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BACKGROUND: Numerous observational studies have demonstrated that circulating lipoprotein(a) [Lp(a)] might be inversely related to the risk of type 2 diabetes (T2D). However, recent Mendelian randomization (MR) studies do not consistently support this association. The results of in vitro research suggest that high insulin concentrations can suppress Lp(a) levels by affecting apolipoprotein(a) [apo(a)] synthesis. This study aimed to identify the relationship between genetically predicted insulin concentrations and Lp(a) levels, which may partly explain the associations between low Lp(a) levels and increased risk of T2D. METHODS: Independent genetic variants strongly associated with fasting insulin levels were identified from meta-analyses of genome-wide association studies in European populations (GWASs) (N = 151,013). Summary level data for Lp(a) in the population of European ancestry were acquired from a GWAS in the UK Biobank (N = 361,194). The inverse-variance weighted (IVW) method approach was applied to perform two-sample summary-level MR. Robust methods for sensitivity analysis were utilized, such as MRâEgger, the weighted median (WME) method, MR pleiotropy residual sum and outlier (MR-PRESSO), leave-one-out analysis, and MR Steiger. RESULTS: Genetically predicted fasting insulin levels were negatively associated with Lp(a) levels (ß = - 0.15, SE = 0.05, P = 0.003). The sensitivity analysis revealed that WME (ß = - 0.26, SE = 0.07, P = 0.0002), but not MRâEgger (ß = - 0.22, SE = 0.13, P = 0.11), supported a causal relationship between genetically predisposed insulin levels and Lp(a). CONCLUSION: Our MR study provides robust evidence supporting the association between genetically predicted increased insulin concentrations and decreased concentrations of Lp(a). These findings suggest that hyperinsulinaemia, which typically accompanies T2D, can partially explain the inverse relationship between low Lp(a) concentrations and an increased risk of T2D.
Assuntos
Diabetes Mellitus Tipo 2 , Insulina , Lipoproteína(a) , População Branca , Feminino , Humanos , Masculino , Biomarcadores/sangue , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/etnologia , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Insulina/sangue , Lipoproteína(a)/sangue , Lipoproteína(a)/genética , Análise da Randomização Mendeliana , Fenótipo , Polimorfismo de Nucleotídeo Único , Medição de Risco , Fatores de Risco , População Branca/genéticaRESUMO
This study aimed to compare the concentration of various xenobiotics in both cerebrospinal fluid (CSF) and blood. We examined 175 autopsy cases covering a wide range of ages, causes of death, and drug ingestion histories, with cerebrospinal fluid and blood samples available for toxicological testing. Analytes studied included opioids, benzodiazepines, antidepressants, antipsychotics, and illicit substances such as cannabinoids, stimulants and new psychoactive substances, including synthetic cathinones and synthetic cannabinoids. We found that concentrations in CSF were generally lower than in blood. A significant correlation was observed between drug concentrations in CSF and blood for many analytes (p < 0.05). However, the strength and direction of the correlation varied considerably depending on the physicochemical properties of the drugs, suggesting that a 'one size fits all' model may not be applicable. The results indicate that cerebrospinal fluid (CSF) can be used to detect a variety of xenobiotics, particularly amphetamines, synthetic cathinones and synthetic cannabinoids, in cases where conventional biological materials are not available. Additionally, using the results obtained in the future can lead to a better understanding of pharmacokinetic processes and the effect of post-mortem redistribution. Further research is needed to refine our understanding of these relationships.
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Background and Objectives: The thyroid is a key endocrine gland for the regulation of metabolic processes. A body composition analysis (BCA) is a valuable complement to the assessment of body mass index, which is derived only from body weight and height. This cross-sectional retrospective study aimed to investigate the relationships between thyroid volume (TV) and thyroid function parameters, anthropometric measurements, BCA parameters, and the presence of metabolic syndrome (MetS) in adults without clinically overt thyroid disease. Material and Methods: This study involved 45 people (females: 57.8%; MetS: 28.9%) hospitalized for planned diagnostics without signs of acute illness or a deterioration of their health and without thyroid disease, who underwent thyroid ultrasound scans, biochemical tests to assess their thyroid function, MetS assessments, anthropometric measurements, and BCAs using the bioelectrical impedance method. Results: The TV was significantly larger in people with MetS compared to people without MetS. The TV was significantly higher and the serum thyrotropin (TSH) concentration was significantly lower in overweight and obese people than in normal and underweight people. The free triiodothyronine (FT3) serum concentration and TV were correlated with waist circumference and some parameters of the BCA, and the FT3 concentration was also correlated with the body mass index, waist-hip ratio, and waist-height ratio. No significant correlations were found between the FT4 and TSH and the results of the anthropometric and BCA measurements. Conclusions: Even in a population of euthyroid patients without clinically overt thyroid disease, there were some significant relationships between the volume and function of the thyroid gland and the results of their anthropometric parameters, BCAs, and the presence of MetS features.
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Antropometria , Composição Corporal , Índice de Massa Corporal , Síndrome Metabólica , Glândula Tireoide , Humanos , Estudos Transversais , Síndrome Metabólica/fisiopatologia , Síndrome Metabólica/sangue , Síndrome Metabólica/diagnóstico , Masculino , Feminino , Estudos Retrospectivos , Glândula Tireoide/diagnóstico por imagem , Glândula Tireoide/fisiopatologia , Glândula Tireoide/fisiologia , Pessoa de Meia-Idade , Composição Corporal/fisiologia , Adulto , Antropometria/métodos , Idoso , Adolescente , Tri-Iodotironina/sangue , Tri-Iodotironina/análise , Tireotropina/sangue , Tireotropina/análiseRESUMO
Background and Objectives: The interrelationship between thyroid function and the state of the cardiovascular system has been investigated both in preclinical and human studies. However, it remains unclear whether there is any association between thyroid hormones and features of subclinical cardiovascular dysfunction in euthyroid patients. Material and Methods: This study involved 45 people (females: 57.8%) with no thyroid disease who, during planned hospitalization, underwent thyroid ultrasound, determination of biochemical parameters of thyroid function, and measurement of ankle-brachial index (ABI) and toe-brachial index (TBI). People with signs of acute illness or a deterioration of their health were excluded. Results: Significant correlations were found between free triiodothyronine (FT3) and several parameters of both ABI (R = 0.347; p = 0.019 for the mean ABI taken from right side and left side values) and TBI (R = 0.396; p = 0.007 for the mean TBI taken from right side and left side values), as well as the maximal toe pressure (TP) taken from right side and left side values (R = 0.304; p = 0.045). Thyrotropin (TSH) was shown to be significantly correlated only with the maximal TBI value (taken from right side and left side values) (R = 0.318; p = 0.033), whereas free thyroxin (FT4) was shown to be significantly correlated only with the minimal TBI value (taken from right side and left side values) (R = 0.381; p = 0.01). Thyroid volume (TV) was shown to be correlated with TP (R = 0.4; p = 0.008 for the mean TP taken from right side and left side values) and some parameters of TBI value (R = 0.332; p = 0.028 for the mean TBI taken from right side and left side values), but no significant correlations were found between TVand ABI parameters. Patients with a mean ABI value ≤ 1.0 or a mean TBI value ≤ 0.75 have lower TSH, FT3, FT4, and TV than the rest of the study population, but the difference was statistically significant only for FT3. Conclusions: Even in a population of euthyroid patients with no diagnosed thyroid disease, there are some significant correlations between the volume and function of the thyroid gland and the selected features of subclinical cardiovascular dysfunction such as ABI and TBI.
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Índice Tornozelo-Braço , Glândula Tireoide , Dedos do Pé , Humanos , Masculino , Feminino , Índice Tornozelo-Braço/métodos , Pessoa de Meia-Idade , Glândula Tireoide/fisiopatologia , Glândula Tireoide/diagnóstico por imagem , Glândula Tireoide/fisiologia , Adulto , Idoso , Dedos do Pé/irrigação sanguínea , Dedos do Pé/fisiopatologia , Adolescente , Pressão Sanguínea/fisiologia , Tireotropina/sangue , Tri-Iodotironina/sangue , Testes de Função Tireóidea/métodos , Ultrassonografia/métodosRESUMO
This paper presents the results of a study on the applicability of cerebrospinal fluid (CSF) collected from the spinal canal in the post-mortem determination of ethyl alcohol. The present study reviewed data of autopsy cases (n = 45), in which ethyl alcohol was detected in CSF using gas chromatography with a flame ionization detector (HS-GC-FID), to investigate ethyl alcohol concentrations in CSF, compared with blood. As a result of statistical analysis of the obtained data, a high positive correlation was found between blood ethanol concentration and cerebrospinal fluid collected from the spinal canal ethanol concentration. The Pearson correlation coefficient was statistically highly significant (p < 0.001) (r = 0.9503). The data obtained allowed us to conclude that cerebrospinal fluid collected from the spinal canal can be collected during an autopsy as an alternative biological specimen to assess the ethanol content. Cerebrospinal fluid collected from the spinal canal can corroborate and lend credibility to the results obtained for blood and, in special cases, when blood is drawn from putrefied bodies and may even be a superior specimen to blood for assessing ethyl alcohol intoxication status.
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Etanol , Mudanças Depois da Morte , Humanos , Autopsia , Concentração Alcoólica no Sangue , Toxicologia Forense/métodos , Medula Espinal/químicaRESUMO
It is estimated that 2.6 million deaths worldwide can be attributed to hypercholesterolemia. The main reason for non-adherence to statin therapy are the statin-associated muscle symptoms (including nocebo/drucebo effect). In this case, apart from ezetimibe, nutraceuticals are prescribed. We aimed to assess the comparative efficacy of different nutraceuticals in terms of lowering low density lipoprotein cholesterol (LDL-C) and improving lipid profile. Electronic and hand searches were performed until February 2021. The inclusion criteria were the following: (1) randomized trial with any of the reportedly LDL-C lowering nutraceutical: artichoke, berberine, bergamot, garlic, green tea extract, plant sterols/stanols, policosanols, red yeast rice (RYR), silymarin or spirulina. (2) outcome either LDL-C (primary outcome), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C) or serum triglycerides (TG). Random effects network meta-analysis (NMA) was performed to rank the effect of each intervention using frequentist approach. Finally, a total of 131 trials enrolling 13,062 participants were included. All analysed nutraceuticals except for policosanols were more effective in lowering LDL-C (-1.21 [-46.8 mg/dL] to -0.17 [-6.6 mg/dL] mmol/l reduction) and TC (-1.75 [-67.7 mg/dL] to -0.18 [7 mg/dL] mmol/l reduction) than placebo/no intervention. The most effective approaches in terms of LDL-C- and TC-lowering were bergamot and RYR (-1.21 [-46.8 mg/dl] and -0.94 [-36.4 mg/dl] mmol/l) reduction respectively. In conclusion, bergamot and RYR appear to be the most effective nutraceuticals in terms of LDL-C and TC reduction. Evidence for bergamot effect was based on relatively small study group and may require further investigations. Policosanols have no effect on the lipid profile.
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Anticolesterolemiantes , Inibidores de Hidroximetilglutaril-CoA Redutases , Hipercolesterolemia , Adulto , LDL-Colesterol , Suplementos Nutricionais , Humanos , Hipercolesterolemia/tratamento farmacológico , Metanálise em RedeRESUMO
BACKGROUND AND AIMS: Elevated homocysteine concentration is associated with a higher risk of cardiovascular disease. The aim of our study was to determine the environmental and genetic factors associated with serum homocysteine concentration in healthy young adults. Moreover, we aimed to determine the cutoff value of homocysteine concentration for predicting unfavorable MTHFR genotype and to investigate whether this association is modified by dietary patterns and serum folate status. METHODS AND RESULTS: A total of 744 healthy individuals, aged 18-35 years, were included in the study. Diet quality was assessed by establishing diet quality scores and adherence to the pro-Healthy Diet Index (pHDI) and non-Healthy Diet Index (nHDI). Genotyping was performed using the TaqMan method. Multivariate analysis showed that pHDI, creatinine, folate concentrations, and the T/T genotype of the C677T polymorphism in MTHFR, as well as the interaction between the T/T genotype of MTHFR (C677T polymorphism) and folate level, were most strongly related to homocysteine concentrations. The specificity of a homocysteine >13.1 µmol/l in predicting T/T homozygous status was 76% (area under the curve 0.68). CONCLUSION: Healthy dietary patterns, folate, and creatinine levels, as well as the C677T polymorphism, proved to be the strongest predictors of homocysteine concentrations. T/T genotype of MTHFR modifies the relationship between folate and homocysteine.
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Dieta Saudável , Comportamento Alimentar , Interação Gene-Ambiente , Homocisteína/sangue , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Polimorfismo Genético , Adolescente , Adulto , Fatores Etários , Biomarcadores/sangue , Creatinina/sangue , Feminino , Ácido Fólico/sangue , Voluntários Saudáveis , Humanos , Masculino , Adulto JovemRESUMO
BACKGROUND: Obesity is considered as an indispensable component of metabolic health assessment and metabolic syndrome diagnosis. The associations between diet quality and metabolic health in lean, young adults have not been yet established whilst data addressing this issue in overweight and obese subjects is scarce. Our analysis aimed to establish the link between diet quality (measured with data-driven dietary patterns and diet quality scores) and metabolic syndrome (MS) in young adults, regardless of their adiposity status. METHODS: A total of 797 participants aged 18-35 years old were included in the study. Participants were assigned into metabolic syndrome (MS) group if at least two abnormalities within the following parameters were present: blood pressure, triglycerides, total cholesterol, HDL cholesterol, blood glucose. Participants with one or none abnormalities were considered as metabolically healthy subjects (MH), Diet quality was assessed with two approaches: 1) a posteriori by drawing dietary patterns (DPs) with principal component analysis (PCA) and 2) a priori by establishing diet quality scores and the adherence to pro-Healthy-Diet-Index (pHDI) and non-Healthy-Diet-Index (nHDI). Logistic regression with backward selection based on Akaike information criterion was carried out, to identify factors independently associated with metabolic health. RESULTS: Within the MS group, 31% were of normal weight. Three PCA-driven DPs were identified, in total explaining 30.0% of the variance: "Western" (11.8%), "Prudent" (11.2%) and "Dairy, breakfast cereals & treats" (7.0%). In the multivariate models which included PCA-driven DPs, higher adherence to middle and upper tertiles of "Western" DP (Odds Ratios [OR] and 95% Confidence Intervals [95% CI]: 1.72, 1.07-2.79 and 1.74, 1.07-2.84, respectively), was associated with MS independently of clinical characteristics including BMI and waist-hip ratio (WHR). Similar results were obtained in the multivariate model with diet quality scores - MS was independently associated with higher scores within nHDI (2.2, 0.92-5.28). CONCLUSIONS: Individuals with MS were more likely to adhere to the western dietary pattern and have a poor diet quality in comparison to metabolically healthy peers, independently of BMI and WHR. It may imply that diet composition, as independent factor, plays a pivotal role in increasing metabolic risk. Professional dietary advice should be offered to all metabolically unhealthy patients, regardless of their body mass status.
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Dieta/métodos , Síndrome Metabólica/sangue , Síndrome Metabólica/fisiopatologia , Obesidade/sangue , Magreza/sangue , Adolescente , Adulto , Glicemia/metabolismo , Pressão Sanguínea/fisiologia , Colesterol/sangue , Estudos de Coortes , Feminino , Humanos , Masculino , Obesidade/fisiopatologia , Magreza/fisiopatologia , Triglicerídeos/sangue , Adulto JovemRESUMO
The aim of the study was to investigate the effect of physical training on bone parameters of rats exposed to alcohol (Al) and/or cadmium (Cd). Young female rats were divided into one control group and six groups exposed to Cd and/or Al. Al (36% calories of diet) and Cd (20 mg Cd/kg feed) were administered with liquid diet. Half of the rats from the treated groups were subjected to treadmill training (20 m/min for 0.5 h, 4 days a week). The experiment was carried out for 5 months. Al decreased the concentration of calcium (Ca) and iron (Fe) in the femur, whereas Cd and Cd + Al intake reduced the contents of Ca, Fe and zinc. Al and/or Cd caused an increase in both C-terminal telopeptide of type I collagen (CTX1; bone resorption marker) and osteocalcin (OC; formation indicator) and enhanced the degree of porosity and flexural strength of the femur. Al partially prevented the loss of Fe from the bone caused by Cd, but intensified the inhibition of growth of body weight in comparison with separate exposure to Cd. In rats co-exposed to Cd + Al, the levels of CTX1 were greater compared with those treated with Al or Cd separately, and the density was less than that in rats exposed to Al separately. The training caused increases of magnesium and Ca contents, decreases in CTX1, as well as increases in OC and bone density, decreasing their porosity. The effect of training on the bone status, however, was limited (especially in rats co-exposed to Cd and Al) because of the increase in their mineralization, stimulated by exercises, was insufficient in relation to collagen production intensity. In conclusion, training had favourable effects on some bone parameters, but did not compensate for the negative effects of Al and/or Cd exposure on the poor mineralization and histopathological and morphological changes in the femur.
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Densidade Óssea/efeitos dos fármacos , Remodelação Óssea/efeitos dos fármacos , Cádmio/farmacologia , Etanol/farmacologia , Condicionamento Físico Animal/fisiologia , Animais , Peso Corporal/efeitos dos fármacos , Reabsorção Óssea , Cálcio/metabolismo , Colágeno Tipo I/metabolismo , Feminino , Fêmur/efeitos dos fármacos , Ferro/metabolismo , Magnésio/metabolismo , Distribuição Aleatória , Ratos , Ratos Wistar , Zinco/metabolismoRESUMO
Associations among lead exposure, blood morphology, and cytokines influencing hematopoiesis are still inconclusive. Therefore, the objective of the present study was to demonstrate whether workers chronically exposed to lead demonstrate changes in complete blood count (CBC) parameters associated with altered levels of selected cytokines influencing hematopoiesis. The study covered 80 male subjects employed in the zinc-lead works in Miasteczko Slaskie. The subjects were divided into two groups: control group (24 healthy administration workers without a history of occupational exposure to lead compounds) and lead exposed group (56 subjects exposed to lead compounds in their work environment). The values of HTC, MCV, MCH, RDW-CV, PDW, and LMR were significantly lower in the exposed group than in the controls by 3%, 5%, 3%, 4%, 15%, and 47%, respectively. However, the levels of MCHC and MPV were higher in the exposed group than in the controls by 3% and 11%, respectively. Analogically, the values of MXD and MXD% were also significantly higher by 118% and 70%, respectively. The concentration of IL-7 was significantly higher in the exposed group compared to the controls by 143%. In this study, chronic lead exposure in the occupational setting at levels <50⯵g/dl does not affect RBC count and hemoglobin level but decreases MCV and hematocrit. Similarly, chronic lead toxicity does not affect WBC count but alters proportions of different types of leukocytes with significant increase of MXD count associated with elevated level of IL-7. Oppositely to a short-term lead exposure, chronic lead exposure elevates MPV and does not alter PLT count.
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Citocinas/sangue , Hematopoese/efeitos dos fármacos , Chumbo/sangue , Chumbo/toxicidade , Exposição Ocupacional/efeitos adversos , Adulto , Contagem de Células Sanguíneas , Contagem de Eritrócitos , Índices de Eritrócitos , Feminino , Humanos , Interleucina-7/sangue , Intoxicação por Chumbo/sangue , Masculino , Metalurgia , Pessoa de Meia-Idade , Protoporfirinas/sangue , Fatores de Risco , Adulto JovemRESUMO
The aim of the present study was to compare a group of workers with stable lead levels with a group of workers with fluctuating lead levels in terms of selected hematological, biochemical, and immunological parameters. The examined group included male workers occupationally exposed to lead. Blood lead (PbB) levels were measured every 3 months during the 5-year observation. Based on standard deviation of mean PbB levels, the examined population was divided into two groups: low level of fluctuation (L-SD) and high level of fluctuation (H-SD) groups. The mean and maximal PbB levels were significantly higher in the H-SD group than in the L-SD group by 9 and 22%, respectively. At the same time, the maximal level of zinc protoporphyrin (ZPP) and standard deviation of mean ZPP level were higher in the H-SD group by 29 and 55%, respectively. The maximal level of hemoglobin and white blood cell (WBC) count as well as standard deviation of the mean hemoglobin level and WBC count were higher in the H-SD group by 2, 8, 58, and 24%, respectively. The expression of nuclear factor kappa-B1 gene and telomerase reverse transcriptase gene was significantly greater in the H-SD group than in the L-SD group by 11 and 28%, respectively. Workers occupationally exposed to lead do not represent a homogenous population. Some present stable lead levels, whereas others have fluctuating lead levels. These fluctuations are related to secondary changes in ZPP and hemoglobin levels as well as WBC count.
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Chumbo/sangue , Exposição Ocupacional , Protoporfirinas/sangue , Adulto , Biomarcadores/sangue , Glutationa/sangue , Glutationa Peroxidase/metabolismo , Glutationa Redutase/metabolismo , Hemoglobinas/metabolismo , Humanos , Contagem de Leucócitos , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Malondialdeído/sangue , Pessoa de Meia-Idade , Subunidade p50 de NF-kappa B/genética , Subunidade p50 de NF-kappa B/metabolismo , Subunidade p52 de NF-kappa B/genética , Subunidade p52 de NF-kappa B/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Polônia , Superóxido Dismutase/metabolismo , Telomerase/genética , Telomerase/metabolismoRESUMO
PURPOSE: This study aimed to compare the influence of lead on the non-enzymatic antioxidant defenses and the levels of chemokines in workers subchronically and chronically exposed to lead. METHODS: The study population was divided into three groups. The first group consisted of male workers subchronically exposed to lead for 40 ± 3.2 days, while the second group included male workers chronically exposed to lead. The third group was a control group. RESULTS: The levels of uric acid and bilirubin were significantly higher after a subchronic exposure to lead compared to the baseline by 22 and 35 %, respectively. Similarly, the values of total antioxidant capacity (TAC), total oxidant status (TOS), and oxidative stress index (OSI) increased by 15, 50, and 33 %, respectively. At the same time, the levels of thiol groups and albumin decreased by 5 and 8 %, respectively. Additionally, the levels of interleukin-8 (IL-8) and macrophage inflammatory protein-1ß (MIP-1ß) were significantly higher after a subchronic exposure to lead compared to the baseline by 34 and 20 %, respectively. Moreover, IL-8 level was significantly higher by 40 % in the group of workers chronically exposed to lead than in the control group, while the level of interferon gamma-induced protein-10 (IP-10) was significantly lower by 28 %. CONCLUSIONS: Similar to chronic lead exposure, subchronic exposure to lead is associated with elevated blood levels of uric acid and bilirubin in humans. This probably results in increased TAC value despite thiol depletion. However, the compensatory activation of non-enzymatic antioxidant defenses seems to be insufficient to protect against lead-induced oxidative stress, which may be additively enhanced by the pro-inflammatory action of chemokines, especially IL-8.
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Antioxidantes/metabolismo , Quimiocinas/sangue , Intoxicação por Chumbo/sangue , Chumbo , Doenças Profissionais/sangue , Adulto , Bilirrubina/sangue , Quimiocina CCL4/sangue , Quimiocina CXCL10/sangue , Humanos , Interleucina-8/sangue , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo , Albumina Sérica/análise , Compostos de Sulfidrila/sangue , Ácido Úrico/sangueRESUMO
N-Acetylcysteine (NAC) could be included in protocols designed for the treatment of lead toxicity. Therefore, in this study, we decided to investigate the influence of NAC administration on homocysteine (Hcy) levels, oxidative damage to proteins, and the levels of iron (Fe), transferrin (TRF), and haptoglobin (HPG) in lead (Pb)-exposed workers. The examined population (n = 171) was composed of male employees who worked with Pb. They were randomized into four groups. Workers who were not administered any antioxidants, drugs, vitamins, or dietary supplements were classified as the reference group (n = 49). The remaining three groups consisted of workers who were treated orally with NAC at three different doses (1 × 200, 2 × 200, or 2 × 400 mg) for 12 weeks. After the treatment, blood Pb levels significantly decreased in the groups receiving NAC compared with the reference group. The protein concentration was not affected by NAC administration. In contrast, Hcy levels significantly decreased or showed a strong tendency toward lower values depending on the NAC dose. Levels of the protein carbonyl groups were significantly decreased in all of the groups receiving NAC. Conversely, glutamate dehydrogenase activity was significantly elevated in all of the groups receiving NAC, while the level of protein thiol groups was significantly elevated only in the group receiving 200 mg of NAC. Treatment with NAC did not significantly affect Fe and TRF levels, whereas HPG levels showed a tendency toward lower values. Treatment with NAC normalized the level of Hcy and decreased oxidative stress as measured by the protein carbonyl content; this effect occurred in a dose-dependent manner. Moreover, small doses of NAC elevated the levels of protein thiol groups. Therefore, NAC could be introduced as an alternative therapy for chronic Pb toxicity in humans.
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Acetilcisteína/uso terapêutico , Anemia Ferropriva/prevenção & controle , Antioxidantes/uso terapêutico , Suplementos Nutricionais , Hiper-Homocisteinemia/prevenção & controle , Intoxicação por Chumbo/prevenção & controle , Doenças Profissionais/prevenção & controle , Acetilcisteína/administração & dosagem , Adulto , Poluentes Ocupacionais do Ar/toxicidade , Anemia Ferropriva/etiologia , Antioxidantes/administração & dosagem , Haptoglobinas/análise , Homocisteína/sangue , Humanos , Hiper-Homocisteinemia/etiologia , Exposição por Inalação/efeitos adversos , Ferro/sangue , Chumbo/sangue , Chumbo/toxicidade , Intoxicação por Chumbo/sangue , Intoxicação por Chumbo/fisiopatologia , Masculino , Pessoa de Meia-Idade , Doenças Profissionais/sangue , Doenças Profissionais/fisiopatologia , Exposição Ocupacional/efeitos adversos , Estresse Oxidativo/efeitos dos fármacos , Polônia , Carbonilação Proteica , Protoporfirinas/sangue , Transferrina/análiseRESUMO
The negative health effects caused by lead (Pb) exposure are widely recognized; however, the molecular mechanisms remain unknown. The aim of this study was to assess the effect of occupational Pb exposure on telomere length and to investigate the potential mechanisms leading to telomere shortening. A cohort of 334 male Pb smelters (exposed group) and 60 age-adjusted males unexposed to Pb (control group) were examined. Assessments of relative telomere length (rTL) and telomerase reverse transcriptase (TERT) gene expression were performed using quantitative real-time polymerase chain reactions. Assessments of whole blood Pb (B-Pb) and whole blood cadmium (B-Cd) concentrations and serum selenium concentration (S-Se) were performed using graphite furnace atomic absorption spectrometry. We analyzed total oxidation status (TOS), lipid hydroperoxides (LHPs), malonylodialdehyde levels in serum (MDA) and in erythrocyte hemolysates (MDA-hgb), and 8-hydroxy-deoxy-guanosine (8-OHdG). The Pb-exposed group had higher B-Pb values and shorter rTL than the control group. The arithmetic mean values calculated for B-Pb were 33 µg/dL versus 2.2 µg/dL (p < 0.0001), and the rTL values were 0.928 and 1.126 relative units (p = 0.001), respectively, for the Pb-exposed and control groups. The rTL was found to gradually shorten in response to the increasing levels of Pb exposure. The Pb-exposed group also demonstrated a higher level of oxidative stress than the control group, which was indicated by increased TOS and MDA-hgb values. rTL was negatively associated with parameters that indicated increased oxidative stress, including TOS (Spearman's rank coefficient (rS) = -0.16; p < 0.01) and MDA-hgb (rS = -0.17; p < 0.001). No correlations were found between rTL and B-Cd and S-Se or smoking and MDA and LHP levels. Univariate analysis indicated that B-Pb was associated with decreased rTL (ß =-0.0041; p = 0.0063) and that the association between B-Pb and rTL remained significant, even when adjusting for age (ß = -0.0041; p = 0.0065) and in multivariable-adjusted model (ß = -0.0042; p = 0.0063). In conclusion, occupational Pb exposure resulted in decreased rTL and may represent a mechanism that contributes to Pb-related diseases.
Assuntos
Chumbo/toxicidade , Exposição Ocupacional/efeitos adversos , Estresse Oxidativo/genética , Telomerase/metabolismo , Telômero/ultraestrutura , 8-Hidroxi-2'-Desoxiguanosina , Cádmio/sangue , Cádmio/toxicidade , Estudos de Casos e Controles , Estudos de Coortes , Desoxiguanosina/análogos & derivados , Desoxiguanosina/sangue , Humanos , Chumbo/sangue , Peróxidos Lipídicos/sangue , Masculino , Malondialdeído/sangue , Pessoa de Meia-Idade , Selênio/sangue , Espectrofotometria Atômica , Telomerase/genéticaRESUMO
Shorter relative telomere length in peripheral blood is a risk marker for some types of cancers and cardiovascular diseases. Several environmental hazards appear to shorten telomeres, and this shortening may predispose individuals to disease. The aim of the present cross-sectional study was to assess the effect of environmental exposure to lead on relative telomere length (rTL) in children. A cohort of 99 8-year-old children was enrolled from 2007-2010. Blood lead concentrations (B-Pb) were measured by graphite furnace atomic absorption spectrometry, and blood rTL was measured by quantitative PCR. The geometric mean of B-Pb was 3.28 µg/dl (range: 0.90-14.2), and the geometric mean of rTL was 1.08 (range: 0.49-2.09). B-Pb was significantly inversely associated with rTL in the children (rS = -0.25, p = 0.013; in further analyses both log-transformed-univariate regression analysis ß = -0.13, p = 0.026, and R(2)adj 4%; and ß = -0.12, p = 0.056 when adjusting for mothers' smoking during pregnancy, Apgar score, mother's and father's ages at delivery, sex and mother's education, R(2)adj 12%, p = 0.011). The effect of lead remained significant in children without prenatal tobacco exposure (N = 87, rS = -0.24, p = 0.024; in further analyses, ß = -0.13, p = 0.029, and R(2)adj 4%). rTL was not affected by sex, the concentrations of other elements in the blood (i.e., cadmium and selenium concentrations), or oxidative injury parameters (total antioxidant status, 8-hydroxydeoxyguanosine and thiobarbituric acid-reactive substances). Lead exposure in childhood appears to be associated with shorter telomeres, which might contribute to diseases, such as cardiovascular disease. The inverse association between blood lead level and the telomeres in children emphasizes the importance of further reducing lead levels in the environment.
Assuntos
Exposição Ambiental/efeitos adversos , Exposição Ambiental/análise , Chumbo/efeitos adversos , Chumbo/sangue , Telômero/efeitos dos fármacos , Criança , Estudos Transversais , Feminino , Humanos , Masculino , Fatores de Risco , Fatores SocioeconômicosRESUMO
OBJECTIVES: Changes in enzymatic antioxidant activity are frequently observed in workers occupationally exposed to lead. Few studies have investigated the influence of lead on the non-enzymatic antioxidant system. The aim of our study was to assess the influence of occupational exposure to lead on the plasma concentration of two hydrophobic forms of vitamin E: α-tocopherol and γ-tocopherol. METHODS: A sample of 401 healthy men, aged 19-62, participated in the study. In total, 340 of these subjects were employed at the Mine and Metallurgical Plant in southern Poland. The workers who were occupationally exposed to lead were divided into quartiles (groups of 85 subjects). The lead concentrations in the blood of the subjects in the control group and in the lead exposure quartiles correspond to the following ranges: 10-72 µg/l (control group); 82-206 µg/l (Q1); 209-308 µg/l (Q2); 308-394 µg/l (Q3) and 395-644 µg/l (Q4), respectively. RESULTS: Significant differences were observed only for the plasma concentration of γ-tocopherol, which differed between the control group and Q1 (by 24.1%, p=0.0368), between Q1 and Q3 (by -18.8%, p=0.0115) and between Q1 and Q4 (by -25.7%, p=0.0002). Multiple linear regression analysis showed that the statistically significant, predictive properties of the γ-tocopherol plasma concentration were as follows: triglycerides (ß=0.440)> age (ß=0.131)> whole cholesterol (ß=0.117)> blood lead concentration (ß=-0.108). For α-tocopherol, significant prognostic properties were triglycerides and total cholesterol (ß=0.485 and ß=0.399, respectively). CONCLUSIONS: Occupational exposure to lead is strongly correlated with the concentration of γ-tocopherol but not α-tocopherol.
Assuntos
Antioxidantes/metabolismo , Chumbo/farmacologia , Exposição Ocupacional/efeitos adversos , alfa-Tocoferol/sangue , gama-Tocoferol/sangue , Adulto , Colesterol/sangue , Humanos , Chumbo/sangue , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Exposição Ocupacional/análise , Polônia , Triglicerídeos/sangue , Adulto JovemRESUMO
A 19-years old, previously healthy male, ingested the higher amount of rifampicin, isoniazyd, pyrazinamide, ketoprofene and alcohol. Within less than 20 hours he developed dyspnoe, pruritus, red man syndrome, and ECG changes suggesting acute coronary syndrome appeared - ST interval elevation. In the next few hours chest pain appeared and troponin I concentration was elevated (13.54 ng/ml). The performed echocardiography revealed global hypokinesis with the decreased left ventricular ejection fraction (approx. 30%). There was no significant pathological changes in coronarography, except for slowed blood flow. Further patient developed cardiogenic shock, pulmonary oedema and died within 32 hours from medication overdose.
Assuntos
Síndrome Coronariana Aguda/induzido quimicamente , Síndrome Coronariana Aguda/diagnóstico , Antituberculosos/intoxicação , Overdose de Drogas/complicações , Overdose de Drogas/diagnóstico , Suicídio , Ecocardiografia , Etanol/intoxicação , Evolução Fatal , Humanos , Isoniazida/intoxicação , Cetoprofeno/intoxicação , Masculino , Pirazinamida/intoxicação , Rifampina/intoxicação , Choque Cardiogênico/induzido quimicamente , Choque Cardiogênico/diagnóstico , Adulto JovemRESUMO
Iron is a transition metal that plays a crucial role in several physiological processes. It can also exhibit toxic effects on cells, due to its role in the formation of free radicals. Iron deficiency and anemia, as well as iron overload, are the result of impaired iron metabolism, in which a number of proteins, such as hepcidin, hemojuvelin and transferrin, take part. Iron deficiency is common in individuals with renal and cardiac transplants, while iron overload is more common in patients with hepatic transplantation. The current knowledge about iron metabolism in lung graft recipients and donors is limited. The problem is even more complex when we consider the fact that iron metabolism may be also driven by certain drugs used by graft recipients and donors. In this work, we overview the available literature reports on iron turnover in the human body, with particular emphasis on transplant patients, and we also attempt to assess the drugs' impact on iron metabolism, which may be useful in perioperative treatment in transplantology.
Assuntos
Anemia , Deficiências de Ferro , Sobrecarga de Ferro , Humanos , Ferro/metabolismo , Hepcidinas/metabolismo , Transferrina , Sobrecarga de Ferro/tratamento farmacológicoRESUMO
New psychoactive substances continue to appear on the drug market, and alpha-pyrrolidinoisohexanophenone (α-PiHP) is one of the most popular cathinone derivatives. In this article, we report a case of death caused by α-PiHP. Based on the toxicological results of the studied case along with autopsy, histopathological findings and crime-scene information, fatal intoxication with α-PiHP was accepted as the final cause of death. α-PiHP and its metabolite (OH-α-PiHP) were detected and quantified in all postmortem materials (blood collected from the heart, the femoral vein and the dural venous sinuses; vitreous humor; cerebrospinal fluid; cerebral cortex; brainstem; cerebellum; bile; liver; kidney; heart; pancreas; spleen; thyroid gland; lung; adipose tissue; stomach and intestine). To date, this is the first case of determination of α-PiHP and its metabolite in postmortem specimens. In our opinion, α-PiHP and its metabolite concentration database can be helpful in the interpretation of fatal cases.
Assuntos
Alcaloides , Líquidos Corporais , Humanos , Autopsia , BileRESUMO
OBJECTIVES: The authors aimed to evaluate whether blood cadmium (B-Cd), lead (B-Pb) and mercury (B-Hg) in children differ regionally in 9 countries, and to identify factors correlating with exposure. MATERIAL AND METHODS: The authors performed a cross-sectional study of children aged 7-14 years, living in 2007-2008 in urban, rural, or potentially polluted ("hot spot") areas (ca. 50 children from each area, in total 1363 children) in 6 European and 3 non-European countries. The authors analyzed Cd, Pb, and total Hg in blood and collected information on potential determinants of exposure through questionnaires. Regional differences in exposure levels were assessed within each country. RESULTS: Children living near industrial "hot-spots" had B-Cd 1.6 (95% CI: 1.4-1.9) times higher in the Czech Republic and 2.1 (95% CI:1.6-2.8) times higher in Poland, as compared to urban children in the same countries (geometric means [GM]: 0.13 µg/l and 0.15 µg/l, respectively). Correspondingly, B-Pb in the "hot spot" areas was 1.8 (95% CI: 1.6-2.1) times higher than in urban areas in Slovakia and 2.3 (95% CI: 1.9-2.7) times higher in Poland (urban GM: 19.4 µg/l and 16.3 µg/l, respectively). In China and Morocco, rural children had significantly lower B-Pb than urban ones (urban GM: 64 µg/l and 71 µg/l, respectively), suggesting urban exposure from leaded petrol, water pipes and/or coal-burning. Hg "hot spot" areas in China had B-Hg 3.1 (95% CI: 2.7-3.5) times higher, and Ecuador 1.5 (95% CI: 1.2-1.9) times higher, as compared to urban areas (urban GM: 2.45 µg/l and 3.23 µg/l, respectively). Besides industrial exposure, traffic correlated with B-Cd; male sex, environmental tobacco smoke, and offal consumption with B-Pb; and fish consumption and amalgam fillings with B-Hg. However, these correlations could only marginally explain regional differences. CONCLUSIONS: These mainly European results indicate that some children experience about doubled exposures to toxic elements just because of where they live. These exposures are unsafe, identifiable, and preventable and therefore call for preventive actions. Int J Occup Med Environ Health. 2023;36(3):349-64.