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1.
Pharmacol Res ; 164: 105277, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33166735

RESUMO

More than 50 million people have various forms of cognitive impairment basically caused by neurodegenerative diseases, such as Alzheimer's, Parkinson's, and cerebrovascular diseases as well as stroke. Often these conditions coexist and exacerbate one another. The damaged area in post-stroke dementia may lead to neurodegenerative lesions. Gut microbiome functions like an endocrine organ by generating bioactive metabolites that can directly or indirectly impact human physiology. An alteration in the composition and function of intestinal flora, i.e. gut dysbiosis, is implicated in neurodegenerative and cerebrovascular diseases. Additionally, gut dysbiosis may accelerate the progression of cognitive impairment. Dysbiosis may result from obesity; metabolic disorders, cardiovascular disease, and sleep disorders, Lack of physical activity is associated with dysbiosis as well. These may coexist in various patterns in older people, enhancing the risk, incidence, and progression of cerebrovascular lesions, neurodegenerative disorders, and cognitive impairment, creating a vicious circle. Recently, it has been reported that several metabolites produced by gut microbiota (e.g., trimethylamine/trimethylamine N-oxide, short-chain fatty acids, secondary bile acids) may be linked to neurodegenerative and cerebrovascular diseases. New treatment modalities, including prebiotic and probiotics, may normalize the gut microbiota composition, change the brain-gut barrier, and decrease the risk of the pathology development. Fecal microbiota transplantation, sometimes in combination with other methods, is used for remodeling and replenishing the symbiotic gut microbiome. This promising field of research is associated with basic findings of bidirectional communication between body organs and gut microbiota that creates new possibilities of pharmacological treatments of many clinical conditions. The authors present the role of gut microbiota in physiology, and the novel therapeutic targets in modulation of intestinal microbiota Personalized therapies based on their personal genome make up could offer benefits by modulating microbiota cross-talk with brain and cardiovascular system. A healthy lifestyle, including pre and probiotic nutrition is generally recommended. Prevention may also be enhanced by correcting gut dysbiosis resulting a reduced risk of post-stroke cognitive impairment including dementia.


Assuntos
Disfunção Cognitiva/etiologia , Disbiose/complicações , Acidente Vascular Cerebral/etiologia , Animais , Toxinas Bacterianas , Disfunção Cognitiva/prevenção & controle , Disbiose/prevenção & controle , Microbioma Gastrointestinal , Humanos , Fatores de Risco , Acidente Vascular Cerebral/prevenção & controle
2.
Pharmacol Res ; 156: 104765, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32217147

RESUMO

Curcumin (Cur) is an active derivative extracted from turmeric which exerts a wide range of interactions with biomolecules through complex signaling pathways. Cur has been extensively shown to possess potential antitumor properties. In addition, there is growing body of evidence suggesting that Cur may exert potential anti-estrogen and anti-androgen activity. In vitro and in vivo studies suggest that anticancer properties of Cur against tumors affecting the reproductive system in females and males may be underlied by the Cur-mediated inhibition of androgen and estrogen signaling pathways. In this review we examine various studies assessing the crosstalk between Cur and both androgen and estrogen hormonal activity. Also, we discuss the potential chemopreventive and antitumor role of Cur in the most prevalent cancers affecting the reproductive system in females and males.


Assuntos
Antagonistas de Androgênios/uso terapêutico , Antineoplásicos Fitogênicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Curcumina/uso terapêutico , Moduladores de Receptor Estrogênico/uso terapêutico , Neoplasias dos Genitais Femininos/tratamento farmacológico , Neoplasias dos Genitais Masculinos/tratamento farmacológico , Hormônios Esteroides Gonadais/antagonistas & inibidores , Antagonistas de Androgênios/efeitos adversos , Animais , Antineoplásicos Fitogênicos/efeitos adversos , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Curcumina/efeitos adversos , Moduladores de Receptor Estrogênico/efeitos adversos , Feminino , Neoplasias dos Genitais Femininos/metabolismo , Neoplasias dos Genitais Femininos/patologia , Neoplasias dos Genitais Masculinos/metabolismo , Neoplasias dos Genitais Masculinos/patologia , Hormônios Esteroides Gonadais/metabolismo , Humanos , Masculino , Transdução de Sinais , Resultado do Tratamento
3.
Curr Genomics ; 21(6): 444-453, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33093806

RESUMO

BACKGROUND: Sleep disorders have emerged as potential cancer risk factors. OBJECTIVE: This review discusses the relationships between sleep, obesity, and breathing disorders with concomitant risks of developing cancer. RESULTS: Sleep disorders result in abnormal expression of clock genes, decreased immunity, and melatonin release disruption. Therefore, these disorders may contribute to cancer development. Moreover, in sleep breathing disorder, which is frequently experienced by obese persons, the sufferer experiences intermittent hypoxia that may stimulate cancer cell proliferation. DISCUSSION: During short- or long- duration sleep, sleep-wake rhythm disruption may occur. Insomnia and obstructive sleep apnea increase cancer risks. In short sleepers, an increased risk of stomach cancer, esophageal squamous cell cancer, and breast cancer was observed. Among long sleepers (>9 hours), the risk of some hematologic malignancies is elevated. CONCLUSION: Several factors including insomnia, circadian disruption, obesity, and intermittent hypoxia in obstructive sleep apnea are contributing risk factors for increased risk of several types of cancers. However, further studies are needed to determine the more significant of these risk factors and their interactions.

4.
Int J Mol Sci ; 21(18)2020 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-32937836

RESUMO

Ischemic stroke is one of the leading causes of death worldwide. Clinical manifestations of stroke are long-lasting and causing economic burden on the patients and society. Current therapeutic modalities to treat ischemic stroke (IS) are unsatisfactory due to the intricate pathophysiology and poor functional recovery of brain cellular compartment. MicroRNAs (miRNA) are endogenously expressed small non-coding RNA molecules, which can act as translation inhibitors and play a pivotal role in the pathophysiology associated with IS. Moreover, miRNAs may be used as potential diagnostic and therapeutic tools in clinical practice; yet, the complete role of miRNAs is enigmatic during IS. In this review, we explored the role of miRNAs in the regulation of stroke risk factors viz., arterial hypertension, metabolic disorders, and atherosclerosis. Furthermore, the role of miRNAs were reviewed during IS pathogenesis accompanied by excitotoxicity, oxidative stress, inflammation, apoptosis, angiogenesis, neurogenesis, and Alzheimer's disease. The functional role of miRNAs is a double-edged sword effect in cerebral ischemia as they could modulate pathological mechanisms associated with risk factors of IS. miRNAs pertaining to IS pathogenesis could be potential biomarkers for stroke; they could help researchers to identify a particular stroke type and enable medical professionals to evaluate the severity of brain injury. Thus, ascertaining the role of miRNAs may be useful in deciphering their diagnostic role consequently it is plausible to envisage a suitable therapeutic modality against IS.


Assuntos
Isquemia Encefálica/diagnóstico , Isquemia Encefálica/metabolismo , AVC Isquêmico/diagnóstico , MicroRNAs/metabolismo , Animais , Encéfalo/metabolismo , Encéfalo/patologia , Humanos , AVC Isquêmico/metabolismo
5.
Front Neuroendocrinol ; 50: 18-30, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-28974386

RESUMO

Parkinson's disease (PD) is the second most frequent age-related neurodegenerative disorder. Sex is an important factor in the development of PD, as reflected by the fact that it is more common in men than in women by an approximate ratio of 2:1. Our hypothesis is that differences in PD among men and women are highly determined by sex-dependent differences in the nigrostriatal dopaminergic system, which arise from environmental, hormonal and genetic influences. Sex hormones, specifically estrogens, influence PD pathogenesis and might play an important role in PD differences between men and women. The objective of this review was to discuss the PD physiopathology and point out sex differences in nigrostriatal degeneration, symptoms, genetics, responsiveness to treatments and biochemical and molecular mechanisms among patients suffering from this disease. Finally, we discuss the role estrogens may have on PD sex differences.


Assuntos
Hormônios Esteroides Gonadais/metabolismo , Avaliação de Resultados em Cuidados de Saúde , Doença de Parkinson , Caracteres Sexuais , Animais , Feminino , Humanos , Masculino , Doença de Parkinson/genética , Doença de Parkinson/metabolismo , Doença de Parkinson/fisiopatologia , Doença de Parkinson/terapia
6.
Int J Mol Sci ; 20(9)2019 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-31035445

RESUMO

Zinc is one of the most important essential trace elements. It is involved in more than 300 enzyme systems and is an indispensable participant in many biochemical processes. Zinc deficiency causes a number of disorders in the human body, the main ones being the delay of growth and puberty, immune disorders, and cognitive dysfunctions. There are over two billion people in the world suffering from zinc deficiency conditions. Acyzol, a zinc-containing medicine, developed as an antidote against carbon monoxide poisoning, demonstrates a wide range of pharmacological activities: Anti-inflammatory, reparative, detoxifying, immunomodulatory, bacteriostatic, hepatoprotective, adaptogenic, antioxidant, antihypoxic, and cardioprotective. The presence of zinc in the composition of Acyzol suggests the potential of the drug in the treatment and prevention of zinc deficiency conditions, such as Prasad's disease, immune system pathology, alopecia, allergodermatoses, prostate dysfunction, psoriasis, stomatitis, periodontitis, and delayed mental and physical development in children. Currently, the efficiency of Acyzol in the cases of zinc deficiency is shown in a large number of experimental studies. So, Acyzol can be used as a highly effective drug for pharmacologic therapy of a wide range of diseases and conditions and it opens up new perspectives in the treatment and prevention of zinc deficiency conditions.


Assuntos
Distúrbios Nutricionais/tratamento farmacológico , Distúrbios Nutricionais/etiologia , Oligoelementos/deficiência , Acetato de Zinco/uso terapêutico , Zinco/deficiência , Animais , Estudos Clínicos como Assunto , Avaliação Pré-Clínica de Medicamentos , Humanos , Imidazóis/química , Camundongos , Distúrbios Nutricionais/diagnóstico , Distúrbios Nutricionais/prevenção & controle , Resultado do Tratamento , Acetato de Zinco/química , Acetato de Zinco/farmacologia
7.
Mol Neurobiol ; 59(4): 2472-2496, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35083660

RESUMO

Schizophrenia (SZ) is a chronic psychiatric disorder affecting several people worldwide. Mitochondrial DNA (mtDNA) variations could invoke changes in the OXPHOS system, calcium buffering, and ROS production, which have significant implications for glial cell survival during SZ. Oxidative stress has been implicated in glial cells-mediated pathogenesis of SZ; the brain comparatively more prone to oxidative damage through NMDAR. A confluence of scientific evidence points to mtDNA alterations, Nrf2 signaling, dynamic alterations in dorsolateral prefrontal cortex (DLPFC), and provocation of oxidative stress that enhance pathophysiology of SZ. Furthermore, the alterations in excitatory signaling related to NMDAR signaling were particularly reported for SZ pathophysiology. Current review reported the recent evidence for the role of mtDNA variations and oxidative stress in relation to pathophysiology of SZ, NMDAR hypofunction, and glutathione deficiency. NMDAR system is influenced by redox dysregulation in oxidative stress, inflammation, and antioxidant mediators. Several studies have demonstrated the relationship of these variables on severity of pathophysiology in SZ. An extensive literature search was conducted using Medline, PubMed, PsycINFO, CINAHL PLUS, BIOSIS Preview, Google scholar, and Cochrane databases. We summarize consistent evidence pointing out a plausible model that may elucidate the crosstalk between mtDNA alterations in glial cells and redox dysregulation during oxidative stress and the perturbation of NMDA neurotransmitter system during current therapeutic modalities for the SZ treatment. This review can be beneficial for the development of promising novel diagnostics, and therapeutic modalities by ascertaining the mtDNA variations, redox state, and efficacy of pharmacological agents to mitigate redox dysregulation and augment NMDAR function to treat cognitive and behavioral symptoms in SZ.


Assuntos
Receptores de N-Metil-D-Aspartato , Esquizofrenia , DNA Mitocondrial/genética , Humanos , Neuroglia/metabolismo , Oxirredução , Receptores de N-Metil-D-Aspartato/metabolismo , Esquizofrenia/genética
8.
Biomedicines ; 10(10)2022 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-36289819

RESUMO

Inflammatory, oxidative, and autoimmune responses cause severe damage to the nervous system inducing loss of myelin layers or demyelination. Even though demyelination is not considered a direct cause of skeletal muscle disease there is extensive damage in skeletal muscles following demyelination and impaired innervation. In vitro and in vivo evidence using exogenous antioxidants in models of demyelination is showing improvements in myelin formation alongside skeletal muscle recovery. For instance, exogenous antioxidants such as EGCG stimulate nerve structure maintenance, activation of glial cells, and reduction of oxidative stress. Consequently, this evidence is also showing structural and functional recovery of impaired skeletal muscles due to demyelination. Exogenous antioxidants mostly target inflammatory pathways and stimulate remyelinating mechanisms that seem to induce skeletal muscle regeneration. Therefore, the aim of this review is to describe recent evidence related to the molecular mechanisms in nerve and skeletal muscle regeneration induced by exogenous antioxidants. This will be relevant to identifying further targets to improve treatments of neuromuscular demyelinating diseases.

9.
Eur J Pharmacol ; 895: 173873, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33460611

RESUMO

Neuronal survival and axonal renewal following central nervous system damage and in neurodegenerative illnesses, such as Alzheimer's disease (AD), can be enhanced by fast clearance of neuronal apoptotic debris, as well as the removal of amyloid beta (Aß) by phagocytic cells through the process of efferocytosis. This process quickly inhibits the release of proinflammatory and antigenic autoimmune constituents, enhancing the formation of a microenvironment vital for neuronal survival and axonal regeneration. Therefore, the detrimental features associated with microglial phagocytosis uncoupling, such as the accumulation of apoptotic cells, inflammation and phagoptosis, could exacerbate the pathology in brain disease. Some mechanisms of efferocytosis could be targeted by several promising agents, such as curcumin, URMC-099 and Y-P30, which have emerged as potential treatments for AD. This review aims to investigate and update the current research regarding the signaling molecules and pathways involved in efferocytosis and how these could be targeted as a potential therapy in AD.


Assuntos
Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/metabolismo , Apoptose , Encéfalo/patologia , Microglia/patologia , Neurônios/patologia , Fagocitose , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Doença de Alzheimer/fisiopatologia , Animais , Anti-Inflamatórios/farmacologia , Apoptose/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/fisiopatologia , Humanos , Microglia/efeitos dos fármacos , Microglia/metabolismo , Terapia de Alvo Molecular , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Fármacos Neuroprotetores/uso terapêutico , Fagocitose/efeitos dos fármacos
10.
Artigo em Inglês | MEDLINE | ID: mdl-33563203

RESUMO

Suicides on railway tracks are one of the most drastic ones. No research concerning this phenomenon has been done to this date in Poland. This article focuses on the connection between suicidal behaviors on Polish railway tracks and sociodemographic traits and presents risk factors. BACKGROUND: The suicide behavior is largely spread among many European countries. Of these, Poland ranks 22nd in terms of suicide attempts. This study aims to highlight the suicide attempts rates on Polish railways lines and their main risk factors. LIMITATIONS: Limited number of available statistical data before 2013. METHOD: Statistical review of the available Central Police headquarters database and analyses of the influence of the risk factors on people's awareness during the suicide attempts and their geographical distribution in Poland during the years 2013 - 2016. The prevalence of railway suicides in individual voivodeships (provinces) in Poland have been indicated in a 3D map. RESULTS: There were 834 cases of railway suicide fatalities across the entire country. Of the total suicide statistics by any means, 3.75% are railway related. The average known age of those committing railway suicides were: 37.9 years for men (n = 627) and 34.6 for women (n = 155). In most cases, suicides were committed by bachelors (54.3%). The largest group of people who committed suicide had a primary level of education (42.0%). Among the suicides, a significant group are unemployed (45.2%). Alcohol intoxication have been established as responsible for a person's lower awareness of his actions in 70.9% of cases. Almost 63.3% of people had a higher propensity for suicidal ideation and behavior, resulting in their being treated for mental health issues. CONCLUSION: Alcohol intoxication, illegal narcotics and psychotropic medication are responsible for a person's lower awareness during his ore her actions, in most of the cases of suicide on Polish railway lines.

11.
Curr Pharm Biotechnol ; 22(5): 636-645, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32679017

RESUMO

BACKGROUND: Cancer is one of the leading cause of death worldwide. Besides current therapies and treatments to counter cancer, new alternatives are required to diminish the cell proliferation of oncogenic processes. METHODS: One of the most promissory therapy includes the use of blue scorpion venom as a specific cytotoxic agent to kill tumoral cells, including Glioblastoma multiforme. OBJECTIVES: We show evidence of the cytotoxic effect of blue scorpion venom in a cellular model of Glioblastoma multiforme. RESULTS: Our results demonstrate that 50 µg/ml of scorpion venom is capable to diminish the viability of Glioblastoma populations. CONCLUSION: It is possible that the action mechanism could be associated with a loss of membrane integrity. Additionally, some metalloproteinases as MMP2 and MMP9 may also participate in the potential action mechanism.


Assuntos
Antineoplásicos/farmacologia , Neoplasias Encefálicas/tratamento farmacológico , Glioblastoma/tratamento farmacológico , Venenos de Escorpião/farmacologia , Animais , Linhagem Celular Tumoral , Membrana Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Humanos , Escorpiões
12.
CNS Neurol Disord Drug Targets ; 20(10): 982-995, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33645491

RESUMO

BACKGROUND: Psychosocial stress-induced depressive behavior is linked to the etiology of several neurological diseases viz., PTSD, and neurodegenerative disease like Alzheimer's Disease (AD). The repeated bouts of social stress defeat can be induced using Resident-Intruder- Paradigm (RIP) and Chronic Mild Social Stress (CMSS) animal models to assess the stress-induced depressive behavioral patterns. OBJECTIVES: The aim of this study to examine the anti-depressive efficacy of 3-methoxythietane- 1,1-dioxide (N-14) in RIP models of behavioral alterations. METHODS: In this study, we have used Sprague-Dawley rats in Resident-Intruder-Paradigm (RIP), where intruders interacted with residents Day 0 to Day +5 for 10 minutes to invoke CMSS in intruders and became defeated/submissive rats due to the depressive-like behavioral alterations in social activity, explorations, grooming, defense, aggressive behavior, social interaction, freeze, rearing etc., with residents. Control intact animals are included in group I, group II received N-14 alone; group III received CMSS, and group IV received cotreatment of N14 with CMSS. N-14 (2 mg/kg) was administered intraperitoneally from Day 0 to Day +5 to intact animals and intruder animals under conditions of CMSS. RESULTS: Several behavioral tests viz., forced swim test, open field test, and elevated-plus maze test were used to examine the above behavioral dynamic parameters. The dynamic interaction between Residents and Intruders during the study showed substantial alterations in exploratory activity, aggressiveness, defensive behavior, body weight, and thymus mass in stressed animals. N-14 cotreatment has mitigated sociability, exploratory activity, aggressiveness increased social adaptability and defensive behavior. An extensive rise in active forms of defense and submission latency indicates that N-14 has induced antidepressant activity with a psycho-sedative component of action. CONCLUSION: Serendipitously, we observed the ameliorative capability of N-14 cotreatment to mitigate depressive-behavioral symptoms in intruders.


Assuntos
Antidepressivos/farmacologia , Depressão/tratamento farmacológico , Doenças Neurodegenerativas/psicologia , Agressão , Animais , Comportamento Animal , Masculino , Atividade Motora/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Comportamento Social , Estresse Psicológico
13.
Curr Pharm Des ; 27(31): 3413-3421, 2021 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-33655824

RESUMO

BACKGROUND: A patient was evaluated with respect to the effects and results of a complex treatment plan for complete dental rehabilitation. Several steps were required. Each step included immunological tests of salivary biomarkers. Clinical and immunological assessments were evaluated on Day 3, Week 2, Month 3, and Month 6 post-surgery. These evaluations guided the decision-making process with regard to preparation of a permanent prosthesis. OBJECTIVE: The aim of the study is to evaluate the response of tissues and organs of the maxillofacial region in patients during dental rehabilitation after maxillofacial surgery. METHODS: Complex treatment and rehabilitation involving cooperation between the specialists in maxillofacial surgery, prosthetic dentistry, and cancer immunology. RESULTS: Long-term monitoring and clinical examination showed a direct relationship between the patient's clinical and dental status and the changes in oral fluid biomarkers. CONCLUSION: The data revealed that the oral fluid biomarkers reflected the patient's adaptation to prosthodontic rehabilitation. Treatment and monitoring of a maxillofacial tumor patient could use biomarkers as a non-invasive indicator.

14.
Curr Pharm Des ; 27(19): 2231-2236, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33243131

RESUMO

A number of elderly patients commit suicide due to the interaction of various factors, including, for example, feelings of loneliness, financial distress, alcohol abuse, chronic pain, progressive diseases, and personality disorders. The data from the EU countries with the highest rates of suicide and suicide attempts among people over 55 years of age warrant the consideration of new approaches to address this social problem. METHODS: PubMed and other databases, including Polish National data, were used for the analyses. RESULTS: The average European suicide-attempt rate is 18 per 100 thousand inhabitants. More cases of suicides were reported among those over 55 years of age. Suicide attempts from the year 2012 to 2014 and deaths in 2012 have been reviewed. The risk factors involved in these events, such as depression and social situations including loneliness, health condition, etc., have been discussed to suggest a plausible preventative approach for this important elderly problem. CONCLUSION: The psychophysiology of elderly persons affected by retirement, socio-economic changes, limited personal autonomy, loneliness, lack of support by the family, and diseases ultimately may lead elderly patients to commit suicide. Thus, financial freedom, family support (respect, love, and care), proper medications, psychological and psychiatric interventions may help the elderly avoid suicidal thoughts and prevent attempts.


Assuntos
Alcoolismo , Tentativa de Suicídio , Idoso , Humanos , Fatores de Risco
15.
Mol Neurobiol ; 57(7): 3014-3026, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32458388

RESUMO

Oxidative stress associated with chronic cerebral hypoperfusion is one of the fundamental factors leading to neurodegenerative diseases. To prevent oxidative stress, physical activity is effective. Physical exercise enables development of rehabilitation techniques that can progressively increase patients' stress resistance. We determined the oxidative stress dynamics in experimental hypoperfusion and modeled rehabilitation measures, comparing sex and stress resistance levels. The experiment was performed on 240 Wistar rats of both sexes over a period of 90 days. Based on behavioral test results obtained using the open field test, the rats were divided into active animals with predicted higher stress resistance (HSR) and passive animals with predicted lower stress resistance (LSR). TBA (thiobarbituric acid) plasma concentration of the active products (malondialdehyde-MDA), blood plasma (NO-X) concentration, and L-citrulline (LC) concentration were determined spectrophotometrically at the corresponding wave length (nm). The intensity of oxidative stress was evaluated using the chemoluminscent method to determine the blood plasma antioxidant activity on the BCL-07 biochemoluminometer. This study revealed two stages of oxidative stress: a less pronounced phase covering the first days after surgery and a main one, which starts from the month after the operation to 3 months. Female sex and a high initial level of stress resistance reduced the severity of oxidative stress. Physical activity commencing a week after the surgery resulted in "reloading" the adaptive mechanisms and slowed the onset of the main stage, leading to a decrease in the free-radical process in all studied subgroups and the greater blood plasma (NO)-X decrease in the male animals. Future neuropharmacological intervention most likely will be able to determine the pathophysiology mechanism of chronic brain hypoperfusion and potentially extending adaptive responses.


Assuntos
Isquemia Encefálica/metabolismo , Encéfalo/metabolismo , Estresse Oxidativo/fisiologia , Condicionamento Físico Animal/fisiologia , Estresse Psicológico/metabolismo , Animais , Feminino , Masculino , Malondialdeído/sangue , Aprendizagem em Labirinto/fisiologia , Ratos Wistar , Fatores Sexuais , Tiobarbitúricos/sangue
16.
Adv Ther ; 37(1): 402-419, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31755038

RESUMO

INTRODUCTION: Hemivertebrae excision with local posterior instrumentation is the most common technique for treatment of patients with congenital spine deformity-it is performed at a very young age. We conducted a comparative analysis for accuracy of pedicle screw positioning in infants with congenital scoliosis of the thoracolumbar area inserted using freehand technique in vivo and 3D-printed guiding templates in vitro. METHODS: The study analyzes the results of 10 surgically treated patients with congenital deformity of the thoracolumbar spine due to vertebrae failure of formation. These patients were included in group 1 (in vivo) comprising six boys and four girls with a mean age of 3 years 8 months (2 years 2 months-6 years 8 month). Group 2 (in vitro) consisted of 27 plastic 3D-printed models of congenitally deformed spine of the same 10 patients in which screws were placed using 3D-printed guiding templates. The accuracy of screw position was assessed using computer tomography data performed postoperatively with Gertzbein-Robbins classification. RESULTS: Results of our study show that screw insertion using 3D-printed guiding templates during surgical treatment of infants with congenital spine deformities is more accurate than using freehand technique (96.3% vs. 78.8% p = 0.011). CONCLUSION: The data show that this method of screw insertion is very promising and can be used in surgical treatment of infants with congenital spine deformities.


Assuntos
Parafusos Pediculares , Procedimentos de Cirurgia Plástica/métodos , Impressão Tridimensional , Escoliose/congênito , Escoliose/cirurgia , Tomografia Computadorizada por Raios X/métodos , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Lactente , Masculino , Estudos Prospectivos , Estudos Retrospectivos , Resultado do Tratamento
17.
J Clin Med ; 9(9)2020 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-32932645

RESUMO

Post-traumatic stress disorder (PTSD) is a well-known psychiatric disorder that affects millions of people worldwide. Pharmacodynamic and cognitive-behavioral therapies (CBT) have been used to treat patients with PTSD. However, it remains unclear whether there are concurrent changes in psychopathological and neurophysiological factors associated with PTSD patients. Past reports described those PTSD patients with efficient fatty acid metabolism, neurogenesis, mitochondrial energy balance could improve ability to cope against the conditioned fear responses and traumatic memories. Furthermore, cognitive, behavioral, cellular, and molecular evidence can be combined to create personalized therapies for PTSD sufferers either with or without comorbidities such as depression or memory impairment. Unfortunately, there is still evidence lacking to establish a full understanding of the underlying neurophysiological and psychopathological aspects associated with PTSD. This review has extensively discussed the single nucleotide polymorphism (SNPs) of genetic factors to cause PTSD, the implications of inflammation, neurotransmitter genomics, metabolic alterations, neuroendocrine disturbance (hypothalamus-pituitary-adrenal (HPA) axis), mitochondrial dynamics, neurogenesis, and premature aging related to PTSD-induced psychopathology and neurophysiology. In addition, the review delineated the importance of CBT and several pharmacodynamic therapies to mitigate symptomatology of PTSD.

18.
Curr Cancer Drug Targets ; 20(9): 666-674, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32316892

RESUMO

BACKGROUND: The conjugates of the sesquiterpene lactone of the eremophilane series of 6- hydroxyxanthanodiene with hydrogenated azines (piperidines and piperazines) have been synthesized and identified by NMR spectrometer. OBJECTIVE: A lactone with an unusual skeleton "6-hydroxyxanthanodiene" was extracted from the plant Elecampane (Inula helenium L) and identified various species with NMR spectrometer. METHODS: The cytotoxic, mitochondrial, and antioxidant activities on different tumor lines such as A549, HCT116, RD and Jurkat were investigated and determined possible mechanisms. RESULTS: The results showed that the most potent compound was IIIi exhibiting highest cytotoxicity against RD cells (IC50 25.23 ± 0.04 µM), depolarized the mitochondrial membrane and was an effective antioxidant (IC50 inhibition of LP 10.68 ± 3.21 µM) without any toxic side effect on healthy cells. CONCLUSION: The conjugates of sesquiterpene lactone 6-hydroxyxanthanodiene III and hydrogenated azines may help to design potential promising anticancer drugs.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Antioxidantes/farmacologia , Inula/química , Lactonas/farmacologia , Extratos Vegetais/farmacologia , Sesquiterpenos/farmacologia , Células A549 , Animais , Antineoplásicos Fitogênicos/química , Antioxidantes/química , Sobrevivência Celular/efeitos dos fármacos , Células HCT116 , Humanos , Concentração Inibidora 50 , Células Jurkat , Lactonas/química , Masculino , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Extratos Vegetais/química , Ratos , Sesquiterpenos/química
19.
Curr Neuropharmacol ; 18(11): 1054-1063, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31729299

RESUMO

Until recently, it was thought that there were no lymphatic vessels in the central nervous system (CNS). Therefore, all metabolic processes were assumed to take place only in the circulation of the cerebrospinal fluid (CSF) and through the blood-brain barrier's (BBB), which regulate ion transport and ensure the functioning of the CNS. However, recent findings yield a new perspective: There is an exchange of CSF with interstitial fluid (ISF), which is drained to the paravenous space and reaches lymphatic nodes at the end. This circulation is known as the glymphatic system. The glymphatic system is an extensive network of meningeal lymphatic vessels (MLV) in the basal area of the skull that provides another path for waste products from CNS to reach the bloodstream. MLV develop postnatally, initially appearing around the foramina in the basal part of the skull and the spinal cord, thereafter sprouting along the skull's blood vessels and spinal nerves in various areas of the meninges. VEGF-C protein (vascular endothelial growth factor), expressed mainly by vascular smooth cells, plays an important role in the development of the MLV. The regenerative potential and plasticity of MLV and the novel discoveries related to CNS drainage offer potential for the treatment of neurodegenerative diseases such as dementia, hydrocephalus, stroke, multiple sclerosis, and Alzheimer disease (AD). Herein, we present an overview of the structure and function of the glymphatic system and MLV, and their potential involvement in the pathology and progression of neurodegenerative diseases.


Assuntos
Sistema Nervoso Central/metabolismo , Peptídeos beta-Amiloides/metabolismo , Animais , Barreira Hematoencefálica/metabolismo , Encéfalo/metabolismo , Encéfalo/patologia , Sistema Glinfático/metabolismo , Humanos , Doenças Neurodegenerativas/metabolismo , Medula Espinal/metabolismo
20.
Curr Pharm Des ; 25(45): 4737-4746, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31957605

RESUMO

Traumatic Brain Injury is considered one of the most prevalent causes of death around the world; more than seventy millions of individuals sustain the condition per year. The consequences of traumatic brain injury on brain tissue are complex and multifactorial, hence, the current palliative treatments are limited to improve patients' quality of life. The subsequent hemorrhage caused by trauma and the ongoing oxidative process generated by biochemical disturbances in the in the brain tissue may increase iron levels and reactive oxygen species. The relationship between oxidative damage and the traumatic brain injury is well known, for that reason, diminishing factors that potentiate the production of reactive oxygen species have a promissory therapeutic use. Iron chelators are molecules capable of scavenging the oxidative damage from the brain tissue and are currently in use for ironoverload- derived diseases. Here, we show an updated overview of the underlying mechanisms of the oxidative damage after traumatic brain injury. Later, we introduced the potential use of iron chelators as neuroprotective compounds for traumatic brain injury, highlighting the action mechanisms of iron chelators and their current clinical applications.


Assuntos
Lesões Encefálicas Traumáticas , Quelantes de Ferro/uso terapêutico , Ferro , Estresse Oxidativo , Humanos , Espécies Reativas de Oxigênio
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