Macrophage HIF-1α increases liver tumor

Aims/Introduction: Chronic inflammation of the liver is often observed with obesity or type 2 diabetes. In these pathological conditions, the immunological cells, such as macrophages, play important roles in the development or growth of liver cancer. Recently, it was reported that hypoxia‐inducible factor‐1α (HIF‐1α) is a key molecule for the acquisition of inflammatory M1 polarity of macrophages. In the present study, we examined the effects of altered macrophage polarity on obesity‐ and diabetes‐associated liver cancer using macrophage‐specific HIF‐1α knockout (KO) mice. Materials and Methods: To induce liver cancer in the mice, diethylnitrosamine, a chemical carcinogen, was used. Both KO mice and wild‐type littermates were fed either a high‐fat diet (HFD) or normal chow. They were mainly analyzed 6 months after HFD feeding. Results: Development of liver cancer after HFD feeding was 45% less in KO mice than in wild‐type littermates mice. Phosphorylation of extracellular signal‐regulated kinase 2 was also lower in the liver of KO mice. Those effects of HIF‐1α deletion in macrophages were not observed in normal chow‐fed mice. Furthermore, the size of liver tumors did not differ between KO and wild‐type littermates mice, even those on a HFD. These results suggest that the activation of macrophage HIF‐1α by HFD is involved not in the growth, but in the development of liver cancer with the enhanced oncogenic extracellular signal‐regulated kinase 2 signaling in hepatocytes. Conclusions: The activation of macrophage HIF‐1α might play important roles in the development of liver cancer associated with diet‐induced obesity and diabetes

Association Between Nerve Conduction Velocity and Clinical Parameters Related to Diabetic Complications inPatients with Type 2 Diabetes

The main purpose of the study was to investigate the association of median motor nerve conduction velocity(MCV) and sural sensory nerve conduction velocity( SCV) with parameters related to diabetic complicationsin patients with type 2 diabetes. A total of 263 patients hospitalized for glycemic control from 1999to 2006 who underwent single or multiple nerve conduction velocity tests (at least a right median MCVtest) were enrolled in the study retrospectively. Right median MCV showed a significant negative correlationwith age and diabetic duration, and was also significantly negatively correlated with systolic blood pressure(SBP) and log urinary albumin excretion (UAE). Right median MCV showed strong positive correlationswith left median MCV and right median SCV, and significant but relatively mild positive correlationswith right peroneal MCV and right sural SCV. In multiple regression analysis, only SBP and diabetic durationshowed a significant association with right median MCV. Although right sural SCV showed significantnegative correlations with SBP and log UAE, the correlations were relatively weak compared with those forright median MCV. Of 215 patients who underwent complete sural SCV measurements, right and left suralSCV were detected in 159( 74%) and 163 patients( 76%), respectively. In conclusion, these results suggestthat median MCV is more closely associated with markers related to diabetic complications such as SBP orUAE, compared with sural SCV, but that sural SCV is more sensitive than median MCV for detection of diabeticneuropathy

SIADH induced by pneumonia in a patient with Shy-Drager syndrome

Patients with Shy-Drager syndrome have impaired baroreceptor-mediated vasopressin release when inan upright position. We report a case of Shy-Drager syndrome in which the syndrome of inappropriate secretionof antidiuretic hormone (SIADH) developed with pneumonia. It has been speculated that pneumonia-induced SIADH is caused by baroreceptor-mediated vasopressin release. Our case presents the possibilitythat pneumonia-induced SIADH is caused by non-baroreceptor-mediated ADH release

Greater Efficacy and Improved Endothelial Dysfunction in Untreated Type 2 Diabetes with Liraglutide versus Sitagliptin

Objective:The incretin hormone glucagon-like peptide 1 (GLP-1) and its analogs, including the glucagonlike peptide 1 receptor agonist liraglutide, use a simple once-daily regimen and can be easily introduced in the outpatient setting. We compared treatment with liraglutide monotherapy and dipeptidyl peptidase-4 (DPP-4) inhibitor monotherapy in patients with untreated type 2 diabetes( T2DM).Methods:This study included 40 outpatients with untreated T2DM who were randomized to receive liraglutide (0.9 mg/day, n=24) or DPP-4 inhibitors (n=16:sitagliptin, 50 mg/day) as initial treatment for 6 months. Glycemic control, urinalysis, blood pressure, body weight, lipid levels, vascular endothelial function, and inflammatory factors were assessed before and after treatment.Results:Significant improvement was observed in HbA1c and fasting blood glucose levels after treatment in both groups;improvements in the liraglutide group were significantly better than in the sitagliptin group. Only the liraglutide group demonstrated significant improvements in blood pressure, low-density lipoprotein cholesterol levels, urinary albumin excretion, flow-mediated dilatation, and high-sensitivity C-reactive protein levels. Linear regression analysis demonstrated a significant negative relation between change in flow-mediated dilatation and high-sensitivity C-reactive protein levels.Conclusion:Liraglutide provided significant glycemic control and improved blood pressure, lipid levels, endothelial function, and inflammatory factors in untreated T2DM. In addition to its impact on blood glucose levels, liraglutide may have beneficial effects on the cardiovascular system in patients with T2DM

A case in which water intoxication due to excessive water ingestion did not inhibit the secretion of arginine vasopressin

We experienced a case of water intoxication due to excessive water ingestion that was complicated by the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). A 60-year-old Japanese woman with nervous depression drank too much lemon tea within several hours, vomited ten times, and developed disturbed consciousness and dysarthria. Her plasma arginine vasopressin (AVP) concentration was not inhibited,although her plasma osmolality was low. Nausea and/or stress may stimulate AVP secretion regardless of the hypo-osmolality. We believe that dilatation of her stomach due to excessive liquid ingestion and cerebral edema due to hypo-osmolality brought on her nausea. Stress induced by a psychiatric problem and/or admission to a hospital may also stimulate AVP secretion by the central nervous system. Treatingnausea and stress may help reduce AVP secretion and resolve hyponatremia

テイNa ケッショウ ノ ビョウタイ セイリ

日常診療において低Na 血症は最も頻回に遭遇する電解質異常である.その治療には,ヒトの体液恒常性維持のメカニズムと,低Na 血症となる病態の正確な理解が必要不可欠である.本稿では低Na 血症の概説と,その代表的疾患であるSIADH について詳しく述べる.最新の知見を紹介しながらSIADH の鑑別診断にも触れる.Hyponatremia is a most common electrolyte abnormalityin routine practice. It is extremely necessary to understandboth the mechanism of maintaining fluid homeostasis of humanbody and the true pathophysiology of hyponatremia. Ifyou meet a male patient who needs fluid management, youmust choose appropriate fuild content or he might causeiatrogenic hyponatremia, even though he is not a patientwith hyponatremia. We tried to summarize hyponatremiaand SIADH as a review in this manuscript

コウレイシャ 2 ガタ トウニョウビョウ カンジャ ニ オケル ニンチ キノウ チョウサ ト ソノ カンレン インシ ニ ツ イテ

目的:2型糖尿病は,認知症発症との関連が報告されている.そこで実際の高齢者2型糖尿病患者において,認知機能が低下している患者の頻度を調査し,また認知機能に影響を与える因子を検討した.方法:2014年2月?4月の間に,入院加療を行った糖尿病多発合併症や心血管病の既往がない2型糖尿病患者64名のうち,60歳以上の高齢者で,臨床研究に同意した35名(男性:23名,女性:12名)を対象とし,Mini-Mental State Examination(MMSE)にて認知機能を評価した.認知機能(MMSE score)と年齢,血糖コントロール(HbA1c),血圧,脂質,喫煙歴,糖尿病罹患歴,動脈硬化の指標として,Cardio Ankle Vascular Index(CAVI)に対する相関を検討した.結果:高齢者糖尿病のうち31.4%に認知機能の低下が疑われた.またそれは,年齢,糖尿病罹患歴,CAVI値にMMSE値は単相関を認め,重回帰分析では,糖尿病罹患歴とCAVI値が有意な影響を与えている因子であった.結論:高齢者2型糖尿病における認知機能は,罹患歴や動脈硬化が影響を与える事が示唆され,中年期からの糖尿病管理や動脈硬化抑制が老年期の認知機能障害の発生と関連する可能性が示唆された.Objective:Type 2 diabetes is reportedly associated with the risk of developing dementia. Hence, we surveyed elderly patients with type 2 diabetes to investigate the actual level of cognitive function decline and examine factors that affect cognitive function. Methods:From among 64 patients with type 2 diabetes who underwent inpatient treatment in the Department of Endocrinology and Metabolism of Dokkyo Medical University between February and April 2014, we selected as study subjects 35 patients aged ? 60 years(23 men and 12 women)who had no history of multiple diabetic complications or cardiovascular disease. The Mini-Mental State Examination(MMSE)was used to assess cognitive function. The correlations of cognitive function(MMSE score) with age, glycemic control(HbA1c), blood pressure, fat, smoking, diabetes history, and cardio-ankle vascular index (CAVI)as an index of arteriosclerosis were investigated. Results:Cognitive function decline was suspected in 31.4% of the elderly patients with diabetes. Simple correlations were found between MMSE score and age, diabetes history, and CAVI score. In particular, diabetes history and CAVI score were identified as significant risk factors in a multivariate analysis. Conclusion:Our results suggest that disease history and arteriosclerosis may affect the cognitive function of elderly patients with type 2 diabetes, and that diabetes management and arteriosclerosis control from middle age may be associated with cognitive function in old age

キュウセイ ジンフゼン, コウCPKケッショウ オ トモナイ, キュウゲキ ニ ケトアシドーシス オ テイシタ ヒ ジコ メンエキセイ ゲキショウガタ 1ガタ トウニョウビョウ ノ 1レイ

We present a 40 year male patient who developed diabetic ketoacidosis with acute renal failure and high serum values of CPK and uric acid. Because of acute onset of ketoacidosis during several days with an elevation of serum amylase, negative findings of antibodies associated with autoimmune type 1 diabetes mellitus, he was diagnosed of a non-autoimmune, fuluminant, type 1 diabetes mellitus, which is a newly established subtype of type 1 diabetes mellitus. Since the patient\u27s post-prandial plasma glucose was extremely high (1123 mg/dl) when he developed ketoacidosis, the severe dehydration due to extreme hyperglycemia might have caused acute renal failtire and rhabdomyolysis