Gas-forming liver abscess associated with rapid hemolysis in a diabetic patient.

We experienced a case of liver abscess due to Clostridium perfringens (CP) complicated with massive hemolysis and rapid death in an adequately controlled type 2 diabetic patient. The patient died 6 h after his first visit to the hospital. CP was later detected in a blood culture. We searched for case reports of CP septicemia and found 124 cases. Fifty patients survived, and 74 died. Of the 30 patients with liver abscess, only 3 cases survived following treatment with emergency surgical drainage. For the early detection of CP infection, detection of Gram-positive rods in the blood or drainage fluid is important. Spherocytes and ghost cells indicate intravascular hemolysis. The prognosis is very poor once massive hemolysis occurs. The major causative organisms of gas-forming liver abscess in diabetic patients are Klebsiella pneumoniae (K. pneumoniae) and Escherichia coli (E. coli). Although CP is relatively rare, the survival rate is very poor compared with those of K. pneumoniae and E. coli. Therefore, for every case that presents with a gas-forming liver abscess, the possibility of CP should be considered, and immediate aspiration of the abscess and Gram staining are important.

Soluble ST2 protein inhibits LPS stimulation on monocyte-derived dendritic cells.

ST2 protein is a soluble splicing variant of ST2L protein, which is the receptor for interleukin-33 (IL-33). Previously, we reported that soluble ST2 suppressed the signal transduction of lipopolysaccharide (LPS) and cytokine production in monocytic cells. To investigate whether or not this inhibitory effect occurs in dendritic cells, which are the key players in innate and adaptive immunity, human monocyte-derived dendritic cells were pre-treated with soluble ST2 protein before LPS stimulation. Although soluble ST2 did not attenuate the LPS-induced maturation of dendritic cells, pre-treatment with soluble ST2 suppressed cytokine production and inhibited LPS signaling. Moreover, the proliferation of naive T cells was inhibited significantly by soluble ST2 pre-treatment. IL-33 had little effect on the cytokine production of immature monocyte-derived dendritic cells. Furthermore, soluble ST2 protein was internalized into dendritic cells, suggesting that soluble ST2 protein acts by a noncanonical mechanism other than the sequestration of IL-33.

Sustained elevation of interleukin-33 in sera and synovial fluids from patients with rheumatoid arthritis non-responsive to anti-tumor necrosis factor: possible association with persistent IL-1ß signaling and a poor clinical response.

Although TNF inhibitors have dramatically improved the outcome of patients with rheumatoid arthritis, 30-40% of patients do not respond well to them and treatment needs to be changed. In an effort to discriminate good and poor responders, we focused on the change in serum and synovial fluid levels of interleukin (IL-) 33 before and after treatment with TNF inhibitors. They were also measured in synovial fluids from 17 TNF inhibitor-naïve patients, and fibroblast-like synoviocytes (FLS) in-culture from 6 patients and correlated with various pro-inflammatory cytokines. Serum levels of IL-33 at 6 months after treatment decreased significantly in responders, while they did not change in non-responders. Synovial fluid levels of IL-33 in 6 patients under treatment with TNF inhibitors stayed high in 3 who were refractory and slightly elevated in 2 moderate responders, while they were undetectable in one patient under remission. Among inflammatory cytokines measured in 17 synovial fluids from TNF inhibitor-naïve patients, levels of IL-33 showed a significant positive correlation only to those of IL-1ß. IL-1ß increased IL-33 expression markedly in FLS in vitro, compared to TNF-α. IL-1ß might be inducing RA inflammation through producing pro-inflammatory IL-33 in TNF inhibitor-hypo-responders. Sustained elevation of serum and/or synovial levels of IL-33 may account for a poor response to TNF inhibitors, although how TNF inhibitors affect the level of IL-33 remains to be elucidated.

Association of subcutaneous and visceral fat mass with serum concentrations of adipokines in subjects with type 2 diabetes mellitus.

The goal of the study was to examine the association of subcutaneous and visceral fat mass with serum concentrations of adipokines in 130 subjects with type 2 diabetes mellitus. The levels of serum high sensitivity C-reactive protein (HS-CRP), adiponectin, high-molecular-weight (HMW) adiponectin, interleukin-18, and retinol-binding protein 4 were measured. Percentage body fat was determined by dual energy X-ray absorptiometry, and subcutaneous and visceral fat areas were measured by abdominal CT. HS-CRP had significant positive correlations with percentage body fat and subcutaneous fat area, and a particularly significant positive correlation with visceral fat area. Serum adiponectin had a negative correlation with the subcutaneous and visceral fat areas, with the strongest correlation with the visceral fat area. Similar results were obtained for HMW adiponectin. Serum adiponectin had a negative correlation with visceral fat area in subjects with a visceral fat area < 100 cm², but not in those with a visceral fat area ≥ 100 cm². In contrast, serum HS-CRP showed a positive correlation with visceral fat area in subjects with visceral fat area ≥ 100 cm², but not in those with a visceral fat area < 100 cm². These findings indicate that an increased visceral fat area is associated with inflammatory changes, and that inflammatory reactions may alter the functional properties of visceral fat in type 2 diabetes mellitus.

Endothelial impairment and bone marrow-derived CD34(+)/133(+) cells in diabetic patients with erectile dysfunction.

AIMS/INTRODUCTION: The present study was undertaken to determine vascular endothelial impairment and endothelial progenitor cells (EPCs) in patients with type 2 diabetes mellitus and erectile dysfunction (ED). MATERIALS AND METHODS: A total of 100 type 2 diabetic men were enrolled. Flow-mediated dilatation (FMD) and anaerobic threshold (AT) were measured. Also, EPCs in the peripheral blood were determined by flow cytometry. RESULTS: In the 42 ED diabetic patients, FMD and AT were significantly less than those in the 58 patients with normal erectile function (FMD 2.84 vs 3.82%, P = 0.038, and AT 11.2 vs 12.7 mL/kg/min, P = 0.022). Exercise tolerance significantly increased the number of EPCs in the patients with and without ED (49-60 cells/100 µL, P = 0.015, and 72-99 cells/100 µL, P = 0.003). In the diabetic patients without autonomic neuropathy, FMD was significantly reduced in the patients with ED than those without ED (P = 0.015). In response to exercise tolerance, the number of EPCs increased in both the diabetic patients with ED (P = 0.003) and without ED (P = 0.007). In contrast, in the diabetic patients with autonomic neuropathy, there was no difference in FMD between the patients with and without ED. The exercise tolerance increased the number of EPCs in the patients without ED (P = 0.023), but it disappeared in those with ED. CONCLUSIONS: ED diabetic patients have endothelial impairment during the early period of diabetic complications, whose deranged endothelial function is concomitantly repaired by promoting bone marrow-derived EPCs.

Characterization of ST2 transgenic mice with resistance to IL-33.

IL-33, a member of the IL-1 family, activates MAPK and NF-kappaB through its receptor ST2L and IL-1RAcP. ST2, a member of the IL-1R superfamily, is a secreted form of ST2 gene products, which has been shown to act as a decoy receptor for IL-33 and to inhibit the IL-33/ST2L/IL-1RAcP signaling pathway. In this work, we generated ST2 transgenic mice. In control mice, intraperitoneal administration of IL-33 caused an increased number of eosinophils in blood and in peritoneal cavity, an increased number of peritoneal M Phi, splenomegaly, accumulation of periodic acid-Schiff-positive material in the lung, and high concentrations of serum IL-5 and IL-13. However, these alterations were hardly detectable in ST2 Tg mice. In peritoneal M Phi from IL-33-stimulated mice, mRNA expression of M2 M Phi marker genes were increased compared with thioglycollate-elicited peritoneal M Phi. The IL-33-stimulation also increased the secretion of IL-6 from M Phi. However, when the IL-33 was preincubated with ST2 prior to its addition to the M Phi cultures, the secretion of IL-6 was attenuated. These data suggest that, though IL-33 induced the Th2-type immune responses and infiltration of M2 type M Phi into the peritoneal cavity, ST2 can downregulate these reactions both in vivo and in vitro.

Increased levels of interleukin 33 in sera and synovial fluid from patients with active rheumatoid arthritis.

OBJECTIVE: To determine levels of interleukin 33 (IL-33) in serum and synovial fluid (SF) and their clinical associations in patients with rheumatoid arthritis (RA). To evaluate the ability of activated peripheral blood mononuclear cells (PBMC) and fibroblast-like synoviocytes (FLS) from RA patients to release IL-33. METHODS: Sera were obtained from 59 patients with RA, 10 patients with infectious diseases, and 42 healthy volunteers. SF samples were obtained from 15 patients with RA and 13 with osteoarthritis. IL-33 levels were measured using a sandwich ELISA after removal of rheumatoid factor with protein A-Sepharose beads. FLS were stimulated with IL-1beta and tumor necrosis factor, and treated with or without chemical damage. PBMC were stimulated with anti-CD3/CD28 antibodies. The levels of IL-33 were measured in the culture supernatants and cell lysates by ELISA or immunoblotting. RESULTS: Serum IL-33 levels were significantly higher in RA patients, especially in the high disease activity group compared to the moderate or low activity group. IL-33 levels in SF were elevated in all 15 RA patients measured. IL-33 levels were higher in SF samples than in sera in 7 RA patients measured simultaneously. The 30-kDa IL-33 precursor was detected in the culture supernatants of damaged FLS but was not detected in those of activated PBMC and non-damaged FLS. CONCLUSION: IL-33 levels were elevated in sera and SF samples from patients with RA, and correlated with disease activity. IL-33 was produced mainly in inflamed joints; IL-33/ST2L signaling might play an important role in joint inflammation of human RA.

Mature interleukin-33 is produced by calpain-mediated cleavage in vivo.

Interleukin (IL)-33 is a novel member of the IL-1 family. IL-33 is primarily synthesized as a 30-kDa precursor (pro-IL-33). Pro-IL-33 is cleaved by caspase-1 into an 18-kDa mature form (mature IL-33) in vitro. Recombinant mature IL-33 has been known to induce T-helper type-2 (Th2)-associated cytokines and inflammatory cytokines via its receptor, ST2L. However, processing of pro-IL-33 in vivo has not been clarified yet. Here, we report that calpain mediates pro-IL-33 processing in vivo. Pro-IL-33 was expressed by stimulating human epithelial cells with phorbol 12-myristate 13-acetate. Calcium ionophore induced pro-IL-33 cleavage and mature IL-33 production. This cleavage was inhibited by treatment with a calcium chelator and calpain inhibitors. Moreover, short interfering RNA-mediated knockdown of calpains suppressed pro-IL-33 cleavage. These results indicate that calpains play a critical role in pro-IL-33 processing in vivo.

Hypotonicity reduces the activity of murine aquaporin-2 promoter induced by dibutyryl cAMP.

The present study was undertaken to determine whether hypotonicity regulates the aquaporin-2 (AQP-2) gene in vitro. The 5'-flanking region of the AQP-2 gene contains the tonicity-response enhancer (TonE) promoter located between -570 and -560 bp, and another distinct hypertonicity-responsive region between -6.1 and -4.3 kb of the AQP-2 gene. The 5'-flanking region of murine AQP-2 gene up to -9.5 kb was cloned into a luciferase (Luc) reporter plasmid. The constructs, which have TonE and/or the hypertonicity-responsive region, together with the murine AQP-2 gene, were co-transfected into murine IMCD(3) cells. When the cells were co-transfected with the construct containing more than 1.1 kb of the 5'-flanking region of murine AQP-2 gene (-9.5AQP2, -6.1AQP2 and -1.1AQP2) and the AQP-2 gene, 24 h exposure to 5 micromol l(-1) dibutyryl cAMP (DBcAMP) significantly increased the Luc activity by 2.3-fold in the isotonic medium (300 mosmol kg(-1)). In the hypotonic medium (225 mosmol kg(-1)), basal activity was not altered, and the response of Luc activity to 24 h exposure to 5 micromol l(-1)DBcAMP was abolished. Similar findings were obtained in isosmotic, urea-supplemented medium (estimated tonicity, 225 mosmol kg(-1)). The response of Luc activity to 5 micromol l(-1) DBcAMP in the hypotonic medium was not affected in cells either transfected with 0.36 kb of the 5'-flanking region of AQP-2 or co-transfected with -1.1AQP2 and a dominant-negative TonE binding protein (pDNTonEBP). Pre-incubation of cells with 1 micromol l(-1) SP600125, an inhibitor of c-Jun N-terminal kinase (JNK), restored the response of Luc activity to 5 micromol l(-1) DBcAMP under hypotonic conditions. These findings may indicate that hypotonicity reduces the cAMP-induced AQP-2 promoter activity mediated via TonE by activating JNK kinase.

Pathogenesis of chronic hypernatremia with dehydrated and non-dehydrated states in hypothalamic space-occupying lesions.

The present study was undertaken to determine pathophysiology of body water control in hypernatremic subjects with hypothalamic space-occupying lesions. Eight subjects with hypothalamic space-occupying lesions were divided into two groups of hypernatremia in the presence or absence of body water deficit. In 5 dehydrated hypernatremic subjects whose ages ranged from 20 to 67 years, serum sodium (Na) levels were 156.4 +/- 3.1 mmol/l; plasma osmolality (Posm), 320.6 +/- 9.8 mmol/kg; and urinary osmolality (Uosm), 246.8 +/- 46.7 mmol/kg under ad libitum water drinking. In 3 non-dehydrated hypernatremic subjects whose ages ranged from 21 to 32 years, serum Na levels were 150.3 +/- 5.4 mmol/l; Posm, 300.3 +/- 11.6 mmol/kg; and Uosm, 738.7 +/- 237.1 mmol/kg. Serum Na levels had a positive correlation with hematocrit (Ht) in 2 of 5 subjects with dehydration, but it totally disappeared in the 3 subjects without dehydration. Plasma arginine vasopressin (AVP) levels were 0.7 +/- 0.1 pmol/l, and there was no response of AVP release to intravenous administration of 5% NaCl in the subjects with dehydration. Plasma AVP was 0.7 +/- 0.1 pmol/l, and there was the reduced response of AVP release to 5% NaCl in those without dehydration. In one of 3 subjects a positive correlation between Posm and plasma AVP levels was obtained. Drinking behavior was totally abolished in the subjects with dehydration, and partly reduced in those without dehydration. The present study indicates that hypothalamic space-occupying lesions causes central diabetes insipidus and hypodipsia, and that sporadic and paradoxical release of AVP, enhanced renal concentrating ability and reduced drinking behavior may possess body water minimally in the hypernatremic subjects without water deficit.

Association of the Glu298Asp polymorphism of the eNOS Gene with ischemic heart disease in Japanese diabetic subjects.

We analysed the association of the Glu298Asp polymorphism of the endothelial nitric oxide synthase (eNOS) gene with ischemic heart disease (IHD) and albuminuria in 337 Japanese diabetes patients. Restriction fragment length polymorphism analysis of Glu298Asp of the eNOS gene was performed by amplification of genomic DNA isolated from whole blood followed by digestion with the restriction enzyme BanII. Individuals with IHD were identified by review of medical records and were identified based on apparent ischemic change of electrocardiography, significant stenosis of coronary artery, or a history of myocardial infarction, coronary artery bypass surgery, or catheter intervention. Albuminuria was confirmed by a positive test on at least two separate examinations. Of the 337 subjects analysed for polymorphisms of the eNOS gene, 45 with the GluAsp and five with the AspAsp genotype were combined into 1 group (GluAsp or AspAsp group). Among these 50 subjects, 16 (32%) had IHD, and among 287 subjects with the GluGlu genotype, 38 (13.2%) had IHD. The number of subjects with IHD was significantly greater in the GluAsp or AspAsp group than in the GluGlu group (P=0.0006). There was no difference in the frequency of albuminuria among the genotypes. The GluAsp or AspAsp genotype of the Glu298Asp polymorphism was significantly associated with IHD, but not albuminuria in these Japanese diabetic subjects.

Clinical and laboratory features of hyponatremia-induced myopathy.

BACKGROUND: The present study was undertaken to determine the clinical and laboratory features of hyponatremia-induced myopathy. METHODS: We collected 14 hyponatremic subjects (six men and eight women) with serum creatine kinase (CK) levels of more than 500 IU/ml during the 5-year period between 2001 and 2005. The mean +/- SD patients' age was 66.5 +/- 16.7 years (range, 37 to 88 years). RESULTS: The causes of the hyponatremia were: syndrome of inappropriate secretion of antidiuretic hormone (SIADH; n = 4), mineralocorticoid-responsive hyponatremia of the elderly (MRHE; n = 2), hypopituitarism (n = 1), psychogenic polydipsia (n = 3), congestive heart failure (n = 3), and unknown cause (n = 1). The subjects were subgrouped into two groups: acute onset of myopathy and slowly progressive onset. The age at onset was 62.0 +/- 5.7 years (mean +/- SEM) in the subjects with acute onset, and 77.8 +/- 1.5 years in those with slowly progressive onset (P = 0.02). At the onset, there was no difference in serum Na levels between the acute onset and the slowly progressive onset groups, but there was a significant difference in maximal serum CK levels between the groups (7072 +/- 2317 vs 722 +/- 104 IU/ml; P = 0.02). Maximal serum CK levels were widely distributed among the ages in the subjects with acute onset, whereas maximal serum CK levels were mildly elevated in the elderly subjects with slowly progressive onset. The elevated serum CK levels were normalized at a maximum of 14 days after the onset in all the subjects. CONCLUSIONS: The present findings indicate that hyponatremia infrequently causes skeletal muscle disruption, and that there are two types of hyponatremia-induced myopathy, acute onset and slowly progressive onset.

New HLA DRB1 and DQB1 haplotypes in a pedigree of familial Graves' disease in Japan.

The present study demonstrated genetic analysis of human leukocyte antigen (HLA) in a familial Graves' disease linked to autoimmune mechanism. The proband was a 17 year-old female. At 15 years, Graves' disease was diagnosed with serum TSH was <0.015 IU/ml; free T(3), 13.6 pg/ml; free T(4), 4.51 ng/dl; and TSH receptor antibody (TRAb), 94.1%. She had two brothers (19 and 13 years-old), who manifested Graves' disease at 18 and 13 years, respectively. They also had elevated TRAb as high as 48.4 and 49.1%, respectively. There was a strong family history of Graves' disease in their maternal pedigree. Namely, their two aunts and a cousin had Graves' disease, and their onset ages of Graves' disease were also during their teen-age years. However, there was no patient with Graves' disease in the paternal pedigree. We checked HLA-DRB and -DQB haplotype in the members of maternal pedigree and proband's father. The members of maternal pedigree including both affected and unaffected Graves' disease had haplotypes of DRB1*150101 and DQB1*0602, except for the cousin who had DRB1*140301 and DQB1*030101. The haplotypes of DRB1*150101 and DQB1*0602 were different from susceptible HLA types in Japanese childhood onset Graves' disease. However, two cases of Graves' disease also had HLA types of DRB1*40501 and DQB1*0401, in addition to the haplotypes of DRB1*150101 and DQB1*0602. There was no other autoimmune disease including type 1 diabetes mellitus in their family. The present findings indicated that familial Graves' disease was found mainly in the maternal females and become overt during their teen-age years. They had new HLA haplotypes distinct from those susceptibly in Japanese Graves' patients. Further study will be necessary to analyze the mutant locus of DNA to elucidate pathogenesis of familial Graves' disease.

Comparison of once-daily glargine plus sulfonylurea with twice-daily 70/30 aspart premix in insulin-naive Japanese patients with diabetes.

BACKGROUND: Type 2 diabetes patients insufficiently controlled with sulfonylurea (SU) are commonly treated by switching to twice-daily premix insulin replacing SU. The efficacy of glargine (GL) added on to SU compared with the premix therapy has not been analyzed in Japan. METHODS: The open-label two-arm study was conducted in 30 type 2 diabetes patients poorly controlled [hemoglobin A(1c) (HbA(1c)) >7.5%] with SU with or without other oral hypoglycemic agents (OHAs). The GL group injected once-daily GL in addition to the OHAs. The aspart 70/30 (70/30) group discontinued SU among the OHAs and injected twice-daily 70/30. Patients were recommended either method in a block random method, and if twice-daily 70/30 was rejected, once-daily GL was selected only at the first time. The insulin dose was titrated to achieve a target fasting plasma glucose of <120 mg/dL and/or HbA(1c) of <7%. RESULTS: Nineteen of 20 patients treated with GL and 11 of 14 patients treated with 70/30 completed the 6-month study. Mean HbA(1c) improved from 8.45% to 7.5% in the GL group and from 9.13% to 7.93% in the 70/30 group. The mean HbA(1c) decrease during 6 months was -0.95% in the GL group and -1.20% in the 70/30 group (P = 0.49). Mean insulin doses at 6 months were 12.0 units/day for the GL group and 26.7 units/day for the 70/30 group. Both therapies were well tolerated without severe hypoglycemia. CONCLUSION: Once-daily GL injection added on to OHAs was equally safe and effective compared with twice-daily injection of aspart 70/30 premix replacing SU in type 2 patients insufficiently controlled with OHAs.

SIADH is only an atypical clinical feature in a patient with prolactinoma.

A 50-year-old man was admitted to determine the pathogenesis of hyponatremia. He had a poor appetite and was easily fatigued. Physical findings showed that he was conscious and alert. He had neither dry skin or tongue, nor pretibial edema. Laboratory data revealed that the serum sodium level was 110 mmol/l; plasma osmolality, 238 mmol/kg; and urinary osmolality, 417 mmol/kg. Plasma arginine vasopressin was 0.5 pg/ml despite plasma osmolality of 242 mmol/kg. An acute water load showed impaired water excretion, as percent excretion of water load was 30% and minimal urinary osmolality was 642 mmol/kg. Serum prolactin was 254 ng/ml, and anterior pituitary hormones of ACTH, TSH and GH were in the normal ranges. Brain magnetic resonance imaging (MRI) showed a pituitary tumor with a size of 20 x 22 x 21 mm and it pushed a pituitary stalk upward. Immunohistochemistry revealed prolactinoma. After the adenomectomy, serum sodium level has been kept normal with free access to water intake. The present study indicates that syndrome of inappropriate secretion of antidiuretic hormone (SIADH) is manifested in association with pituitary macroadenoma of prolactinoma.

Hypoadiponectinemia in patients with cerebral infarction: comparison with other atherosclerotic disorders.

The present study was undertaken to determine serum adiponectin level in patients with cerebral infarction and to further analyze any difference in serum adiponectin levels among atherosclerotic disorders. One hundred fifty-two subjects with atherosclerotic disorders were enrolled, 110 males and 42 females, with the age of 67.0 +/- 9.9 years (mean +/- SD). They were divided into 62 patients with cerebral infarction, 48 patients with ischemic heart disease, and 42 patients with arteriosclerosis obliterans. Thirty-two subjects matched by age, gender, and body mass index served as controls. Serum adiponectin levels were 7.2 +/- 0.6 microg/mL (mean +/- SE) in the patients with cerebral infarction, 7.2 +/- 0.8 microg/mL in those with ischemic heart disease, and 6.9 +/- 0.9 microg/mL in those with arteriosclerosis obliterans. They were significantly less than the level of 12.6 +/- 1.9 microg/mL in the control group (P < 0.01). However, there was no difference in serum adiponectin level among three groups of atherosclerotic disorders. In the patients with acute cerebral infarction, serum adiponectin level was temporarily reduced from 7.3 +/- 0.9 to 6.2 +/- 0.8 microg/mL 14 days after the hospitalization (P < 0.01), followed by recovery to the basal value. The present findings indicate that serum adiponectin levels are equivalently reduced in patients with atherosclerotic disorders, and that serum adiponectin is changeable under acute phase of cerebral infarction.

Elevation of serum adiponectin and CD146 levels in diabetic nephropathy.

OBJECTIVE: The present study was undertaken to measure serum levels of adiponectin and CD146, an endothelial cell injury marker, and to clarify the property of adiponectin and CD146 in patients with diabetic nephropathy. DESIGN: A total of 280 diabetic patients, and 49 control subjects were enrolled. Serum levels of adiponectin and CD146 were measured by ELISA. RESULTS: Serum adiponectin levels were relatively low in the diabetic patients as compared to the control subjects. Inversely, serum adiponectin levels were significantly greater in those with stages IV and V of diabetic nephropathy than the control subjects. Serum CD146 levels were gradually increased according to the progression of diabetic nephropathy, and that in the stages IIIb-V was significantly greater than that in the control group. Serum adiponectin positively correlated with serum creatinine and negatively correlated with 1/creatinine. Similar results were obtained with serum CD146 levels. However, there was no relationship between serum adiponectin and CD146 levels. CONCLUSION: These results indicate that serum adiponectin levels seem to reduce in the diabetic patients, and finally increase in end stage of diabetic nephropathy. In contrast, serum CD146 may closely associate with development of micro- and macrovascular complications in diabetic patients. Further study is required to elucidate the exact role of adiponectin and CD146 in the development of vascular complication in end stage of diabetic nephropathy.

Possibly simultaneous primary aldosteronism and preclinical Cushing's syndrome in a patient with double adenomas of right adrenal gland.

We reported a rare case of simultaneous primary aldosteronism and preclinical Cushing's syndrome due to unilateral double adrenocortical adenomas in a 57 year-old woman who had had hypertension for the last 10 years. Abdominal computed tomography showed double tumors in her right adrenal gland. Physical findings revealed simple obesity and hypertension, but no other abnormal findings were detected. Laboratory findings demonstrated that serum potassium was 3.8 mmol/l; plasma renin activity, 0.3 ng/ml/h; plasma aldosterone, 100 pg/ml, and aldosterone renin ratio (ARR), 33. Serum cortisol was 15.7 microg/dl. There was no circadian rhythm of serum cortisol, and no suppression of serum cortisol in response to exogenous dexamethasone administration. Right adrenalectomy was performed under laparoscopy. Two well-circumscribed tumors, whose sizes were 21 and 19 mm in greatest diameter, were detected. They were macroscopically composed of a golden-yellow portion admixed with a brown portion, which corresponded to clear cells and compact cells, respectively. Immunohistochemical staining for steroidogenic enzymes demonstrated the presence of all the enzymes involved in corticosteroidogenesis in these two adenomas, indicating that the two adenomas produced both cortisol and mineralocorticoid. Specifically, one adenoma mainly caused excessive production of cortisol as compared to the other one. These findings indicate that overproduction of both cortisol and mineralocorticoid was evident in the two adenomas of the right adrenal gland in immunohistochemical study for steroidogenic enzymes, whereas there was less clinical manifestation of primary aldosteronism and Cushing's syndrome in the present patient.

Characteristics of diabetic retinopathy in SDT rats.

BACKGROUND: We previously reported a new diabetic strain of the Sprague-Dawley rat, named the Spontaneously Diabetic Torii (SDT) rat. The purpose of the present study was to report the histologic and ultrastructural characteristics of diabetic retinopathy (DR) in a new animal model, the SDT rat. METHODS: Fifty-three eyes of 43 SDT rats of various ages (35-82 weeks) were examined, of which 33 underwent histopathologic examination, 15 eyes fluorescein-dextran microscopy, and five eyes the trypsin digestion method. RESULTS: Of the 33 eyes examined histopathologically, DR was identified in 20 eyes (61%). Large retinal folds mimicking diabetic tractional retinal detachment were observed in 20 eyes (61%). Retinal hemorrhages were seen in four eyes (12%). A neovascular fibrous membrane around the iris developed in five eyes (15%), of which two eyes had a massive anterior chamber hemorrhage. Of the 15 eyes examined by fluorescein-dextran microscopy, an area of nonperfusion and/or extensive hyperfluorescence was observed in 12 eyes (80%). Of the five eyes examined using the trypsin digestion method, acellular capillaries and pericyte loss were observed in four eyes (80%). Of the 53 eyes, the previously mentioned retinal changes of DR were observed in 36 eyes (68%). The rats with DR (49-82 weeks; mean, 60 weeks) were older than the rats without DR (35-55 weeks; mean, 40 weeks) (p < 0.001). CONCLUSION: Large retinal folds mimicking tractional retinal detachment with extensive leakage of fluorescein around the optic disk was the most prominent finding of DR in SDT rats.