Effect of Organic Selenium on the Homeostasis of Trace Elements, Lipid Peroxidation, and mRNA Expression of Antioxidant Proteins in Mouse Organs.

(1) In this study we determined the effect of long-term selenomethionine administration on the oxidative stress level and changes in antioxidant protein/enzyme activity; mRNA expression; and the levels of iron, zinc, and copper. (2) Experiments were performed on 4-6-week-old BALB/c mice, which were given selenomethionine (0.4 mg Se/kg b.w.) solution for 8 weeks. The element concentration was determined via inductively coupled plasma mass spectrometry. mRNA expression of SelenoP, Cat, and Sod1 was quantified using real-time quantitative reverse transcription. Malondialdehyde content and catalase activity were determined spectrophotometrically. (3) After long-term SeMet administration, the amount of Se increased by 12-fold in mouse blood, 15-fold in the liver, and 42-fold in the brain, as compared to that in the control. Exposure to SeMet decreased amounts of Fe and Cu in blood, but increased Fe and Zn levels in the liver and increased the levels of all examined elements in the brain. Se increased malondialdehyde content in the blood and brain but decreased it in liver. SeMet administration increased the mRNA expression of selenoprotein P, dismutase, and catalase, but decreased catalase activity in brain and liver. (4) Eight-week-long selenomethionine consumption elevated Se levels in the blood, liver, and especially in the brain and disturbed the homeostasis of Fe, Zn, and Cu. Moreover, Se induced lipid peroxidation in the blood and brain, but not in the liver. In response to SeMet exposure, significant up-regulation of the mRNA expression of catalase, superoxide dismutase 1, and selenoprotein P in the brain, and especially in the liver, was determined.

Post-exposure distribution of selenium and aluminum ions and their effects on superoxide dismutase activity in mouse brain.

The study was conducted to determine how aluminum (Al) and selenium (Se) ions alone and in combination affect superoxide dismutase (SOD) activity and to evaluate the distribution of these elements in the blood and the brain of laboratory mice. SOD activity in mouse brain was evaluated after single-time (within 24 h) and repeated (over 14 days) intraperitoneal (IP) injections of SeO32-, Al3+, and (SeO32-+Al3+) solutions. The control mice received IP injections of the same volume of saline. Aluminum concentration in mouse blood increased both after single-time and repeated injections of AlCl3 and the combined (AlCl3 + Na2SeO3) solutions. The concentration of Se increased in blood after single-time and repeated injections of Na2SeO3 and the combined (AlCl3 + Na2SeO3) solutions. After the single-time injection of the experimental solutions, the concentrations of both Al and Se in mouse brain remained at baseline, but after repeated injections of (AlCl3 + Na2SeO3) solutions increased aluminum concentration. A single IP injection of Al did not change SOD activity in mouse brain, while a single injection of Se or the Se + Al mixture decreased it. After 14 days, IP injections of Al or Se alone did not affect SOD activity, while their combination decreased it. Our results showed that Se ions decreased SOD activity in mouse brain after both single-time and repeated IP injections of selenium-containing solutions. The study failed to show a direct or linear effect of increased Al or Se concentrations on SOD activity in mouse brain.

Determination of Heavy Metal Content: Arsenic, Cadmium, Mercury, and Lead in Cyano-Phycocyanin Isolated from the Cyanobacterial Biomass.

Cyano-phycocyanin (C-PC) is a light-absorbing biliprotein found in cyanobacteria, commonly known as blue-green algae. Due to its antioxidative, anti-inflammatory, and anticancer properties, this protein is a promising substance in medicine and pharmaceuticals. However, cyanobacteria tend to bind heavy metals from the environment, making it necessary to ensure the safety of C-PC for the development of pharmaceutical products, with C-PC isolated from naturally collected cyanobacterial biomass. This study aimed to determine the content of the most toxic heavy metals, arsenic (As), cadmium (Cd), mercury (Hg), and lead (Pb) in C-PC isolated from different cyanobacterial biomasses collected in the Kaunas Lagoon during 2019-2022, and compare them with the content of heavy metals in C-PC isolated from cultivated Spirulina platensis (S. platensis). Cyanobacteria of Aphanizomenon flos-aquae (A. flos-aquae) dominated the biomass collected in 2019, while the genus Microcystis dominated the biomasses collected in the years 2020 and 2022. Heavy metals were determined using inductively coupled plasma mass spectrometry (ICP-MS). ICP-MS analysis revealed higher levels of the most investigated heavy metals (Pb, Cd, and As) in C-PC isolated from the biomass with the dominant Microcystis spp. compared to C-PC isolated from the biomass with the predominant A. flos-aquae. Meanwhile, C-PC isolated from cultivated S. platensis exhibited lower concentrations of As and Pb than C-PC isolated from naturally collected cyanobacterial biomass.

Association between lithium levels in drinking water and suicide rates: Role of affective disorders.

OBJECTIVE: The study aimed to assess the association between lithium levels in drinking water from public supplies and suicide rates in different municipalities of Lithuania in relation with incidence of affective disorders. METHODS: 53 drinking water samples were analysed from the main public drinking water systems of the country's municipalities. Lithium levels were determined using the ion chromatography method. Information on all registered affective disorders across all age groups and gender within the 5-year period was obtained from the Department of Statistics, and was averaged across the investigation time period. For the statistical analysis, lithium levels were averaged per municipality and plotted against suicide standardized mortality rates per 100,000 populations, within the 5-year period. RESULTS: We found that lithium levels in drinking water are positively associated with the incidence of affective disorders. Our findings suggest higher incidence rates of affective disorders in the municipalities with a lithium level in drinking water above median compared to those in the municipalities with a lithium level below median and with the same socio-demographic and psychiatric characteristics. Suicide mortality rates are inversely associated with lithium levels in drinking water only in municipalities with higher lithium levels (above median) and with a high rate of affective disorders. CONCLUSION: Based on our study results and insights we generate the following hypothesis for the further research, that lithium level in drinking water might have an important protective effect against suicide rates in the population with affective disorders.

Alzheimer's Disease Association with Metals and Metalloids Concentration in Blood and Urine.

As there is some evidence that the risk for Alzheimer's disease (AD) is partially attributable to environmental exposure to some metals and metalloids, we examined an association between AD and arsenic, chromium, and selenium in 53 AD patients and 217 controls. Urinary arsenic, blood chromium, and selenium were determined by inductively coupled plasma mass spectrometry. Logistic regression models calculating odds ratios (ORs) and 95% confidence intervals (CI) were used to estimate AD association with arsenic, chromium, and selenium. In AD patients, urinary arsenic and blood chromium were significantly higher, while blood selenium was significantly lower compared to controls. Increased blood selenium was related to a significant decrease in the odds of AD after adjustment for risk factors. Blood selenium per 1 kg × 10-9/m3 × 10-4 increment was associated with 1.4 times lower risk of AD (OR = 0.71; 95% CI 0.58-0.87). A significant increase in the odds of AD associated with increased blood chromium was also seen in the adjusted model: the OR per 1 kg × 10-9/m3 × 10-3 chromium increment was 2.39 (95% CI 1.32-4.31). The association of urinary arsenic with the risk of AD was not significant. The data obtained provide evidence that selenium reduces the risk of Alzheimer's disease, while chromium increases it.

Validation of the patient health questionnaire-9 and the generalized anxiety disorder-7 in Lithuanian student sample.

BACKGROUND: The Patient Health Questionnaire-9 (PHQ-9) and the Generalized Anxiety Disorder Questionnaire- 7 (GAD-7) are short screening instruments used for detection of depression and anxiety symptoms in various settings, including general and mental health care as well as the general population. The aim of this study is to evaluate psychometric properties and factorial structure of the PHQ-9 and the GAD-7 in a sample of Lithuanian university students. METHODS: 1368 students (mean age 22.5±4.8) completed the PHQ-9 and the GAD-7 questionnaires online; after the completion of the survey, students were asked to provide phone contact for an additional interview. Eligible students were approached later by trained interviewers and completed The Clinical Interview Schedule-Revised for assessment of depressive and anxiety disorders. RESULTS: Results showed that the PHQ-9 and the GAD-7 are reliable screening tools for depression and anxiety (Cronbach alpha 0.86 and 0.91, respectively). The one-factor structure of the PHQ-9 and the GAD-7 was confirmed by the Confirmatory Factor Analysis. A cut-off of ≥10 for the PHQ-9 resulted in 71% sensitivity and 66% specificity recognizing students with increased risk for mood or anxiety disorder. For the GAD-7, a cut-off ≥9 resulted in 73% sensitivity and 70% specificity recognizing students at risk. The PHQ-9 was sensitive but not specific in recognizing students with depressive disorders. The sensitivity and specificity of the GAD-7 in differentiating students with generalized anxiety disorders were low. CONCLUSIONS: The PHQ-9 and the GAD-7 have sufficient formal psychometric properties, but their clinical utility as diagnostic tools for recognition of depressive and anxiety disorders in students is limited. Due to low specificity and high false positive rates, both scales are recommended only as an initial screening tool for recognition of subjects with increased risk of mental disorders, however positive cases should be later assessed using more comprehensive instruments.

Effect of Selenium on the Iron Homeostasis and Oxidative Damage in Brain and Liver of Mice.

Selenium is an essential trace element that maintains normal brain function, mainly due its antioxidant properties. Although the amount of Se in the body is tightly regulated by the liver, both an excess of and deficiency in Se can modulate the cellular redox status and affect the homeostasis of other essential elements for both humans and animals. The aim of this study was to determine the effect of inorganic selenium excess on oxidative stress and iron homeostasis in brain and liver of laboratory BALB/c mice, which were supplemented with Na2SeO3 solution (0.2 mg and 0.4 mg Se/kg body weight) for 8 weeks. The content of the lipid peroxidation product malondialdehyde and antioxidant enzyme catalase activity/gene expression were used as markers of oxidative damage and were evaluated by spectrophotometric assays. Selenium and iron concentrations were determined by inductively coupled plasma mass spectrometry (ICP-MS). Catalase gene expression was analyzed by qRT-PCR and ΔΔCt methods. Our results showed that doses of 0.2 mg Se and 0.4 mg Se caused a relatively low accumulation of Se in the brain of mice; however, it induced a 10-fold increase in its accumulation in the liver and also increased iron accumulation in both tested organs. Both doses of Se increased the content of malondialdehyde as well as decreased catalase activity in the liver, while the 0.4 mg Se dose has also activated catalase gene expression. Brain of mice exposed to 0.2 mg Se showed reduced lipid peroxidation; however, the exposure to 0.4 mg of Se increased the catalase activity as well as gene expression. One may conclude that exposure to both doses of Se caused the accumulation of this micronutrient in mice brain and liver and have also provided a disrupting effect on the levels of iron. Both doses of Se have triggered oxidative liver damage. In the brain, the effect of Se was dose dependent, where -0.2 mg of Se provided antioxidant activity, which was observed through a decrease in lipid peroxidation. On the contrary, the 0.4 mg dose increased brain catalase activity as well as gene expression, which may have contributed to maintaining brain lipid peroxidation at the control level.

Antibiotic resistance mechanisms of clinically important bacteria.

Bacterial resistance to antimicrobial drugs is an increasing health and economic problem. Bacteria may be innate resistant or acquire resistance to one or few classes of antimicrobial agents. Acquired resistance arises from: (i) mutations in cell genes (chromosomal mutation) leading to cross-resistance, (ii) gene transfer from one microorganism to other by plasmids (conjugation or transformation), transposons (conjugation), integrons and bacteriophages (transduction). After a bacterium gains resistance genes to protect itself from various antimicrobial agents, bacteria can use several biochemical types of resistance mechanisms: antibiotic inactivation (interference with cell wall synthesis, e.g., ß-lactams and glycopeptide), target modification (inhibition of protein synthesis, e.g., macrolides and tetracyclines; interference with nucleic acid synthesis, e.g., fluoroquinolones and rifampin), altered permeability (changes in outer membrane, e.g., aminoglycosides; new membrane transporters, e.g., chloramphenicol), and "bypass" metabolic pathway (inhibition of metabolic pathway, e.g., trimethoprim-sulfamethoxazole).

Relationship between Lithium Levels in Drinking Water and Suicide Rates: A Nationwide Study in Lithuania.

OBJECTIVE: To investigate an association of lithium levels in the drinking water with suicide mortality rates in Lithuania. Methods: Samples from public drinking water systems were taken in all districts of Lithuania. Lithium levels were determined using the ion chromatography method. For the statistical calculations, lithium levels were averaged per district municipality and plotted against suicide standardized mortality rates (SMR) per 100,000 populations, within the 5-year period from 2012 to 2016. Results: We found that lithium concentrations in drinking water were significantly negatively associated with total suicide rates in a nonlinear way. Conclusion: Lithium intake with drinking water may affect suicide rates in some geographical areas.

Impulsivity Mediates Associations Between Problematic Internet Use, Anxiety, and Depressive Symptoms in Students: A Cross-Sectional COVID-19 Study.

Background: Problematic internet use (PIU) is a serious global mental health issue that especially manifested during the Coronavirus disease (COVID-19) pandemic. Engagement in PIU as an impulsive coping with mental distress may pose a long-lasting threat to develop anxiety and depressive disorders. The first aim of our study was to investigate the prevalence of PIU and mental distress symptoms during the COVID-19 pandemic among university students in Lithuania. The second aim was to test the hypothesis that PIU affects anxiety and depressive symptoms through the mediating role of impulsivity. Methods: The cross-sectional study was comprised of 619 university students (92.9% females and 7.1% males) with a mean age of 22 ± 3 years who participated in an online survey from May to November, 2020. Participants completed the following scales: the Problematic Internet Use Questionnaire-9, the Generalized Anxiety Disorder Questionnaire-7, the Patient Health Questionnaire-9, and the Barratt Impulsiveness Scale-11. K-means cluster analysis and one-way multivariate analysis of variance were used for group comparison in terms of internet use time and habit change during COVID-19 pandemic. Structural equation modeling was applied to examine the mediating effect of impulsivity in association between PIU and mental distress, while controlling for age. Results: In sum, 45.1% of the participants reported PIU and 38.1% had markedly expressed symptoms of anxiety while 43.6% of the students reported moderate to severe depressive symptoms. During the COVID-19 pandemic 76% of the students reported at least moderate increase in their internet use time. Anxiety and depressive symptoms were significantly higher in the group of frequent internet users. The results of the structural equational modeling analysis showed a statistically significant effect of PIU on subjective anxiety symptoms and the statistically significant effect of PIU on subjective depression symptoms, both mediated via impulsivity. Conclusions: During COVID-19 pandemic, PIU, anxiety and depression symptoms are highly prevalent among students. Findings also suggest that relationships between PIU, anxiety and depressive symptoms are mediated via impulsivity. These results underscore the importance of the inclusion of impulsivity factor in the studies analyzing longitudinal effects of PIU on mental distress during COVID-19 pandemic.

Effect of Zinc on the Oxidative Stress Biomarkers in the Brain of Nickel-Treated Mice.

The overexposure to nickel due to the extensive use of it in modern technology remains a major public health concern. The mechanisms of pathological effects of this metal remain elusive. The present study was devoted to evaluate the effect of nickel on the oxidative state of the brain cells of mice and to assess whether zinc as redox state modulator could efficiently protect cells against nickel's neurotoxicity. As oxidative stress biomarkers in the present study, we have measured the concentrations of reduced glutathione, metallothioneins, and malondialdehyde and the activity of the enzyme δ-aminolevulinate dehydratase. For the single metal exposure, mice were i.p. injected once with solutions of NiCl2 and/or ZnSO4; repeated exposure was performed i.p. injecting metal salt solutions for 14 days (once a day). The control mice received i.p. injections of saline. Results of our study demonstrate that single and 14 days of Ni2+ exposure decreased reduced glutathione and increased malondialdehyde contents in the brain of mice. Repeated Ni2+ administration significantly inhibited δ-aminolevulinate dehydratase while increasing brain metallothionein concentration at both exposure periods. Zinc exhibited a protective effect against nickel-induced glutathione and lipid peroxidation in brain cells of mice at both intervals of time, while repeated exposure to this metal significantly raised the brain metallothionein content. Repeated Zn2+ pretreatment protected δ-aminolevulinate dehydratase from Ni2+-induced inhibition and significantly increased metallothionein concentration at both investigated time intervals.

High frequency of the c.3207C>A (p.H1069Q) mutation in ATP7B gene of Lithuanian patients with hepatic presentation of Wilson's disease.

AIM: To investigate the prevalence of the ATP7B gene mutation in patients with hepatic presentation of Wilson's disease (WD) in Lithuania. METHODS: Eleven unrelated Lithuanian families, including 13 WD patients were tested. Clinically WD diagnosis was established in accordance to the Leipzig scoring system. Genomic DNA was extracted from whole venous blood using a salt precipitation method. Firstly, the semi-nested polymerase chain reaction (PCR) technique was used to detect the c.3207C>A (p.H1069Q) mutation. Patients not homozygous for the c.3207C>A (p.H1069Q) mutation were further analyzed. The 21 exons of the WD gene were amplified in a thermal cycler (Biometra T3 Thermocycler, Gottingen, Germany). Direct sequencing of the amplified PCR products was performed by cycle sequencing using fluorescent dye terminators in an automatic sequencer (Applied Biosystems, Darmstadt, Germany). RESULTS: Total of 13 WD patients (mean age 26.4 years; range 17-40; male/female 3/10) presented with hepatic disorders and 16 their first degree relatives (including 12 siblings) were studied. Some of WD patients, in addition to hepatic symptoms, have had extrahepatic disorders (hemolytic anemia 3; Fanconi syndrome 1; neurophsychiatric and behavioural disorder 2). Liver biopsy specimens were available in all of 13 WD patients (8 had cirrhosis; 1-chronic hepatitis; 3-acute liver failure, 1-liver steatosis). Twelve of 13 (92.3%) WD patients had the c.3207C>A (p.H1069Q) mutation, 6 of them in both chromosomes, 6 were presented as compound heterozygotes with additional c.3472-82delGGTTTAACCAT, c.3402delC, c.3121C>T (p.R1041W) or unknown mutations. For one patient with liver cirrhosis and psychiatric disorder (Leipzig score 6), no mutations were found. Out of 16 first degree WD relatives, 11 (68.7%) were heterozygous for the c.3207C>A (p.H1069Q) mutation. Two patients with fulminant WD died from acute liver failure and 11 are in full remission under penicillamine or zinc acetate treatment. Three women with WD successfully delivered healthy babies. CONCLUSION: The c.3207C>A (p.H1069Q) missense mutation is the most characteristic mutation for Lithuanian patients with WD. Even 92.3% of WD patients with hepatic presentation of the disease are homozygous or compound heterozygotes for the p.H1069Q mutation.

Acute liver failure in Lithuania.

OBJECTIVES: Acute liver failure (ALF) is a life-threatening condition that can rapidly progress into coma and death due to the cerebral edema and multi-organ dysfunction. The ALF etiology and risk factors have been investigated in West Europe, North America, and Asia; however, there are still no published data about the causes and prognosis of ALF in Central and East European countries. The aim of our study was to analyze the causes, outcomes, and prognostic factors of ALF in patients referred to tertiary care center in Lithuania. MATERIAL AND METHODS: A total of 28 consecutive patients admitted to the tertiary care center (one of two university-level medical centers in Lithuania) over the period of January 1996 and December 2004 and who fulfilled the entry criteria of ALF (presence of hepatic encephalopathy (HE) and prothrombin international normalized ratio (INR) >1.5) were included into a prospective study. RESULTS: In our study the most frequent causes of ALF were acute viral hepatitis B (21.4 %), drug-induced hepatitis (21.4%), and indeterminate hepatitis (17.9%); other etiologies included Budd-Chiari syndrome (10.7%), ischemic hepatitis (10.7%), Wilson's disease (7.1%), Amanita phalloides-induced liver damage (3.6%), acute fatty liver of pregnancy (3.6%), and malignant infiltration of the liver (3.6%). Among patients with drug-induced liver injury, only one case of acetaminophen poisoning was diagnosed. Clinical status of 9 persons in all patients with ALF corresponded to criteria for liver transplantation (LT) (one liver transplantation was performed), 6 of them had contraindications, and 13 patients did not fulfill requirements for urgent LT. The patients' survival rate in these groups was 11.1%, 16.7% and 69.2%, respectively. In 27 non-transplanted patients univariate analysis revealed the grade of HE on the day of enrolment, total serum bilirubin, pH, and prothrombin INR as risk factors for death from ALF. Multivariate logistic regressive analysis determined only prothrombin INR >3.24 and serum pH

Narrow line between benefit and harm: Additivity of hyperthermia to cisplatin cytotoxicity in different gastrointestinal cancer cells.

AIM: To investigate the response to hyperthermia and chemotherapy, analyzing apoptosis, cytotoxicity, and cisplatin concentration in different digestive system cancer cells. METHODS: AGS (gastric cancer cell line), Caco-2 (colon cancer cell line) and T3M4 (pancreatic cancer cell line) were treated by cisplatin and different temperature setting (37 °C to 45 °C) either in isolation, or in combination. Treatment lasted for one hour. 48 h after the treatment viability was evaluated by MTT, cell apoptosis by Annexin V-PE and 7ADD flow cytometry. Intracellular cisplatin concentration was measured immediately after the treatment, using mass spectrometry. Isobologram analysis was performed to evaluate the mathematical combined effect of temperature and cisplatin. RESULTS: AGS cells were the most sensitive to isolated application of hyperthermia. Hyperthermia, in addition to cisplatin treatment, did not provoke a synergistic effect at intervals from 37 °C to 41 °C in neither cancer cell line. However, a temperature of 43 °C enhanced cisplatin cytotoxicity for Caco-2 cells. Moreover, isobologram analysis revealed mathematical antagonistic effects of cisplatin and temperature combined treatment in AGS cells; variations between synergistic, additive, and antagonistic effects in Caco-2 cells; and additive and antagonistic effects in T3M4 cells. Combined treatment enhanced initiation of cell apoptosis in AGS, Caco-2, and T3M4 cells by 61%, 20%, and 19% respectively. The increase of intracellular cisplatin concentration was observed at 43 °C by 30%, 20%, and 18% in AGS, Caco-2, and T3M4 cells, respectively. CONCLUSION: In addition to cisplatin, hyperthermia up to 43 °C does not affect the viability of cancer cells in a synergistic manner.

Lithium levels in the public drinking water supply and risk of suicide: A pilot study.

Suicide is a major public health concern affecting both the society and family life. There are data indicating that higher level lithium intake with drinking water is associated with lower suicide rate. This pilot study examined the relationship between lithium levels in drinking water and suicide rates in Lithuania. Twenty-two samples from public drinking water systems were taken in 9 cities of Lithuania. The lithium concentration in these samples was determined by inductively coupled plasma mass spectrometry (ICP-MS). The suicide data were obtained from the Lithuania Database of Health Indicators, and comprised all registered suicides across all ages and gender within the 5-year period from 2009 to 2013. The study demonstrated an inverse correlation between levels of lithium (log natural transformed), number of women for 1000 men and standardized mortality rate for suicide among total study population. After adjusting for confounder (the number of women for 1000 men), the lithium level remained statistically significant in men, but not in women. Our study suggested that higher levels of lithium in public drinking water are associated with lower suicide rates in men. It might have a protective effect on the risk of suicide in men.

Cadmium and children: exposure and health effects.

Cadmium exposure and accumulation in the body start at young age. Exposure routes in children are mainly via food, environmental tobacco smoke and house dust. Excretion from the body is limited. Cadmium accumulation in the kidney is responsible for effects such as nephrotoxicity and osteoporosis which are observed at adult age. Cadmium exposure through inhalation is also associated with lung cancer in adulthood. Although transfer to the neonate through the placenta and through breast milk is limited, teratogenic and developmental effects were observed in experimental animals. The database on human studies involving children is limited, yet effects on motoric and perceptual behaviour in children have been associated with elevated in utero cadmium exposure. In school age children urinary cadmium levels were associated with immune suppressive effects. More studies are needed to confirm these results. Experimental data in vitro and in animals refer to effects of cadmium on the hypothalamus-pituitary axis at different levels. This may lead to disorders of the endocrine and/or immune system. Cadmium exposure at early age should be limited as much as possible to prevent direct effects on children and to prevent accumulation of cadmium which may have serious health effects only becoming manifest at older age.

Today's epidemics in children: possible relations to environmental pollution and suggested preventive measures.

BACKGROUND: Facts and hypotheses on the relationship between some children's diseases or disorders and external stressors during the developmental stage of a child, both prenatally and postnatally are described in literature. In this paper the following changes in patterns and causes of the main childhood illnesses are summarized and recommendations for actions are made. Prematurity. Intra-uterine growth restriction. Testicular dysgenesis syndrome. Type I and Type II diabetes. Asthma, atopy and hay fever. Autism. Attention deficit hyperactivity disorder (ADHD). Learning disabilities. Cancer. Obesity. Hearing problems. RESULTS: Literature provides a growing amount of information on changing patterns in childhood diseases. CONCLUSIONS: The following recommendations for action are formulated: Immediate research on endocrine disrupters in relation to prematurity. Diabetes: avoid Maillard Compounds in liquid baby food and in food in general: promote breastfeeding. Asthma: avoid exposure to smoking, the use of chemical household products, dioxin and dioxin-like chemicals, and avoid air pollution with high levels of particulate matter, especially around conception, during pregnancy and in the first years of life. Autism: more research on incidence and causes. ADHD and learning disabilities: more research on prevalence and causes. Preventions: 1) preconception counselling to avoid potentially harmful substances; 2) controlling and further lowering levels of polychlorinated biphenyls, lead and methyl mercury. Cancer: promote breastfeeding, carry out research into effects of foetal exposure to internal fission-product radionuclides. Obesity: stop smoking in pregnancy, avoid parental obesity, longer night sleep. Hearing problems: lower noise levels in discothèques, promote the day-evening-night level to avoid noise (longer night sleep).

Exposure to multiple environmental agents and their effect.

INTRODUCTION: All children are exposed to multiple physical, chemical and biological challenges that can result in adverse health effects before and after birth. In this context, the danger of multiple exposures cannot be assessed from a single-chemical approach as used in classical toxicology. AIM: To open up a 'negotiation space' for the problem of multiple exposure to environmental stressors, defined as any physical, chemical or biological entity that can induce an adverse response. In this context, two further questions obtain: to what extent can synergistic risks be assessed, and how far could potential adverse effects be prevented by enhanced regulation? METHODS: A discussion of two general approaches is taken: 1) the investigation of mixtures such as smoking or air pollution without specifying the individual agents, and 2) the investigation of individual substances with a focus on possible interactions in the context of dose to receptor. RESULTS: Although mixtures of compounds can have effects, it may not be possible to ascribe causation to a single compound. Furthermore, cumulative low-dose insult can, in some circumstances, be more toxic than a single high-dose exposure, e.g. endocrine disruptive effects of a combination of PCBs and dioxins which disrupt the thyroid hormone status; this tends to contradict elements of classical toxicology, . These cumulative insults may further combine with heavy metals and can disrupt the heme synthesis. It is possible that groups of pollutants could be used to test their cumulative capacity to multiple stress-susceptible receptor targets as is done in smoking and air pollution. This methodology could be used for further groups of potential pollutants, for example those associated with cleaning products, or cosmetics. Testing individual substances with a focus on interactions means that not only chemicals but also concurrent diseases should be taken into account. We suggest that the enhanced regulation of potential multiple stressors falls into two discrete categories. The first comprises a more precautionary approach (as demonstrated by the banning of chemicals such as some brominated flame retardants in Europe). The second comprises a more 'permissive' liberal approach involving the initial study of an individual compound, and subsequent interrogation of that compound in combination with another (as demonstrated by lowering the carcinogenicity of aflatoxin by vaccination against hepatitis B). CONCLUSIONS: It is necessary to define and study groups of multiple stressors as in US EPA's Framework for Cumulative Risk Assessment (U.S. EPA 2003). Recent increased knowledge of the greater sensitivity of the unborn baby, the infant and the child, has led to general recognition that a higher degree of precaution is now needed in regulating for multiple stressors on the young. The more liberal permissive approach proceeding from established effects of the individual exposures is becoming less acceptable now that we know that there is much we do not understand about chronic effects of stressors during the early development phases. Conflicts over which approach to take may have to be resolved through engagement and negotiation with a wide community of stakeholders. This "community of interest" may include fundamental research scientists, practicing clinical paediatricians, patient groups, and others concerned with the health and wellbeing of infants and children.

[Chronic poisoning by metallic lead from locations of gunshot wound]. / Letinis apsinuodijimas metaliniu svinu is sautines zaizdos zidiniu.

A patient injured by shooting to head and shoulder with lead pellets was treated. Fragments of lead pellets were lodged in areas of cheek, forehead and neck. After three months symptoms of lead intoxication occurred, however there was no accumulation of lead in hair. During surgical treatment, it was determined by methods of computed tomography and Zeeman atomic absorption spectrometry that particles of metallic lead dissolved mostly in highly vascularized areas of tissues. The main intoxication occurred from the area of venter frontalis where lead particles were mostly deformed. Intoxication did not disappear as long as all fragments of lead pellets were removed surgically. Resorbed lead was partially accumulated in the bone, because amount of lead eliminated with urine was less than that resorbed into the blood.

[Water treatment systems of hemodialysis centers in Lithuania and trace metals in purified water in 2002]. / Lietuvos hemodializes centru vandens valymo irenginiai ir metalu kiekis valytame dializei naudotame vandenyje 2002 metais.

The objective of this survey was to obtain information on hemodialysis chemical water quality and on water treatment systems of hemodialysis centers in Lithuania. Five trace metals (Al, Pb, Cd, Zn, Cu) were examined in the purified water (sample from a point after the water treatment system) of 28 hemodialysis centers. Atomic absorption spectrophotometry was applied to measure water trace metals levels. All hemodialysis centers in Lithuania used treated water. Softeners were used by 100%, reverse osmosis by 86.2% of the centers. Concomitant use of sand filter, softeners, activated carbon, reverse osmosis was found in 72.4% of the centers. The age of the water treatment system varied from 1 to 117 months (mean=39.7+/-30.4). Concentrations of Al, Pb, Cd, Zn, Cu in the purified water of 28 hemodialysis centers did not exceed standards of the European Pharmacopoeia. There was significant decrease in the mean levels of investigated trace elements in the treated water in Lithuania in 2002 compared with examined in 1998.