-
Rene Baudrand,
Carmen Campino,
Cristian A Carvajal,
Oliviero Olivieri,
Giancesare Guidi,
Giovanni Faccini,
Javiera Sateler, Javiera Cornejo,
Betty San Martin,
Jose M Dominguez,
Jaime Cerda,
Lorena M Mosso,
Gareth I Owen,
Alexis M Kalergis,
Carlos E Fardella
[show abstract]
[hide abstract]
ABSTRACT: Metabolic syndrome (MetS) may have increased cortisol (F) production caused by 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) in liver and adipose tissue and/or by HPA axis dysregulation. F is then mainly metabolized by liver reductases into inactive tetrahydrometabolites (THMs). We measured THM levels in patients with or without MetS and evaluate the correlation between THMs and anthropometric and biochemical parameters. We recruited 221 subjects, of whom 130 had MetS by ATP III. We evaluated F, cortisone (E), adipokines, glucose, insulin and lipid profiles as well as urinary (24h) F, E and THM levels. β Cell function was estimated by the HOMA Calculator. We observed that patients with MetS showed higher levels of THMs, HOMA-IR and leptin and lower levels of adiponectin and HOMA-β but no differences in F and E in plasma or urine. THM was associated with weight (r = +0.44, p<0.001), waist circumference (r = +0.38, p<0.01), glycemia (r = +0.37, p<0.01), and triglycerides (r = +0.18, p=0.06) and negatively correlated with adiponectin (r = -0.36, p<0.001), HOMA-β (r = -0.21, p<0.001) and HDL (r = -0.29, p<0.01). In a logistic regression model, THM levels were associated with hypertension, hyperglycemia and dyslipidemia. We conclude that MetS is associated with increased urinary THMs but not with F and E levels in plasma or urine. Increased levels of THM, reflecting the daily cortisol production subsequently metabolized, are correlated with hypoadiponectinemia, hypertension, dyslipidemia, insulin resistance and β cell dysfunction. A subtle increased in glucocorticoid production may further account for the phenotypic and biochemical similarities observed in central obesity and Cushing's syndrome.
Steroids 12/2011; 76(14):1575-81. · 2.83 Impact Factor
-
Carmen Campino,
Cristian A Carvajal, Javiera Cornejo,
Betty San Martín,
Oliviero Olivieri,
Giancesare Guidi,
Giovanni Faccini,
Francesco Pasini,
Javiera Sateler,
Rene Baudrand,
Lorena Mosso,
Gareth I Owen,
Alexis M Kalergis,
Oslando Padilla,
Carlos E Fardella
[show abstract]
[hide abstract]
ABSTRACT: Cortisol availability is modulated by several enzymes: 11β-HSD2, which transforms cortisol (F) to cortisone (E) and 11β-HSD1 which predominantly converts inactive E to active F. Additionally, the A-ring reductases (5α- and 5β-reductase) inactivate cortisol (together with 3α-HSD) to tetrahydrometabolites: 5αTHF, 5βTHF, and THE. The aim was to assess 11β-HSD2, 11β-HSD1, and 5β-reductase activity in hypertensive patients. Free urinary F, E, THF, and THE were measured by HPLC-MS/MS in 102 essential hypertensive patients and 18 normotensive controls. 11β-HSD2 enzyme activity was estimated by the F/E ratio, the activity of 11β-HSD1 in compare to 11β-HSD2 was inferred by the (5αTHF + 5βTHF)/THE ratio and 5β-reductase activity assessed using the E/THE ratio. Activity was considered altered when respective ratios exceeded the maximum value observed in the normotensive controls. A 15.7% of patients presented high F/E ratio suggesting a deficit of 11β-HSD2 activity. Of the remaining 86 hypertensive patients, two possessed high (5αTHF + 5βTHF)/THE ratios and 12.8% had high E/THE ratios. We observed a high percentage of alterations in cortisol metabolism at pre-receptor level in hypertensive patients, previously misclassified as essential. 11β-HSD2 and 5β-reductase decreased activity and imbalance of 11β-HSDs should be considered in the future management of hypertensive patients.
Endocrine 10/2009; 37(1):106-14. · 1.42 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The aim of this research was to identify the presence of integrons among Escherichia coli strains isolated from poultry and swine and to characterize the topological association of these integrons with resistance genes and assess their potential ability to transfer these elements by conjugation. One hundred and seventy-two strains of E. coli were isolated. Their resistance to tetracycline, streptomycin, sulfamethoxazole-trimethoprim, ciprofloxacin, and enrofloxacin was studied by plate dilution. In resistant strains the presence of integrons and resistance genes was assessed by PCR. In the variable region, genes aadA1, dfrA1, and qnr were analyzed. Also, presence of tetA, tetB, and sul1 was assessed. Transference of these genes and integrons in vitro was evaluated by conjugation assays, using E. coli J53 Az(r) as recipient strain. Seventy-eight percent and 83% of the poultry and swine strains, respectively, were resistant to at least one of the studied antimicrobials. Of the isolated strains 91 presented integrons. Resistance genes detected within the integrons were aadA1, dfrA1, and sat1. Gene qnr was not detected. Genes tet and sul1 were identified in 105 and 53 strains, respectively. Seven strains transferred their resistance determinants by conjugation. The results verify the high percentage of antibiotic resistance in the E. coli strains isolated, and these represent a reservoir of resistance genes and integrons.
Microbial drug resistance (Larchmont, N.Y.) 01/2009; 14(4):265-72. · 1.99 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The aim of this study was to characterize the antibiotic resistance profiles, the integron-associated resistance determinants, and the potential ability of transferring these determinants by conjugation in Salmonella enterica isolated from swine. Fifty-four strains of Salmonella spp. were isolated from healthy swine. The percentages of resistance, determined by the plate dilution method were as follows: oxytetracycline (41%), streptomycin (39%), sulphamethoxazol+trimethoprim (19%), enrofloxacin-ciprofloxacin (13%), and amoxicillin (0%). The most important resistance serovars were Salmonella Branderburg, Salmonella Derby, Salmonella Typhimurium, and Salmonella Heidelberg. The oxytetracycline-resistant strains amplified the genes tetA (36%), tetB (64%); and the strains resistant to streptomycin and trimethoprim amplified the genes aadA1 (100%) and dfrA1 (100%), respectively. None of the fluoroquinolone-resistant strains amplified the gene qnr. Ten strains amplified the class 1 integron harboring the cassette aadA1. Six strains amplified the class 2 integron harboring the cassettes dfrA1, sat1, and aadA1. The conjugation assays showed that 2 strains transferred the tetA and aadA1 genes and the class 1 integron to a recipient strain. Taken together, the results obtained in this study show a high percentage of resistance in and the presence of integrons in strains of S. enterica isolated from swine. This information should support the implementation of regulations for the prudent use of antimicrobial agents in food-producing animals.
Canadian Journal of Microbiology 07/2008; 54(7):569-76. · 1.36 Impact Factor
