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Frieler R.A.,University of Michigan | Berger S.,German Cancer Research Center | Schutz G.,German Cancer Research Center | Wang M.M.,Veterans Administration Ann Arbor Healthcare System | And 2 more authors.
Stroke | Year: 2011

Background and Purpose-Mineralocorticoid receptor (MR) antagonists have protective effects in rodent models of ischemic stroke, but the cell type-specific actions of these drugs are unknown. In the present study, we examined the contribution of myeloid cell MR during focal cerebral ischemia using myeloid-specific MR knockout mice. Methods-Myeloid-specific MR knockout mice were subjected to transient (90 minutes) middle cerebral artery occlusion followed by 24 hours reperfusion (n=5 to 7 per group). Ischemic cerebral infarcts were identified by hematoxylin and eosin staining and quantified with image analysis software. Immunohistochemical localization of microglia and macrophages was performed using Iba1 staining, and the expression of inflammatory markers was measured after 24 hours of reperfusion by quantitative reverse transcription-polymerase chain reaction. Results-Myeloid-specific MR knockout resulted in a 65% reduction in infarct volume (P=0.005) after middle cerebral artery occlusion. This was accompanied by a significant reduction in activated microglia and macrophages in the ischemic core. Furthermore, myeloid-specific MR knockout suppressed classically activated M1 macrophage markers tumor necrosis factor-α, interleukin-1β, monocyte chemoattractant protein-1, macrophage inflammatory protein-1α, and interleukin-6 at the same time as partially preserving the induction of alternatively activated, M2, markers Arg1, and Ym1. Conclusions-These data demonstrate that myeloid MR activation exacerbates stroke and identify myeloid MR as a critical target for MR antagonists. Furthermore, these data indicate that MR activation has an important role in controlling immune cell function during the inflammatory response to stroke. © 2010 American Heart Association, Inc.


Charmandari E.,Metabolism | Charmandari E.,Biomedical Research Foundation of the Academy of Athens | Achermann J.C.,University College London | Carel J.-C.,Robert Debre Hospital | And 3 more authors.
Science Signaling | Year: 2012

Stress is defi ned as a state of real or perceived threat to homeostasis. The principal effectors of the stress system are corticotropin-releasing hormone (CRH), arginine vasopressin, the proopiomelanocortin-derived peptides -melanocyte-stimulating hormone and -endorphin, the glucocorticoids, and the catecholamines norepinephrine and epinephrine. Appropriate responsiveness of the stress system to stressors is a crucial prerequisite for a sense of well-being, adequate performance of tasks, and positive social interactions. By contrast, inappropriate responsiveness of the stress system may impair growth and development and may account for various endocrine, metabolic, autoimmune, and psychiatric disorders. The development and severity of these conditions primarily depend on the genetic vulnerability of the individual, the exposure to adverse environmental factors, and the timing of stressful event(s). Prenatal life, infancy, childhood, and adolescence are critical periods characterized by increased vulnerability to stressors. This review summarizes the topics presented at the fi fth New Inroads to Child Health (NICHe) Conference Stress Response and Child Health held at Heraklion, Crete.


Lin C.-H.,Taipei Medical University | Lin C.-H.,Taipei Medical University Hospital | Chang W.-P.,Metabolism | Tai D.-Y.,Wei Gong Memorial Hospital | Yang S.-H.,Taipei Medical University
Journal of Internal Medicine of Taiwan | Year: 2015

Metformin has been considered the first choice of oral antidiabetic drugs (OADs) for typo 2 diabetes melitus (T2DM) patients. It has been proposed that Metformin could reduce Vitamin B12 absorption since 1971. Vitamin B12 is one of the essential nutrients for body and human cells growth, red blood cells formation and maintains epithelium and neuron myelin function. The symptoms of Vitamin B12 deficiency Include precious anemia and nervous system disorders, such as neuropathy, spinal cord lesions, and memory disorders. We observed whether Metformin treatment for T2DM patients with adequate Vitamin B12 intake may cause serum Vitamin B12 deficiency or not. This was a cross-sectional study and recruited T2DM subjects aged from 20-85 yrs., excluded patients of vegetarians, postgastrotomy, and taking vitamin supplements more than thrice a week regularly. We collected medicaJ history and blood data, dietary information by 24 hours dietary recalls and food frequency questionnaire (FFQ). TotaJ 200 subjects were recruited in this study, Vitamin B12 Intake was 1.8 ± 1.7 μg/day by 24- hour dietary recalls, 3.7 ± 2.6 μg/day by FFQ, serum Vitamin B12 levels was 493.6 ± 318.3 pg/ml. There were strong correlations between 24 hours and FFQ (p < 0.000) in Vitamin Bl2 intake, but no correlation between dietary Vitamin B12and serum Vitamin B12 (p > 0.05). No significant correlation existed among Metformin dosage and dietary Vitamin B12, blood Vitamin B12 level. No serum Vitamin B12 deficiency existed when Metformin treatment forT2DM patients with adequate Vitamin B12 intake in a Taiwan regional teaching hospital.


Jia G.,Metabolism | Jia G.,Diabetes Cardiovascular Center | Jia G.,Harry S Truman Memorial Veterans Hospital | Jia G.,University of Missouri | And 6 more authors.
CardioRenal Medicine | Year: 2014

Vascular disease is the leading cause of morbidity and mortality in the Western world, and vascular function is determined by structural and functional properties of the arterial vascular wall. Cardiorenal metabolic syndrome such as obesity, diabetes, hypertension, kidney disease, and aging are conditions that predispose to arterial stiffening, which is a pathological alteration of the vascular wall and ultimately results in target organ damage in heart and kidney. In this review, we provide new insights on the interactions between arterial stiffness, vascular resistance and pulse wave velocity as well as final end-organ damage in heart and kidney. Better understanding of the mechanisms of arterial functional and hemodynamic alteration may help in developing more refined therapeutic strategies aimed to reduce cardiovascular and chronic kidney diseases. © 2014 S. Karger AG, Basel.


Lorenz L.,University of Tübingen | Herbst J.,University of Tübingen | Engel C.,University of Tübingen | Peter A.,Metabolism | And 4 more authors.
Neonatology | Year: 2014

Background: Iron deficiency (ID) contributes to anaemia of prematurity, and hence the reliable assessment of iron nutrition status appears to be mandatory. Objective: To establish gestational age (GA)-specific reference ranges for hepcidin concentrations in cord blood [Hep(CB)] of preterm and term infants and to identify pre- and perinatal confounding factors. Methods: This is a prospective observational study including 221 infants (GA at birth: 24-42 weeks). Hep(CB) along with complete blood counts, ferritin and parameters of inflammation and clinical data were recorded. Data are presented as medians (IQR). Results: The Hep(CB) of very preterm infants (GA <30 weeks, n = 40) was 26.9 ng/ml (13.5-63.1), for moderately preterm infants (GA 30-36 weeks, n = 81) it was 45.9 ng/ml (24.7-74.5) and for term infants (GA ≥37 weeks, n = 100) it was 103.9 ng/ml (61.4-149.2). The Hep(CB) of infants with ID was lower [36.9 ng/ml (18.0-58.3)] than that of iron-replete infants [86.6 ng/ml (51.9-143.8)]. The Hep(CB) of infants delivered by elective caesarean section was lower [38.3 ng/ml (15.5-73.7)] than that of infants after spontaneous vaginal delivery or secondary caesarean section [80.3 ng/ml (48.5-137.6)]. Infants with a standard deviation score for birth weight (SDSBW) <-2 had a lower Hep(CB) [23.1 ng/ml (11.7-61.5)] compared to infants with SDSBW ≥-2 [71.1 ng/ml (34.0-121.7)]. The highest Hep(CB) (437.6 ng/ml) was recorded in an infant with Enterococcus faecalis sepsis. Multiple logistic regression analysis confirmed ferritin, GA and mode of delivery as important factors associated with Hep(CB). Conclusion: This is the first report on GA-specific reference ranges for Hep(CB) in preterm infants. Whereas iron stores, GA and mode of delivery were associated with Hep(CB), the association with inflammation and intra-uterine growth retardation was less clear. © 2014 S. Karger AG, Basel.


Tanaka N.,Yamaguchi University | Tanaka N.,Saiseikai Yamaguchi General Hospital | Kunihiro Y.,Yamaguchi University | Kobayashi T.,Yamaguchi University | And 4 more authors.
Clinical Radiology | Year: 2016

Idiopathic pneumonia syndrome (IPS) is an acute lung dysfunction of non-infectious aetiology and a severe complication following haematopoietic stem cell transplantation (HSCT). Recently, the American Thoracic Society (ATS) updated the concept of IPS and extended the concept to a wider range; it defined IPS as “an idiopathic syndrome of pneumopathy after HSCT, with evidence of widespread alveolar injury and in which infectious aetiologies and cardiac dysfunction, acute renal failure, or iatrogenic fluid overload have been excluded.” The ATS also categorised the presumed site of primary tissue injury into three patterns (pulmonary parenchyma, vascular endothelium, and airway epithelium), each of which has several entities. Since the therapeutic strategies for IPS are clearly different from those of infectious diseases, and therapeutic delay causes a poor prognosis, radiologists should be aware of some characteristic HRCT findings of IPS, which includes a wide spectrum of entities. In this article, the characteristic HRCT findings of these entities, including acute interstitial pneumonia/acute respiratory distress syndrome, eosinophilic pneumonia, non-cardiogenic capillary leak syndrome, diffuse alveolar haemorrhage, transfusion-related acute lung injury, organising pneumonia, and bronchiolitis obliterans syndrome, are shown. © 2016 The Royal College of Radiologists


Among women, the polycystic ovarian syndrome (PCOS) is considered a form of metabolic syndrome with reproductive abnormalities. Women with PCOS show increased sympathetic tone, visceral adiposity with enlarged adipocytes, hypoadiponectinemia, insulin resistance, glucose intolerance, increased inactive osteocalcin, and hypertension. Excess fetal exposure to androgens has been hypothesized to play a role in the pathogenesis of PCOS. Previously, we showed that neonatal exposure to the androgen testosterone (NT) programs leptin resistance in adult female mice. Here, we studied the impact of NT on lean and adipose tissues, sympathetic tone in cardiometabolic tissues, and the development of metabolic dysfunction in mice. Neonatally androgenized adult female mice (NTF) displayed masculinization of lean tissues with increased cardiac and skeletal muscle as well as kidney masses. NTF mice showed increased and dysfunctional white adipose tissue with increased sympathetic tone in both visceral and subcutaneous fat as well as increased number of enlarged and insulin-resistant adipocytes that displayed altered expression of developmental genes and hypoadiponectinemia. NTF exhibited dysfunctional brown adipose tissue with increased mass and decreased energy expenditure. They also displayed decreased undercarboxylated and active osteocalcin and were predisposed to obesity during chronic androgen excess. NTF showed increased renal sympathetic tone associated with increased blood pressure, and they developed glucose intolerance and insulin resistance. Thus, developmental exposure to testosterone in female mice programs features of cardiometabolic dysfunction, as can be observed in women with PCOS, including increased sympathetic tone, visceral adiposity, insulin resistance, prediabetes, and hypertension.


Idiopathic pneumonia syndrome (IPS) is an acute lung dysfunction of non-infectious aetiology and a severe complication following haematopoietic stem cell transplantation (HSCT). Recently, the American Thoracic Society (ATS) updated the concept of IPS and extended the concept to a wider range; it defined IPS as an idiopathic syndrome of pneumopathy after HSCT, with evidence of widespread alveolar injury and in which infectious aetiologies and cardiac dysfunction, acute renal failure, or iatrogenic fluid overload have been excluded. The ATS also categorised the presumed site of primary tissue injury into three patterns (pulmonary parenchyma, vascular endothelium, and airway epithelium), each of which has several entities. Since the therapeutic strategies for IPS are clearly different from those of infectious diseases, and therapeutic delay causes a poor prognosis, radiologists should be aware of some characteristic HRCT findings of IPS, which includes a wide spectrum of entities. In this article, the characteristic HRCT findings of these entities, including acute interstitial pneumonia/acute respiratory distress syndrome, eosinophilic pneumonia, non-cardiogenic capillary leak syndrome, diffuse alveolar haemorrhage, transfusion-related acute lung injury, organising pneumonia, and bronchiolitis obliterans syndrome, are shown.


PubMed | Metabolism
Type: | Journal: Bone | Year: 2016

Sclerostin, the product of the SOST gene, is a secreted inhibitor of Wnt signaling that is produced by osteocytes to regulate bone formation. While it is often considered an osteocyte-specific protein, SOST expression has been reported in numerous other cell types, including hypertrophic chondrocytes and cementocytes. Of interest, SOST/sclerostin expression is altered in certain pathogenic conditions, including osteoarthritis and rheumatic joint disease, and it is unclear whether sclerostin plays a protective role or whether sclerostin may mediate disease pathogenesis. Therefore, as anti-sclerostin antibodies are being developed for the treatment of osteoporosis, it is important to understand the functions of sclerostin beyond the regulation of bone formation.


PubMed | Metabolism
Type: Journal Article | Journal: American journal of physiology. Endocrinology and metabolism | Year: 2013

Among women, the polycystic ovarian syndrome (PCOS) is considered a form of metabolic syndrome with reproductive abnormalities. Women with PCOS show increased sympathetic tone, visceral adiposity with enlarged adipocytes, hypoadiponectinemia, insulin resistance, glucose intolerance, increased inactive osteocalcin, and hypertension. Excess fetal exposure to androgens has been hypothesized to play a role in the pathogenesis of PCOS. Previously, we showed that neonatal exposure to the androgen testosterone (NT) programs leptin resistance in adult female mice. Here, we studied the impact of NT on lean and adipose tissues, sympathetic tone in cardiometabolic tissues, and the development of metabolic dysfunction in mice. Neonatally androgenized adult female mice (NTF) displayed masculinization of lean tissues with increased cardiac and skeletal muscle as well as kidney masses. NTF mice showed increased and dysfunctional white adipose tissue with increased sympathetic tone in both visceral and subcutaneous fat as well as increased number of enlarged and insulin-resistant adipocytes that displayed altered expression of developmental genes and hypoadiponectinemia. NTF exhibited dysfunctional brown adipose tissue with increased mass and decreased energy expenditure. They also displayed decreased undercarboxylated and active osteocalcin and were predisposed to obesity during chronic androgen excess. NTF showed increased renal sympathetic tone associated with increased blood pressure, and they developed glucose intolerance and insulin resistance. Thus, developmental exposure to testosterone in female mice programs features of cardiometabolic dysfunction, as can be observed in women with PCOS, including increased sympathetic tone, visceral adiposity, insulin resistance, prediabetes, and hypertension.

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