A 54-year-old man had been drinking approximately 1.2 L of soy milk (equivalent to approximately 310 mg of isoflavones) per day for the previous 3 years. He then developed erectile dysfunction and ...gynecomastia. On an examination in our department in May, blood tests showed low gonadotropin and testosterone levels, indicative of secondary hypogonadism. He stopped drinking soy milk on his own in June of that year. When he was admitted in August, blood tests showed an improved gonadal function. Secondary hypogonadism caused by the excessive intake of isoflavones in soy milk was diagnosed. In men, an excessive intake of isoflavones may cause feminization and secondary hypogonadism.
NADPH oxidases (NOX) are enzymes that catalyze the production of reactive oxygen species (ROS). Four species of NOX catalytic homologs (NOX1, NOX2, NOX4, and NOX5) are reportedly expressed in ...vascular tissues. The pro-atherogenic roles of NOX1, NOX2, and their organizer protein p47ph°x were manifested, and it was noted that the hydrogen peroxide-generating enzyme NOX4 possesses atheroprotective effects. Loss of NOX1 or p47ph°x appears to ameliorate murine aortic dissection and subsequent aneurysmal diseases; in contrast, the ablation of NOX2 exacerbates the aneurysmal diseases. It is possible that the loss of NOX2 activates inflammatory cascades in macrophages in the lesions. Roles of NOX5 in vascular functions are currently undetermined, owing to the absence of this enzyme in rodents and the limitation of the experimental procedure. Thus, it is possible that the NOX family of enzymes exhibits heterogeneity in the atherosclerotic diseases. In this aspect, subtype-selective NOX inhibitor may be promising when NOX systems serve as a molecular target for atherosclerotic and aneurysmal diseases.
Associations of arterial stiffness with glucose, insulin, and proinsulin dynamics during the oral glucose tolerance test (OGTT) remain under debate. The aim of this study was to investigate whether ...plasma glucose (PG), insulin, and proinsulin (Pro) contribute to arterial stiffness, measured by pulse wave velocity (PWV), in young Japanese persons. PG, immunoreactive insulin (IRI), and Pro levels were determined in 1193 young Japanese subjects (<40 years of age) with normal glucose tolerance or nondiabetic hyperglycemia before and at 30, 60, and 120 min during a 75-g OGTT. Participants were divided into two groups according to the median PWV. Background factors, PG, IRI, and Pro levels during the OGTT, and insulin sensitivity (SI) indices in each group were compared. Several multiple regression analysis models were used to evaluate factors contributing to PWV. All IRI and Pro levels before and after glucose loading and the area under the curve (AUC) values for IRI and Pro increased with higher PWV. 1/HOMA-IR and ISI-Matsuda as measures of SI decreased with higher PWV. The IRI AUC and Pro level before glucose loading (Pro0) were independently associated with PWV, in addition to male sex, heart rate, and mean blood pressure. The IRI AUC had a stronger relationship with PWV than Pro0. The IRI AUC had an independent relationship with PWV, whereas both SI indices did not. Postloading insulinemia, but not reduced SI, was independently associated with arterial stiffness in young Japanese persons.
Familial partial lipodystrophy (FPLD) 3 is a rare genetic disorder caused by peroxisome proliferator-activated receptor γ gene (PPARG) mutations. Most cases have been reported in Western patients. ...Here, we describe a first pedigree of FPLD 3 in Japanese. The proband was a 51-year-old woman. She was diagnosed with fatty liver at age 32 years, dyslipidemia at age 37 years, and diabetes mellitus at age 41 years. Her body mass index was 18.5 kg/m2, and body fat percentage was 19.2%. On physical examination, she had less subcutaneous fat in the upper limbs than in other sites. On magnetic resonance imaging, atrophy of subcutaneous adipose tissue was seen in the upper limbs and lower legs. Fasting serum C-peptide immunoreactivity was high (3.4 ng/mL), and the plasma glucose disappearance rate was low (2.07%/min) on an insulin tolerance test, both suggesting apparent insulin resistance. The serum total adiponectin level was low (2.3 μg/mL). Mild fatty liver was seen on abdominal computed tomography. On genetic analysis, a P495L mutation in PPARG was identified. The same mutation was also seen in her father, who had non-obese diabetes mellitus, and FPLD 3 was diagnosed. Modest increases in body fat and serum total adiponectin were seen with pioglitazone treatment. Attention should be paid to avoid overlooking lipodystrophy syndromes even in non-obese diabetic patients if they show features of insulin resistance.
Aims/Introduction
This study examined the association between the severity of diabetic polyneuropathy (DPN) based on the Baba classification, and sarcopenia and its related factors.
Materials and ...Methods
The participants were 261 patients with type 2 diabetes mellitus. DPN was classified as stages 0–4 according to the Baba classification. Sarcopenia was diagnosed based on measurements of the skeletal mass index, grip strength and walking speed, using the Asia Working Group for Sarcopenia 2019 diagnostic criteria.
Results
The median age of the participants was 67 years, the proportion of men was 58.6%, the median estimated duration of diabetes was 10 years and the median values for glycated hemoglobin were 10.3%. With regard to DPN, the prevalence of Baba classification stages 0–2 was 90.8% (n = 237), and that of stage 3 or 4 was 9.2% (n = 24). The prevalence of sarcopenia was 19.9%. A trend toward an increase in the frequency of slow walking speed was seen as the stage of DPN progressed. The frequencies of sarcopenia and slow walking speed were higher in the group with the Baba classification stages 3 and 4 than in the group with stages 0–2. On multiple logistic regression analyses, however, DPN was not significantly related to sarcopenia and walking speed.
Conclusions
Although severe DPN might be related to sarcopenia, the frequency of severe DPN is low in the clinical setting, indicating that its contribution to sarcopenia is modest.
We evaluated the association between the severity of diabetic polyneuropathy and sarcopenia in type 2 diabetes patients. The results showed that the severity of diabetic polyneuropathy was not associated with sarcopenia, and factors such as age, were significantly associated with it.
OBJECTIVE—Although nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2) is reportedly essential for phagocyte host defenses, it has been found to aggravate atherosclerosis in apolipoprotein E ...(Apoe)-null mice through excess production of superoxide. We therefore assessed the role of NOX2 in an experimental model of abdominal aortic aneurysm (AAA) and assessed the mechanism of NOX2 action in AAA.
APPROACH AND RESULTS—AAA was induced in low-density lipoprotein receptor-null (Ldlr) mice by infusing angiotensin II. Nox2 expression was elevated in the abdominal aortae of these mice during infusion of angiotensin II, with enhanced Nox2 expression mainly because of the recruitment of NOX2-enriched macrophages into AAA lesions. Unexpectedly, systemic Nox2 deficiency promoted AAA development but reduced the level of reactive oxygen species in AAA lesions. Nox2 deficiency stimulated macrophage conversion toward the M1 subset, enhancing expression of interleukin (IL)-1β and matrix metalloproteinase-9/12 mRNA. Administration of neutralizing antibody against IL-1β abolished AAA development in Nox2-deficient mice. Bone marrow transplantation experiments revealed that AAA aggravation by Nox2 deficiency is because of bone marrow–derived cells. Isolated bone marrow–derived macrophages from Nox2-null mice could not generate reactive oxygen species. In contrast, IL-1β expression in peritoneal and bone marrow–derived macrophages, but not in peritoneal neutrophils, was substantially enhanced by Nox2 deficiency. Pharmacological inhibition of Janus kinase/signal transducers and activators of transcription signaling inhibited excess IL-1β expression in Nox2-deficient macrophages, whereas matrix metalloproteinase-9 secretion was constitutively stimulated via nuclear factor-κB signals.
CONCLUSIONS—Nox2 deficiency enhances macrophage secretion of IL-1β and matrix metalloproteinase-9, disrupting tissue-remodeling functions in AAA lesions. These actions are unfavorable if NOX2 is to serve as a molecular target for AAA.
A 38-year-old woman who consulted a local doctor with chief complaints of sudden palpitations, headaches, and chest pain is herein presented. After admission, pheochromocytoma crisis was suspected. ...Since the patient had a history of acute heart failure and had once survived an episode of cardiac arrest, a rapid decrease in the catecholamine levels was needed. After resuscitation, pharmacological therapy with agents such as phentolamine and landiolol was administered, and continuous hemodiafiltration (CHDF) was performed to reduce the catecholamine levels. Elective surgery was then performed, and a positive outcome was achieved. This case suggests that the preoperative use of CHDF to control pheochromocytoma crisis may therefore be effective.
Calpain and Atherosclerosis Miyazaki, Takuro; Koya, Takayuki; Kigawa, Yasuyoshi ...
Journal of Atherosclerosis and Thrombosis,
01/2013, Letnik:
20, Številka:
3
Journal Article
Odprti dostop
This review highlights the pro-atherogenic roles of Ca2+-sensitive intracellular protease calpains. Among more than ten species of calpain isozymes, µ- and m-calpains have been characterized most ...extensively. These two isozymes are ubiquitously expressed in mammalian tissues, including blood vessels, and tightly regulate functional molecules in the vascular component cells through limited proteolytic cleavage. Indeed, previous cell-based experiments showed that calpains play significant roles in nitric oxide production in vascular endothelial cells (ECs), maintenance of EC barrier function and angiogenesis for maintaining vascular homeostasis. Recently, we demonstrated that modified-low density lipoprotein (LDL)-induced m-calpain causes hyperpermeability in ECs, leading to the infiltration of monocytes/macrophages and plasma lipids into the intimal spaces (Miyazaki T. et al., Circulation. 2011; 124: 2522-2532). Calpains also mediate oxidized LDL-induced apoptotic death in ECs. In monocytes/macrophages, calpains induce proteolytic degradation of ATP-binding cassette transporter A1 (ABCA1) and G1 (ABCG1), which results in impaired cholesterol efflux and subsequent macrophage foam cell formation. In vascular smooth muscle cells, calpains may be involved in the conversion from contractile phenotype to proliferative phenotype. In hepatocytes, calpains disrupt the biogenesis of high-density lipoprotein via proteolytic degradation of ABCA1. Thus, calpains may serve as novel candidate molecular targets for control of atherosclerosis.
A 38-year-old man who was delivered in a breech position presented with delayed development of secondary sexual characteristics and malaise. He was diagnosed with panhypopituitarism caused by ...interruption of the pituitary stalk due to perinatal complications. Brain magnetic resonance imaging findings for pituitary stalk interruption syndrome are well-documented; however, reports of the imaging findings of the bones and several organs related to the effects of panhypopituitarism are limited. In this patient with anterior pituitary dysfunction, imaging revealed diverse sequelae, including delayed skeletal maturation, osteopenia, genital atrophy, fatty liver, and adrenal atrophy. Radiologists may find it difficult to discern complex imaging findings unless they are informed of the clinical course of the patient. Therefore, radiologists should coordinate with clinicians to arrive at a diagnosis.
Background. Endocrine hormones are closely associated with homeostasis, so it is important to clarify hormone secretion dynamics in shock. Few reports, however, have examined the dynamics of ...endogenous hormone secretion relative to prognosis in cardiac arrest patients. Therefore, to clarify the roles of endocrine hormones in out-of-hospital cardiac arrest (OHCA) patients, the concentrations of anterior pituitary, thyroid, and adrenocortical hormones were measured, and their associations with return of spontaneous circulation (ROSC) were examined. Methods. The subjects were OHCA patients transported to our Emergency Department. In addition to conventional clinical laboratory tests, the following were measured: serum TSH, serum free T3, serum free T4 (F-T4), plasma ACTH, serum cortisol, serum GH, serum IGF-1, plasma aldosterone concentration (PAC), and plasma renin activity. The primary endpoint was the presence or absence of ROSC, and the secondary endpoint was 24-hour survival. Results. A total of 29 patients, 17 in the ROSC group and 12 in the non-ROSC group, were studied. There were associations between ROSC and low serum potassium, high F-T4, low cortisol, and low PAC on bivariate analyses. There were associations between ROSC and serum potassium, F-T4, and GH using the step-wise method. On multiple logistic regression analysis, a relationship between ROSC and high serum F-T4 level was identified by both methods. There were also associations between 24-hour survival and both low serum potassium and elevated blood glucose levels. Conclusions. The present findings suggest a possible relationship between the serum F-T4 level and ROSC in OHCA patients. A higher serum F-T4 level might cause an increase in the β-adrenergic response in cardiomyocytes and increased responsiveness to catecholamines and was possibly associated with ROSC.
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