RESUMO
The human microbiota refers to a large variety of microorganisms (bacteria, viruses, and fungi) that live in different human body sites, including the gut, oral cavity, skin, and eyes. In particular, the presence of an ocular surface microbiota with a crucial role in maintaining ocular surface homeostasis by preventing colonization from pathogen species has been recently demonstrated. Moreover, recent studies underline a potential association between gut microbiota (GM) and ocular health. In this respect, some evidence supports the existence of a gut-eye axis involved in the pathogenesis of several ocular diseases, including age-related macular degeneration, uveitis, diabetic retinopathy, dry eye, and glaucoma. Therefore, understanding the link between the GM and these ocular disorders might be useful for the development of new therapeutic approaches, such as probiotics, prebiotics, symbiotics, or faecal microbiota transplantation through which the GM could be modulated, thus allowing better management of these diseases.
Assuntos
Retinopatia Diabética , Glaucoma , Degeneração Macular , Humanos , Olho , FaceRESUMO
The endogenous antioxidant defense plays a big part in the pathogenesis of non-alcoholic fatty liver disease (NAFLD), a common metabolic disorder that can lead to serious complications such as cirrhosis and cancer. HuR, an RNA-binding protein of the ELAV family, controls, among others, the stability of MnSOD and HO-1 mRNA. These two enzymes protect the liver cells from oxidative damage caused by excessive fat accumulation. Our aim was to investigate the expression of HuR and its targets in a methionine-choline deficient (MCD) model of NAFLD. To this aim, we fed male Wistar rats with an MCD diet for 3 and 6 weeks to induce NAFLD; then, we evaluated the expression of HuR, MnSOD, and HO-1. The MCD diet induced fat accumulation, hepatic injury, oxidative stress, and mitochondrial dysfunction. A HuR downregulation was also observed in association with a reduced expression of MnSOD and HO-1. Moreover, the changes in the expression of HuR and its targets were significantly correlated with oxidative stress and mitochondrial injury. Since HuR plays a protective role against oxidative stress, targeting this protein could be a therapeutic strategy to both prevent and counteract NAFLD.
Assuntos
Hepatopatia Gordurosa não Alcoólica , Ratos , Masculino , Animais , Camundongos , Hepatopatia Gordurosa não Alcoólica/genética , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Colina/metabolismo , Metionina/metabolismo , Ratos Wistar , Fígado/metabolismo , Estresse Oxidativo , Racemetionina/metabolismo , Dieta/efeitos adversos , Camundongos Endogâmicos C57BL , Modelos Animais de DoençasRESUMO
The RNA-binding protein HuD has been shown to play a crucial role in gene regulation in the nervous system and is involved in various neurological and psychiatric diseases. In this study, through the creation of an interaction network on HuD and its potential targets, we identified a strong association between HuD and several diseases of the nervous system. Specifically, we focused on the relationship between HuD and the brain-derived neurotrophic factor (BDNF), whose protein is implicated in several neuronal diseases and is involved in the regulation of neuronal development, survival, and function. To better investigate this relationship and given that we previously demonstrated that folic acid (FA) is able to directly bind HuD itself, we performed in vitro experiments in neuron-like human SH-SY5Y cells in the presence of FA, also known to be a pivotal environmental factor influencing the nervous system development. Our findings show that FA exposure results in a significant increase in both HuD and BDNF transcripts and proteins after 2 and 4 h of treatment, respectively. Similar data were obtained after 2 h of FA incubation followed by 2 h of washout. This increase was no longer detected upon 24 h of FA exposure, probably due to a signaling shutdown mechanism. Indeed, we observed that following 24 h of FA exposure HuD is methylated. These findings indicate that FA regulates BDNF expression via HuD and suggest that FA can behave as an epigenetic modulator of HuD in the nervous system acting via short- and long-term mechanisms. Finally, the present results also highlight the potential of BDNF as a therapeutic target for specific neurological and psychiatric diseases.
Assuntos
Fator Neurotrófico Derivado do Encéfalo , Neuroblastoma , Humanos , Fator Neurotrófico Derivado do Encéfalo/genética , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Proteínas ELAV/genética , Proteínas ELAV/metabolismo , Proteína Semelhante a ELAV 4/genética , Neuroblastoma/metabolismo , Neurônios/metabolismoRESUMO
The purposes of this retrospective study were to document the prevalence of serum C-reactive protein (CRP), a biomarker of inflammation, and its potential predictive value for Rehabilitation outcomes in post-acute elderly inpatients. The medical records of 304 elderly subjects admitted to our Rehabilitation Institute for any disease following an acute event were examined. High levels of CRP (> 0.5 mg/dl) were present in 100% of the subjects, and the value > 1.5 mg/dl (n = 86) predicted unfavourable outcomes (n = 28; 32.5% of the patients: death or transfer to other institutions). Among the patients with favourable outcomes (discharge home n = 255), 62.7% still exhibited severe disabilities. Pressure ulcers and low functional status also predicted unfavourable outcomes. The study highlights the need for future investigations into the possible reduction of CRP levels, after an intensive nutritional approach and combined physical interventions.
Assuntos
Úlcera por Pressão , Idoso , Estado Funcional , Humanos , Inflamação , Úlcera por Pressão/epidemiologia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
There is increasing interest in the role of the gut microbiota in health and disease. In particular, gut microbiota influences the Central Nervous System (CNS) development and homeostasis through neural pathways or routes involving the immune and circulatory systems. The CNS, in turn, shapes the intestinal flora through endocrine or stress-mediated responses. These overall bidirectional interactions, known as gut microbiota-brain axis, profoundly affect some brain functions, such as neurogenesis and the production of neurotransmitters, up to influence behavioral aspects of healthy subjects. Consequently, a dysfunction within this axis, as observed in case of dysbiosis, can have an impact on the behavior of a given individual (e.g. anxiety and depression) or on the development of pathologies affecting the CNS, such as autism spectrum disorders and neurodegenerative diseases (e.g. Alzheimer's disease and Parkinson's disease). It should be considered that the whole microbiota has a significant role not only on aspects concerning human physiology, such as harvesting of nutrients and energy from the ingested food or production of a wide range of bioactive compounds, but also has positive effects on the gastrointestinal barrier function and actively contributes to the pharmacokinetics of several compounds including neuropsychiatric drugs. Indeed, the microbiota is able to affect drug absorption and metabolism up to have an impact on drug activity and/or toxicity. On the other hand, drugs are able to shape the human gut microbiota itself, where these changes may contribute to their pharmacologic profile. Therefore, the emerging picture on the complex drug-microbiota bidirectional interplay will have considerable implications in the future not only in terms of clinical practice but also, upstream, on drug development.
Assuntos
Antipsicóticos/uso terapêutico , Bactérias/metabolismo , Encéfalo/efeitos dos fármacos , Microbioma Gastrointestinal , Intestinos/microbiologia , Transtornos Mentais/tratamento farmacológico , Animais , Antipsicóticos/efeitos adversos , Antipsicóticos/farmacocinética , Encéfalo/metabolismo , Encéfalo/fisiopatologia , Citocinas/metabolismo , Disbiose , Interações Hospedeiro-Patógeno , Humanos , Mediadores da Inflamação/metabolismo , Transtornos Mentais/microbiologia , Transtornos Mentais/fisiopatologia , Transtornos Mentais/psicologia , Saúde MentalRESUMO
Aging represents the major risk factor for the onset and/or progression of various disorders including neurodegenerative diseases, metabolic disorders, and bone-related defects. As the average age of the population is predicted to exponentially increase in the coming years, understanding the molecular mechanisms underlying the development of aging-related diseases and the discovery of new therapeutic approaches remain pivotal. Well-reported hallmarks of aging are cellular senescence, genome instability, autophagy impairment, mitochondria dysfunction, dysbiosis, telomere attrition, metabolic dysregulation, epigenetic alterations, low-grade chronic inflammation, stem cell exhaustion, altered cell-to-cell communication and impaired proteostasis. With few exceptions, however, many of the molecular players implicated within these processes as well as their role in disease development remain largely unknown. RNA binding proteins (RBPs) are known to regulate gene expression by dictating at post-transcriptional level the fate of nascent transcripts. Their activity ranges from directing primary mRNA maturation and trafficking to modulation of transcript stability and/or translation. Accumulating evidence has shown that RBPs are emerging as key regulators of aging and aging-related diseases, with the potential to become new diagnostic and therapeutic tools to prevent or delay aging processes. In this review, we summarize the role of RBPs in promoting cellular senescence and we highlight their dysregulation in the pathogenesis and progression of the main aging-related diseases, with the aim of encouraging further investigations that will help to better disclose this novel and captivating molecular scenario.
Assuntos
Doenças Metabólicas , Doenças Neurodegenerativas , Humanos , Envelhecimento/metabolismo , Senescência Celular/genética , Doenças Neurodegenerativas/metabolismo , Proteínas de Ligação a RNA/genéticaRESUMO
Various forms of low urinary tract symptoms (LUTS) seem dependant upon dysregulation of the purinergic pathway which produces sensory- or motor-activated incontinence. A body of evidence in human urinary bladders supports a link between up-regulation of purinergic activity and the pathogenesis of detrusor instability. This study investigated the potential role of adenosine 5'-triphosphate (ATP) in the control of detrusor motor drive in a model of porcine urinary bladder. The involvement of ATP on excitatory activity was assessed by measuring neurally-evoked [(3)H]-acetylcholine (ACh) release and smooth muscle contraction in detrusor strips. Epithelium-deprived preparations were used to minimize the influence of non-neural sources of ACh and ATP on parasympathetic neurotransmission. ACh release and smooth muscle contractility were not significantly affected by neural ATP in normal detrusor, but markedly enhanced when ATP hydrolysis was reduced by ectoATPase inhibitors, as well as by α,ß-methylene-ATP (ABMA), agonist resistant to ecto-enzymes degradation. Prejunctional P2X receptors located on cholinergic nerves are involved in such potentiating effect. These purinergic heteroreceptors were characterized as P2X(3) subunits by means of the putative antagonists: NF449 (P2X(1,3) selective), NF023 (P2X(1,3) selective), PPNDS (P2X(1) selective) and A-317491 (P2X(3) selective). In porcine detrusor, P2X(3) receptors are functionally expressed at neural site facilitating neurogenic ACh release. When purine breakdown is experimentally down-regulated to mimicking the impaired purinergic pathway observed in pathological human bladders, endogenous ATP can markedly enhance detrusor contractility through activation of these receptors. Since P2X(3) blockade represents a potential therapeutic approach for diseases of the urinary tract, isolated porcine detrusor represents a reliable model for development of novel selective P2X(3) antagonists beneficial in the treatment of detrusor hyperactivity.
Assuntos
Trifosfato de Adenosina/metabolismo , Neurônios Motores/efeitos dos fármacos , Contração Muscular/efeitos dos fármacos , Músculo Liso/efeitos dos fármacos , Sistema Nervoso Parassimpático/efeitos dos fármacos , Antagonistas do Receptor Purinérgico P2X/farmacologia , Receptores Purinérgicos P2X3/efeitos dos fármacos , Bexiga Urinária Hiperativa/tratamento farmacológico , Bexiga Urinária/efeitos dos fármacos , Acetilcolina/metabolismo , Animais , Relação Dose-Resposta a Droga , Estimulação Elétrica , Hidrólise , Técnicas In Vitro , Neurônios Motores/metabolismo , Músculo Liso/inervação , Músculo Liso/metabolismo , Sistema Nervoso Parassimpático/metabolismo , Receptores Purinérgicos P2X3/metabolismo , Suínos , Transmissão Sináptica/efeitos dos fármacos , Fatores de Tempo , Bexiga Urinária/inervação , Bexiga Urinária/metabolismo , Bexiga Urinária Hiperativa/metabolismo , Bexiga Urinária Hiperativa/fisiopatologiaRESUMO
Glaucoma is a major ocular neurodegenerative disease characterized by progressive retinal ganglion cells degeneration and sight loss. Current treatment options have been limited to reducing intraocular pressure (IOP), known as the leading risk factor for this disease; however, glaucoma can develop even with low or normal IOP and progress despite controlling IOP values. Lifestyle, dietary habits, and supplementation may influence some of the risk factors and pathophysiological mechanisms underlying glaucoma development and progression; thus, the role of this complementary and alternative medicine in glaucoma has received great interest from both patients and ophthalmologists. We provide a summary of the current evidence concerning the relationship between lifestyle, dietary habits, and effects of supplements on the incidence and progression of glaucoma and their targets and associated mechanisms. The data suggest the existence of a therapeutic potential that needs to be further explored with both preclinical and rigorous clinical studies.
Assuntos
Glaucoma , Doenças Neurodegenerativas , Dieta , Suplementos Nutricionais , Humanos , Pressão Intraocular , Estilo de VidaRESUMO
Human aging, a natural process characterized by structural and physiological changes, leads to alterations of homeostatic mechanisms, decline of biological functions, and subsequently, the organism becomes vulnerable to external stress or damage. In fact, the elderly population is prone to develop diseases due to deterioration of physiological and biological systems. With aging, the production of reactive oxygen species (ROS) increases, and this causes lipid, protein, and DNA damage, leading to cellular dysfunction and altered cellular processes. Indeed, oxidative stress plays a key role in the pathogenesis of several chronic disorders, including hepatic diseases, such as non-alcoholic fatty liver disease (NAFLD). NAFLD, the most common liver disorder in the Western world, is characterized by intrahepatic lipid accumulation; is highly prevalent in the aging population; and is closely associated with obesity, insulin resistance, hypertension, and dyslipidemia. Among the risk factors involved in the pathogenesis of NAFLD, the dysbiotic gut microbiota plays an essential role, leading to low-grade chronic inflammation, oxidative stress, and production of various toxic metabolites. The intestinal microbiota is a dynamic ecosystem of microbes involved in the maintenance of physiological homeostasis; the alteration of its composition and function, during aging, is implicated in different liver diseases. Therefore, gut microbiota restoration might be a complementary approach for treating NAFLD. The administration of probiotics, which can relieve oxidative stress and elicit several anti-aging properties, could be a strategy to modify the composition and restore a healthy gut microbiota. Indeed, probiotics could represent a valid supplement to prevent and/or help treating some diseases, such as NAFLD, thus improving the already available pharmacological intervention. Moreover, in aging, intervention of prebiotics and fecal microbiota transplantation, as well as probiotics, will provide novel therapeutic approaches. However, the relevant research is limited, and several scientific research works need to be done in the near future to confirm their efficacy.
Assuntos
Hepatopatia Gordurosa não Alcoólica , Probióticos , Idoso , Ecossistema , Humanos , Lipídeos , Hepatopatia Gordurosa não Alcoólica/metabolismo , Probióticos/uso terapêutico , Espécies Reativas de OxigênioRESUMO
The possible interconnection between the eye and central nervous system (CNS) has been a topic of discussion for several years just based on fact that the eye is properly considered an extension of the brain. Both organs consist of neurons and derived from a neural tube. The visual process involves photoreceptors that receive light stimulus from the external environment and send it to retinal ganglionic cells (RGC), one of the cell types of which the retina is composed. The retina, the internal visual membrane of the eye, processes the visual stimuli in electric stimuli to transfer it to the brain, through the optic nerve. Retinal chronic progressive neurodegeneration, which may occur among the elderly, can lead to different disorders of the eye such as glaucoma, age-related macular degeneration (AMD), and diabetic retinopathy (DR). Mainly in the elderly population, but also among younger people, such ocular pathologies are the cause of irreversible blindness or impaired, reduced vision. Typical neurodegenerative diseases of the CSN are a group of pathologies with common characteristics and etiology not fully understood; some risk factors have been identified, but they are not enough to justify all the cases observed. Furthermore, several studies have shown that also ocular disorders present characteristics of neurodegenerative diseases and, on the other hand, CNS pathologies, i.e., Alzheimer disease (AD) and Parkinson disease (PD), which are causes of morbidity and mortality worldwide, show peculiar alterations at the ocular level. The knowledge of possible correlations could help to understand the mechanisms of onset. Moreover, the underlying mechanisms of these heterogeneous disorders are still debated. This review discusses the characteristics of the ocular illnesses, focusing on the relationship between the eye and the brain. A better comprehension could help in future new therapies, thus reducing or avoiding loss of vision and improve quality of life.
Assuntos
Oftalmopatias/patologia , Doenças Neurodegenerativas/patologia , Retina/patologia , Córtex Visual/patologia , Animais , Oftalmopatias/complicações , Humanos , Doenças Neurodegenerativas/complicaçõesRESUMO
To investigate the role of vascular endothelial growth factor (VEGF) at different phases of diabetic retinopathy (DR), we assessed the retinal protein expression of VEGF-A164 (corresponding to the VEGF165 isoform present in humans, which is the predominant member implicated in vascular hyperpermeability and proliferation), HIF-1α and PKCß/HuR pathway in Ins2 Akita (diabetic) mice at different ages. We used C57BL6J mice (WT) at different ages as control. Retina status, in terms of tissue morphology and neovascularization, was monitored in vivo at different time points by optical coherence tomography (OCT) and fluorescein angiography (FA), respectively. The results showed that VEGF-A164 protein expression increased along time to become significantly elevated (p < 0.05) at 9 and 46 weeks of age compared to WT mice. The HIF-1α protein level was significantly (p < 0.05) increased at 9 weeks of age, while PKCßII and HuR protein levels were increased at 46 weeks of age compared to WT mice. The thickness of retinal nerve fiber layer as measured by OCT was decreased in Ins2 Akita mice at 9 and 46 weeks of age, while no difference in the retinal vasculature were observed by FA. The present findings show that the retina of the diabetic Ins2 Akita mice, as expected for mice, does not develop proliferative retinopathy even after 46 weeks. However, diabetic Ins2 Akita mice recapitulate the same evolution of patients with DR in terms of both retinal neurodegeneration and pro-angiogenic shift, this latter indicated by the progressive protein expression of the pro-angiogenic isoform VEGF-A164, which can be sustained by the PKCßII/HuR pathway acting at post-transcriptional level. In agreement with this last concept, this rise in VEGF-A164 protein is not paralleled by an increment of the corresponding transcript. Nevertheless, the observed increase in HIF-1α at 9 weeks indicates that this transcription factor may favor, in the early phase of the disease, the transcription of other isoforms, possibly neuroprotective, in the attempt to counteract the neurodegenerative effects of VEGF-A164. The time-dependent VEGF-A164 expression in the retina of diabetic Ins2 Akita mice suggests that pharmacological intervention in DR might be chosen, among other reasons, on the basis of the specific stages of the pathology in order to pursue the best clinical outcome.
RESUMO
Pancreatic Carcinoma (PC) cells have the ability to induce patient immunosuppression and to escape immunosurveillance. Low circulating lymphocytes are associated with an advanced stage of PC and reduced survival. Blood lymphocytes expressed as a percentage of Total White Blood Cells (L% TWBC) could predict chemotolerance (n° of tolerated cycles), survival time and Body Weight (BW) more effectively than lymphocytes expressed as an absolute value (LAB > 1500 n°/mm3) or lymphocytes >22%, which is the lowest limit of normal values in our laboratory. Forty-one patients with advanced PC, treated with chemotherapy, were selected for this observational retrospective study. Patients were evaluated at baseline (pre-chemotherapy), and at 6, 12 and 18 months, respectively, after diagnosis of PC. The study found L ≥ 29.7% to be a better predictor of survival (COX model, using age, sex, BW, serum creatinine, bilirubin and lymphocytes as covariates), chemotolerance (r = +0.50, p = 0.001) and BW (r = +0.35, p = 0.027) than LAB > 1500 or L > 22%. BW did not significantly correlate with chemotolerance or survival. The preliminary results of this study suggest that L ≥ 29.7% is more effective than LAB > 1500 or L > 22% at predicting chemotolerance, survival time and nutritional status. A possible impact of nutritional status on chemotherapy and survival seems to be lymphocyte-mediated given the association between BW and L%. This study may serve as the basis for future research to explore whether nutritional interventions can improve lymphopenia, and if so, how this may be possible.
Assuntos
Estado Nutricional , Neoplasias Pancreáticas , Imunidade Adaptativa , Humanos , Linfócitos , Neoplasias Pancreáticas/tratamento farmacológico , Prognóstico , Estudos Retrospectivos , Neoplasias PancreáticasRESUMO
Chronic conditions requiring long-term rehabilitation therapies, such as hypertension, stroke, or cancer, involve complex interactions between various systems/organs of the body and mutual influences, thus implicating a multiorgan approach. The dual-flow IVTech LiveBox2 bioreactor is a recently developed inter-connected dynamic cell culture model able to mimic organ crosstalk, since cells belonging to different organs can be connected and grown under flow conditions in a more physiological environment. This study aims to setup for the first time a 2-way connected culture of human neuroblastoma cells, SH-SY5Y, and Human Coronary Artery Smooth Muscle Cells, HCASMC through a dual-flow IVTech LiveBox2 bioreactor, in order to represent a simplified model of nervous-cardiovascular systems crosstalk, possibly relevant for the above-mentioned diseases. The system was tested by treating the cells with 10nM angiotensin II (AngII) inducing PKCßII/HuR/VEGF pathway activation, since AngII and PKCßII/HuR/VEGF pathway are relevant in cardiovascular and neuroscience research. Three different conditions were applied: 1- HCASMC and SH-SY5Y separately seeded in petri dishes (static condition); 2- the two cell lines separately seeded under flow (dynamic condition); 3- the two lines, seeded in dynamic conditions, connected, each maintaining its own medium, with a membrane as interface for biohumoral changes between the two mediums, and then treated. We detected that only in condition 3 there was a synergic AngII-dependent VEGF production in SH-SY5Y cells coupled to an AngII-dependent PKCßII/HuR/VEGF pathway activation in HCASMC, consistent with the observed physiological response in vivo. HCASMC response to AngII seems therefore to be generated by/derived from the reciprocal cell crosstalk under the dynamic inter-connection ensured by the dual flow LiveBox 2 bioreactor. This system can represent a useful tool for studying the crosstalk between organs, helpful for instance in rehabilitation research or when investigating chronic diseases; further, it offers the advantageous opportunity of cultivating each cell line in its own medium, thus mimicking, at least in part, distinct tissue milieu.
Assuntos
Reatores Biológicos , Comunicação Celular , Modelos Cardiovasculares , Modelos Neurológicos , Miócitos de Músculo Liso/metabolismo , Neurônios/metabolismo , Transdução de Sinais , Linhagem Celular Tumoral , Humanos , Miócitos de Músculo Liso/citologia , Neurônios/citologiaRESUMO
BACKGROUND: This retrospective study had two main aims: (1) to document possible correlations between plasma Amino Acids (AAs) and circulating Albumin (Alb) and Haemoglobin (Hb); and (2) to identify which AAs were predictors of Alb and Hb. METHODS: The study considered 125 stroke subjects (ST) (61.6% males; 65.6 +/- 14.9 years) who met the eligibility criteria (absence of co morbidities associated with altered plasma AAs and presence of plasma AAs determined after overnight fasting). Fifteen matched healthy subjects with measured plasma AAs served as controls. RESULTS: The best correlations of Alb were with tryptophan (Trp) and histidine (His) (r = + 0.53; p < 0.0001), and those of Hb were with histidine (r = +0.47) and Essential AAs (r = +0.47) (both p<0.0001). In multivariate analysis, Trp (p< 0.0001) and His (p = 0.01) were shown to be the best positive predictors of Alb, whereas glutamine (p = 0.006) was the best positive predictor of Hb. CONCLUSIONS: The study shows that the majority of plasma AAs were positively correlated with Alb and Hb. The best predictors of circulating Alb and Hb were the levels of tryptophan and glutamine, respectively.
Assuntos
Aminoácidos/sangue , Hemoglobinas/análise , Albumina Sérica/análise , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/diagnóstico , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Prognóstico , Estudos RetrospectivosRESUMO
The goal of this study was to measure arterial amino acid levels in patients with chronic heart failure (CHF), and relate them to left ventricular function and disease severity. Amino acids (AAs) play a crucial role for heart protein-energy metabolism. In heart failure, arterial AAs, which are the major determinant of AA uptake by the myocardium, are rarely measured. Forty-one subjects with clinically stable CHF (New York Heart Association (NYHA) class II to IV) were analyzed. After overnight fasting, blood samples from the radial artery were taken to measure AA concentrations. Calorie (KcalI), protein-, fat-, carbohydrate-intake, resting energy expenditure (REE), total daily energy expenditure (REE × 1.3), and cardiac right catheterization variables were all measured. Eight matched controls were compared for all measurements, with the exception of cardiac catheterization. Compared with controls, CHF patients had reduced arterial AA levels, of which both their number and reduced rates are related to Heart Failure (HF) severity. Arterial aspartic acid correlated with stroke volume index (r = 0.6263; p < 0.0001) and cardiac index (r = 0.4243; p = 0.0028). The value of arterial aspartic acid (µmol/L) multiplied by the cardiac index was associated with left ventricular ejection fraction (r = 0.3765; p = 0.0076). All NYHA groups had adequate protein intake (≥1.1 g/kg/day) and inadequate calorie intake (KcalI < REE × 1.3) was found only in class IV patients. This study showed that CHF patients had reduced arterial AA levels directly related to clinical disease severity and left ventricular dysfunction.
Assuntos
Aminoácidos/sangue , Metabolismo Energético , Insuficiência Cardíaca/sangue , Miocárdio/metabolismo , Idoso , Estudos de Casos e Controles , Doença Crônica , Feminino , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Estado Nutricional , Índice de Gravidade de Doença , Função Ventricular EsquerdaRESUMO
In the present paper, we report on the synthesis and antinociceptive activity of a new series of N-methyl-arylpyrrolidinols that we designed for a rational structure-activity relationship (SAR) study. The antinociceptive properties were investigated in vivo by the hot plate and formalin tests in mice and control on the locomotory activity was also monitored by the rota rod test. With this aim, the evaluation of the lipophilicity of all compounds was performed by the Daylight computational method in order to better understand the SAR. Interesting properties were proven for the compounds of the entire series.
Assuntos
Analgésicos/farmacologia , Pirrolidinas/farmacologia , Analgésicos/síntese química , Animais , Anti-Inflamatórios/síntese química , Anti-Inflamatórios/farmacologia , Comportamento Animal/efeitos dos fármacos , Masculino , Camundongos , Atividade Motora/efeitos dos fármacos , Medição da Dor , Pirrolidinas/síntese química , Relação Estrutura-AtividadeRESUMO
Exercise intolerance remains problematic in subjects with chronic heart failure (CHF) and/or chronic obstructive pulmonary disease (COPD). Recent studies show that supplemented essential amino acids (EAAs) may exert beneficial effects on CHF/COPD physical capacity. The results from 3 investigations (2 conducted on CHF and 1 on COPD subjects) served as the basis for this paper. The 3 studies consistently showed that elderly CHF and COPD improved exercise intolerance after 1-3 months of EAA supplementation (8 g/d). In CHF exercise capacity increased 18.7% to 23% (watts; bicycle test), and 12% to 22% (meters) in 6 min walking test. Moreover, patients reduced their resting plasma lactate levels (by 25%) and improved tissue insulin sensitivity by 16% (HOMA index). COPD subjects enjoyed similar benefits as CHF ones. They increased physical autonomy by 78.6% steps/day and decreased resting plasma lactate concentrations by 23%. EAA mechanisms explaining improved exercise intolerance could be increases in muscle aerobic metabolism, mass and function, and improvement of tissue insulin sensitivity (the latter only for the CHF population). These mechanisms could be accounted for by EAA's intrinsic physiological activity which increases myofibrils and mitochondria genesis in skeletal muscle and myocardium and glucose control. Supplemented EAAs can improve the physical autonomy of subjects with CHF/COPD.
Assuntos
Terapia por Exercício , Tolerância ao Exercício , Insuficiência Cardíaca , Músculo Esquelético , Doença Pulmonar Obstrutiva Crônica , Caminhada , Idoso , Idoso de 80 Anos ou mais , Doença Crônica , Feminino , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/fisiopatologia , Insuficiência Cardíaca/reabilitação , Humanos , Ácido Láctico/sangue , Masculino , Músculo Esquelético/metabolismo , Músculo Esquelético/fisiopatologia , Doença Pulmonar Obstrutiva Crônica/sangue , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Doença Pulmonar Obstrutiva Crônica/reabilitaçãoRESUMO
Alterations in muscle protein turnover of the unaffected side of stroke patients could contribute to physical disability. We investigated whether hypercatabolic activity occurred in unaffected arm muscle and whether supplemented essential amino acids (EAAs) could limit muscle hypercatabolism (MH). Thirty-eight dysphagic subacute stroke subjects (<3 months after acute event) (29 males+9 females; 69.7±11.4 yrs) were enrolled and randomized to receive 8 g/day EAAs (n=19; EAA group) or isocaloric placebo (maltodextrin; n=19, Plac group). Before randomization, all patients had their arterial (A) and venous (V) amino acids measured and muscle (A-V) differences calculated in the unaffected arm. Eight matched and healthy subjects served as controls. When compared to healthy controls, the entire stroke population showed significant muscle release (=negative value A-V) of the amino acid phenylalanine (phenyl-) indicating a prevalence of MH. Moreover, randomized EAA and Plac groups had similar rates of MH. After 38 days from the start of the protocol, the EAA group but not the Plac group had MH converted to balanced protein turnover or anabolic activity. We concluded that muscle protein metabolism of the unaffected arm of dysphagic subacute stroke individuals could be characterized by MH which can be corrected by supplemented EAAs.
Assuntos
Aminoácidos Essenciais/administração & dosagem , Braço/fisiopatologia , Suplementos Nutricionais , Acidente Vascular Cerebral/metabolismo , Idoso , Idoso de 80 Anos ou mais , Aminoácidos Essenciais/efeitos adversos , Feminino , Humanos , Insulina/metabolismo , Masculino , Metabolismo/efeitos dos fármacos , Pessoa de Meia-Idade , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , Músculo Esquelético/patologia , Acidente Vascular Cerebral/dietoterapia , Acidente Vascular Cerebral/patologiaRESUMO
BACKGROUND: To investigate whether supplementation with oral essential amino acids (EAAs) may reduce the occurrence of nosocomial infection among patients with brain injury (BI: stroke, trauma, anoxic coma). METHODS: Patients (n = 125; 77 men, 48 women; mean age 63 ± 15 years) with stroke (68.8%), subarachnoid hemorrhage (17.6%), traumatic BI (7.2%), and anoxic BI (6.4%) 88 ± 15 days after the index event. Patients were randomly assigned to 2 months of oral EAAs (n = 63; 8 g/d) or placebo (n = 62). RESULTS: Over the first month of rehabilitation, there were 60 infections in the whole population of 125 patients (48%); however, the rate was 23.2% lower in the EAA group (23 episodes/63 patients; 36.5%) than in the placebo group (37 episodes/62 patients; 59.7%) (P < .01). The types of infection were similarly distributed between the 2 groups. Serum levels of prealbumin <20 mg/dL and C-reactive protein (CRP) >0.3 mg/dL were the best predictors of future infection (prealbumin: odds ratio [OR] = 4.17, confidence interval [CI] 1.84-9.45, P < .001; CRP: OR = 3.8, CI 1.71-8.44, P < .001). CONCLUSION: Supplementary EAAs may reduce the occurrence of nosocomial infections in rehabilitation patients with BI. Prealbumin and CRP are the best predictors of future infections.