Eighteen male Wistar rats aged six weeks were divided equally into Methamphetamine (MA), Placebo and Control group. MA group were injected with 50mg/kg body weight of Methamphetamine hydrochloride (MAHCl) in normal saline, Placebo group were injected with normal saline only, while Control group not injected with anything. Five MA group rats died within four hours of injection and their hearts collected on the same day. Another MA group rat was sacrificed two days after injection. Placebo and control group were sacrificed at similar intervals. Collected hearts were studied for cardiac lesions under light microscopy using special staining and immunohistochemistry. Microscopic examination of the myocardium of the rats that died on the first day of injection showed loss of nuclei in some myocytes, indicating cell death. Some areas in the sub-endocardium region showed internalization and enlargement of myocyte nuclei, consistent with regeneration of cells. There were very few foci of necrosis observed in these samples. The heart samples from the single rat that survived injection for two days showed foci of infiltration of macrophage-like cells that were later revealed to be regenerating myocytes. There were also spindle-like fibroblasts, macrophages and a few leucocytes found within these foci. The overall appearance of the myocardium did not indicate any inflammatory response, and the expected signs of necrosis were not observed. These results suggest a need to re-evaluate the toxic and lethal dosages of MA for use in animals testing. Cause of death was suspected to be due to failure of other major organs from acute administration of MA. Death occurred within a time period where significant changes due to necrosis may not be evident in the myocardium. Further investigations of other organs are necessary to help detect death due to acute dosage of MA.

Interleukin (IL)-20, a proinflammatory cytokine of the IL-10 family, is involved in acute and chronic renal failure. The aim of this study was to elucidate the role of IL-20 during diabetic nephropathy development. We found that IL-20 and its receptor IL-20R1 were upregulated in the kidneys of mice and rats with STZ-induced diabetes. In vitro, IL-20 induced MMP-9, MCP-1, TGF-β1 and VEGF expression in podocytes. IL-20 was upregulated by hydrogen peroxide, high-dose glucose and TGF-β1. In addition, IL-20 induced apoptosis in podocytes by activating caspase-8. In STZ-induced early diabetic nephropathy, IL-20R1-deficient mice had lower blood glucose and serum BUN levels and a smaller glomerular area than did wild-type controls. Anti-IL-20 monoclonal antibody (7E) treatment reduced blood glucose and the glomerular area and improved renal functions in mice in the early stage of STZ-induced diabetic nephropathy. ELISA showed that the serum IL-20 level was higher in patients with diabetes mellitus than in healthy controls. The findings of this study suggest that IL-20 induces cell apoptosis of podocytes and plays a role in the pathogenesis of early diabetic nephropathy.
Animals ; Apoptosis ; Blood Glucose ; Caspase 8 ; Diabetes Mellitus ; Diabetic Nephropathies* ; Enzyme-Linked Immunosorbent Assay ; Glucose ; Humans ; Hydrogen Peroxide ; In Vitro Techniques ; Interleukin-10 ; Interleukins ; Kidney ; Kidney Failure, Chronic ; Mice ; Podocytes* ; Rats ; Vascular Endothelial Growth Factor A

Objective: The characteristics of patients with metachronous breast and ovarian malignancies and the pathogenic role of BRCA1/2 mutations remain poorly understood. We investigated these issues through a review of hospital records and nationwide Taiwanese registry data, followed by BRCA1/2 mutation analysis in hospital-based cases. Methods: We retrospectively retrieved consecutive clinical records of Taiwanese patients who presented with these malignancies to our hospital between 2001 and 2017. We also collected information from the Data Science Center of the Taiwan Cancer Registry (TCR) between 2007 and 2015. Next-generation sequencing and multiplex ligation-dependent probe amplification were used to identify BRCA1/2 mutations and large genomic rearrangements, respectively. When BRCA1/2 mutations were identified in index cases, pedigrees were reconstructed and genetic testing was offered to family members. Results: A total of 12,769 patients with breast cancer and 1,537 with ovarian cancer were retrieved from our hospital records. Of them, 28 had metachronous breast and ovarian malignancies. We also identified 113 cases from the TCR dataset. Eighteen hospital-based cases underwent BRCA1/2 sequencing and germline pathogenic mutations were detected in 7 patients (38.9%, 5 in BRCA1 and 2 in BRCA2). All BRCA1/2 mutation carriers had ovarian high-grade serous carcinomas. Of the 12 patients who were alive at the time of analysis, 5 were BRCA1/2 mutation carriers. All of them had family members with BRCA1/2-associated malignancies. Conclusions Our results provide pilot evidence that BRCA1/2 mutations are common in Taiwanese patients with metachronous breast and ovarian malignancies, supporting the clinical utility of genetic counseling.