Type 2 diabetes (T2D) increases the risk for cerebrovascular disease (CVD) and dementia. The underlying molecular mechanisms remain elusive, which hampers the development of treatment or/and effective prevention strategies. Recent studies suggest that dyshomeostasis of amylin, a satiety hormone that forms pancreatic amyloid in patients with T2D, promotes accumulation of amylin in cerebral small blood vessels and interaction with Alzheimer's disease (AD) pathology. Overexpression of human amylin in rodents (rodent amylin does not form amyloid) leads to late-life onset T2D and neurologic deficits. In this Review, we discuss clinical evidence of amylin pathology in CVD and AD and identify critical characteristics of animal models that could help to better understand molecular mechanisms underlying the increased risk of CVD and AD in patients with prediabetes or T2D.
Alzheimer Disease ; Amyloid ; Blood Vessels ; Cerebrovascular Disorders ; Dementia ; Diabetes Complications ; Diabetes Mellitus, Type 2 ; Humans ; Islet Amyloid Polypeptide ; Models, Animal ; Neurologic Manifestations ; Pathology ; Prediabetic State ; Rodentia

BACKGROUND/OBJECTIVES: Atopic dermatitis (AD) is a chronic disease with an increasing incidence globally; therefore, there is a growing demand for natural compounds effective in treating dermatitis. In this study, the protective effects of Lycium barbarum leaves with and without chlorophyll (LLE and LLE[Ch-]) on AD were investigated in animal models of AD and HaCaT cells. Further, we investigated whether LLE and LLE(Ch-) show any differences in physiological activity.MATERIALS/METHODS: AD was induced by 2,4-dinitrochlorobenzene (DNCB) for three weeks, while NC/Nga mice were fed LLE or LLE(Ch-) extracts for 7 weeks. Serum immunoglobulin E (IgE) and cytokine (tumor necrosis factor [TNF]-α, interleukin [IL]-6, and IL-4) concentrations and the degree of DNA fragmentation in lymphocytes were examined. A histopathological examination (haematoxylin & eosin staining and blue spots of toluidine) of the dorsal skin of mice was performed. To elucidate the mechanism of action, the expression of the thymus and activation-regulated chemokine (TARC) and macrophage-derived chemokine (MDC) were measured in HaCaT cells. RESULTS: Serum IgE and cytokines (TNF-α and IL-6) levels as well as DNA fragmentation of lymphocytes were significantly decreased in AD-induced mice treated with LLE or LLE(Ch-) compared to those of the control group. The epidermal thickness of the dorsal skin and mast cell infiltration in the LLE group significantly reduced compared to that in the control group. The LLE extracts showed no cytotoxicity up to 1,000 µg/mL in HaCaT cells. LLE or LLE(Ch-)-treated group showed a reduction of TARC and MDC in TNF-α-and IFN-γ-stimulated HaCaT cells. CONCLUSIONS These results suggest that LLE potentially improves inflammation by reducing the expression of chemokines that inhibit T helper 2 cell migration. LLE(Ch-) showed similar effects to LLE on blood levels of IgE, TNF-α and IL-6 and protein expression in HaCat cells, but the ultimate effect of skin improvement was not statistically significant.Therefore, both LLE and LLE(Ch-) can be used as functional materials to alleviate AD, but LLE(Ch-) appears to require more research to improve inflammation.

Probiotics have emerged as a potential treatment modality for numerous gastrointestinal disorders, including IBD. However, few probiotics have undergone appropriate preclinical screening in vivo. Kefir is considered a probiotic, benefiting the host through its effects in the intestinal tract. Despite numerous studies examining the action of probiotics on the host organism, few have analyzed the effects on intestinal environment. We assessed the protective effect of kefir for three weeks before inducing colitis with 2% dextran sodium sulfate for five days. The DSS loads were similar in all DSS treatment group. The results of the experiment are as follows. Food intake and FER of experimental groups were not significantly different each other, but water consumption tended to be higher in all DSS treatment groups as compared with the normal control. And visual inspection of feces revealed mild diarrhea in rat given 2% DSS. The anti-inflammatory activity of kefir was determined by myeloperoxidase activity during the DSS treatment, and there was no significant difference in any group. The levels of thiobarbituric acid reactive substances (TBARS) as a colonic lipid peroxidation were significantly lower in the kefir intake groups than in rats treated with 2% DSS alone. The DNA % in tail and tail moment values as a DNA damage level of the blood lymphocytes in kefir intake groups tended to be lower than 2% DSS treatment alone, especially tail lengths were significantly diminished. According to the colonic histopathological assay, there were a severe inflammation of lamina propria and submucosa and mild edema in mucosa and sub mucosa in DSS alone treated group. We found a slight regenerative change in kefir treatment groups. In our experiments, this means that ulcerative colitis related to oxidative injury might be prevented by kefir as a probiotic. Further studies of the potential benefits of kefir as a probiotic in inflammatory condition are encouraged.
Animals ; Edible Grain ; Colitis ; Colitis, Ulcerative ; Colon ; Cultured Milk Products ; Dextrans ; Diarrhea ; DNA ; DNA Damage ; DNA Fragmentation ; Drinking ; Eating ; Edema ; Feces ; Inflammation ; Lipid Peroxidation ; Lymphocytes ; Mass Screening ; Mucous Membrane ; Peroxidase ; Probiotics ; Rats ; Sodium ; Sulfates ; Thiobarbiturates ; Thiobarbituric Acid Reactive Substances

PURPOSE: This study was conducted in order to investigate the effect of Sargassum confusum extracts on the reduction of body fat for eight weeks in overweight women (BMI > or = 23 kg/m2). METHODS: Subjects were classified by double-blind randomized trial as the control group (C group, n = 14) and the Sargassum confusum extract supplementation group (SC group, n = 16), which consumed 12 tablets per day. Questionnaires related to their health status were assessed twice (week 0 and week 8). Their dietary intake status was evaluated by 24-recall method and body compositions were measured using a bioelectrical impedance analyzer. In addition, we assessed the anti-obesity effect and the occurrence possibility of health risk factors during the supplementation periods by hematological and clinical analysis of blood. RESULTS: Waist circumference and body fat (%) were significantly decreased in the SC group. Serum leptin level was also significantly decreased in the SC group. Defecation frequency was significantly increased in the SC group. The above results indicate that Sargassum confusum extract supplementation improves overweight on visceral fat and blood leptin level by increasing bowel movement. These results imply a decrease of health risk factors in overweight women. Seven subjects withdrew from the study due to adverse events; however, no differences regarding adverse events were observed between the control and treatment group. CONCLUSION: Therefore, Sargassum confusum extract is a plausible effective agent for body fat reduction in humans.
Adipose Tissue* ; Body Composition ; Defecation ; Electric Impedance ; Female ; Humans ; Intra-Abdominal Fat ; Leptin ; Overweight ; Surveys and Questionnaires ; Risk Factors ; Sargassum* ; Tablets ; Waist Circumference

PURPOSE: Despite new treatment strategies, anemia remains the most prevalent complication in patients with end-stage renal disease (ESRD). We investigated whether 25-hydroxyvitamin D [25(OH)D3] deficiency was associated with anemia in ESRD patients. MATERIALS AND METHODS: We reviewed the medical records of 410 ESRD patients who had undergone renal transplantation (RTx) at Yonsei University Health System and who had 25(OH)D3 levels measured at the time of RTx. Patients were divided into two groups based on baseline 25(OH)D3 concentrations: group 1, 25(OH)D3 levels <10 ng/mL; and group 2, 25(OH)D3 levels ≥10 ng/mL. RESULTS: Using multivariate regression models, 25(OH)D3, age, and erythrocyte-stimulating agent (ESA) dose were found to be significantly associated with hemoglobin (Hb) levels [25(OH)D3: β=0.263, p<0.001; age: β=0.122, p=0.010; ESA dose: β=-0.069, p=0.005]. In addition, logistic regression analysis revealed that patients in group 1 had a significantly higher risk for developing anemia (Hb level <10 g/dL) compared to group 2 patients, even after adjusting for potential risk factors for anemia (odds ratio=3.857; confidence interval=1.091-13.632; p=0.036). CONCLUSION: 25(OH)D3 deficiency was significantly associated with anemia in patients with ESRD. Randomized controlled trials are needed to determine whether vitamin D supplementation can improve anemia in these patients.
Adult ; Aged ; Anemia/blood/*etiology ; Calcifediol ; Cross-Sectional Studies ; Female ; Hemoglobin A/analysis ; Humans ; Kidney Failure, Chronic/*complications ; Kidney Transplantation ; Male ; Middle Aged ; Odds Ratio ; Prevalence ; Regression Analysis ; Risk Factors ; Vitamin D/analogs & derivatives/blood ; Vitamin D Deficiency/blood/*complications

Nephrotic syndrome is most commonly observed in membranous lupus nephritis in patients with systemic lupus erythematosus (SLE). However, other forms of idiopathic nephrotic syndrome rarely occur in these patients. Here, we report a case of SLE complicated by minimal change disease (MCD). A 24-year-old woman with SLE visited our hospital for generalized edema and heavy proteinuria. Laboratory tests did not support immunological exacerbation of lupus, while renal biopsy revealed diffusely effaced foot processes without electron-dense deposits that were consistent with MCD. Administration of high-dose corticosteroids and 6 subsequent cycles of monthly intravenous cyclophosphamide resulted in complete remission. Although nephrotic-range proteinuria recurred 1 month after switching to maintenance therapy with mycophenolate mofetil, complete remission was reestablished after a 6-month treatment with corticosteroids and cyclosporine. Physicians should be cautious in assessment and management of such a rare renal manifestation.
Adrenal Cortex Hormones ; Biopsy ; Cyclophosphamide ; Cyclosporine ; Edema ; Female ; Humans ; Lupus Erythematosus, Systemic* ; Lupus Nephritis ; Mycophenolic Acid ; Nephrosis, Lipoid* ; Nephrotic Syndrome ; Proteinuria ; Young Adult

Primary amyloidosis has unfavorable prognosis, particularly with organ involvement. Here, we report a case of clinical remission of renal amyloidosis after autologous hematopoietic cell transplantation. A 51-year-old female patient visited our hospital due to generalized edema. Initial evaluation showed hyperlipidemia, hypoalbuminemia, and heavy proteinuria, which were consistent with nephrotic syndrome. However, IgM lamda type monoclonal gammopathy was detected in serum and urine electrophoresis studies. Renal biopsy showed Congo red-positive amyloid deposition in mesangial area, glomerular capillary walls, and arterioles and amyloid fibers were confirmed by electron microscopy. Immunohistochemial study of the biopsy tissue demonstrated systemic light-chain amyloidosis (AL amyloidosis). Multiple myeloma was not evident on bone marrow examination. She received autologous hematopoietic cell transplantation after high dose melphalan treatment. Complete remissions were achieved after the treatment, respectively. Our findings suggest the potential role of autologous peripheral blood stem cell transplantation in treatment of AL amyloidosis.
Amyloid ; Amyloidosis* ; Arterioles ; Biopsy ; Bone Marrow Examination ; Capillaries ; Cell Transplantation ; Congo ; Edema ; Electrophoresis ; Female ; Humans ; Hyperlipidemias ; Hypoalbuminemia ; Immunoglobulin M ; Melphalan ; Microscopy, Electron ; Middle Aged ; Multiple Myeloma ; Nephrotic Syndrome ; Paraproteinemias ; Peripheral Blood Stem Cell Transplantation* ; Plaque, Amyloid ; Prognosis ; Proteinuria ; Transplants

Primary amyloidosis has unfavorable prognosis, particularly with organ involvement. Here, we report a case of clinical remission of renal amyloidosis after autologous hematopoietic cell transplantation. A 51-year-old female patient visited our hospital due to generalized edema. Initial evaluation showed hyperlipidemia, hypoalbuminemia, and heavy proteinuria, which were consistent with nephrotic syndrome. However, IgM lamda type monoclonal gammopathy was detected in serum and urine electrophoresis studies. Renal biopsy showed Congo red-positive amyloid deposition in mesangial area, glomerular capillary walls, and arterioles and amyloid fibers were confirmed by electron microscopy. Immunohistochemial study of the biopsy tissue demonstrated systemic light-chain amyloidosis (AL amyloidosis). Multiple myeloma was not evident on bone marrow examination. She received autologous hematopoietic cell transplantation after high dose melphalan treatment. Complete remissions were achieved after the treatment, respectively. Our findings suggest the potential role of autologous peripheral blood stem cell transplantation in treatment of AL amyloidosis.
Amyloid ; Amyloidosis* ; Arterioles ; Biopsy ; Bone Marrow Examination ; Capillaries ; Cell Transplantation ; Congo ; Edema ; Electrophoresis ; Female ; Humans ; Hyperlipidemias ; Hypoalbuminemia ; Immunoglobulin M ; Melphalan ; Microscopy, Electron ; Middle Aged ; Multiple Myeloma ; Nephrotic Syndrome ; Paraproteinemias ; Peripheral Blood Stem Cell Transplantation* ; Plaque, Amyloid ; Prognosis ; Proteinuria ; Transplants

PURPOSE: The effect of different peritoneal dialysis (PD) modalities on the decline in residual renal function (RRF) is unclear due to inconsistencies among studies. In particular, the effect of automated peritoneal dialysis (APD) modalities [continuous cyclic peritoneal dialysis (CCPD) and nightly intermittent peritoneal dialysis (NIPD)] on RRF has not been examined in a large cohort. MATERIALS AND METHODS: We conducted a single-center retrospective study to investigate the association between PD modalities and decline in RRF in 142 incident PD patients [34 on CCPD, 36 on NIPD, and 72 on continuous ambulatory peritoneal dialysis (CAPD)]. RRF was measured within 2 months from PD start and at 1 year after PD initiation. RESULTS: The RRF at 1 year after PD initiation was 1.98+/-2.20 mL/min/1.73 m2 in CCPD patients and 3.63+/-3.67 mL/min/1.73 m2 in NIPD patients, which were moderately lower than 4.23+/-3.51 mL/min/1.73 m2 in CAPD patients (p=0.064). Moreover, there was no significant difference in the 1-year rate of decline of RRF between CCPD and NIPD patients, although APD patients had a faster 1-year RRF decline rate than CAPD patients (CCPD and NIPD vs. CAPD: -45.68 and -36.69 vs. 1.17%/year, p=0.045). APD was associated with a more rapid decline in RRF in patients with end-stage renal disease undergoing PD, although multivariate analysis attenuated the significance of this finding (beta=-31.50; 95% CI, -63.61 to 0.62; p=0.052). CONCLUSION: Our results suggest that CAPD might be more helpful than APD for preserving RRF during the first year of dialysis therapy, although there was no significant difference in the 1-year rate of decline of RRF between the two APD modalities.
Adult ; Female ; Glomerular Filtration Rate/physiology ; Humans ; Kidney/pathology/physiopathology ; Kidney Failure, Chronic/*therapy ; Male ; Middle Aged ; Peritoneal Dialysis/*adverse effects ; Retrospective Studies

Objective To evaluate the survival and prognostic factors of esophageal cancer treated with definitive ( chemo ) radiotherapy by applying novel radiation techniques including three-dimensional conformal radiotherapy (3DCRT) or intensity-modulated radiotherapy (IMRT). Methods Clinical data of 2762 patients with non-operated esophageal squamous cell carcinoma who underwent definitive ( chemo ) radiotherapy from 2002 to 2016 in 10 hospitals were retrospectively analyzed.The prognostic factors were also identified and analyzed. Results The median follow-up time was 60. 8 months. The 1-, 2-, 3-and 5-year overall survival (OS) of all patients was 71. 4％,48. 9％,39. 3％,and 30. 9％,respectively.The 1-,2-,3-and 5-year progression-free survival (PFS) was 59.5％,41.5％,35.2％,and 30％,respectively.The median survival was 23 months.The median time to progression was 17. 2 months.Multivariate analysis demonstrated that age, primary tumor location, clinical stage, tumor target volume, EQD2 and treatment mode were the independent prognostic factors for OS.Primary tumor location,clinical stage,tumor target volume and EQD2 were the independent prognostic factors for PFS. Conclusions In this first large-scale multi-center retrospective analysis of definitive ( chemo) radiotherapy for esophageal squamous cell carcinoma in China, the 5-year OS of patients with esophageal squamous cell carcinoma is significantly improved by 3DCRT, IMRT combined with chemotherapy drugs. However, the findings remain to be validated by prospective clinical trials with high-level medical evidence.