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Communication between neighboring or distant cells is made through a complex network that includes extracellular vesicles (EVs). Exosomes, which are a subgroup of EVs, are released from most cell types and have been found in biological fluids such as urine, plasma, and airway secretions like bronchoalveolar lavage (BAL), nasal lavage, saliva, and sputum. Mainly, the cargo exosomes are enriched with mRNAs and microRNAs (miRNAs), which can be transferred to a recipient cell consequently modifying and redirecting its biological function. The effects of miRNAs derive from their role as gene expression regulators by repressing or degrading their target mRNAs. Nowadays, various types of research are focused on evaluating the potential of exosomal miRNAs as biomarkers for the prognosis and diagnosis of different pathologies. Nevertheless, there are few reports on their role in the pathophysiology of idiopathic pulmonary fibrosis (IPF), a chronic lung disease characterized by progressive lung scarring with no cure. In this review, we focus on the role and effect of exosomal miRNAs as intercellular communicators in the onset and progression of IPF, as well as discussing their potential utility as therapeutic agents for the treatment of this disease.
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Exossomos , Vesículas Extracelulares , Fibrose Pulmonar Idiopática , MicroRNAs , Biomarcadores/metabolismo , Exossomos/genética , Exossomos/metabolismo , Vesículas Extracelulares/metabolismo , Humanos , Fibrose Pulmonar Idiopática/genética , Fibrose Pulmonar Idiopática/metabolismo , MicroRNAs/metabolismo , RNA Mensageiro/genéticaRESUMO
The SARS-CoV-2 pandemic has confirmed the apocalyptic predictions that virologists have been making for several decades. The challenge the world is facing is that of trying to find a possible treatment, and a viable and expedient option for addressing this challenge is the repurposing of drugs. However, in some cases, although these drugs are approved for use in humans, the mechanisms of action involved are unknown. In this sense, to justify its therapeutic application to a new disease, it is ideal, but not necessary, to know the basic mechanisms of action involved in a drug's biological effects. This review compiled the available information regarding the various effects attributed to Ivermectin. The controversy over its use for the treatment of COVID-19 is demonstrated by this report that considers the proposal unfeasible because the therapeutic doses proposed to achieve this effect cannot be achieved. However, due to the urgent need to find a treatment, an exhaustive and impartial review is necessary in order to integrate the knowledge that exists, to date, of the possible mechanisms through which the treatment may be helpful in defining safe doses and schedules of Ivermectin.
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Background: Infection by SARS-CoV-2 has been associated with multiple symptoms; however, still, little is known about persistent symptoms and their probable association with the risk of developing pulmonary fibrosis in patients post-COVID-19. Methods: A longitudinal prospective study on health workers infected by SARS-CoV-2 was conducted. In this work, signs and symptoms were recorded of 149 health workers with a positive PCR test for SARS-CoV-2 at the beginning of the diagnosis, during the active infection, and during post-COVID-19 follow-up. The McNemar chi-square test was used to compare the proportions and percentages of symptoms between the baseline and each follow-up period. Results: The signs and symptoms after follow-up were cardiorespiratory, neurological, and inflammatory. Gastrointestinal symptoms were unusual at the disease onset, but unexpectedly, their frequency was higher in the post-infection stage. The multivariate analysis showed that pneumonia (HR 2.4, IC95%: 1.5−3.8, p < 0.001) and positive PCR tests still after four weeks (HR 5.3, IC95%: 2.3-12.3, p < 0.001) were factors associated with the diagnosis of post-COVID-19 pulmonary fibrosis in this study group. Conclusions: Our results showed that pneumonia and virus infection persistence were risk factors for developing pulmonary fibrosis post-COVID-19, after months of initial infection.
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COVID-19 , Fibrose Pulmonar , COVID-19/complicações , Humanos , Pacientes Ambulatoriais , Estudos Prospectivos , Fibrose Pulmonar/epidemiologia , SARS-CoV-2RESUMO
Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive disease with high mortality and unclear etiology. Previous evidence supports that the origin of this disease is associated with epigenetic alterations, age, and environmental factors. IPF initiates with chronic epithelial lung injuries, followed by basal membrane destruction, which promotes the activation of myofibroblasts and excessive synthesis of extracellular matrix (ECM) proteins, as well as epithelial-mesenchymal transition (EMT). Due to miRNAs' role as regulators of apoptosis, proliferation, differentiation, and cell-cell interaction processes, some studies have involved miRNAs in the biogenesis and progression of IPF. In this context, the analysis and discussion of the probable association of miRNAs with the signaling pathways involved in the development of IPF would improve our knowledge of the associated molecular mechanisms, thereby facilitating its evaluation as a therapeutic target for this severe lung disease. In this work, the most recent publications evaluating the role of miRNAs as regulators or activators of signal pathways associated with the pathogenesis of IPF were analyzed. The search in Pubmed was made using the following terms: "miRNAs and idiopathic pulmonary fibrosis (IPF)"; "miRNAs and IPF and signaling pathways (SP)"; and "miRNAs and IPF and SP and IPF pathogenesis". Additionally, we focus mainly on those works where the signaling pathways involved with EMT, fibroblast differentiation, and synthesis of ECM components were assessed. Finally, the importance and significance of miRNAs as potential therapeutic or diagnostic tools for the treatment of IPF are discussed.
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Fibrose Pulmonar Idiopática , MicroRNAs , Transição Epitelial-Mesenquimal/genética , Humanos , Fibrose Pulmonar Idiopática/genética , Fibrose Pulmonar Idiopática/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Miofibroblastos/metabolismo , Transdução de SinaisRESUMO
Salvia amarissima Ortega is an endemic species of Mexico used in folk medicine to alleviate pain and as a nervous tranquilizer. The S. amarissima extract and one of its abundant metabolites, identified and isolated through chromatographic techniques, were investigated to obtain scientific evidence of its potential effects to relieve nociplastic pain such as fibromyalgia. Then, the extract and amarisolide A (3-300 mg/kg, i.p.) were pharmacologically evaluated in reserpine-induced fibromyalgia-type chronic pain and in depressive-like behavior (as a common comorbidity) by using the forced swimming test in rats. The 5-HT1A serotonin receptor (selective antagonist WAY100635, 1 mg/kg, i.p.) was explored after the prediction of a chemical interaction using in silico analysis to look for a possible mechanism of action of amarisolide A. Both the extract and amarisolide A produced significant and dose-dependent antihyperalgesic and antiallodynic effects in rats, as well as significant antidepressive behavior without sedative effects when the antinociceptive dosages were used. The 5-HT1A serotonin receptor participation was predicted by the in silico descriptors and was corroborated in the presence of WAY100635. In conclusion, S. amarissima possesses antihyperalgesic, antiallodynic, and anti-depressive activities, partially due to the presence of amarisolide A, which involves the 5-HT1A serotonin receptor. This pharmacological evidence suggests that S. amarissima and amarisolide A are both potential alternatives to relieve pain-like fibromyalgia.
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Pulmonary hypertension is a rare condition that impairs patients' quality of life and life expectancy. The development of noninvasive instruments may help elucidate the prognosis of this cardiorespiratory disease. We aimed to evaluate the utility of routinely performed noninvasive test results as prognostic markers in patients with pulmonary hypertension. We enrolled 198 patients with mean pulmonary artery pressure >25 mmHg measured at cardiac catheterisation or echocardiographic pulmonary artery systolic pressure > 40 mmHg and tricuspid regurgitation Vmax >2.9 m/s, and clinical information regarding management and follow-up studies from the date of diagnosis. Multivariate analysis revealed that female sex [HR: 0.21, (95% CI: 0.07-0.64); p = 0.006], the presence of collagenopathies [HR: 8.63, (95% CI: 2.38-31.32); p = 0.001], an increased red blood cell distribution width [HR: 1.25, (95% CI: 1.04-1.49); p = 0.017] and an increased electrocardiographic P axis (P°)/T axis (T°) ratio [HR: 0.93, (95% CI: 0.88-0.98); p = 0.009] were severity-associated factors, while older age [HR: 1.57, (95% CI: 1.04-1.28); p = 0.006], an increased QRS axis (QRS°)/T° ratio [HR: 1.21, (95% CI: 1.09-1.34); p < 0.001], forced expiratory volume in 1 s [HR: 0.94, (95% CI: 0.91-0.98); p = 0.01] and haematocrit [HR: 0.93, (95% CI: 0.87-0.99); p = 0.04] were mortality-associated factors. Our results support the importance of red blood cell distribution width, electrocardiographic ratios and collagenopathies for assessing pulmonary hypertension prognosis.
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Although thiamine pyrophosphate (TPP) is considered a protective agent for endothelial cells, it is still unknown if this is associated with nitric oxide (NO) synthesis. Our aim was to evaluate the synthesis of NO in endothelial cells incubated with TPP and high glucose concentrations. Endothelial cells from the umbilical cord vein from newborns (n = 20), were incubated with 5, 15 or 30 mmol/L glucose, in absence or presence of 0.625 mg/ml of TPP. Our results showed a significant increase in cell proliferation (> 40%; P < 0.05), and cell viability (> 90%; P < 0.001) after 48 h in endothelial cells cultured with glucose plus TPP. Likewise, in the presence of glucose and TPP an important rise in the consumption of glucose by the endothelial cells was observed after 24 h (> 7%; P < 0.001) and 48 h (> 10%; P < 0.05). Additionally, the levels of lactate after incubation with glucose and TPP showed only slight variations after 48 h (P < 0.05). However, these changes were clearly different from those observed in the absence of TPP. Interestingly, we found that the changes mentioned were linked with reduced levels of nitrites both at 24 h (< 171 pmol/µg protein; P < 0.001), and 48 h (< 250 pmol/µg protein; P < 0.05), which was associated with a reduced expression of mRNA of eNOS in endothelial cells incubated with TPP and high glucose. In conclusion, the presence of TPP regulates the consumption of glucose and the synthesis of NO, which would explain its protective effect in the endothelium of diabetic patients.
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Diabetes Mellitus , Tiamina Pirofosfato , Células Cultivadas , Células Endoteliais , Glucose , Humanos , Recém-Nascido , Óxido Nítrico , TiaminaRESUMO
Nowadays, glycine is used in nutritional supplements and to attenuate chronic complications of diabetes and obesity; however, its use has side effects as insulin resistance. Our aim was to evaluate the effect of chronic glycine supplementation on insulin, glucose and triglyceride levels in healthy Wistar rats. Groups were: Control (C), that received sterilized water only, glycine (GG), that received 1% glycine and taurine (TG), that received 0.5% taurine during 6 months (n = 10). Our results showed no differences in plasma insulin levels after six months of supplementation (C: 13.22 ± 2.0; GG: 11.4 ± 2.0; TG: 11.13 ± 2.0 ng/ml; p = 0.64). Likewise, neither glucose plasma concentration (C: 99.9 ± 3.9 mg/dl; GG: 104.3 ± 4.3 mg/dl; TG: 104.5 ± 4.8 mg/dl) (p = 0.88) nor triglyceride levels (C: 58.4 ± 5.6 mg/dl; GG: 46.9 ± 2.3 mg/dl; TG: 50.68 ± 3.3 mg/dl), showed differences after six months supplementation (p = 0.22). Furthermore, the analysis of glycine (C: 80 ± 24.6; GG: 83.9 ± 25.9; TG: 90.7 ± 13.5 nmol/ml) (p = 0.19) and taurine (C: 169 ± 15.17; GG: 148.7 ± 23.9; TG: 165.8 ± 22.5 nmol/ml) (p = 0.4) in the plasma of animals with supplementation showed no significant changes. Additionally, general urine tests and histological analysis of liver or kidneys showed no alterations. In conclusion, chronic supplementation with 1% glycine did not have any significant detrimental side effects in our model. However, more studies are still necessary to evaluate the effect of 1% glycine supplementation in humans.
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Resistência à Insulina , Insulina , Animais , Glicemia , Suplementos Nutricionais , Glucose , Glicina , Ratos , Ratos Wistar , TriglicerídeosRESUMO
Demodex folliculorum shows a high occurrence in the general population, however, its pathologic relevance is still controversial. In this prospective study, we evaluated the prevalence of D. folliculorum on eyelashes from 8,033 subjects of a university population (including 7,782 students, and 251 academics). Additional information on some risk factors to infection by the mites was evaluated, as well. A prevalence of 1.47% was found, where 118 individuals were positive for D. folliculorum; and, among them, 63 (53.4%) were women and 55 (46.6%) were men. Results showed a negative correlation with the age (r = -0.45), the highest prevalence was found in individuals between 19 and 22 years of age (2.1%, 84 patients). The number of D. folliculorum mites did not differ between the right and left eye; however, the use of cosmetics or facial cream, contact lens, hair removers, were factors present in patients infected with D. folliculorum. Although Demodex prevalence did not increase in line with weight, we found significantly higher prevalence in the 51-60 kg and 71-80 kg weight groups, and a particularly high prevalence in the over 81 kg weight group (2.6%). In conclusion, it was observed that the main population positive to infection consisted of young adults; this is in contrast with the international evidence reporting a high rate of infection in older adults. Besides, our results suggest that items of daily use such as cosmetics, facial cream, eyeliner, glasses, or contact lenses may be some of the main culprits of the infection by D. folliculorum.
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Pestanas/parasitologia , Folículo Piloso/parasitologia , Infestações por Ácaros/epidemiologia , Ácaros , Adolescente , Adulto , Animais , Peso Corporal , Lentes de Contato/efeitos adversos , Cosméticos/efeitos adversos , Óculos/efeitos adversos , Feminino , Humanos , Masculino , México/epidemiologia , Pessoa de Meia-Idade , Prevalência , Estudos Prospectivos , Fatores de Risco , Adulto JovemRESUMO
BACKGROUND & AIMS: Adequate nutrition from which amino acids are part gives us protection against infectious or metabolic diseases. In particular, glycine has immunomodulatory properties and is a secretagogue of insulin. However, its absorption rate or plasma levels are impaired in bacterial infection or high glucose levels. The aim of this study was to evaluate the association between glycine and insulin plasma levels in patients with pulmonary tuberculosis (PTB) and type 2 diabetes mellitus (DM2). METHODS: Plasma levels of insulin and glycine were determined in four groups: 1) patients with PTB; 2) patients with PTB-DM2; 3) household contacts with DM2 (C-DM2), and 4) healthy household contacts (H-C). Likewise, we analyzed the plasma levels of glucose, serine, arginine, lysine, taurine, and glutamic acid. RESULTS: We observed significant differences in the glycine levels between PTB and PTB-DM2 vs C-DM2 and H-C groups (P < 0.05). We observed also important differences in insulin and glucose levels after comparisons between PTB, PTB-DM2, and C-DM2 vs. H-C groups (P < 0.05). A correlation between glycine and insulin levels in the PTB (r = 0.326) and PTB-DM2 (r = 0.318) groups was found. CONCLUSION: Our results showed a significant association between glycine and insulin plasma levels in patients with PTB and PTB-DM2, which suggests that the determination of glycine levels could be used as a reference test to evaluate both pathologic conditions. An additional support to the above is that significant changes in the glucose levels in these groups were observed, too.
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Diabetes Mellitus Tipo 2/sangue , Glicina/sangue , Insulina/sangue , Tuberculose Pulmonar/sangue , Adulto , Biomarcadores/sangue , Glicemia/análise , Estudos de Casos e Controles , Estudos Transversais , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico , Feminino , Hemoglobinas Glicadas/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Estado Nutricional , Tuberculose Pulmonar/complicações , Tuberculose Pulmonar/diagnósticoRESUMO
IL-15 is part of the immune response in pulmonary tuberculosis (PTB) but amazingly, it may also induce physiological effects similar to those of insulin. We evaluated the IL-15 and insulin plasmatic levels in adults with PTB and with or without type 2 diabetes mellitus (DM2), who received previous antituberculosis therapy for at least 2 months. We analyzed the concentrations of glucose, glycated hemoglobin, insulin, as well as levels of IL-15, IL-2, IFN-γ, and TNF-α in patients with PTB, patients with PTB-DM2, household contacts with DM2 (C-DM2), and healthy household contacts (H-C). Our results showed unexpected high levels of glucose, insulin, and IL-15 in the PTB and C-DM2 groups. In comparison, low levels of these same indicators were observed in the PTB-DM2 and H-C groups. Interestingly, our analysis showed a positive correlation of IL-15 with insulin in the PTB group (râ¯=â¯0.73) and in the C-DM2 group (râ¯=â¯0.66). In comparison, a weak correlation between IL-15 and insulin was observed in the PTB-DM group (râ¯=â¯0.10) and in the H-C group (ρâ¯=â¯0.26). Our results suggest an association between IL-15 and insulin levels in the patient with PTB. Intriguingly, this association was weaker in the patient with PTB-DM2.
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Diabetes Mellitus Tipo 2/sangue , Insulina/sangue , Interleucina-15/sangue , Tuberculose Pulmonar/sangue , Adulto , Idoso , Antituberculosos/uso terapêutico , Biomarcadores/sangue , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Estudos de Casos e Controles , Estudos Transversais , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Feminino , Hemoglobinas Glicadas/metabolismo , Humanos , Hipoglicemiantes/uso terapêutico , Resistência à Insulina , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Tuberculose Pulmonar/complicações , Tuberculose Pulmonar/diagnóstico , Tuberculose Pulmonar/tratamento farmacológicoRESUMO
Evidence indicates that more than 90 % of infected individuals never develop active tuberculosis. This fact highlights the relevance of the immune response in tuberculosis control. The inducible co-stimulator (ICOS) is a regulator of the function, differentiation, proliferation, and activation of T cells. Moreover, T cells synthesise nitric oxide (NO), interferon gamma (IFN-γ), and interleukin (IL)-10, which help regulate the immune response to tuberculosis. Therefore, we assessed the synthesis of NO, IFN-γ, and IL-10 in CD3+ICOS+ T cells from healthy individuals, household contacts (HHC), and patients with active pulmonary tuberculosis (PTB), previously stimulated with the antigen H37Rv. Our results indicated a significant increase in both the percentage of ICOS+ cells and CD3+ICOS+ T cells producing NO, IFN-γ, and IL-10 in cells obtained from patients with PTB (p < 0.01). In addition, a high mitochondrial membrane potential (ΔΨ m) in CD3+ICOS+ T cells was observed in the cells from HHC and from PTB patients, and is associated with the activation of T cells. In conclusion, results show that the CD3+ICOS+ T cells obtained from PTB patients are the main producers of NO, IFN-γ, and IL-10. In addition, our results imply that NO is a modulator of ICOS expression of T cells from PTB patients.
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Interferon gama/metabolismo , Interleucina-10/metabolismo , Óxido Nítrico/metabolismo , Linfócitos T/imunologia , Tuberculose Pulmonar/imunologia , Adulto , Complexo CD3/metabolismo , Células Cultivadas , Família , Feminino , Voluntários Saudáveis , Humanos , Hidrolases/imunologia , Proteína Coestimuladora de Linfócitos T Induzíveis/metabolismo , Ativação Linfocitária , Masculino , Linfócitos T/metabolismo , Tuberculose Pulmonar/metabolismoRESUMO
Non-small cell lung cancer (NSCLC) is one of the most common types of aggressive cancer. The tumor tissue, which shows an active angiogenesis, is composed of neoplastic and stromal cells, and an abundant inflammatory infiltrate. Angiogenesis is important to support tumor growth, while infiltrating cells contribute to the tumor microenvironment through the secretion of growth factors, cytokines and chemokines, important molecules in the progression of the disease. Chemokines are important in development, activation of the immune response, and physiological angiogenesis. Chemokines have emerged as important regulators in the pathophysiology of cancer. These molecules are involved in the angiogenesis/angiostasis balance and in the recruitment of tumor infiltrating hematopoietic cells. In addition, chemokines promote tumor cell survival, as well as the directing and establishment of tumor cells to metastasis sites. The findings summarized here emphasize the central role of chemokines as modulators of tumor angiogenesis and their potential role as therapeutic targets in the inflammatory process of NSCLC angiogenesis.
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Diabetes mellitus (DM) is considered a risk factor for the development of Alzheimer disease (AD); however, how DM favors evolution of AD is still insufficiently understood. Hyperglycemia in DM is associated to an increase in mitochondrial reactive oxygen species (ROS) generation, as well as damage of hippocampal cells, reflected by changes in morphological and mitochondrial functionality. Similar mitochondrial damage has been observed when amyloid beta (Aß) accumulates in the brain of AD patients. In DM, the excess of glucose in the brain induces higher activity of the hexosamine biosynthesis pathway (HBP), it synthesizes UDP-N-acetylglucosamine (UDP-GlcNAc), which is used by O-linked N-acetylglucosamine transferase (OGT) to catalyze O-GlcNAcylation of numerous proteins. Although O-GlcNAcylation plays an important role in maintaining structure and cellular functionality, chronic activity of this pathway has been associated with insulin resistance and hyperglycemia-induced glucose toxicity. Three different forms of OGT are known: nucleocytoplasmic (ncOGT), short (sOGT), and mitochondrial (mOGT). Previous reports showed that overexpression of ncOGT is not toxic to the cell; in contrast, overexpression of mOGT is associated with cellular apoptosis. In this work, we suggest that hyperglycemia in the diabetic patient could induce greater expression and activity of mOGT, modifying the structure and functionality of mitochondria in hippocampal cells, accelerating neuronal damage, and favoring the start of AD. In consequence, mOGT activity could be a key point for AD development in patients with DM.
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Doença de Alzheimer/etiologia , Peptídeos beta-Amiloides/metabolismo , Complicações do Diabetes/enzimologia , Hipocampo/enzimologia , Mitocôndrias/enzimologia , N-Acetilglucosaminiltransferases/metabolismo , Doença de Alzheimer/enzimologia , Doença de Alzheimer/patologia , Animais , Glicemia/metabolismo , Complicações do Diabetes/sangue , Complicações do Diabetes/complicações , Complicações do Diabetes/patologia , Glicosilação , Hipocampo/patologia , Humanos , Mitocôndrias/patologia , Processamento de Proteína Pós-Traducional , Fatores de RiscoRESUMO
ß-1,3-Glucan is important for infective forms (mycelial phase) of Histoplasma capsulatum and shares many features allotted to pathogen-associated molecular patterns. These cell wall carbohydrates interact with phagocytes by binding to Toll and lectin-like receptors, present on cell surfaces of macrophages, neutrophils, and dendritic cells. This review focuses on recent findings of the major H. capsulatum and host carbohydrate-driven interactions that account for internalization of fungal infective forms into phagocytes, and its subsequent avoidance of intracellular elimination. The yeast phase of H. capsulatum possesses different modulating factors of the macrophagic-anti-fungal mechanisms, mainly α-1,3-glucan, which is considered relevant for virulence. This manuscript is part of the series of works presented at the "V International Workshop: Molecular genetic approaches to the study of human pathogenic fungi" (Oaxaca, Mexico, 2012).
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Glucanos/imunologia , Histoplasma/imunologia , Histoplasmose/imunologia , Interações Hospedeiro-Patógeno/imunologia , Imunidade Inata , beta-Glucanas/imunologia , Configuração de Carboidratos , Sequência de Carboidratos , Parede Celular , Células Dendríticas/imunologia , Humanos , Lectinas/imunologia , Macrófagos/imunologia , Dados de Sequência Molecular , Micélio/imunologia , Neutrófilos/imunologia , Fagócitos/fisiologia , Fagocitose , Receptores Mitogênicos/imunologia , Receptores Toll-Like/imunologia , Virulência/imunologiaRESUMO
Diabetes mellitus type 2 (DM2), obesity, and the metabolic syndrome are considered that a low-grade chronic inflammatory condition. Although synthesis of different pro- and anti-inflammatory cytokines has been implicated in this process, this low-grade inflammatory condition is characterized especially by an increase in Tumor Necrosis Factor alpha (TNF-α), a cytokine that has been associated to the development of insulin resistance and muscle wasting in the diabetic patients. In consequence, mechanisms implicated in attenuating the deleterious effects of TNF-α are activated. One of these mechanisms may involve interleukin 15 (IL-15), which has proven effect on intermediate metabolisms, regulating blood glucose and lipid levels, and diminishing proteolysis in striated muscle. This suggests that the induction of endogenous IL-15 production by a simple event as physical activity may aid in decreasing or even inhibiting the negative effects of TNF-α in patient with DM2 or obesity, in which a low grade chronic inflammatory condition is present.
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Diabetes Mellitus Tipo 2/metabolismo , Interleucina-15/metabolismo , Atividade Motora/fisiologia , Fator de Necrose Tumoral alfa/metabolismo , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/metabolismo , Diabetes Mellitus Tipo 2/terapia , Terapia por Exercício/métodos , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/fisiologia , Glucose/metabolismo , Humanos , Resistência à Insulina/fisiologia , Interleucina-15/farmacologia , Fator de Necrose Tumoral alfa/efeitos adversosRESUMO
Alterations in platelet activity have been associated with the onset of major depressive disorder (MDD) and with ischemic cardiovascular events through mechanisms that remain unknown. The present study evaluated nitric oxide (NO) levels, mitochondrial membrane potential (PMMP), and P-selectin expression in platelets from 30 untreated MDD patients and 30 matched controls by flow cytometry. In addition, tryptophan and serotonin concentrations were measured in the whole blood by high performance liquid chromatography. Patients were assessed with the Mini International Neuropsychiatric Interview and the Hamilton Depression Rating Scale. The patients had not had antidepressant treatment or any other pharmacological interventions for at least 1 year. MDD patients significantly differed from controls in levels of major fluorescent platelets for NO, PMMP, and P-selectin compared with those observed in control subjects. Serotonin concentrations in MDD patients did not differ from those in controls These results demonstrate that untreated MDD patients show increased platelet activation, suggesting an alteration in the platelet function.
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Transtorno Depressivo Maior/sangue , Transtorno Depressivo Maior/fisiopatologia , Potencial da Membrana Mitocondrial/fisiologia , Óxido Nítrico/sangue , Selectina-P/sangue , Adolescente , Adulto , Cromatografia Líquida de Alta Pressão , Feminino , Citometria de Fluxo , Humanos , Masculino , Escalas de Graduação Psiquiátrica , Serotonina/sangue , Triptofano/sangue , Adulto JovemRESUMO
The aim of this work was to determine the presence of galectin-10 in nasal lavage fluid (NLF) of patients with aspirin-sensitive respiratory disease (ASRD) before and after challenge with L-ASA (aspirin) by ELISA. Fifteen ASRD patients, ten aspirin-tolerant asthmatics (ATA), and fifteen healthy controls (HC) were studied. The baseline presence of Galectin-10 in PBMC was determined using real time PCR. Galectin-10 was evaluated in tissue of nasal polyps by western blot. Our results showed a lower expression in PBMC of ASRD patients than in ATA and healthy controls. However, a higher concentration of galectin-10 in NLF was found in ASRD patients before and after L-ASA challenge; western blot confirmed a high expression of galectin-10 in tissue from nasal polyps obtained from ASRD patients. Our results suggest a probable role of galectin-10 in the inflammatory response observed in ASRD patients; however, confirmatory studies are needed.
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Aspirina/efeitos adversos , Galectinas/metabolismo , Líquido da Lavagem Nasal/química , Doenças Respiratórias/induzido quimicamente , Doenças Respiratórias/metabolismo , Adolescente , Adulto , Idoso , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Adulto JovemRESUMO
Biochemical markers associated with the prognosis of depression in humans are being described in the literature, whereas experimental studies in animal models in search for antidepressant strategies are lacking. The aim of this study was to evaluate platelet morphology, platelet activity and nitric oxide (NO) synthesis as possible biomarkers of depressive-like behavior by using FST alone and in the presence of fluoxetine. Naïve rats were compared to those receiving vehicle or fluoxetine at 10mg/kg i.p. in acute, subchronic and chronic administration in the FST. After behavioral assessment, platelets were isolated from blood samples and analyzed by flow cytometry to determine the platelet mitochondrial membrane potential and NO synthesis. In addition, HPLC and electron microscopy were used to examine 5-HT and tryptophan levels and morphology of platelets, respectively. Rats receiving vehicle and exposed to FST showed depressive-like behavior at all the times tested; after chronic FST rats showed a similar pattern of alteration in platelet morphology and in the studied as possible biochemical markers as those previously recognized in depressive humans. Depressive-like behavior in rats exposed to FST was prevented in the presence of fluoxetine administration at all the times tested and associated with the prevention of alterations in platelet morphology, platelet activity and NO synthesis, and/or in 5-HT concentrations. The results of the present study suggest that platelet function and morphology might be relevant markers for the prognosis of depression and the search for functional treatments. Besides, the relevance of FST as model to study this psychiatric illness is reinforced.
Assuntos
Biomarcadores/sangue , Plaquetas/efeitos dos fármacos , Depressão/tratamento farmacológico , Fluoxetina/uso terapêutico , Óxido Nítrico/biossíntese , Inibidores Seletivos de Recaptação de Serotonina/uso terapêutico , Animais , Comportamento Animal/efeitos dos fármacos , Plaquetas/metabolismo , Plaquetas/ultraestrutura , Depressão/sangue , Fluoxetina/farmacologia , Masculino , Potenciais da Membrana , Ratos , Ratos Wistar , Serotonina/sangue , Inibidores Seletivos de Recaptação de Serotonina/farmacologia , Triptofano/sangueRESUMO
Thiamine (Vitamin B1) is considered an essential micronutrient for humans; its deficient intake brings about the Wernicke-Korsakoff syndrome (encephalopathy and psychosis) or beriberi (a neurological and cardiovascular disease). Once thiamine enters the cells it is phosphorylated by thiamine pyrophosphokinase (TPPK), and converted into the coenzyme thiamine pyrophosphate (TPP), the active form of thiamine. TPP is a relevant cofactor for transketolase (TK), α-ketoglutarate dehydrogenase (αKDH), and pyruvate dehydrogenase (PDH), all these enzymes are fundamental for glucose metabolism. Diabetes mellitus (DM), however, is considered both a deficient thiamine and deficient energy state, as a consequence of the limited TPP synthesis. Recent evidences have shown that the administration of thiamine or lipid-soluble derivatives, such as benfotiamine (developed to improve the bioavailability of thiamine), has positive effects in the diabetic patient (after thiamine is transformed into TPP). For this reason, administration of supplements with TPP in the diabetic patients is recommended to avoid complications, like neuropathy and nephropathy. It has been suggested that these beneficial effects are a consequence of the activation of TK (pentose pathway) or the PDH complex in mitochondria. Nitric oxide (NO) is synthesized by the endothelial cell and is also an important element for the viability and functionality of this cell type. However, in the DM patient, a deficient synthesis of NO has been reported. It is relevant to mention that recent evidences have led to propose mitochondrial activity as an important regulator of nitric oxide synthesis (ON). We consider that the exogenous administration of TPP facilitates the utilization of this molecule, regulating some metabolic processes such as phosphorylation of thiamine by TPPK, energy consumption (ATP), as well as mitochondrial activity, inducing eventually NO synthesis. If this is confirmed, the administration of TPP to the diabetic patient would provide additional protection to endothelial cells, reducing the risk of vascular damage, to which the diabetic patient is highly susceptible.