. LPA-induced migration of PC-3M-luc-C6 cells was abrogated by pretreatment of PC-3M-luc-C6 cells with the LPA receptor 1/3 inhibitor Ki16425 or small interfering RNA (siRNA)-mediated silencing of endogenous LPA receptor 1, implicating a key role of the LPA-LPA receptor 1 signaling axis in migration of PC-3M-luc-C6 cells. In addition, LPA treatment resulted in augmented expression levels of Kruppel-like factor 4 (KLF4), and siRNA or short-hairpin RNA (shRNA)-mediated silencing of KLF4 expression resulted in the abolishment of LPA-stimulated migration and proliferation of PC-3M-luc-C6 cells. shRNA-mediated silencing of KLF4 expression resulted in the inhibition of in vivo growth of PC-3M-luc-C6 cells in a xenograft transplantation animal model. Taken together, these results suggest a key role of LPA-induced KLF4 expression in cell migration and proliferation of prostate cancer cells in vitro and in vivo.
Animals ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Gene Silencing ; Humans ; Kruppel-Like Transcription Factors/genetics/*metabolism ; Lysophospholipids/*metabolism ; Male ; Mice, Inbred BALB C ; Prostate/metabolism/*pathology ; Prostatic Neoplasms/genetics/*metabolism/*pathology

Antidiabetic and beta cell-protection activities of purple corn anthocyanins (PCA) were examined in pancreatic beta cell culture and db/db mice. Only PCA among several plant anthocyanins and polyphenols showed insulin secretion activity in culture of HIT-T15 cells. PCA had excellent antihyperglycemic activity (in terms of blood glucose level and OGTT) and HbA1c-decreasing activity when compared with glimepiride, a sulfonylurea in db/db mice. In addition, PCA showed efficient protection activity of pancreatic beta cell from cell death in HIT-T15 cell culture and db/db mice. The result showed that PCA had antidiabetic and beta cell-protection activities in pancreatic beta cell culture and db/db mice.
Animals ; Anthocyanins* ; Blood Glucose ; Cell Culture Techniques ; Cell Death ; Insulin ; Insulin-Secreting Cells ; Mice ; Passive Cutaneous Anaphylaxis ; Plants ; Polyphenols ; Zea mays*

Many aging male suffer various andropause symptoms including loss of physical and mental activities. This study evaluated the putative alleviative effects of CRS-10 dandelion and rooibos extract complex (CRS-10) on the symptoms of andropause. The survival rate of TM3 Leydig cells (TM3 cells) treated with CRS-10 was measured based on typical physiological stress. After daily intake of CRS-10 for 4 weeks, the level of testosterone, physical activity and both the number and activity of sperm in older rats (18 weeks) were measured. Furthermore, thirty males were surveyed with AMS (Aging Males' Symptoms) questionnaire after intake of 400 mg of CRS-10. Overall, CRS-10 protected TM3 cells from serum restriction and oxidative stress via activation of ERK and Akt pathways. The level of testosterone and activation of spermatogenesis in rats were significantly enhanced. In addition, physical locomotion was markedly improved. Daily intake of 400 mg of CRS-10 improved the quality of life among agingmale respondents, according to a clinical survey using the AMS. The results indicate the potential of CRS-10 as a safe and efficacious natural substance for reducing or alleviating andropause symptoms.
Aging ; Andropause ; Animals ; Aspalathus ; Humans ; Leydig Cells ; Locomotion ; Male ; Motor Activity ; Oxidative Stress ; Quality of Life ; Surveys and Questionnaires ; Rats ; Spermatogenesis ; Spermatozoa ; Stress, Physiological ; Survival Rate ; Taraxacum ; Testosterone

PURPOSE: Osteoarthritis (OA) of the temporomandibular joint (TMJ) elicits cartilage and subchondral bone defects. Growth hormone (GH) promotes chondrocyte growth. The aim of this study was to evaluate the efficacy of intra-articular injections of GH to treat TMJ-OA.MATERIALS AND METHODS: Monosodium iodoacetate (MIA) was used to induce OA in the TMJs of rats. After confirming the induction of OA, recombinant human GH was injected into the articular cavities of rats. Concentrations of GH and IGF-1 were measured in the blood and synovial fluid, and OA grades of cartilage and subchondral bone degradation were recorded by histological examination and micro-computed tomography.RESULTS: MIA-induced OA in the rat TMJ upregulated insulin-like growth factor-1 (IGF-1) rather than GH levels. GH and IGF-1 concentrations were increased after local injection of GH, compared with controls. Locally injected GH lowered osteoarthritic scores in the cartilage and subchondral bone of the TMJ.CONCLUSION: Intra-articular injection of GH improved OA scores in rat TMJs in both cartilage and subchondral bone of the condyles without affecting condylar bone growth. These results suggest that intra-articular injection of human GH could be a suitable treatment option for TMJ-OA patients in the future.