The aim of the study was the assessment of the concentrations and establishment of mutual relationships between three main protease inhibitors: alpha-1-antitrypsin (AAT), alpha-2-macroglobulin (alpha-2-M) and antithrombin-III (AT-III), and of the total trypsin inhibitory capacity (TIC) in the serum of diabetic and non-diabetic children during adolescence. Forty-nine children (24 girls and 25 boys) with type 1 diabetes mellitus and 24 non-diabetic children (13 girls and 11 boys) were divided according to the Tanner scale into three groups: pre-, peri- and post-pubertal. The concentrations of AAT, alpha-2-M and AT-III were determined by the radial immunodiffusion method on NOR-Partigen plates (Dade-Behring), while TIC was determined by the method using BAPNA as substrate. Means and medians of serum AAT [1.55 g/l, 1.40 (95% confidence interval, 1.42-1.68), respectively] and TIC [10.6 mg trypsin/100 ml, 10.3 (95% CI, 9.5-11.7)] in diabetic children were lower than means and medians of AAT [1.81 g/l, 1.60 (95% CI 1.55-2.07), respectively] and TIC [12.5 mg trypsin/100 ml, 13.2 (95% CI, 10.9-14.1)] in non-diabetic children. A comparison of variables between Tanner groups shows an increasing trend of AAT concentration in diabetic children and a decreasing trend of TIC in non-diabetic subjects. In contrast to pre- and peri-puberty, no correlations were found in the postpubertal period between the studied parameters, either in diabetic or non-diabetic patients. Hyperglycaemia and the duration of diabetes were found to have a significant association with alpha-2-M and AT-III concentrations, but not with AAT serum concentrations. The concentrations and correlations between serum protease inhibitors in diabetic children during adolescence are disrupted compared with non-diabetic children. Taking into account the unfavourable consequences of vascular complications resulting from serum trypsin inhibitor changes and protease- antiprotease imbalance, diabetic children are at greater risk of this occurring during adolescence.
Background: Meconium is a series of layers formed in the foetal intestine from the 12th week of gestation. High content of meconial alpha-1-antitrypsin (AAT), decreasing within the first several days of extrauterine life appears to reflect the meconium clearance of the gut. At birth, IgA is not present in the meconium and breast-fed infants receive this antibody postnatally with human milk. The aim of the study was to determine changes in AAT concentrations, functional activity of that inhibitor expressed as trypsin inhibitory capacity (TIC) and IgA concentration in serial meconium and faeces, as endogenous biochemical markers discriminating between faeces portions formed in intrauterine and extrauterine life periods of healthy breast-fed newborns. Methods: A group of 24 healthy breast-fed newborns delivered by spontaneous labour were studied prospectively during the first 4 days of postnatal life. AAT and IgA concentrations in the newborn‘s meconial and faecal samples and IgA concentration in mother’s milk samples taken on the third day after delivery, were determined by radial immunodiffusion. TIC was assessed using BAPNA (N-benzoyl-DL-arginine-p-nitroanilide). Results: The medians (range) of AAT concentrations in milligrams per gram of dry meconium or faeces were: 68.8(29.2–138.4) (day 1), 56.9 (30.8–112.8) (day 2), 26.2 (6.8–80.7) (day 3), and 6.6 (1.4–27.1) (day 4). The medians (range) of TIC in milligrams of trypsin/g dry mass of meconium or faeces were: 0.76 (0.33–1.79) (day 1), 0.44 (0.17–1.08) (day 2), 0.16 (0.03–0.56) (day 3), and 0.03 (0–0.11) (day 4). The median (range) of IgA concentration in mothers’ milk was 715 mg/dl (420–890). IgA was absent in meconium portions from the first day of life while on the successive days the medians (range) of IgA concentration in mg/g dry mass of meconium and faeces were as follows: 0 (0–2.90) (day 2), 2.50 (1.10–9.60) (day 3), 7.05 (4.10–30.60) (day 4). On day 4 of extrauterine life a negative correlation was found between AAT and IgA concentrations in faeces of the newborns (r = –0.46) and a positive correlation was seen between IgA concentrations in faeces and milk (r = 0.93). Conclusions: Analyses of the systematic decrease in AAT and increase of IgA concentration in serial portions of meconium and faeces over the first days of extrauterine life of breast-fed newborns can date newborn’s faeces portions formed during intrauterine and extrauterine maturation. AAT deposited in foetal intestine is an active antiprotease.
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