Obesity can influence children’s and adolescents’ airway hyperresponsiveness differently

BACKGROUND: Literature is still arguing about a possible relationship between airway hyperresponsiveness (AHR) and body mass index (BMI). This study aimed at evaluating the influence of BMI on AHR and pulmonary function in children and adolescents that performed a methacholine test for suggestive asthma symptoms. METHODS: 799 consecutive children/adolescents (535 M; mean age: 15 ± 3 yrs; median FEV(1)% predicted: 101.94% [93.46-111.95] and FEV(1)/FVC predicted: 91.07 [86.17-95.38]), were considered and divided into underweight, normal, overweight and obese. Different AHR levels were considered as moderate/severe (PD(20) ≤ 400 μg) and borderline (PD(20) > 400 μg). RESULTS: 536 children/adolescents resulted hyperreactive with a median PD(20) of 366 μg [IQR:168–1010.5]; 317 patients were affected by moderate/severe AHR, whereas 219 showed borderline hyperresponsiveness. Obese subjects aged > 13 years showed a lower (p = 0.026) median PD(20) (187μg [IQR:110–519]) compared to overweight (377 μg [IQR:204–774]) and normal-weight individuals’ values (370.5 μg [IQR:189–877]). On the contrary, median PD(20) observed in obese children aged ≤ 13 years (761 μg [IQR:731–1212]) was higher (p = 0.052) compared to normal-weight children’s PD20 (193 μg [IQR:81–542]) and to obese adolescents’ values (aged > 13 years) (p = 0.019). Obesity was a significant AHR risk factor (OR:2.853[1.037-7.855]; p = 0.042) in moderate/severe AHR adolescents. Females showed a higher AHR risk (OR:1.696[1.046-2.751] p = 0.032) compared to males. A significant relationship was found between BMI and functional parameters (FEV(1), FVC, FEV(1)/FVC) only in hyperreactive females. CONCLUSIONS: Obesity seems to influence AHR negatively in female but not in male adolescents and children. In fact, AHR is higher in obese teenagers, in particular in those with moderate/severe hyperresponsiveness, and may be mediated by obesity-associated changes in baseline lung function

Interaction of glutathione transferase from horse erythrocytes with 7-chloro-4-nitrobenzo-2-oxa-1,3-diazole

7-Chloro-4-nitrobenzo-2-oxa-1,3-diazole reacts with two thiol groups of the dimeric horse erythrocyte glutathione transferase at pH 5.0, with strong inactivation reversible on dithiothreitol treatment. The inactivation kinetic follows a biphasic pattern, similar to that caused by other thiol reagents as recently reported. Both S-methylglutathione and 1-chloro-2,4-dinitrobenzene protect the enzyme from inactivation. Analysis of the reactive SH group-containing peptide gives the sequence Ala-Ser-Cys-Leu-Tyr, identical with that of the peptide that contains the reactive cysteine 47 of the human placental transferase. In the presence of glutathione, the enzyme is not inactivated by this reagent, but it catalyzes its conjugation to glutathione. At higher pH values, 7-chloro-4-nitrobenzo-2-oxa-1,3-diazole reacts with 2 tyrosines/dimer and lysines, as well as with cysteines. Reaction with lysine seems essentially without effect on activity; whether the reactive tyrosines are important for activity could not be determined using this reagent only. However, 2 tyrosines among the 4 that are nitrated by tetranitro-methane are important for activity

Treatment of doxorubicin resistant MCF7/Dx cells with nitric oxide causes histone glutathionylation and reversal of drug resistance.

Acquired drug resistance was found to be suppressed in the doxorubicin-resistant breast cancer cell line MCF7/Dx after pre-treatment with GSNO (nitrosoglutathione). The effect was accompanied by enhanced protein glutathionylation and accumulation of doxorubicin in the nucleus. Among the glutathionylated proteins, we identified three members of the histone family; this is, to our knowledge, the first time that histone glutathionylation has been reported. Formation of the potential NO donor dinitrosyl–diglutathionyl–iron complex, bound to GSTP1-1 (glutathione transferase P1-1), was observed in both MCF7/Dx cells and drug-sensitive MCF7 cells to a similar extent. In contrast, histone glutathionylation was found to be markedly increased in the resistant MCF7/Dx cells, which also showed a 14-fold higher amount of GSTP1-1 and increased glutathione concentration compared with MCF7 cells. These results suggest that the increased cytotoxic effect of combined doxorubicin and GSNO treatment involves the glutathionylation of histones through a mechanism that requires high glutathione levels and increased expression of GSTP1-1. Owing to the critical role of histones in the regulation of gene expression, the implication of this finding may go beyond the phenomenon of doxorubicin resistance