Juan J. Corrales

Monoallelic Deletion in the 5' Gene as a Cause of Sporadic Nonendemic Simple Goiter Region of the Thyroglobulin

The cause of sporadic simple goiter is unknown in most cases. Family studies have suggested that this disorder may have a genetic component in some patients. We have previously demonstrated that some cases of endemic and nonendemic simple goiter are associated with a mutation within exon 10 of the thyroglobulin gene. Here we report a study of 50 cases diagnosed as having nonendemic simple goiter, and found 1 case with a large heterozygous deletion within the thyroglobulin gene. The deletion involves the promoter region and the 11 first exons of this gene and is associated with a euthyroid state. We hypothesize that the absence of thyroglobulin synthesis from the deleted allele may be responsible for a decreased level of thyroglobulin mRNA. Euthyroidism would be achieved by thyrotropin (TSH) stimulation but at the expense of goiter development.

N-Acetyl β-d-glucosaminidase and α-l-fucosidase activities in relation to glycosylated hemoglobin levels and to retinopathy in diabetes

Abstract N -Acetyl β- d -glucosaminidase and α- l -fucosidase were determined in human sera from 25 control subjects, in 23 diabetic patients without retinopathy and in 22 diabetic patients with retinopathy. The results show significantly higher N -acetyl β- d -glucosaminidase activity in diabetic patients independently of the development of retinopathy and also independently of the length of diabetes. No correlation was found between either serum enzymes and serum glucose concentration and glycosylated hemoglobin (HbA,).

Abnormalities in sperm acid glycosidases from infertile men with idiopathic oligoasthenoteratozoospermia

OBJECTIVE To analyze and compare acid beta-glucuronidase, alpha-mannosidase, alpha-glycosidase, alpha-galactosidase, beta-galactosidase, and beta-N-acetylglucosaminidase activities in fertile and infertile patients. DESIGN An observational, controlled, clinical study. SETTING A university tertiary hospital. PATIENT(S) Thirty-six fertile controls, 24 infertile oligoasthenoteratozoospermic (OAT) patients, and 10 azoospermic patients, who served as negative controls. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Analysis of the six glycosidase activities in seminal plasma and in solubilized spermatozoa. RESULT(S) alpha-galactosidase and beta-galactosidase activities in spermatozoa were significantly correlated with the serum levels of gonadotropins both in fertile controls and in OAT patients. The relative contribution of alpha-galactosidase and beta-galactosidase from the soluble fraction of spermatozoa to the total activity measured in the ejaculate of OAT patients was significantly lower than in fertile controls. The activities of beta-galactosidase and beta-N-acetylglucosaminidase in the soluble fraction of spermatozoa from OAT patients were significantly lower than in fertile controls. In seminal plasma, the activity of alpha-mannosidase from OAT patients was significantly higher than in fertile controls. The activity of beta-N-acetylglucosaminidase in the nonsoluble fraction of spermatozoa from OAT patients was three times higher than in fertile controls. CONCLUSION(S) The abnormalities in the distributions and contents of alpha-galactosidase, beta-galactosidase, and beta-N-acetylglucosaminidase in sperm suggest possible functional defects in spermatozoa from OAT infertile patients.

Serum glycosidases in diabetes mellitus in relation to the retinopathy and to the length of the disease

The following glycosidase activities in sera have been studied: alpha-D-mannosidase, beta-D-glucuronidase, N-acetyl-beta-D-galactosaminidase, alpha-D-galactosidase, beta-D-galactosidase, alpha-D-glucosidase, beta-D-glucosidase and beta-D-fucosidase, in diabetic patients in relation to the presence of microangiopathy, evident by retinopathy, and to the length of the disease. A significant increase of all the enzyme activities, except for alpha-D-galactosidase was found. These elevations were independent of the development of retinopathy and the duration of the diabetic process.

Persistence of androgenic effects on the production of proinflammatory cytokines by circulating antigen-presenting cells after withdrawal of testosterone treatment in aging type 2 diabetic men with partial androgen deficiency

OBJECTIVE To test the hypothesis that T treatment withdrawal could be associated with an enhancement of proinflammatory cytokine production by peripheral blood monocytes and dendritic cells. DESIGN A prospective intervention study. SETTING Tertiary university hospital. PATIENT(S) Thirteen type 2 diabetic men aged >55 years with partial androgen deficiency and eight age-matched healthy men (controls). INTERVENTION(S) Analyses were performed before and 12 months after T replacement therapy and the results compared with those obtained for the same patients after a 3-month T withdrawal period. MAIN OUTCOME MEASURE(S) Distribution of circulating T, B, and natural killer lymphocytes, monocytes, and CD33(hi) myeloid, CD16+, and plasmacytoid dendritic cell subsets. Spontaneous and stimulated ex vivo production of inflammatory cytokines (interleukin-1beta, interleukin-6, and tumor necrosis factor-alpha) by circulating monocytes and dendritic cells, which represent the most potent antigen-presenting cells. RESULT(S) The reduction or complete abrogation of spontaneous ex vivo production of proinflammatory cytokines by monocytes and dendritic cells observed after 12 months of T replacement therapy was maintained 3 months after T withdrawal. CONCLUSION(S) These are the first results showing that exogenous T treatment deprivation is not associated with an immunologic enhancement of proinflammatory cytokine production by antigen-presenting cells.

Enhanced immunological response by dendritic cells in male hypogonadism.

Eur J Clin Invest 2012; 42 (11): 1205–1212

Increased serum N-acetyl-?-d-glucosaminidase and ?-ddd-mannosidase activities in obese subjects

SummaryWe have studied N-acetyl-β-d-glucosaminidase and α-d-mannosidase activities in human sera from 35 control subjects, 47 normo- and hyperinsulinemic obese persons, and 12 diabetic patients after a fasting period of 12 h and at 30, 60, 90, and 120 min after an oral glucose overload. The results show a significantly higher activity of these 2 enzymes in obese subjects and diabetic patients, of similar magnitude, especially in those obese persons with a higher grade of obesity. Moreover, the activity of these glycosidases decreases in a similar way in all these 3 groups after the oral glucose overload.

Androgen receptor content in cytosol from non-tumoral human kidney and its relation to steroid hormone environment.

The content of cytoplasmic androgen receptors (Bmax) was analyzed in non-tumoral renal tissue of 12 men and 15 postmenopausal women using a synthetic androgen (methyltrienolone) as ligand and a method of dextran-coated charcoal. The Bmax in both sexes was compared, establishing correlations between it and circulating levels of testosterone, dehydroepiandrosterone sulfate, androstenedione, and estradiol to find out the possible influence of the hormonal environment on androgen receptors in the human kidney. No differences in Bmax were observed between males (46.3 +/- 24 fmol/g of tissue) and females (45.4 +/- 26 fmol/g), in spite of the significantly greater (p less than 0.01) levels of circulating testosterone in the former group. No significant linear correlations existed between any of the steroids analyzed and the Bmax. These results demonstrate the existence of androgenic receptors in non-tumoral human kidney and indicate that its content is not regulated by circulating levels of testosterone. The concentrations of the principal extratesticular androgens and estradiol do not seem to have a quantitative influence on these androphilic proteins either.

Prospective study of the enzymatic activities in urine of n-acetyl-β-d-glucosaminidase, α-d-mannosidase, α- and β-d-glucosidases, α-l- and β-d-fucosidases, and β-d-galactosidase in type I diabetes mellitus with early nephropathy

Different surveys have been carried out on the plasma activities of different glycosidases in patients with insulin-dependent diabetes mellitus, but research on urinary glycosidases in this disease is scanty and incomplete. To elucidate the behavior of these lysosomal enzymes in the metabolic alterations occurring in the glomerular basal membrane during the initial stages of diabetic nephropathy, we conducted a prospective study to examine the urinary activities of N-acetyl-beta-D-glucosaminidase (NAG), alpha-D-mannosidase, alpha- and beta-D-glucosidase, alpha-L- and beta-D-fucosidase, and beta-D-galactosidase in patients with type I insulin-dependent diabetes mellitus, surveyed over 18 months, whose early diabetic nephropathy was detected by the presence of microalbuminuria. The simultaneous determination of beta 2-microglobulin in urine confirmed the glomerular origin of the albuminuria. No statistically significant correlation was found between the levels of albuminuria and the activities of any of the glycosidases analyzed. In the diabetic patients, a significant decrease was observed in the activities of all the enzymes (p < 0.05), except NAG and alpha-D-mannosidase, although the decrease in the latter was very close to statistical significance (p = 0.028, unilateral; p = 0.057 bilateral). Similarly, in the patients, there was a significant negative correlation (p < 0.05) with the serum levels of fructosamine, except with beta-D-galactosidase, which showed a positive correlation (p < 0.05) with fructosamine and blood HbA1c.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical and biochemical correlates of male hypogonadism in type 2 diabetes

The origin of hypogonadism, a condition including both symptoms and biochemical criteria of androgen deficiency, in type 2 diabetes is poorly known. In a cross‐sectional study of 267 unselected patients, we analyzed the potential correlation of several clinical and biochemical variables as well as chronic micro‐ and macrovascular diabetic complications with hypogonadism. Hypogonadism was present in 46 patients (17.2%) using a cutoff of total testosterone 10.4 nmol/L and in 31 (11.6%) with a cutoff of 8 nmol/L. Among these patients, hypogonadotropic hypogonadism was the most prevalent form (82.6%). Compared to eugonadal subjects, hypogonadal men had significantly lower glomerular filtration rate (67.1 ± 23.4 vs. 78.4 ± 24.6 mL/min/1.73 m2, p = 0.005) and higher prevalence of chronic kidney disease (43.5% vs. 20.4%, p = 0.002), abnormal liver function tests (26.7% vs. 12%, p = 0.019), and psychiatric treatment (23.9% vs. 10.4%, p = 0.025). Total testosterone levels correlated inversely with age (R = −0.164, p = 0.007), fasting blood glucose (R = −0.127, p = 0.037), and triglycerides (R = −0.134, p = 0.029) and directly with glomerular filtration rate (R = 0.148, p = 0.015). Calculated free testosterone and bioavailable testosterone correlated directly with hemoglobin (R = 0.171, p = 0.015 and R = 0.234, p = 0.001, respectively). Multivariate logistic regression analysis, after adjusting for relevant confounding variables, showed that age >60 years (OR = 3.58, CI 95% = 1.48–8.69, p = 0.005), body mass index >27 kg/m2 (OR = 2.85, CI 95% = 1.14–7.11, p = 0.025), hypertriglyceridemia (OR = 2.16, CI 95% = 1.05–4.41, p = 0.035), glomerular filtration rate <60 mL/min/1.73 m2 (OR = 2.51, CI 95% = 1.19–5.29, p = 0.015), and abnormal liver function tests (OR = 3.57, CI 95% = 1.48–8.60, p = 0.005) were independently associated with male hypogonadism. Although older age, body mass index, and hypertriglyceridemia have been previously related to hypogonadism, our results describe that chronic kidney disease and abnormal liver function tests are independently correlated with hypogonadism in type 2 diabetic men.