Matrix metalloproteinases in ureteropelvic junction obstruction.

BACKGROUND: Management of ureteropelvic junction obstruction (UPJO) remains controversial. The aim of the present study was to measure the levels of matrix metalloproteinases (MMPs) in UPJO patients who were planned to undergo surgery and thus clarify if MMPs levels could serve as potential biomarkers of surgical obstruction in UPJO. METHODS: Serum samples of infants with UPJO diagnosis were compared to serum samples of healthy age-matched controls. MMP2 and MMP9 were quantified using enzyme-linked immunosorbent assay (ELISA). RESULTS: A total of 17 infants with UPJO diagnosis, and median age 1.5 months, were prospectively recruited. MMP9 levels were significantly decreased in the serum samples of UPJO infants compared to controls (p =0.037). Also MMP2 values were higher in UPJO infants compared to controls, but the difference was not statistically significant (p =0.206). CONCLUSIONS: This study found decreased concentrations of MMP9 in infants with obstructive hydronephrosis. However, the results should be tested in larger population samples and even be evaluated simultaneously with urine samples in order to delineate the ability of MMPs to serve as obstruction biomarkers. HIPPOKRATIA 2017, 21(3): 136-139.

Two different corticosteroid-binding globulin variants that lack cortisol-binding activity in a greek woman.

BACKGROUND: Corticosteroid-binding globulin (CBG), encoded by SERPINA6, is the principal plasma binding protein for cortisol. Most nonsynonymous single-nucleotide polymorphisms that alter the production or function of CBG occur rarely, and their clinical significance remains obscure. METHODS: Serum and DNA were obtained from a Greek woman with low morning cortisol levels and from family members. SERPINA6 exons were sequenced, and serum CBG was measured by ELISA and cortisol-binding capacity assay. Recombinant CBG variants were produced for detailed functional studies. RESULTS: A novel heterozygous c.1282G>C transversion in exon 5 of SERPINA6, resulting in a p.Trp393Ser (W371S) substitution, was identified in the proband, who was also heterozygous for single-nucleotide polymorphisms encoding the CBG Lyon (D367N) and CBG A224S variants. The proband had no measurable plasma cortisol-binding activity despite a CBG level of 273 nm by ELISA. She inherited CBG W371S from her mother whose plasma cortisol-binding capacity was approximately 50% lower than the CBG measurements by ELISA (314 nm). The proband's father and four children were heterozygous for CBG D367N; their CBG levels by ELISA were normal, but corresponding cortisol-binding capacity measurements were 50% lower. Pedigree analysis revealed that W371S segregates with A224 and that D367N and W371S segregate separately. Recombinant CBG D367N and CBG W371S had no measureable cortisol-binding activity. CONCLUSION: A new CBG Athens (W371S) variant that lacks cortisol-binding activity has been identified in a carrier of the cortisol-binding deficient CBG Lyon (D367N) variant. Analyses of CBG levels in this pedigree illustrate how immunoassays fail to accurately reflect cortisol-binding activity.