RESUMO
OBJECTIVE: To describe the use of nutritional supplements and blood status (hemogram, lipidogram, hepatic function, inflammatory markers, minerals, and homocysteine) in a sample of Brazilian T21 children with private health support before their first consultation with a T21 expert. METHOD: This descriptive cross-sectional study enrolled 102 participants. Brazilian families with a T21 member under 18 years old were contacted and those that consented answered a survey regarding socio-demographics and the use of nutritional supplements and shared the blood tests that their T21 members have collected for the first consultation with a T21 expert. RESULTS: Frequencies and percentages were used to describe the variables. The most used supplements included vitamins (A, C and D), minerals (zinc and iron), omega-3, and antioxidants (curcumin). Hypothyroidism was observed in 56.9% of the participants. Hemogram alterations (increased hemoglobin, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin and red cell distribution width, leukopenia, and lymphocytopenia), dyslipidemia, altered hepatic and inflammatory blood markers were frequently found. CONCLUSIONS: Nutritional supplements (mainly vitamins, minerals, omega-3 and antioxidants) are frequently used by Brazilian T21 children independently of professional counseling and/or supervision and should be a question to be raised during the clinical anamnesis since some of them may impact medical conduct. Moreover, many blood tests are altered in this population and clinicians should be aware of them in order to warrant an appropriate screening and the implementation of risk management measures as soon as possible and improve the general health of these persons.
Assuntos
Síndrome de Down , Humanos , Criança , Adolescente , Brasil , Estudos Transversais , Suplementos Nutricionais , Vitaminas , Minerais , Antioxidantes , Vitamina A , Testes HematológicosRESUMO
Paracetamol (PAR) is an over-the-counter analgesic/antipyretic used during pregnancy worldwide. Epidemiological studies have been associating gestational PAR exposure with neurobehavioral alterations in the progeny resembling autism spectrum disorders and attention-deficit hyperactivity disorder symptoms. The endocannabinoid (eCB) dysfunction was previously hypothesized as one of the modes of action by which PAR may harm the developing nervous system. We aimed to evaluate possible effects of gestational exposure to PAR on male and female rat's offspring behavior and if an acute injection of WIN 55,212-2 (WIN, 0.3 mg/kg), a non-specific cannabinoid agonist, prior to behavioral tests, would induce different effects in PAR exposed and non-exposed animals. Pregnant Wistar rats were gavaged with PAR (350 mg/kg/day) or water from gestational day 6 until delivery. Nest-seeking, open field, apomorphine-induced stereotypy, marble burying and three-chamber tests were conducted in 10-, 24-, 25- or 30-days-old rats, respectively. PAR exposure resulted in increased apomorphine-induced stereotyped behavior and time spent in the central area of the open field in exposed female pups. Additionally, it induced hyperactivity in the open field and increased marble burying behavior in both male and female pups. WIN injection modified the behavioral response only in the nest seeking test, and opposite effects were observed in control and PAR-exposed neonate females. Reported alterations are relevant for the neurodevelopmental disorders that have been associated with maternal PAR exposure and suggest that eCB dysfunction may play a role in the action by which PAR may harm the developing brain.
Assuntos
Transtorno do Espectro Autista , Efeitos Tardios da Exposição Pré-Natal , Humanos , Gravidez , Ratos , Animais , Masculino , Feminino , Agonistas de Receptores de Canabinoides/efeitos adversos , Acetaminofen/toxicidade , Apomorfina , Ratos Wistar , Endocanabinoides , Transtorno do Espectro Autista/induzido quimicamente , Carbonato de Cálcio/efeitos adversos , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamenteRESUMO
Abstract Objective: To describe the use of nutritional supplements and blood status (hemogram, lipidogram, hepatic function, inflammatory markers, minerals, and homocysteine) in a sample of Brazilian T21 children with private health support before their first consultation with a T21 expert. Method: This descriptive cross-sectional study enrolled 102 participants. Brazilian families with a T21 member under 18 years old were contacted and those that consented answered a survey regarding socio-demographics and the use of nutritional supplements and shared the blood tests that their T21 members have collected for the first consultation with a T21 expert. Results: Frequencies and percentages were used to describe the variables. The most used supplements included vitamins (A, C and D), minerals (zinc and iron), omega-3, and antioxidants (curcumin). Hypothyroidism was observed in 56.9% of the participants. Hemogram alterations (increased hemoglobin, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin and red cell distribution width, leukopenia, and lymphocytopenia), dyslipidemia, altered hepatic and inflammatory blood markers were frequently found. Conclusions: Nutritional supplements (mainly vitamins, minerals, omega-3 and antioxidants) are frequently used by Brazilian T21 children independently of professional counseling and/or supervision and should be a question to be raised during the clinical anamnesis since some of them may impact medical conduct. Moreover, many blood tests are altered in this population and clinicians should be aware of them in order to warrant an appropriate screening and the implementation of risk management measures as soon as possible and improve the general health of these persons.
RESUMO
BACKGROUND: Temporal lobe epilepsy (TLE) is the most common focal epilepsy subtype in adults and is frequently accompanied by depression, anxiety and psychosis. Aberrations in total paraoxonase 1 (PON1) status may occur in TLE and these psychiatric conditions. AIM: To examine PON1 status, namely Q192R PON1 genotypes and PON1 enzymatic activities, in TLE. METHODS: We recruited 40 normal controls and 104 TLE patients, 27 without comorbidities and 77 with comorbidities including mood disorders (n = 25), anxiety disorders (n = 27) and psychosis (n = 25). RESULTS: Four-(chloromethyl)phenyl acetate hydrolysis (CMPAase) and arylesterase activities were significantly lower in TLE and mesial temporal sclerosis (MTS) with and without psychiatric comorbidities than those in normal controls. The areas under the receiver operating characteristic curve of CMPAase were 0.893 (0.037) for TLE and 0.895 (± 0.037) for MTS. Partial least squares path analysis showed that there were specific indirect effects of PON1 genotype on TLE severity (P < 0.0001) and psychopathology (P < 0.0001), which were both mediated by lowered CMPAase activity, while arylesterase activity was not significant. The severity of TLE was significantly associated with psychopathology scores. Furthermore, PON1 CMPAase activity was inversely associated with Mini Mental State Examination score. CONCLUSION: The severity of TLE and comorbidities are to a large extent explained by reduced PON1 enzyme activities and by effects of the Q192R genotype, which are mediated by reduced CMPAase activity. Total PON1 status plays a key role in the pathophysiology of TLE, MTS and psychiatric comorbidities by increasing the risk of oxidative toxicity. PON1 enzyme activities are new drug targets in TLE to treat seizure frequency and psychiatric comorbidities.
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BACKGROUND: Increased generation of reactive oxygen and nitrogen species in chronic kidney disease (CKD) patients leads to increased oxidative stress. The antioxidant capacity of folic acid has been shown to scavenge radicals efficiently. OBJECTIVE: The current study was carried out to examine the effects of folic acid treatment on biochemical and oxidative stress biomarkers in patients in different stages of CKD. METHODS: This was a randomized, non-blinded, clinical trial that assessed the effects of 3 months of treatment with 5 mg of folic acid daily or no treatment in 113 outpatients within CKD stages 3a and 3b. At the end of the intervention, we analyzed the data of 66 patients treated with folic acid and 47 in the control group. Serum homocysteine levels and biochemical and oxidative/nitrosative stress biomarkers were analyzed in all patients. RESULTS: In most patients, folic acid treatment normalized homocysteine levels and increased antioxidant enzyme activity (paraoxonase 1) and decreased sulfhydryl (SH) groups. In addition, oxidative biomarkers (products of nitric oxide and lipid hydroperoxide) were significantly lower post-treatment compared to baseline in the active intervention group. In the no active intervention group, no statistically significant effects were found on the oxidative and biochemical biomarkers. CONCLUSION: Folic acid treatment in stages 3a-4 CKD patients effectively ameliorated their hyperhomocysteinemia and increased the activity of antioxidant enzymes, as well as decreased the levels of pro-oxidant biomarkers in stage G3a and G3b CKD patients. Folic acid treatment attenuated oxidative/nitrosative stress and may be considered as a possible strategy to improve redox status and diminish the damages associated with oxidative/nitrosative stress in CKD patients. Further studies are needed to confirm these findings. Clinical Trials Registration No.: This study is registered in the Brazilian Record of Clinical Trials (ReBEC), under reference RBR-2bfthr.
Assuntos
Antioxidantes/administração & dosagem , Ácido Fólico/administração & dosagem , Estresse Oxidativo/efeitos dos fármacos , Insuficiência Renal Crônica/tratamento farmacológico , Idoso , Antioxidantes/farmacologia , Feminino , Ácido Fólico/farmacologia , Humanos , Hiper-Homocisteinemia/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Estresse Nitrosativo/efeitos dos fármacos , Oxirredução/efeitos dos fármacos , Resultado do TratamentoRESUMO
Triclosan (TCS) is a phenolic compound with broad-spectrum antimicrobial action that has been incorporated into a variety of personal care products and other industry segments such as toys, textiles, and plastics. Due to its widespread use, TCS and its derivatives have been detected in several environmental compartments, with potential bioaccumulation and persistence. Indeed, some studies have demonstrated that TCS may act as a potential endocrine disruptor for the reproductive system. In the current study, we are reporting on the results obtained for male rats after a two-generation reproduction toxicity study conducted with TCS. Female and male Wistar rats were treated daily by gavage with TCS at doses of 0.8, 2.4, and 8.0 mg/kg/day or corn oil (control group) over 10 weeks (F0) and over 14 weeks (F1) before mating and then throughout mating, until weaning F2 generations, respectively. TCS exposure decreased sperm viability and motility of F1 rats at the dose of 2.4 mg/kg. The effects of TCS on sperm quality may be related to the exposure window, which includes the programming of reproductive cells that occurs during fetal/neonatal development.
Assuntos
Anti-Infecciosos Locais/administração & dosagem , Disruptores Endócrinos/administração & dosagem , Reprodução/efeitos dos fármacos , Comportamento Sexual/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos , Triclosan/administração & dosagem , Administração Oral , Animais , Comportamento Animal/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Ingestão de Alimentos/efeitos dos fármacos , Feminino , Masculino , Ratos , Ratos Wistar , Contagem de Espermatozoides , Motilidade dos Espermatozoides/efeitos dos fármacos , Testosterona/sangueRESUMO
ABSTRACT: Paracetamol (PAR) is the most common over-the-counter drug recommended by physicians for treatment of pain and fever during gestation. This drug is not teratogenic, being considered safe for fetus; however, PAR crosses the blood-placental barrier. Considering that, the present study aimed to evaluate the vascular and metabolic safety of PAR exposure during intrauterine and neonatal development in adult male and female-exposed offspring. Wistar female rats were gavaged, with PAR (350 mg/kg/d), from gestational day 6-21 or from gestational day 6 until postnatal day 21. Control dams received water by gavage at the same periods. The male and female offspring were evaluated at adulthood (80 days of life). The thoracic aorta reactivity to acetylcholine, sodium nitroprusside, and phenylephrine was evaluated in male and female adult offspring. It was observed that aortic relaxation was similar between the PAR and control offspring. In addition, the contraction to phenylephrine was similar between the groups. Further, the insulin sensitivity, adipose tissue deposition and blood pressure were not different between PAR and control adult offspring. These results suggest that the protocol of PAR exposure used in the present study did not program vascular and metabolic alterations that would contribute to the development of cardiometabolic diseases in adult life, being safe for the exposed offspring.
Assuntos
Acetaminofen/toxicidade , Analgésicos não Narcóticos/toxicidade , Doenças Cardiovasculares/induzido quimicamente , Lactação , Doenças Metabólicas/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal , Adiposidade/efeitos dos fármacos , Animais , Aorta Torácica/efeitos dos fármacos , Aorta Torácica/fisiopatologia , Doenças Cardiovasculares/fisiopatologia , Feminino , Idade Gestacional , Hemodinâmica/efeitos dos fármacos , Resistência à Insulina , Masculino , Doenças Metabólicas/sangue , Doenças Metabólicas/fisiopatologia , Gravidez , Ratos Wistar , Medição de RiscoRESUMO
Paracetamol (PAR) has been employed worldwide for pain and fever treatment during pregnancy and lactation. Epidemiologic studies have shown that exposure to PAR can increase the risk for developmental disorders, such as attention-deficit hyperactive disorder and autism spectrum disorder. This study aimed to investigate if gestational and lactational exposure to human-relevant doses of PAR could alter behavioural and brain oxidative stress parameters in the rat`s offspring. Wistar dams were gavaged daily with water or PAR (35 mg/kg/ or 350 mg/kg) during gestational day 6 to weaning (postnatal day 21). Behavioural assessments occurred at post-natal days 10 (nest seeking test), 27 (behavioural stereotypy) and 28 (three chamber sociability test and open field). Concentration of advanced oxidation protein products (AOPP), reduced glutathione (GSH), lipid hydroperoxides (LOOH) and activity of superoxide dismutase (SOD) were estimate in prefrontal cortex, hippocampus, striatum and cerebellum of 22-day-old rats. Compared to CON animals, males exposed to PAR during pregnancy and lactation augmented apomorphine-induced stereotyped behaviour (350 mg/kg) and ambulation in open-field test (35 mg/kg). Reduced exploratory behaviour in three chamber sociability test was observed in pups exposed to PAR at 350 mg/kg in both sexes. PAR treatment decreased hippocampal GSH level and striatal SOD activity in males exposed to 35 mg/kg, suggesting the vulnerability of these areas in PAR-induced developmental neurotoxicity. Findings suggest PAR use during pregnancy and lactation as a potential risk factor for neurodevelopmental disorders with males being more susceptible.
Assuntos
Acetaminofen/farmacologia , Comportamento Animal/efeitos dos fármacos , Fármacos do Sistema Nervoso Central/farmacologia , Comportamento Exploratório/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Transtornos do Neurodesenvolvimento/induzido quimicamente , Estresse Oxidativo/efeitos dos fármacos , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Acetaminofen/administração & dosagem , Animais , Comportamento Animal/fisiologia , Aleitamento Materno , Fármacos do Sistema Nervoso Central/administração & dosagem , Modelos Animais de Doenças , Comportamento Exploratório/fisiologia , Feminino , Hipocampo/metabolismo , Masculino , Transtornos do Neurodesenvolvimento/fisiopatologia , Gravidez , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Ratos , Ratos Wistar , Fatores SexuaisRESUMO
BACKGROUND: Primary deficit schizophrenia (DS) is characterized by enduring negative symptoms and represents a qualitatively different disease entity with respect to non-deficit schizophrenia (NDS). No studies investigated the association between the enzyme paraoxonase 1 (PON1) and DS and its phenomenology. METHODS: In this case-control study, Thai women and men, aged 18 to 65 years, were divided in DS (n = 40) and NDS (n = 40) and were compared to controls (n = 40). PON1 activities against 4-(chloromethyl)phenyl acetate (CMPA) and phenylacetate were determined. Moreover, subjects were genotyped for their PON1 Q192R polymorphism and immunoglobulin A (IgA) levels responses directed to Gram-negative bacteria were measured. RESULTS: DS is significantly associated with the QQ genotype and the Q allele as compared with NDS and controls. PON1 activities are significantly and inversely associated with negative symptoms, formal thought disorders, psychomotor retardation, excitation and DS. The presence of the Q allele is associated with increased IgA responses to Pseudomonas aeruginosa, Morganella morganii, and Pseudomonas putida as compared with RR carriers. CONCLUSIONS: The PON1 Q allele and lower PON1 activities especially against CMPA are associated with DS, indicating lowered quorum quenching abilities as well as lowered defenses against lipoperoxidation and immune activation. It is suggested that lowered PON1 activity in DS constitutes an impairment in the innate immune system which together with lowered natural IgM may cause lower immune regulation thereby predisposing toward greater neurotoxic effects of immune-inflammatory, oxidative and nitrosative pathways and Gram-negative microbiota.
Assuntos
Arildialquilfosfatase/genética , Genótipo , Polimorfismo Genético , Esquizofrenia/genética , Adulto , Arildialquilfosfatase/metabolismo , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Esquizofrenia/metabolismo , TailândiaRESUMO
BACKGROUND: Hypertension, atherogenicity and insulin resistance are major risk factors of cardiovascular disorder (CVD), which shows a strong comorbidity with major depression (MDD) and bipolar disorder (BD). Activated oxidative and nitrosative stress (O&NS), inflammatory pathways, and increased atherogenicity are shared pathways underpinning CVD and mood disorders. METHODS: The current study examined the effects of lipid hydroperoxides (LOOH), superoxide dismutase (SOD), nitric oxide metabolites (NOx), advanced oxidation protein products (AOPP), and malondialdehyde (MDA) on systolic (SBP) and diastolic (DBP) blood pressure in 96 mood disordered patients and 60 healthy controls. RESULTS: A large part of the variance in SBP (31.6%) was explained by the regression on a z unit-weighted composite score (based on LOOH, AOPP, SOD, NOx) reflecting nitro-oxidative stress toxicity (NOSTOX), coupled with highly sensitive C-reactive protein, body weight and use of antihypertensives. Increased DBP was best predicted (23.8%) by body mass index and NOSTOX. The most important O&NS biomarkers predicting an increased SBP were in descending order of significance: LOOH, AOPP and SOD. Higher levels of the atherogenic index of plasma, HOMA2 insulin resistance index and basal thyroid-stimulating hormone also contributed to increased SBP independently from NOSTOX. Although there were no significant changes in SBP/DBP in mood disorders, the associations between NOSTOX and blood pressure were significant in patients with mood disorders but not in healthy controls. CONCLUSIONS: Activated O&NS pathways including increased lipid peroxidation and protein oxidation, which indicates hypochlorous stress, are the most important predictors of an increased BP, especially in patients with mood disorders.