Extracellular matrix metalloproteinases inducer gene polymorphism and reduced serum matrix metalloprotease-2 activity in preeclampsia patients.

Preeclampsia increases the risk of pregnancy-related complications, nevertheless a successful spiral vessel remodeling, and trophoblast invasion reduces disorders of pregnancy. Matrix metalloproteinase-2 (MMP-2) clears the path for trophoblast invasion, and activation of MMP-2 largely depends on extracellular matrix metalloproteinases inducer (EMMPRIN) protein. This study aimed to investigate EMMPRIN gene polymorphism and MMP-2 activity in preeclampsia patients. Archival whole blood and serum samples of 74 preeclampsia and 66 normotensive pregnant women age-matched were used in this case-control study. Genomic DNA was extracted from the whole blood samples and EMMPRIN gene amplified with specific primers following fragments sequence mutation analysis. Serum MMP-2 activity was determined using enzyme-linked immunosorbent assay (ELISA) and socio-demographic data of participants retrieved from the database. Age of preeclampsia patients (32.78 ± 6.39) years and body mass index (BMI) (33.09 ± 7.27) kg/m2 compared with the normotensive counterparts (32.33 ± 5.56) years and (32.33 ± 5.56) kg/m2,respectively, were not statistically significant (P > 0.05). Serum matrix metalloprotease-2 (MMP-2) activity was significantly reduced in preeclampsia group (16.34 ± 7.07) compared with the normotensives (25.63 ± 4.56) (P < 0.001), and rs424243T/G variant (55.6%) was overrepresented among the cases compared with the normotensives (16.7%). The single-nucleotide polymorphism T/G was found to be associated with preeclampsia (odds ratio [OR] = 7.63; 95% confidence interval [CI] = 3.95-14.75; P < 0.0001). Decreased activity of MMP-2 and rs424243T/G SNP of EMMPRIN gene was reported in preeclampsia. These preliminary data warrant a further investigation into the relationship between EMMPRIN gene polymorphism and MMP-2 activity in preeclampsia.

Refractoriness to inhaled mannitol 3 hours after allergen challenge.

BACKGROUND: A positive response to indirect airway challenges (eg, mannitol) that cause release of mast cell mediators causes refractoriness to a repeat exposure to the same or different indirect stimulus that lasts for at least several hours. Allergen challenge causes increased response to methacholine measured at 3 hours. OBJECTIVE: To compare allergen-induced changes in airway response to methacholine and mannitol 3 hours after completion of an allergen challenge. METHODS: Ten atopic patients with asthma completed a randomized clinical trial. The provocation concentration of methacholine causing a 20% decrease in forced expiratory volume in 1 second (FEV1) was measured 24 hours before and 3 hours after a standard allergen challenge. The provocation dose of mannitol causing a 15% decrease in FEV1 was also measured 24 hours before and 3 hours after allergen challenge. The allergen challenges were separated by 7 to 14 days. RESULTS: The allergen-induced early responses, expressed as the maximum (SD) percent decrease in FEV1, were 29.7% (11.1%) and 27.8% (7.6%) on the methacholine and mannitol days, respectively. Airway response to methacholine increased significantly after allergen challenge (P = .02). By contrast, the airway response to mannitol was reduced by almost a doubling dose (P = .02) after allergen. CONCLUSION: Three hours after allergen challenge at a time when the airways are more responsive to methacholine, there is a significant refractoriness to the indirect stimulus mannitol. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01699594.