River pollution in the Kosovo: Cyto- and genotoxic effects of water samples in the primary rat hepatocyte assay.

The actual stage of the development of Kosovo is characterized by the concerning levels of environmental pollution and the serious health problems attributed to the emission of pollutants into air, soil and water. In this context, river pollution is one of the main threats due to the discharge of untreated urban and industrial waste waters that affect the quality of surface and ground water. In addition, urban and agricultural discharges are affecting the river water quality. In this article, we are presenting data on the cyto- and genotoxic potential of water samples from three rivers (Sitnica, Drenica and Lepenci) in the Kosovo as determined in the cultures of primary rat hepatocytes. Sitnica and Drenica (as the most important Sitnica tributary) drain into the Black Sea, whereas the Lepenci river drains into the Aegean Sea. These rivers are polluted mainly by industry in the Kosovo together with municipal discharges. The results of this study show that the samples have primarily a cytotoxic potential by causing necrotic cell death that was not accompanied by any increase of the rate of micronucleated cells as an indicator for a genotoxic potential. The different effects in 2 consecutive years can be attributed to variations in physico-chemical parameters such as water levels, intake of pollutants, and so on, indicating the need for continuous monitoring and risk assessment.

Cyto- and genotoxic potential of water samples from polluted areas in Kosovo.

Reports on the state of the environment in Kosovo have emphasized that river and ground water quality is affected by pollution from untreated urban water as well as the waste water from the industry. One of the main contributors to this pollution is located in Obiliq (coal power plants). Prishtina-the capital city of Kosovo-is heavily influenced too. Furthermore, the pollutants combined together with those from heavy traffic are dissolved in Prishtina runoff water, which is discharged into the creek entering the river Sitnica together with urban waste water. The available data show the complex pollution with excessive quantities of nitrites, suspended materials, organic compounds, detergents, heavy metals, polychlorinated biphenyls, etc. In this study, the cytotoxic and genotoxic potential of water samples taken at these sites was tested in primary rat hepatocytes. The results obtained indicate that water samples collected in Prishtina and Obiliq had a significant cytotoxic potential in primary rat hepatocyte cultures even when diluted to 1 %. The increased cytotoxicity, however, was not accompanied by an increased genotoxicity as measured by the percentage of micronucleated cells. Further investigations addressing the chemical composition of the samples and the identification of the toxicants responsible for the cytotoxic effects found will be carried out in a next step.

Introduction of Solid Foods in Preterm Infants and Its Impact on Growth in the First Year of Life-A Prospective Observational Study.

The aim of this study was to investigate whether age at introduction of solid foods in preterm infants influences growth in the first year of life. This was a prospective observational study in very low birth weight infants stratified to an early (<17 weeks corrected age) or a late (≥17 weeks corrected age) feeding group according to the individual timing of weaning. In total, 115 infants were assigned to the early group, and 82 were assigned to the late group. Mean birth weight and gestational age were comparable between groups (early: 926 g, 26 + 6 weeks; late: 881 g, 26 + 5 weeks). Mean age at weaning was 13.2 weeks corrected age in the early group and 20.4 weeks corrected age in the late group. At 12 months corrected age, anthropometric parameters showed no significant differences between groups (early vs. late, mean length 75.0 vs. 74.1 cm, weight 9.2 vs. 8.9 kg, head circumference 45.5 vs. 45.0 cm). A machine learning model showed no effect of age at weaning on length and length z-scores at 12 months corrected age. Infants with comorbidities had significantly lower anthropometric z-scores compared to infants without comorbidities. Therefore, regardless of growth considerations, we recommend weaning preterm infants according to their neurological abilities.

Phytosterol content and fatty acid pattern of ten different nut types.

Ten different nut kinds (almonds, Brazil nuts, cashews, hazelnuts, macadamias, peanuts, pecans, pine nuts, pistachios, and walnuts) were evaluated for their total oil and phytosterol content as well as their fatty acid composition. The total oil content was the predominant component; mean values oscillated between 45.2 % (cashews) and 74.7 % (macadamias). Mean total phytosterol content ranged from 71.7 mg (Brazil nuts) to 271.9 mg (pistachios) per 100 g oil. ß-sitosterol was the major sterol (mean >71.7 mg/100 g oil) followed by minor contents of campesterol, ergosterol, and stigmasterol. Almonds, cashews, hazelnuts, macadamias, and pistachios were high in monounsaturated fatty acids (MUFA; > 55 %). MUFA- and polyunsaturated fatty acid (PUFA)-rich nuts were peanuts and pecans, whereas Brazil nuts, pine nuts, and walnuts had the highest PUFA content (> 50 %); the high unsaturated/saturated fatty acid ratio ranged from 4.5 to 11.8. However, the fatty acid pattern of every nut is unique.

Preterm Infants on Early Solid Foods and Iron Status in the First Year of Life-A Secondary Outcome Analysis of a Randomized Controlled Trial.

Introduction of solid foods and iron status in the first year of life of preterm infants are highly discussed topics. The aim of this study was to examine whether two timepoints of introduction of standardized solid foods in preterm infants have an impact on ferritin and other hematologic parameters important for iron status in the first year of life. This is a secondary outcome analysis of a prospective, randomized intervention trial in very low birth weight (VLBW) infants randomized to an early (10-12th week corrected age) or a late (16-18th week corrected age) complementary feeding group. Iron status was assessed with blood samples taken at 6 weeks, 6 months, and 12 months corrected age. In total, 177 infants were randomized (early group: n = 89, late group: n = 88). Ferritin showed no differences between study groups throughout the first year of life, as did all other parameters associated with iron status. At 12 months corrected age, the incidence of iron deficiency was significantly higher in the early feeding group. There is room for improvement of iron status in VLBW preterm infants, regular blood checks should be introduced, and current recommendations may need to be a reconsidered.

Randomized Controlled Trial of Two Timepoints for Introduction of Standardized Complementary Food in Preterm Infants.

In term infants it is recommended to introduce solids between the 17th and 26th week of life, whereas data for preterm infants are missing. In a prospective, two-arm interventional study we investigated longitudinal growth of VLBW infants after early (10-12th) or late (16-18th) week of life, corrected for term, introduction of standardized complementary food. Primary endpoint was height at one year of age, corrected for term, and secondary endpoints were other anthropometric parameters such as weight, head circumference, BMI, and z-scores. Among 177 infants who underwent randomization, the primary outcome could be assessed in 83 (93%) assigned to the early and 83 (94%) to the late group. Mean birthweight was 941 (SD ± 253) g in the early and 932 (SD ± 256) g in the late group, mean gestational age at birth was 27 + 1/7 weeks in both groups. Height was 74.7 (mean; SD ± 2.7) cm in the early and 74.4 cm (mean; SD ± 2.8; n.s.) cm in the late group at one year of age, corrected for term. There were no differences in anthropometric parameters between the study groups except for a transient effect on weight z-score at 6 months. In preterm infants, starting solids should rather be related to neurological ability than to considerations of nutritional intake and growth.

Preterm Infants on Early Solid Foods and Vitamin D Status in the First Year of Life-A Secondary Outcome Analysis of a Randomized Controlled Trial.

Preterm birth places infants at high risk for mineral and micronutrient deficiencies important for bone health. The aim of this study was to examine whether two timepoints for the introduction of solid foods in preterm infants have an impact on vitamin D status in the first year of life. This is a secondary outcome analysis of a prospective, randomized trial on very low birth weight (VLBW) infants, randomized to an early (10-12th week corrected age) or a late (16-18th week corrected age) complementary-feeding group. Vitamin D status was assessed by blood samples taken at 6 weeks, 6, and 12 months corrected age. In total, 177 infants were randomized (early group: n = 89, late group: n = 88). There was a tendency toward lower levels of serum 25-OH-vitamin D in the early group throughout the first year of life (p = not significant (n.s.)); no differences were detected in the other parameters. At 6 months corrected age, infants of the early group had a significantly higher incidence of vitamin D deficiency. The timepoint of the introduction of solid foods had no impact on the serum 25-OH-vitamin D levels and other parameters important for bone health but showed a tendency toward lower levels in the early-feeding group.

Can Sequential Coagulation Monitoring Predict Major Haemorrhage in Extremely Low Birth Weight Infants?

INTRODUCTION: Bleeds such as intra-ventricular (IVH) and pulmonary haemorrhage (PH) are life-threatening events in extremely low birth weight (ELBW) infants. Serial coagulation monitoring by measuring the international normalized ratio (INR) with small volume samples might facilitate early diagnosis and possibly prevent major bleeds. MATERIALS AND METHODS: This was a prospective longitudinal study performed in ELBW infants, who received serial INR monitoring by point of care testing during their first 30 days of life. The primary objective was to explore whether INR monitoring could predict major bleeding events (IVH, PH). Secondary objectives were mortality and feasibility in this patient population. RESULTS: A total of 127 ELBW infants were stratified into a bleeding and a non-bleeding group. Bleeding events occurred in 31% (39/127) of the infants, whereupon 24% developed IVH and 9% PH. Infants in the bleeding group were 4 days younger at birth (p = 0.05) and had a substantially higher mortality rate of 26% versus 5% in controls (p = 0.005). Median INR during the first 3 days before a bleeding event was 1.55 (95% confidence interval [CI]: 1.39-1.74) compared with the control group with 1.45 (95% CI: 1.44-1.58; p = 0.81). Platelet counts were significantly lower in the bleeding group on the 3rd day and during the 2nd to 4th week of life. DISCUSSION: Serial coagulation monitoring by an INR point of care testing is feasible in ELBW infants but could not predict bleeding events. Further studies with daily monitoring of INR and platelet counts during the first days of life might be able to more precisely detect a risk of major haemorrhage in ELBW infants.

Ferritin-stimulated lipid peroxidation, lysosomal leak, and macroautophagy promote lysosomal "metastability" in primary hepatocytes determining in vitro cell survival.

Several pathologies are associated with elevated levels of serum ferritin, for which growth inhibitory properties have been reported; however, the underlying mechanisms are still poorly defined. Previously we have described cytotoxic properties of isoferritins released from primary hepatocytes in vitro, which induce apoptosis in an iron and oxidative stress-dependent mode. Here we show that this ferritin species stimulates endosome clustering and giant endosome formation in primary hepatocytes accompanied by enhanced lysosomal membrane permeability (LMP). In parallel, protein modification by lipid peroxidation-derived 4-hydroxynonenal (HNE) is strongly promoted by ferritin, the HNE-modified proteins (HNE-P) showing remarkable aggregation. Emphasizing the prooxidant context, GSH is rapidly depleted and the GSH/GSSG ratio is substantially declining in ferritin-treated cells. Furthermore, ferritin triggers a transient upregulation of macroautophagy which is abolished by iron chelation and apparently supports HNE-P clearance. Macroautophagy inhibition by 3-methyladenine strongly amplifies ferritin cytotoxicity in a time- and concentration-dependent mode, suggesting an important role of macroautophagy on cellular responses to ferritin endocytosis. Moreover, pointing at an involvement of lysosomal proteolysis, ferritin cytotoxicity and lysosome fragility are aggravated by the protease inhibitor leupeptin. In contrast, EGF which suppresses ferritin-induced cell death attenuates ferritin-mediated LMP. In conclusion, we propose that HNE-P accumulation, lysosome dysfunction, and macroautophagy stimulated by ferritin endocytosis provoke lysosomal "metastability" in primary hepatocytes which permits cell survival as long as in- and extrinsic determinants (e.g., antioxidant availability, damage repair, EGF signaling) keep the degree of lysosomal destabilization below cell death-inducing thresholds.