RESUMO
Research on the relationships between oligoelements (OE) and the development of cancer or its prevention is a field that is gaining increasing relevance. The aim was to evaluate OE and their interactions with oncology treatments (cytarabine or etoposide) to determine the effects of this combination on biogenic amines and oxidative stress biomarkers in the brain regions of young Wistar rats. Dopamine (DA), 5-Hydroxyindoleacetic acid (5-Hiaa), Glutathione (Gsh), Tiobarbituric acid reactive substances (TBARS) and Ca+2, Mg+2 ATPase enzyme activity were measured in brain regions tissues using spectrophometric and fluorometric methods previously validated. The combination of oligoelements and cytarabine increased dopamine in the striatum but decreased it in cerebellum/medulla-oblongata, whereas the combination of oligoelements and etoposide reduced lipid peroxidation. These results suggest that supplementation with oligoelements modifies the effects of cytarabine and etoposide by redox pathways, and may become promising therapeutic targets in patients with cancer.
Assuntos
Encéfalo , Citarabina , Dopamina , Etoposídeo , Estresse Oxidativo , Ratos Wistar , Animais , Etoposídeo/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Citarabina/farmacologia , Dopamina/metabolismo , Ratos , Encéfalo/metabolismo , Encéfalo/efeitos dos fármacos , Masculino , Peroxidação de Lipídeos/efeitos dos fármacos , Suplementos Nutricionais , Glutationa/metabolismoRESUMO
The ability and facility of magnesium (Mg2+) and zinc (Zn2+) to interact with phosphate ions confer them the characteristics of essential trace elements. Trace elements are extremely necessary for the basic nucleic acid chemistry of cells of all known living organisms. More than 300 enzymes require zinc and magnesium ions for their catalytic actions, including all the enzymes involved in the synthesis of ATP. In addition, enzymes such as isomerases, oxidoreductases, lyases, transferases, ligases and hydrolases that use other nucleotides to synthesize DNA and RNA require magnesium and zinc. These nucleotides may trigger oxidative damage or important changes against free radicals. In the same way, nucleotides may play an important role in the pathophysiology of degenerative diseases, including in some clinical disorders, where vascular risk factors, oxidative stress and inflammation work to destabilize the patients` homeostatic equilibrium. Indeed, reduced levels of zinc and magnesium may lead to inadequate amount of antioxidant enzymes, and thus, acts as an important contributing factor for the induction of oxidative stress leading to cellular or tissue dysfunction. Hence, the development of zinc or magnesium enzyme inhibitors could be a novel opportunity for the treatment of some human disorders. Therefore, the objective of the present work was to assess the clinical benefits of zinc and magnesium in human health and their effects in some clinical disorders.
Assuntos
Oligoelementos , Zinco , Humanos , Magnésio/farmacologia , Nucleotídeos , ÍonsRESUMO
Major depressive disorder (MDD) is one of the most common psychiatric illnesses in the general population. In mental disorders, the activation of inflammatory pathways in the brain is a major producer of excitotoxicity and an inducer of oxidative stress. The occurrence of these 2 events is partly responsible for the neuronal damage inherent in patients with mental disorders. In the case of MDD, the release of hormone and increase in pro-inflammatory cytokines in plasma and indicators of oxidative stress have been identified as consequences of this event. The most important affectations in patients with MDD are changes in their cognitive and executive functions due to brain inflammation. Hence, these biomarkers can serve as diagnostic and severity classification tools and treatment. In this work, we described the communication pathway between the immune and neuroendocrine systems in MDD and suggested possible therapeutic options for the disease.
Assuntos
Transtorno Depressivo Maior/imunologia , Doenças Neuroinflamatórias/imunologia , Biomarcadores/metabolismo , Encéfalo/metabolismo , Citocinas/metabolismo , Humanos , Sistema Imunitário/metabolismo , Estresse OxidativoRESUMO
Tuberculosis (TB) remains a global problem and a diagnostic challenge, especially in pediatrics. The aim of this study was to describe the clinical, microbiological, radiological, and histopathological data of TB in children. A 7-year retrospective and descriptive cohort study that included 127 patients under 18 years of age with diagnosis of active TB was conducted from 2011 to 2018 in a pediatric hospital. Tuberculosis was microbiologically confirmed using Ziehl-Neelsen (ZN) staining, culture or polymerase chain reaction (PCR) in a total of 94 (74%) cases. Thirty-three cases were defined as probable TB based on tuberculin skin test result and epidemiological evaluation. The TB forms found were lymph node (39.3%), bone (15.7%), lung (13.6%), and meningeal TB (8.6%). The most common symptoms were fever (48.8%) and adenopathy (45.6%). History of contact was established in 34.6%. Positive ZN staining (sensitivity 30%) and culture (sensitivity 37%) were found in 29% and 37.7% of subjects, respectively. About 64.5% depicted abnormal chest X-ray. Xpert MTB/RIF® (PCR) was positive in 9.4% and biopsy was compatible in 52.7% of these samples. It is fundamental to have laboratory and epidemiological evaluation that support the diagnosis of the disease in children and thus, define its management; since, in most cases, early microbiologic confirmation is lacking.
Assuntos
Hospitais Pediátricos , Tuberculose , Adolescente , Criança , Pré-Escolar , Estudos de Coortes , Corantes , Feminino , Humanos , Masculino , México/epidemiologia , Mycobacterium tuberculosis/isolamento & purificação , Patologia Molecular , Estudos Retrospectivos , Sensibilidade e Especificidade , Tuberculose/diagnóstico , Tuberculose/epidemiologia , Tuberculose/patologia , Tuberculose dos Linfonodos/diagnóstico , Tuberculose dos Linfonodos/epidemiologia , Tuberculose dos Linfonodos/patologia , Tuberculose Meníngea/diagnóstico , Tuberculose Meníngea/epidemiologia , Tuberculose Meníngea/patologia , Tuberculose Pulmonar/diagnóstico , Tuberculose Pulmonar/epidemiologia , Tuberculose Pulmonar/patologiaRESUMO
BACKGROUND: Simultaneous infection in tuberculosis (TB) is rare. The mixed infection between Streptococcus anginosus group (SAG) and M. tuberculosis (MTB) has not been reported in children. The aim of this report was to describe a pediatric case with a pulmonary abscess caused by the duality SAG-MTB co-infection. CASE PRESENTATION: An 11-year-old boy with an acute onset of throbbing pain of two-day evolution located in the anterior chest wall. The patient reported a history of fever, cough and rhinorrhea during the last seven days. An anterior chest radiography revealed a heterogenic opacity at the lower right lobe while the lateral projection showed an obliteration at the anterior diaphragmatic insertion. Parenteral Ceftriaxone (100 mg/kg/day) and Dicloxacillin (200 mg/kg/day) was started. The abscess was subsequently drained and analyzed. After a year of follow-up, the patient remained asymptomatic. CONCLUSION: This case represents the first reported case of pulmonary co-infection involving MTB and SAG in an immunocompetent pediatric patient.
Assuntos
Coinfecção/microbiologia , Abscesso Pulmonar/microbiologia , Mycobacterium tuberculosis/isolamento & purificação , Infecções Estreptocócicas/complicações , Streptococcus anginosus/isolamento & purificação , Tuberculose/complicações , Antibacterianos/uso terapêutico , Criança , Drenagem , Humanos , Imunocompetência , Abscesso Pulmonar/terapia , Masculino , Derrame Pleural/diagnóstico por imagem , Radiografia Torácica , Infecções Estreptocócicas/tratamento farmacológico , Resultado do Tratamento , Tuberculose/tratamento farmacológicoRESUMO
The aim of the present study was to determine the effect of sildenafil on dopamine, 5-hydroxyindol acetic acid (5-HIAA) and selected biomarkers of oxidative stress in the brain of hypoglycemic rats. The animals were treated intraperitoneally as follows: group 1 (control), saline solution; group 2, insulin (10 U per rat or 50 U kg-1); group 3, insulin + single dose of sildenafil (50 U kg-1 + 50 mg kg-1); group 4, insulin + three doses of sildenafil every 24 hours (50 U kg-1 + 50 mg kg-1). In groups 2, 3 and 4, insulin was administered every 24 hours for 10 days. Blood glucose was measured after the last treatment. On the last day of the treatment, the animals´ brains were extracted to measure the levels of oxidative stress markers [H2O2, Ca2+,Mg2+-ATPase, glutathione and lipid peroxidation (TBARS)], dopamine and 5-HIAA in the cortex, striatum and cerebellum/medulla oblongata by validated methods. The results suggest that administration of insulin in combination with sildenafil induces hypoglycemia and hypotension, enhances oxidative damage and provokes changes in the brain metabolism of biogenic amines. Administration of insulin and sildenafil promotes biometabolic responses in glucose control, namely, it induces hypoglycemia and hypotension. It also enhances oxidative damage and provokes changes in the brain metabolism of biogenic amines.
Assuntos
Aminas Biogênicas/metabolismo , Hipoglicemia/fisiopatologia , Estresse Oxidativo/efeitos dos fármacos , Citrato de Sildenafila/toxicidade , Animais , Glicemia/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Dopamina/metabolismo , Ácido Hidroxi-Indolacético/metabolismo , Insulina/administração & dosagem , Insulina/farmacologia , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Ratos , Ratos WistarRESUMO
BACKGROUND & OBJECTIVE: The purpose of this study was to measure the effect on brain biomarkers after treatment with anticancer compounds - cytarabine (CT) and ferric carboxymaltose (FC) (Fe+3) in Wistar rats. METHODS: The Wistar rats were treated as follows: group 1 (control), NaCl 0.9%; group 2, CT (25 mg/k), group 3, FC(Fe+3) (50 mg/k) and group 4, CT + FC(Fe+3). The animals were sacrificed and their brains were obtained and used to measure lipoperoxidation (TBARS), H2O2, Na+, K+ ATPase, glutathione (GSH), serotonin metabolite (5-HIAA) and dopamine. The results indicated an enhancement of lipid peroxidation in the cortex and striatum of groups treated with FC(Fe+3) and CT, while GSH decreased in the cortex of group treated with CT + FC(Fe+3). Dopamine decreased in the cortex of the rats that received CT, while in the striatum, 5HIAA increased in all groups. RESULTS & CONCLUSION: These results suggest that the treatment with CT and FC(Fe+3) boosted oxidative stress and led to an alteration in momoamine concentrations in the brain.
Assuntos
Encéfalo/efeitos dos fármacos , Citarabina/farmacologia , Compostos Férricos/farmacologia , Peroxidação de Lipídeos/efeitos dos fármacos , Maltose/análogos & derivados , Estresse Oxidativo/efeitos dos fármacos , Animais , Encéfalo/metabolismo , Dopamina/metabolismo , Peróxido de Hidrogênio/farmacologia , Maltose/farmacologia , Oxirredução/efeitos dos fármacos , Ratos Wistar , Serotonina/metabolismoRESUMO
BACKGROUND: Neurological disorders suggest that the excitotoxicity involves a drastic increase in intracellular Ca2+ concentrations and the formation of reactive oxygen species. The presence of these free radicals may also affect the dopaminergic system. The aim of this work was to determine if riboflavin (B2) and pyridoxine (B6) provide protection to the brain against free radicals generated by 3-nitropropionic acid (3-NPA) by measuring the levels of dopamine (DA) and selected oxidative stress markers. METHODS: Male Fisher rats were grouped (n = 6) and treated as follows: group 1, control (NaCl 0.9%); group 2, 3-NPA (20 mg/kg); group 3, B2 (10 mg/kg); group 4, B2 (10 mg/kg) + 3-NPA (20 mg/kg); group 5, B6 (10 mg/kg) and group 6, B6 + 3-NPA. All treatments were administered every 24 h for 5 days by intraperitoneal route. After sacrifice, the brain was obtained to measure DA, GSH, and lipid peroxidation, Ca2+, Mg2+, ATPase and H2O2. MAIN FINDINGS: Levels of dopamine increased in cortex, striatum and cerebellum/medulla oblongata of animals that received 3-NPA alone. The lipid peroxidation increased in cortex, striatum, and cerebellum/medulla oblongata, of animals treated with B2 vitamin alone. ATPase dependent on Ca+2, Mg+2 and H2O2 increased in all regions of animals that received 3-NPA alone. CONCLUSION: The results confirm the capacity of 3-NPA to generate oxidative stress. Besides, the study suggests that B2 or B6 vitamins restored the levels of DA and reduced oxidative stress in brain of rats. We believe that these results would help in the study of neurodegenerative diseases.
Assuntos
Antioxidantes/farmacologia , Encéfalo/efeitos dos fármacos , Dopamina/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Piridoxina/farmacologia , Riboflavina/farmacologia , Animais , Encéfalo/metabolismo , Radicais Livres/metabolismo , Doença de Huntington/metabolismo , Masculino , Fármacos Neuroprotetores/farmacologia , Nitrocompostos , Estresse Oxidativo/fisiologia , Propionatos , Ratos Endogâmicos F344 , Ratos WistarRESUMO
For many years, depressive disorder (DD) was considered a transient and natural disease of people's mood. Its etiology had been attributed mainly to biochemical alterations of the monoamines and their receptors. Nevertheless, its prevalence and considerable impact on the family and social environment of those afflicted by it have placed the disease as a global public health problem. Neuroprogression is the term used to describe the changes in several psychiatric conditions evidenced and observed in the clinical manifestations, biochemical markers, and cerebral structures of the patients with major depressive disorder (MDD), which frequently overlap with neurodegenerative disorders. DD is considered a potentially aggressive state of neuronal deterioration involving apoptosis, reduced neurogenesis, decreased neuronal plasticity, and increased immune response. Clinically, it encompasses a poor response to treatment and an increase in depressive episodes, both of which bring about vulnerability and decline of functions associated with structural changes in the brain. The interest of this work is to review the metabolic processes involved in the morphologic alterations in the limbic system reported in patients with MDD, as well as the neurologic bases of this complex pathology that include environmental stress, genetic vulnerability, alterations in the neurotransmission, and changes in the neuroplasticity, all of which today bring into limelight a mechanism of progressive neuronal damage.