Impact of adiposity and plasma adipocytokines on diabetic angiopathies in Japanese Type 2 diabetic subjects.

AIMS: Adipocytokines, products from adipose tissue, have biological activities on the vascular system, and may affect diabetic angiopathy. In this study, we assessed the relationship between adiposity and plasma adipocytokine levels, and investigated the clinical significance of adiposity and plasma adipocytokine levels on diabetic micro- and macroangiopathy in Type 2 diabetic subjects. METHODS: We studied 231 Japanese Type 2 diabetic subjects (135 men and 96 women, aged 60.4 +/- 12.3 years, body mass index 24.8 +/- 5.2 kg/m2). We measured adipocytokine [adiponectin, leptin, resistin, and tumour necrosis factor (TNF)-alpha] levels, lipid profiles and urine albumin excretion. We also performed optic fundus examination and measured carotid intramedia thickness (IMT) using B-mode ultrasonography, and the localization of fat with abdominal computed tomography. A group of 93 subjects with microalbuminuria or overt proteinuria was compared with the other 148 to assess the effect on nephropathy. A group of 191 eyes with simple retinopathy or more advanced changes was compared with 263 eyes without retinal changes to assess the effect on retinopathy. RESULTS: Plasma adiponectin level was negatively correlated with both visceral (r = -0.37, P < 0.01) and subcutaneous (r = -0.25, P < 0.01) fat areas. Resistin concentration was positively related with visceral fat area (r = 0.15, P < 0.05). Adiponectin concentration was positively correlated with age (r = 0.26, P < 0.01). TNF-alpha was correlated with IMT (r = 0.16, P < 0.05) after correction for age. Logistic regression analysis indicates a 4085 times greater chance of having retinopathy with a one unit increase in TNF-alpha (pmol/l) and a 30.64 times greater chance of having nephropathy with one unit increase in leptin (nmol/l). CONCLUSIONS: The present observations suggest that visceral and subcutaneous fat has an impact on microangiopathy as well as macroangiopathy, possibly through different adipocytokines.     

Ultrasonographic evaluation of lansoprazole-induced improvement of submucosal injury in patients with gastroesophageal reflux

OBJECTIVE: Endoscopic ultrasonographic (EUS) changes in gastroesophageal reflux disease (GERD) after treatment with proton pump inhibitor have been poorly evaluated. We conducted a randomized, double-blind 12-wk clinical trial to compare the EUS effects of lansoprazole to histamine H2-receptor antagonist therapy in GERD. METHODS: Seventeen patients with reflux-related symptoms received 40 mg of famotidine for 6 wk or 30 mg of lansoprazole for 6 wk followed by 40 mg of famotidine or 30 mg of lansoprazole for another 6 wk, respectively. Patients underwent EUS before and at 6 and 12 wk after treatment. RESULTS: Before treatment, a variable degree of wall thickening was noted on EUS in the lower esophagus, compared with 20 normal subjects. After 6 wk of therapy, esophageal wall was significantly thicker in the famotidine group compared with the lansoprazole group (p<0.01). Surprisingly, thickening of esophageal wall and abnormal architecture were also detected in endoscopically negative reflux disease. Lansoprazole was superior to famotidine in reducing the thickness of esophageal wall. CONCLUSIONS: EUS was very useful for evaluation of submucosal injury in patients with GERD. EUS showed that a 6-wk course of lansoprazole therapy reduced thickening of esophageal wall, which was resistant to histamine H2-receptor antagonist therapy. Our results also suggest that inflammatory damage to the submucosal and muscle layers of the lower esophagus is the underlying mechanism of heartburn and associated symptoms in patients with endoscopically negative reflux disease.     

Sequential evaluation of left ventricular myocardial performance in children after anthracycline therapy

This study prospectively assessed subclinical cardiotoxicity in patients undergoing chemotherapy by using the Tei index combining systolic and diastolic time intervals. A significant difference in the Tei index was observed between patients who received a low dose and those who received a moderate to high dose of anthracycline antibiotic drugs. The Tei index is a sensitive, accurate, and easy approach for detecting subclinical anthracycline cardiotoxicity.     

Age-related changes of NGF, BDNF, parvalbumin and neuronal nitric oxide synthase immunoreactivity in the mouse hippocampal CA1 sector

We investigated the age-related alterations in nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), parvalbumin and neuronal nitric oxide synthase (nNOS) immunoreactivity of the mouse hippocampal CA1 sector. NGF and BDNF immunoreactivity was unchanged in the hippocampal CA1 pyramidal neurons from 2 to 50-59 weeks of birth. In contrast, a significant increase in the NGF and BDNF immunoreactivity was observed in glial cells of the hippocampal CA1 sector from 40-42 to 50-59 weeks of birth. On the other hand, the number of parvalbumin- and nNOS-positive interneurons was unchanged in the hippocampal CA1 sector during aging processes, except for a significant decrease of nNOS-positive interneurons 2 weeks of birth. Our results indicate that NGF and BDNF immunoreactivity was unaltered in the hippocampal CA1 pyramidal neurons during aging processes. In contrast, a significant increase in the NGF and BDNF immunoreactivity was observed in glial cells of the hippocampal CA1 sector during aging processes. The present study also shows that the number of parvalbumin- and nNOS-positive interneurons was unchanged in the hippocampal CA1 sector during aging processes, except for a significant decrease of nNOS-positive interneurons 2 weeks of birth. These results demonstrate that the expression of glial NGF and BDNF may play a key role for helping survival and maintenance of pyramidal neurons and neuronal functions in the hippocampal CA1 sector during aging processes. Furthermore, our findings suggest that parvalbumin- and nNOS-positive interneurons in the hippocampal CA1 sector are resistant to aging processes. Moreover, our findings suggest that nitric oxide synthesized by the nNOS may play some role for neuronal growth during postnatal development.     

Chronic salt loading upregulates expression of adrenomedullin and its receptors in adrenal glands and kidneys of the rat

The vasodilator peptide adrenomedullin (AM) elicits diuresis and natriuresis and inhibits aldosterone secretion. The aim of this study was to better understand the role of AM in maintaining water and electrolyte balance during chronic salt loading. Male Wistar rats were divided into a high salt (HS) group that received a diet containing 8% sodium chloride (NaCl) and a normal salt group that received a diet containing 0.4% NaCl. Plasma AM concentrations as well as expression of AM mRNA in the adrenal gland and kidney were then measured after 3, 7, 14, and 28 days. After 28 days, sodium and water excretion were significantly higher in HS rats than in control, although blood pressure and fluid volume were not significantly affected. Moreover, although plasma AM remained unchanged for up to 14 days, it was increased 2.5-fold in HS rats after 28 days on a high salt diet, and there were corresponding 3-fold and 1.5-fold increases in the levels of AM mRNA in the adrenal gland and kidney, respectively. At the same time, expression of calcitonin receptor-like receptor mRNA was significantly upregulated in both kidney and adrenal gland, as was expression of receptor activity-modify protein 1 (RAMP1) and RAMP2 mRNA in the adrenals and expression of RAMP3 in kidneys. Taken together, these results suggest that AM plays a role in the regulation of water and electrolyte balance in animals chronically ingesting high levels of salt.     

Protein-losing gastropathy associated with autoimmune disease: successful treatment with prednisolone

99m Tc-labeled human serum albumin scintigram showing abnormal radioactivity in the stomach. Endoscopic gastric biopsies revealed nonspecific inflammation, but marked intramural edema. Based on a slight elevation of antinuclear antibody level, autoimmune disease was suspected to be involved in this patient. Administration of prednisolone, as a diagnostic therapy, alleviated the hypoproteinemia, hypoalbuminemia, and hypercholesteremia. These findings suggest that an autoimmune mechanism could have been involved in this case of protein-losing gastropathy. Received: September 4, 2000 / Accepted: February 23, 2001     

Evidence for the participation of endogenous activin A/erythroid differentiation factor in the regulation of erythropoiesis.

Activin A/erythroid differentiation factor (EDF) is a human protein that induces differentiation of a murine erythroleukemia cell (the Friend cell). In this study, we demonstrate that endogenous activin A/EDF activity is present in murine bone marrow and spleen. In addition, this activity is secreted by bone marrow and spleen cells in primary culture. Administration of follistatin (a specific binding protein for activin A/EDF) to mice results in a decrease of erythroid progenitors in the bone marrow and spleen. These findings support the concept that activin A/EDF and follistatin have opposing actions in the regulation of erythropoiesis.     

In vivo action of activin-A on pituitary-gonadal system.

Activin, a dimer of the beta-subunits of inhibin, has been found to stimulate FSH secretion from the cultured pituitary cells. However, in vivo action of activin is poorly elucidated. Daily sc injections of 40 micrograms activin-A over a period of 1-3 days to intact immature female rats caused a significant increase in serum FSH, inhibin, estradiol, uterine weight, and ovarian FSH receptors. Daily sc injections of 5 micrograms or 20 micrograms activin-A for 6 days caused a marked increase in ovarian weight and the development of large ovarian follicles. However, daily sc injections of 20 micrograms activin-A to hypophysectomized immature female rats for 3 days induced no significant changes in ovarian and uterine weight, serum inhibin, estradiol, and progesterone levels. Simultaneous injections of both activin-A and 5 IU PMSG induced a significant increase in ovarian and uterine weight, serum inhibin, and estradiol levels, compared to simultaneous injections of both vehicle and PMSG in the hypophysectomized immature female rats. These results demonstrate that activin-A induces not only an increase of FSH secretion from the pituitary but also a direct autocrine or paracrine ovarian stimulation resulting in an increase of the number of ovarian FSH receptors and ovarian and uterine weight, as well as an increase in the level of inhibin and estradiol secretion from the ovary.     

Multicystic aneurysmal dilatation of bilateral coronary artery fistula

Bilateral coronary artery fistula constitutes an uncommon subgroup of coronary artery fistulas that may have a distinct embryologic origin. Coronary artery fistulas usually show a tortuous arrangement upon coronary angiography, but aneurysmal dilatation is rare. We report here an extremely rare case of coronary artery fistula originating from both coronary arteries, which showed multicystic aneurysmal dilatation.     

Insulin and glucagon response of the diabetic Chinese hamster in the Asahikawa colony

The relationship between pancreatic hormone content and pattern of hormone release has not been completely elucidated because of heterogeneity in diabetes. Accordingly, this study was performed to establish the relationship, using spontaneously diabetic Chinese hamsters in the Asahikawa colony, a newly discovered experimental model resembling insulin-deficient diabetes in humans. As a result of investigations of insulin and glucagon responses to glucose or arginine in vivo and in vitro using isolated islets obtained by the collagenase procedure, a decreased insulin response and paradoxical glucagon response to glucose, and an excessive glucagon response to arginine were found in the diabetic animals. While the yield of isolated islets tended to decrease, a decreased pancreatic insulin content and increased pancreatic glucagon content were found as the diabetic state advanced. It may be suggested, therefore, that the relationship between pancreatic hormone content and pattern of hormone release in diabetic animals in the Asahikawa colony is based on the disruption of islets, disruption or dysfunction of B-cells and hyperplasia or hypertrophy of A-cells by some cause genetically determined.