Increased frequency of metabolic syndrome and its individual metabolic abnormalities in Japanese patients with primary gout.

BACKGROUND: Gout patients are frequently complicated with hypertension, obesity, dyslipidemia, and/or impaired glucose tolerance, which are components of the metabolic syndrome and risks for atherosclerotic diseases. OBJECTIVES: To determine the relationship between metabolic syndrome and gout, as well as plasma concentrations of adipocytokines in gout patients. SUBJECTS AND METHODS: The frequency of metabolic syndrome as well as its constituents were investigated in 258 male gout patients and 111 males who attended an annual check-up examination. In addition, plasma concentrations of adipocytokines were measured in 107 of the patients. RESULTS: Gout patients had a higher prevalence of metabolic syndrome as compared with the controls (36.4% vs. 15.3%, P < 0.0001). In addition, frequencies of individual metabolic abnormalities, such as waist circumference >85 cm, hypertension, and hypertriglyceridemia, were significantly increased in the gout patients as compared with the controls. Furthermore, uric acid over-production gout had a significantly higher prevalence of metabolic syndrome as compared with uric acid under-excretion gout (48.6% vs. 32.4%, P < 0.001). The plasma concentrations of leptin and plasminogen activator inhibitor-1 were significantly higher in the patients (P < 0.05, respectively), while that of adiponectin and the adiponectin/leptin ratio were significantly decreased in the gout patients as compared with the controls (P < 0.05, respectively). CONCLUSION: A higher prevalence of metabolic syndrome in gout patients may in part contribute to susceptibility to atherosclerotic diseases. Therefore, more attention should be paid to the presence of metabolic syndrome in gout patients to reduce their risk for cardiovascular disease complications.

Effect of TNF-alpha inhibition on urinary albumin excretion in experimental diabetic rats.

The objective is to assess the effect of TNF-alpha inhibition on urinary albumin excretion in experimental diabetic rats. Male Wistar rats, 8-week-old, were categorized into four groups, which were the control (n = 9), diabetes (n = 9), infliximab-treated diabetes (n = 10), and FR167653-treated diabetes (n = 9) groups. Diabetes was induced by intraperitoneal injection of STZ (40 mg/kg). Thereafter, infliximab was injected intraperitoneally once a month (5.5 mg/kg) and FR167653 was administered orally by mixing with the rat chow (0.08%). The effects of infliximab and FR167653 on urinary albumin excretion were observed for 12 weeks. Body weight, blood sugar, 24-h urinary TNF-alpha, and 24-h urinary albumin/creatinine ratio (Ualb/Ucr) levels were determined at 1, 4, 8, and 12 weeks after the STZ-injection. Treatment of rats with STZ caused a significant loss of body weight, as well as polyuria and hyperglycemia within 1 week, while the urinary excretions of albumin and TNF-alpha were increased. Neither infliximab nor FR167653 affected body weight or blood sugar levels, whereas both decreased urinary albumin excretion, together with a modest decrease in the urinary excretion of TNF-alpha. These results suggest a role of TNF-alpha in the pathogenesis of diabetic nephropathy and show that TNF-alpha inhibition is a potential therapeutic strategy.

Autoimmune thyroid disease (Graves' disease and hashimoto's thyroiditis) in two patients with Crohn's disease: case reports and literature review.

An increased prevalence of the association between autoimmune thyroid diseases and ulcerative colitis has been suggested, however, not with Crohn's disease, as only 7 cases of thyroid disease coexisting with Crohn's disease have been reported. Herein, we describe 2 patients with Crohn's disease complicated with Graves' disease or autoimmune thyroiditis, and also review other cases with those complications. Some immunological processes are suggested to be implicated in the pathogenesis of this association, however, the exact mechanism remains unclear.

Effect of beer on the plasma concentrations of uridine and purine bases.

We conducted the present study to determine whether beer, both with and without ethanol content, increases the plasma concentration and urinary excretion of purine bases and uridine. Because 10 mL of regular beer (with ethanol) was found to contain 0.34 g of freeze-dried beer (without ethanol) and 0.5 mg of uridine, 5 healthy males were given regular beer (10 mL/kg of body weight) and freeze-dried beer (0.34 g/kg of body weight) or uridine (0.5 mg/kg of body weight). The plasma concentrations of hypoxanthine, xanthine, and uridine increased by 3.5-fold (P <.05), 4.7-fold (P <.05), and 1.8-fold (P <.05), respectively, 30 minutes after regular beer ingestion, and the urinary excretion of hypoxanthine, xanthine, and uridine increased by 4.0-fold (P <.05), 4.5-fold (P <.01), and 1.7-fold (P <.05), respectively, when measured 1 hour after ingestion. The plasma concentrations of uric acid and total purine bases increased by 6.5% (P <.05) and 7.6% (P <.05), respectively, 30 minutes after regular beer ingestion, whereas the urinary excretion of uric acid did not increase, while that of total purine bases increased by 1.3-fold (P <.05) when measured 1 hour after ingestion. As for freeze-dried beer, the plasma concentrations of uric acid total purine bases increased by 4.4% (P <.05) and 4.6% (P <.05), respectively, and that of uridine by 1.5-fold (P <.01) 30 minutes after ingestion, while the urinary excretion of uridine increased by 1.4-fold (P <.01) 1 hour after ingestion. However, the plasma concentrations and urinary excretion of hypoxanthine and xanthine and the urinary excretion of uric acid and total purine bases did not change significantly. As for uridine ingestion, the plasma concentration of uridine increased by 1.37-fold (P <.01) 30 minutes after ingestion, and the urinary excretion of uridine increased by 1.3-fold (P <.01) 1 hour after ingestion. However, the plasma concentrations and urinary excretion of hypoxanthine, xanthine, uric acid, and total purine bases did not change significantly. These results suggest that the purines in beer played a major role in the increase in the plasma concentration of uric acid, while both uridine and ethanol in beer had a significant effect on the increase in plasma concentration of uridine.

Oxidized low-density lipoprotein autoantibodies in patients with primary gout: effect of urate-lowering therapy.

BACKGROUND: Uric acid is a strong scavenger of reactive oxygen species, which are known to contribute to the development of atherosclerosis, while the incidence of atherosclerotic diseases is rather high in patients with gout. Among the established risk factors for atherosclerosis, oxidized LDL is believed to play a major role in its development and progression. Allopurinol and its active metabolite, oxypurinol, have been suggested to possess an antioxidant ability to scavenge the hydroxyl radical. Therefore, allopurinol may be beneficial in the prevention of LDL oxidation, as well as in the treatment of hyperuricemia. The objective of this work was to determine the degree of LDL oxidation in gout and the effect of allopurinol on LDL oxidation. METHODS: Age-matched male patients with primary intercritical gout and healthy male adults were included in the study. The serum concentrations of oxidized LDL autoantibodies and total antioxidant status were measured using an enzyme immunoassay. RESULTS: Serum concentrations of oxidized LDL autoantibodies were significantly higher in patients with gout than the control subjects (p < 0.05) and were significantly decreased after allopurinol treatment (p < 0.05), but not by benzbromarone treatment, in spite of the similar concentrations of uric acid and total antioxidant status in serum following their separate administration. CONCLUSIONS: Although the exact mechanism remains unclear, increased serum concentrations of oxidized LDL may play a role in the high incidence of coronary artery disease in gout. In addition, allopurinol may be more preferable to benzbromarone for treatment of gout in light of its inhibitory action toward LDL oxidation.

Compound heterozygous mutation of aquaporin 2 gene in woman patient with congenital nephrogenic diabetes insipidus.

We performed mutational analyses of a woman patient with congenital nephrogenic diabetes insipidus referred to us during pregnancy. The diagnosis was made during the neonatal period, after which she was treated with spironolactone and hydrochlorothiazide. Our examination showed the patient to be apparently in good health without definite evidence of dehydration. Serum and urine osmolality were 220 mOsm/L and 50 mOsm/L, respectively, and the serum concentration of AVP was 2.7 pg/mL. Results of a water-deprivation test performed after delivery were compatible with nephrogenic diabetes insipidus. Mutational analyses showed that the patient was a compound heterozygote with point mutations at nucleotide position 298 (G to A; G100R) in exon 1 and nucleotide position 374 (C to T; T125M) in exon 2 of the aquaporin 2 gene, which have been previously described.

Insulin autoimmune syndrome in a patient with ANCA-associated glomerulonephritis.

The patient, a 66-year-old woman, who has been under hemodialysis due to antineutrophil cytoplasm autoantibody (ANCA)-associated glomerulonephritis since 2003, was hospitalized because of cold sweating, general fatigue, and somnolence. Hypoglycemia (43 mg/dL) with markedly elevated insulin level (1410 µU/mL) and insulin antibody was found in her serum. She was diagnosed as having insulin autoimmune syndrome. She has not taken any medication that might cause insulin autoimmune syndrome. The possible association of ANCA-associated glomerulonephritis with insulin autoimmune syndrome is discussed.

Coexistent B-cell lymphoma and cutaneous T-cell lymphoma.

A 78-year-old man with a history of mycosis fungoides was referred for evaluation of a right adrenal mass. A physical examination showed the left cervical lymph node to be palpable, which was later shown to be caused by a diffuse large B-cell lymphoma. The patient was diagnosed with concurrent mycosis fungoides and a diffuse large B-cell lymphoma. Three courses of chemotherapy were performed, however, the patient died of advanced disease. Autopsy findings showed that the right adrenal and soft tissue masses had an identical B-cell origin. Although the exact mechanism remains unclear, the pathogenesis of this rare association is discussed.

Effect of octreotide acetate on the plasma concentration and urinary excretion of uridine and purine bases.

To determine the effect of octreotide acetate on urinary excretion of uric acid and plasma concentration of uridine, we subcutaneously administered octreotide acetate (1 microg/kg of body weight) to 5 healthy subjects. Ninety minutes after administration, octreotide acetate increased the plasma concentration of uridine by 15% and decreased the plasma concentration of glucagon by 24% and that of insulin to below the detection limits. In addition, octreotide acetate decreased the urinary excretion of uric acid, sodium, and chloride by 60%, 40%, and 38%, respectively, at 1 hour after administration. However, octreotide acetate did not affect the concentrations of hypoxanthine, xanthine, uric acid, cyclic AMP in plasma, lactic acid and pyruvic acid in blood, urinary excretion of hypoxanthine and xanthine, or creatinine clearance. From these results, we speculated that octreotide acetate decreases the urinary excretion of uric acid by decreasing the concentration of glucagon and/or urinary excretion of sodium, and increases the plasma concentration of uridine via decreased concentrations of glucagon and insulin.