- Fanconi Syndrome in Irish Wolfhound Siblings. [Journal Article]
- JAJ Am Anim Hosp Assoc 2018 Mar 20
- Three juvenile male Irish wolfhound littermates presented with marked polyuria and polydipsia. The four female siblings were apparently unaffected. Diagnostic testing revealed glucosuria with normogl...
Three juvenile male Irish wolfhound littermates presented with marked polyuria and polydipsia. The four female siblings were apparently unaffected. Diagnostic testing revealed glucosuria with normoglycemia, generalized aminoaciduria, hypokalemia and metabolic acidosis consistent with Fanconi syndrome. Renal ultrasonographic and histologic findings are presented. Cases were managed with a supplementation regimen based on a treatment protocol for Fanconi syndrome in basenjis. These dogs did not have angular limb deformities as documented previously in juvenile canine siblings with Fanconi syndrome. Fanconi syndrome has not been previously described in Irish wolfhound siblings.
- Sulforaphane prevents maleic acid-induced nephropathy by modulating renal hemodynamics, mitochondrial bioenergetics and oxidative stress. [Journal Article]
- FCFood Chem Toxicol 2018 Mar 13; 115:185-197
- Maleic acid (MA)-induced nephropathy that is characterized by proteinuria, glycosuria, phosphaturia and a deficient urinary acidification and concentration. Sulforaphane (SF) is an indirect antioxida...
Maleic acid (MA)-induced nephropathy that is characterized by proteinuria, glycosuria, phosphaturia and a deficient urinary acidification and concentration. Sulforaphane (SF) is an indirect antioxidant that shows nephroprotective effects. The aim of the present work was to test the pre-treatment with SF against the MA-induced nephropathy. Wistar rats (230-260 g) were separated in the following groups: control, MA (which received 400 mg/kg of MA), SF + MA (which received MA and 1 mg/kg of SF each day for four days) and SF (which only received SF). MA induced proteinuria, an increase in urinary excretion of N-acetyl-β-d-glucosaminidase, and a decrease in plasma glutathione peroxidase activity, renal blood flow, and oxygenation and perfusion of renal cortex. All these impairments correlated with higher levels of oxidative damage markers and exacerbated superoxide anion production on renal cortex. Moreover, MA impaired mitochondrial bioenergetics associated to complex I, mitochondrial membrane potential and respiratory control index and increased the mitochondrial production of hydrogen peroxide. Further it disrupted mitochondrial morphology. SF prevented all the above-described alterations. In conclusion, the protective effect of SF against MA-induced nephropathy is associated with preservation of mitochondrial bioenergetics, amelioration of oxidative stress and improvement of renal hemodynamics and renal cortex oxygenation.
- Deletion of NLRX1 increases fatty acid metabolism and prevents diet-induced hepatic steatosis and metabolic syndrome. [Journal Article]
- BBBiochim Biophys Acta 2018 Mar 04; 1864(5 Pt A):1883-1895
- NOD-like receptor (NLR)X1 (NLRX1) is an ubiquitously expressed inflammasome-independent NLR that is uniquely localized in mitochondria with as yet unknown effects on metabolic diseases. Here, we repo...
NOD-like receptor (NLR)X1 (NLRX1) is an ubiquitously expressed inflammasome-independent NLR that is uniquely localized in mitochondria with as yet unknown effects on metabolic diseases. Here, we report that NLRX1 is essential in regulating cellular metabolism in non-immune parenchymal hepatocytes by decreasing mitochondrial fatty acid-dependent oxidative phosphorylation (OXPHOS) and promoting glycolysis. NLRX1 loss in mice has a profound impact on the prevention of diet-induced metabolic syndrome parameters, non-alcoholic fatty liver disease (NAFLD) progression, and renal dysfunction. Despite enhanced caloric intake, NLRX1 deletion in mice fed a western diet (WD) results in protection from liver steatosis, hepatic fibrosis, obesity, insulin resistance, glycosuria and kidney dysfunction parameters independent from inflammation. While mitochondrial content was equal, NLRX1 loss in hepatocytes leads to increased fatty acid oxidation and decreased steatosis. In contrast, glycolysis was decreased in NLRX1-deficient cells versus controls. Thus, although first implicated in immune regulation, we show that NLRX1 function extends to the control of hepatocyte energy metabolism via the restriction of mitochondrial fatty acid-dependent OXPHOS and enhancement of glycolysis. As such NLRX1 may be an attractive novel therapeutic target for NAFLD and metabolic syndrome.
- Protection Against Doxorubicin-induced Nephropathy by Plantago major in Rat. [Journal Article]
- IJIran J Kidney Dis 2018; 12(2):99-106
- CONCLUSIONS: These findings suggested that hydroalcoholic extract of P major protected renal tissue against doxorubicin-induced nephropathy. The protective effects of P major on renal lesions associated with doxorubicin may be due to its antioxidant and anti-inflammatory actions.
- Iodine Status during Pregnancy in a Region of Mild-to-Moderate Iodine Deficiency is not Associated with Adverse Obstetric Outcomes; Results from the Avon Longitudinal Study of Parents and Children (ALSPAC). [Journal Article]
- NNutrients 2018 Mar 01; 10(3)
- Severe iodine deficiency during pregnancy has been associated with pregnancy/neonatal loss, and adverse pregnancy outcomes; however, the impact of mild-to-moderate iodine insufficiency, though preval...
Severe iodine deficiency during pregnancy has been associated with pregnancy/neonatal loss, and adverse pregnancy outcomes; however, the impact of mild-to-moderate iodine insufficiency, though prevalent in pregnancy, is not well-documented. We assessed whether mild iodine deficiency during pregnancy was associated with pregnancy/infant loss, or with other adverse pregnancy outcomes. We used samples and data from the Avon Longitudinal Study of Parents and Children (ALSPAC), from 3140 singleton pregnancies and from a further 42 women with pregnancy/infant loss. The group was classified as mildly-to-moderately iodine deficient with a median urinary iodine concentration of 95.3 µg/L (IQR 57.0-153.0; median urinary iodine-to-creatinine ratio (UI/Creat) 124 µg/g, IQR 82-198). The likelihood of pregnancy/infant loss was not different across four UI/Creat groups (<50, 50-149, 150-250, >250 µg/g). The incidence of pre-eclampsia, non-proteinuric gestational hypertension, gestational diabetes, glycosuria, anaemia, post-partum haemorrhage, preterm delivery, mode of delivery, being small for gestational age, and large for gestational age did not differ significantly among UI/Creat groups, nor were there any significant differences in the median UI/Creat. We conclude that maternal iodine status was not associated with adverse pregnancy outcomes in a mildly-to-moderately iodine-deficient pregnant population. However, in view of the low number of women with pregnancy/infant loss in our study, further research is required.
- StatPearls [BOOK]
- BOOKStatPearls Publishing: Treasure Island (FL)
- Hyperosmolar hyperglycemic syndrome (HHS) is a clinical condition that arises from a complication of diabetes mellitus. This problem is most commonly seen in type 2 diabetes. Won Frerichs and Dreschf...
Hyperosmolar hyperglycemic syndrome (HHS) is a clinical condition that arises from a complication of diabetes mellitus. This problem is most commonly seen in type 2 diabetes. Won Frerichs and Dreschfeld first described the disorder around 1880. They described diabetic patients with profound hyperglycemia and glycosuria without the classic Kussmaul breathing or acetone in the urine seen in diabetic ketoacidosis. This clinical condition was formerly called non-ketotic hyperglycemic coma; hyperosmolar hyperglycemic non-ketotic syndrome, and hyperosmolar non-ketotic coma (HONK). Diabetes mellitus is a clinical condition associated with hyperglycemia as the main metabolic disorder. This is as a result of an absolute or relative deficiency of insulin. Insulin is an anabolic hormone produced by the beta cells in the islets of Langerhans in the pancreas. The main function of this hormone is to lower the level of glucose in the blood by promoting the uptake of glucose by the adipose tissue and skeletal muscle, known as glycogenesis. Insulin also inhibits the breakdown of fat in the adipose tissue, known as lipolysis. The metabolic effect of insulin is countered by hormones such as glucagon and catecholamines. In type 1 diabetes, there is the autoimmune destruction of the beta cells in the pancreas. Only about 5% to 10% of all diabetes falls into this category. The most common complication of type 1 diabetes is diabetic ketoacidosis (DKA). Type 2 diabetes accounts for about 90% to 95% of diabetes cases. It is most commonly seen in obese patients. As a consequence of the obesity and high body mass index (BMI), there is the resistance of the peripheral tissue to the action of insulin. The beta cell in the pancreas continues to produce insulin, but the amount is not enough to counter the effect of the resistance of the end organ to its effect. HHS is a serious and potentially fatal complication of type 2 diabetes. The mortality rate in HHS can be as high as 20% which is about 10 times higher than the mortality seen in diabetic ketoacidosis. Clinical outcome and prognosis in HHS are determined by several factors: age, the degree of dehydration, and the presence or lack of other comorbidities.
- Empagliflozin Induces Transient Diuresis Without Changing Long-Term Overall Fluid Balance in Japanese Patients With Type 2 Diabetes. [Journal Article]
- DTDiabetes Ther 2018 Feb 27
- CONCLUSIONS: Treatment initiation with empagliflozin in Japanese patients with T2D was associated with transient diuresis; however, overall urine volume returned towards baseline levels within 4 weeks of treatment. These findings are consistent with a physiological, adaptive mechanism of the kidney to maintain overall body fluid balance in response to treatment initiation with a SGLT2 inhibitor.
- Early intervention with mesenchymal stem cells prevents nephropathy in diabetic rats by ameliorating the inflammatory microenvironment. [Journal Article]
- IJInt J Mol Med 2018; 41(5):2629-2639
- Diabetic nephropathy (DN) is a major complication of diabetes and represents the leading cause of end-stage renal disease. Mesenchymal stem cell (MSC) treatment has been demonstrated to be effective ...
Diabetic nephropathy (DN) is a major complication of diabetes and represents the leading cause of end-stage renal disease. Mesenchymal stem cell (MSC) treatment has been demonstrated to be effective in DN models by reducing albuminuria and attenuating glomerular injury; however, limited in-depth understanding of the underlying mechanism and a lack of clinical trials hinders its clinical use. Additionally, most of these experimental studies were conducted on the advanced stage of nephropathy, which is difficult to reverse and consequently showed limited therapeutic efficacy. We sought to evaluate whether early intervention by MSCs has the potential to prevent DN onset and progression as well as protect kidney function when intravenously administered to rats with diabetes. Diabetes was induced in adult male SD rats by streptozotocin (STZ) injection (55 mg/kg, i.p.). The diabetic rats were injected with or without bone marrow-derived MSCs (5x106 per rat), via tail vein at 2, 4, 5 and 7 weeks after diabetes onset. Fasting blood glucose (FBG), blood urea nitrogen (BUN) and serum creatinine (Scr) levels in serum samples and glycosuria (GLU), microalbumin (MAU), and albumin to creatinine ratio (ACR) in urine samples were determined. Renal pathology and immunohistochemistry (IHC) for CD68, MCP-1, fibronectin (FN), transforming growth factor-β (TGF-β) and pro-inflammatory cytokines were also performed. Expression levels of the above factors as well as interleukin-10 (IL-10), and epidermal growth factor (EGF) were assessed by qPCR and multiplex bead-based suspension array system, respectively. Additionally, MSC tracing in vivo was performed. Ex vivo, peritoneal macrophages were co-cultured with MSCs, and expression of inflammatory cytokines was detected as well. MSC treatment profoundly suppressed renal macrophage infiltration and inflammatory cytokine secretion in diabetic rats, resulting in prominently improved kidney histology, systemic homeostasis, and animal survival, although no significant effect on hyperglycemia was observed. Engrafted MSCs were primarily localized in deteriorated areas of the kidney and immune organs 48 h after infusion. MSC treatment upregulated serum anti-inflammatory cytokines IL-10 and EGF. Ex vivo, MSCs inhibited lipopolysaccharide (LPS)-stimulated rat peritoneal macrophage activation via the downregulation of inflammatory-related cytokines such as IL-6, MCP-1, tumor necrosis factor-α (TNF-α) and IL-1β. Our results demonstrated that early intervention with MSCs prevented renal injury via immune regulation in diabetic rats, which restored the homeostasis of the immune microenvironment, contributing to the prevention of kidney dysfunction and glomerulosclerosis.
- A COMPLEX ROLE FOR LIPOCALIN 2 IN BONE METABOLISM: GLOBAL ABLATION IN MICE INDUCES OSTEOPENIA CAUSED BY AN ALTERED ENERGY METABOLISM. [Journal Article]
- JBJ Bone Miner Res 2018 Feb 14
- Lipocalin 2 (Lcn2) is an adipokine that carries out a variety of functions in diverse organs. We investigated the bone phenotype and the energy metabolism of Lcn2 globally deleted mice (Lcn2-/-) at d...
Lipocalin 2 (Lcn2) is an adipokine that carries out a variety of functions in diverse organs. We investigated the bone phenotype and the energy metabolism of Lcn2 globally deleted mice (Lcn2-/-) at different ages. Lcn2-/-mice were largely osteopenic, exhibiting lower trabecular bone volume, lesser trabecular number and higher trabecular separation when compared to wild type (WT) mice. Lcn2-/-mice showed a lower osteoblast number and surface over bone surface, and subsequently a significantly lower bone formation rate, while osteoclast variables were unremarkable. Surprisingly, we found no difference in Alkaline Phosphatase (ALP) activity or in nodule mineralization in Lcn2-/-calvaria osteoblast cultures, while less ALP-positive colonies were obtained from freshly isolated Lcn2-/-bone marrow stromal cells, suggesting a non-autonomous osteoblast response to Lcn2 ablation. Given that Lcn2-/-mice showed higher body weight and hyperphagia, we investigated whether their osteoblast impairment could be due to altered energy metabolism. Lcn2-/-mice showed lower fasted glycemia and hyperinsulinemia. Consistently, glucose tolerance was significantly higher in Lcn2-/-compared to WT mice, while insulin tolerance was similar. Lcn2-/-mice also exhibited polyuria, glycosuria, proteinuria and renal cortex vacuolization, suggesting a kidney contribution to their phenotype. Interestingly, the expression of the glucose transporter protein type 1, that conveys glucose into the osteoblasts and is essential for osteogenesis, was significantly lower in the Lcn2-/-bone, possibly explaining the in vivo osteoblast impairment induced by the global Lcn2 ablation. Taken together, these results unveil an important role of Lcn2 in bone metabolism, highlighting a link with glucose metabolism that is more complex than expected from the current knowledge. This article is protected by copyright. All rights reserved.
New Search Next
- Interaction Between the Sodium-Glucose-Linked Transporter 2 Inhibitor Dapagliflozin and the Loop Diuretic Bumetanide in Normal Human Subjects. [Journal Article]
- JAJ Am Heart Assoc 2018 Feb 10; 7(4)
- CONCLUSIONS: First-dose Na+excretion with bumetanide and dapagliflozin is not additive, but the weekly administration of one diuretic enhances the initial Na+excretion with the other, thereby demonstrating mutual adaptive natriuretic synergy. Combined therapy reverses bumetanide-induced hyperuricemia. This requires further study in diabetic patients with hyperglycemia who have enhanced glycosuria and natriuresis with dapagliflozin.