Increase in Serum MMP-9 and TIMP-1 Concentrations during Alcohol Intoxication in Adolescents-A Preliminary Study.

Background: Alcohol consumption by adolescents is responsible for a number of adverse health and social outcomes. Despite the well-established effect of alcohol use on the development of alcoholic liver disease, the relationship between the pattern of alcohol consumption and liver fibrosis is still unclear. This study is a follow-up to work on liver damage from alcohol intoxication. The aim of our study was to explore the early effects of alcohol intoxication on liver fibrosis in adolescents. Methods: The prospective study included 57 adolescents aged 14−17 years admitted to the emergency department (ED) from February 2017 to June 2018 due to acute alcohol intoxication. Serum levels of amino terminal propeptide of type III procollagen (PIIINP), type IV collagen, matrix metallopeptidase 9 (MMP-9) and tissue inhibitor of metalloproteinase 1 (TIMP-1) were determined by enzyme-linked immunosorbent assays. Results: There were significant differences in MMP-9 (p = 0.02) and TIMP-1 (p = 0.007) levels between the study and control groups. Liver parameters and selected markers of fibrosis were similar in groups in terms of blood alcohol concentrations (BAC). MMP-9 was positively correlated with alanine aminotransferase (ALT) (r = 0.38; p = 0.004) and total bilirubin (r = 0.39; p = 0.004). Positive significant correlations were also found between TIMP-1 and ALT (r = 0.47; p < 0.001), AST (r = 0.29; p = 0.03) and total bilirubin (r = 0.32; p = 0.02). In receiver operating characteristic (ROC) analysis, MMP-9 (AUC = 0.67, p = 0.02) and TIMP-1 (AUC = 0.69, p = 0.003) allowed for the differentiation of patients with and without alcohol intoxication. Conclusion: Our results show that even a single episode of alcohol intoxication in adolescents can lead to imbalance in markers of fibrosis.

Total Keratin-18 (M65) as a Potential, Early, Non-Invasive Biomarker of Hepatocyte Injury in Alcohol Intoxicated Adolescents-A Preliminary Study.

BACKGROUND: Underage drinking is associated with health risk behaviors. Serum keratin-18 (CK18) levels are increased in liver diseases and may be biomarkers of outcome. The purpose of this study was to determine if the total CK18 (M65) or caspase-cleaved CK18 (M30) levels were different in adolescents admitted to hospital because of alcohol intoxication and controls with excluded liver diseases. METHODS: A prospective study included 57 adolescents after alcohol use and 23 control subjects. The concentrations of M30 and M65 in the serum samples were evaluated using an enzyme-linked immunosorbent assay. RESULTS: The median age was 15 (14-17) years and 49% were male. There were significant differences in M65 levels between the study and control groups (p = 0.03). The concentrations of M30 and M65 were insignificant in adolescents divided into subgroups according to blood alcohol concentrations (BAC). Significant positive correlations were found between BAC and M65 levels (p = 0.038; r = 0.3). In receiver operating characteristic (ROC) analysis M65 (cut-off = 125.966 IU/l, Se = 70.2%, Sp = 43.5%) allowed to differentiate between patients with and without alcohol intoxication (AUC = 0.66, p = 0.03). CONCLUSION: M65 appears to be a promising non-invasive biomarker of hepatocyte injury during alcohol intoxication in adolescents. Moreover, a higher concentration of M65 may indicate early organ injury before the increase in the activity of liver enzymes, alanine aminotransferase (ALT) and aspartate aminotransferase (AST).

Correlation of Salusin Beta with hs-CRP and ADMA in Hypertensive Children and Adolescents.

PURPOSE: The emerging evidence has recently shown an evident dependence between recently identified salusin peptides and atherosclerosis, and their important roles as endogenous modulators of atherogenesis. It was reported that the development of atherosclerosis could also be affected by endogenous salusin- ß overproduction in vascular lesions. MATERIALS/METHODS: This prospective cohort study was conducted in two groups of children: HT - 58 patients with essential hypertension (HT); R - 30 participants with white-coat HT (R). We analysed the relationship between serum salusin- α and salusin- ß levels and ADMA, SDMA and hs- CRP in children and adolescents with essential hypertension. RESULTS: Serum level of salusin- ɑ in each sample was under the sensitivity of method. Serum level of salusin-ß was statistically significantly higher in hypertension group when compared to the reference group (p<0.05) and correlated positively with serum hs-CRP [rho=0.47; p<0.01] and asymmetric dimethylarginine (ADMA) [rho=0.32; p<0.05]. There was no significant association between salusin-ß and symmetric dimethylarginine (SDMA) [rho=0.27; p>0.05]. CONCLUSION: This preliminary study showed that the concentration of salusin-ß is associated with circulating level of hs-CRP and ADMA in teenagers with hypertension. Further studies are needed to find out if salusin-ß levels may indicate for endothelial dysfunction and form the basis for the development of new therapeutic agent.

Serum Exoglycosidases in Children and Adolescents With Harmful Alcohol Use.

OBJECTIVE: There is a lack of accurate alcohol-use biomarkers in children/adolescents due to a short drinking duration/rapid normalization of elevated markers. We checked if lysosomal exoglycosidases, elevated earlier in binge-drinking young adults, can be applicable in children/adolescents as markers of harmful alcohol use. METHODS: The serum activities (pKat/mL) of α-fucosidase (FUC), ß-galactosidase (GAL), ß-glucuronidase (GLU), ß-hexosaminidase (HEX; its HEX A and HEX B isoenzymes), and α-mannosidase (MAN) were determined in 20 healthy controls (C) and 25 children/adolescents with harmful alcohol use (intoxicated by alcohol at hospital admission -AI1 and on the next day -AI2). RESULTS: The serum HEX A and alanine aminotransferase (ALT) activity was significantly higher in the AI1 group than in the control. The activities of FUC, GAL, GLU, HEX B, and MAN were lower in the AI group. We found fair and poor accuracy, respectively, for increased enzymes HEX A and ALT. We found fair accuracy for decreased HEX B (AI1) and MAN (AI1), good accuracy for GLU (AI2), FUC (AI2), GAL (AI1, AI2), MAN (AI2), and excellent for FUC (AI1). Correlations were found: ALT with C-reactive protein (CRP), HEX A with white blood cell (WBC) count, blood alcohol concentration with FUC, MAN and HEX B, and WBC with FUC. CONCLUSIONS: Decreased FUC, GLU, GAL, MAN values, and especially FUC (AI1) have the potential to be markers of harmful alcohol use in children/adolescents. The raised activity of HEX A and ALT points to the need for further research to check another inflammatory agent as potential alcohol marker in children and adolescents. Samples need to be collected before intravenous fluid therapy.

Salusins in Hypertension and Related Cardiovascular Diseases.

The salusins are bioactive peptides with hemodynamic effects. They play a role in hypertension, atherogenesis and cardiovascular diseases. In this review we focus on new actions, which are related to the regulation of blood pressure. Decrease in salusin-̛ and the increase in salusin-̜ concentrations are known to contribute to the development of the metabolic syndrome and atherosclerosis. Microinjections of salusin-̜. in the paraventricular nucleus (PVN) increases the plasma argininevasopressin (AVP) and norepinephrine levels, which contribute to hypertension. It also increases the AVP release from the rostral ventrolateral medulla (RVLM) via the projection from PVN to RVLM. Increased activity of the RVLM neurons is transmitted to the intermediolateral nucleus (IML) cell column of the spinal cord, where peripheral sympathetic nerves to the heart, arterioles and kidneys are activated, thus increasing blood pressure. Microinjection of salusin-̜ into the RVLM increased renal sympathetic nerve activity, median arterial pressure (MAP) and heart rate (HR). There was no significant effect on the AVP level in the RVLM and plasma. Microinjection of salusin-̜. in the nucleus tractus solitarii (NTS) produces a dose dependent hypotension and bradycardia. Intravenous injection of salusin-̜. significant increased MAP, but did not have a meaningful outcome on HR. Nevertheless, intravenous injection of a very high dose of salusin-̜. caused instantaneous decrease in both MAP and HR. Salusin-̜. overexpression provoked severe and prolonged hypertension accompanied by tachycardia in rats. It is clear that more research needs to be done to evaluate the function of salusin-̜ in the mechanism of essential hypertension, atherosclerosis, and the metabolic syndrome.

Is the serum level of salusin-ß associated with hypertension and atherosclerosis in the pediatric population?

BACKGROUND: Salusins are recently identified endogenous bioactive peptides that have hypotensive and bradycardiac effects. Salusin-ß is involved in the pathogenesis of human atherosclerosis. METHODS: This was a prospective cohort study of a young patient population with hypertension (HTN). Based on ambulatory blood pressure monitoring (ABPM), the adolescents were categorized into two groups, namely, a hypertensive group consisting of patients with essential (primary) HTN (HTN group) and a group consisting of patients with white-coat HTN [reference (R) group]. Correlations between serum salusin-ß level and clinical, laboratory and ambulatory blood pressure (BP) variables were assessed. RESULTS: The median salusin-ß concentration was significantly higher in patients with essential HTN than in those with white-coat HTN (R group). Salusin-ß was positively correlated with the body mass index Z-score, systolic and diastolic blood pressure (BP) from three independent measurements, mean systolic BP during the daytime, triglyceride (TG) level, and atherogenic index (TG/high-density lipoprotein-cholesterol ratio). CONCLUSIONS: The results of this preliminary study suggest that salusin-ß may play an important role in the pathogenesis of HTN in a young population. Further research should focus on the role of salusin-ß in the mechanism of essential HTN and the assessment of possible correlations between salusin-ß and other well-known markers of atherosclerosis in both teenagers and adults. This research should serve as a base for future studies in this field.

Epidemiological study of acute poisoning in children: a 5-year retrospective study in the Paediatric University Hospital in Bialystok, Poland.

BACKGROUND: Poisoning among children and youths in the northeastern part of Poland accounted for 25% of the total number of patients admitted to the Hospital Emergency Department of the Paediatric University Hospital of Bialystok. We hypothesise that the epidemiology of poisoned paediatric patients admitted is related to increase in 'designer drugs' (mainly amphetamine- and ecstasy-like psychostimulants, hallucinogens and synthetic cannabinoids ('spice') intake, which became popular 5 years ago in our country. METHODS: A retrospective chart review of medical records of 489 patients admitted due to poisoning in the 5-year period (2006-2010). The data included: age, sex, place of residence, nature of the substance, causes of poisoning, former use of psychoactive stimulants, accompanying self-mutilation and injuries and length of hospitalisation. Categorical variables were expressed as percentages, and continuous variables as mean and SD. The data were collected in a Microsoft Excel database. Statistical analysis was performed using the Statistical Programme for Social Sciences. RESULTS: Out of 2176 hospitalised children, 489 were admitted because of poisoning. Out of these, 244 (49.9%) were hospitalised due to intoxication by alcohol. Only eight children used designer drugs. The mean age of all patients in our group was 12.86±5.04 years, of which 52.4% were male. Poisoning was intentional in 75.5%, and accidental in 24.5% of cases. Appearance of 'designer drugs' had no significant impact on the number and epidemiology of poisonings in our group.