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We examined the effects of chronic salt loading on the hypothalamic expressions of the enhanced green fluorescent protein (eGFP), arginine vasopressin (AVP) and oxytocin (OXT) genes in AVP-eGFP transgenic rats that expressed eGFP in the hypothalamic AVP-containing neurones. In these rats, salt loading for 5 days caused a marked increase of the eGFP fluorescence in the magnocellular divisions of the paraventricular nucleus (PVN), the supraoptic nucleus (SON) and the internal layer of the median eminence. Expression of the eGFP gene was increased seven- to eight-fold in the PVN and SON of salt-loaded rats in comparison with euhydrated rats. By contrast, none of these changes were observed in the suprachiasmatic nucleus. The expression of the AVP and OXT genes was increased 1.5- to two-fold in the PVN and SON of salt-loaded nontransgenic (control) and transgenic rats. There were no differences in the expression levels of the AVP and OXT genes in the PVN and SON between nontransgenic (control) and transgenic animals under normal conditions and after salt loading. In the posterior pituitary gland, the intensity of the eGFP fluorescence did not change after salt loading for 5 days, but increased after 10 days of salt loading. Upon salt loading, significant increases in the plasma AVP concentrations, plasma osmolality and plasma Na+ were observed. Furthermore, there were no significant differences in changes of water intake, food intake, urine volume, urine osmolality, urine Na+ concentrations, and the body weights in both models under normal or salt-loaded conditions. Our results show that the response of the AVP-eGFP fusion gene to chronic salt loading is exaggerated, and humoral responses such as AVP and OXT and the body fluid homeostasis are maintained in AVP-eGFP transgenic rats. The AVP-eGFP transgenic rat gives us a new opportunity to study the dynamics of the AVP system in vivo.

Hyperuricemia have been thought to be caused by the ingestion of large amounts of purines, and prevention or treatment of hyperuricemia has intended to prevent gout. Xanthine dehydrogenase/xanthine oxidase (XDH/ XO) is rate-limiting enzyme of uric acid generation, and allopurinol was developed as a uric acid (UA) generation inhibitor in the 1950s and has been routinely used for gout prevention since then. Serum UA levels are an important risk factor of disease progression for various diseases, including those related to lifestyle. Recently, other UA generation inhibitors such as febuxostat and topiroxostat were launched. The emergence of these novel medications has promoted new research in the field. Lifestyle-related diseases, such as metabolic syndrome or type 2 diabetes mellitus, often have a common pathological foundation. As such, hyperuricemia is often present among these patients. Many in vitro and animal studies have implicated inflammation and oxidative stress in UA metabolism and vascular injury because XDH/XO act as one of the major source of reactive oxygen species Many studies on UA levels and associated diseases implicate involvement of UA generation in disease onset and/or progression. Interventional studies for UA generation, not UA excretion revealed XDH/XO can be the therapeutic target for vascular injury and renal dysfunction. In this review, the relationship between UA metabolism and diabetic complications is highlighted.© 2014 Baishideng Publishing Group Inc. All rights reserved.Key words: Uric acid; Xanthine dehydrogenase/xanthine oxidase; Diabetes mellitus; Diabetic complications; Xanthine oxidase inhibitor; Metabolism Core tip: Uric acid (UA) is derived from essential metabolism, and UA metabolism is becoming a novel risk and interventional factor of lifestyle-related diseases in this obesity-prone era. The relationship between UA metabolism and diabetic complications is highlighted in this review and supposed molecular mechanisms are mentioned.Kushiyama A, Tanaka K, Hara S, Kawazu S. Linking uric acid metabolism to diabetic complications. World J Diabetes 2014; 5(6): 787-795 Available from:

Objectives The present study aimed to investigate the association between body mass index (BMI) and uric acid (UA) using the twin study methodology to adjust for genetic factors. Methods The association between BMI and UA was investigated in a cross-sectional study using data from both monozygotic and dizygotic twins registered at the Osaka University Center for Twin Research and the Osaka University Graduate School of Medicine. From January 2011 to March 2014, 422 individuals participated in the health examination. We measured height, weight, age, BMI, lifestyle habits (Breslow's Health Practice Index), serum UA, and serum creatinine. To investigate the association between UA and BMI with adjustment for the clustering of a twin within a pair, individual-level analyses were performed using generalized linear mixed models (GLMMs). To investigate an association with adjustment for genetic and family environmental factors, twin-pair difference values analyses were performed. Results In all analysis, BMI was associated with UA in men and women. Using the GLMMs, standardized regression coefficients were 0. Conclusions The present study shows that BMI was significantly associated with UA, after adjusting for both genetic and familial environment factors in both men and women.

Abstract. We developed robust, three-dimensional methods, as opposed to traditional A-line analysis, for estimating the optical properties of calcified, fibrotic, and lipid atherosclerotic plaques from in vivo coronary artery intravascular optical coherence tomography clinical pullbacks. We estimated attenuation μ t and backscattered intensity I 0 from small volumes of interest annotated by experts in 35 pullbacks. Some results were as follows: noise reduction filtering was desirable, parallel line (PL) methods outperformed individual line methods, root mean square error was the best goodness-of-fit, and α-trimmed PL (α-T-PL) was the best overall method. Estimates of μ t were calcified (3.84 AE 0.95 mm −1 ), fibrotic (2.15 AE 1.08 mm −1 ), and lipid (9.99 AE 2.37 mm −1 ), similar to those in the literature, and tissue classification from optical properties alone was promising. © The Authors. Published by SPIE under a Creative Commons Attribution 3.0 Unported License. Distribution or reproduction of this work in whole or in part requires full attribution of the original publication, including its DOI.

Aims/IntroductionDespite the use of intensive therapies, declining renal function is often observed during the overt nephropathy stage of type 2 diabetes. We aimed at investigating the role of serum uric acid (SUA) levels at the onset of overt nephropathy in the risk of renal function decline in type 2 diabetes patients.Materials and MethodsThe present cohort study included 290 type 2 diabetes patients who were followed from the onset of overt nephropathy. The relationship between SUA and declining renal function was assessed using Cox regression models after adjusting for known risk factors.ResultsOver a median 4.8-year follow-up period, 85 patients (4.9/100 person-years) showed serum creatinine (Cr) doubling with a total cumulative incidence of 71.9% at 20 years of follow up. The highest SUA tertile resulted in significantly a higher incidence (7.7/100 person-years) and cumulative incidence at 20 years (85.7%) than the middle (3.9/100 person-years, 54.2%) and lowest (3.0/100 person-years, 55.5%) tertiles. The univariate Cox hazard model resulted in significant risks for Cr doubling related to female sex, short diabetes duration, smoking and elevated levels of low-density lipoprotein cholesterol (LDL-c), glycated hemoglobin and SUA tertiles. SUA tertiles remained statistically significant in the multivariate model (highest vs lowest hazard ratio 2.68, 95% confidence interval 1.48−5.00, P = 0.0009).ConclusionsElevated SUA levels within the normal range (men >6.3 mg/dL, women >5.1) at the onset of overt nephropathy resulted in an increased risk for declining renal function in type 2 diabetes patients.

This study was aimed at investigating the degree of calcification of coronary arteries in type II diabetes mellitus for the purpose of examining as risk factors for coronary disease as well as parameters of diabetic complications. One hundred and three patients with type II diabetes were studied by the newly developed noninvasive technology of electron beam computed tomography, in which the degree of calcification was expressed as coronary calcification scores. The mean +/- SE value of coronary calcification scores were 247.5 +/- 48.1, which were significantly greater than the control patients without diabetes (148.9 +/- 48.3, p<0.05). In the diabetics, the coronary calcification scores had a significant (p < 0.01) correlation with patient age and duration of diabetes. The scores also had a significant (p<0.05) difference between patients who did and did not smoke cigarettes, and between patients with and without hypertension. The scores were significantly (p < 0.01) different between patients with and without hypertension. The scores were significantly (p < 0.01) different between presence and absence of diabetes-specific complications including retinopathy, neuropathy, and nephropathy. In a subgroup of patients without any signs of coronary disease, the scores showed a significant (p<0.01) difference between presence and absence of diabetes-specific complications, but no significant difference with smoking or hypertension. These data suggest that the extent of coronary calcifications and the development of ischemic heart disease seem to be closely related to the association of diabetic complications. Use of electron beam computed tomography seems to be useful in obtaining the information to predict future development of diabetic-specific complications.

Background The impact of SARS-CoV-2 infection on the gut fungal (mycobiota) and bacterial (microbiota) communities has been elucidated individually. This study analyzed both gut mycobiota and microbiota and their correlation in the COVID-19 patients with severe and mild conditions and follow-up to monitor their alterations after recovery. Methods We analyzed the gut mycobiota and microbiota by bacterial 16S and fungal ITS1 metagenomic sequencing of 40 severe patients, 38 mild patients, and 30 healthy individuals and reanalyzed those of 10 patients with severe COVID-19 approximately 6 months after discharge. Results The mycobiota of the severe and mild groups showed lower diversity than the healthy group, and in some, characteristic patterns dominated by a single fungal species, Candida albicans, were detected. Lower microbial diversity in the severe group was observed, but no differences in its diversity or community structure were detected between the mild and healthy groups. The microbiota of the severe group was characterized by an increase in Enterococcus and Lactobacillus, and a decrease in Faecalibacterium and Bacteroides. The abundance of Candida was positively correlated with that of Enterococcus in patients with COVID-19. After the recovery of severe patients, alteration of the microbiota remained, but the mycobiota recovered its diversity comparable to that of mild and healthy groups. Conclusion In mild cases, the microbiota is stable during SARS-CoV-2 infection, but in severe cases, alterations persist for 6 months after recovery.