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1.
Postgrad Med J ; 100(1185): 469-474, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38377471

RESUMO

PURPOSE OF THE STUDY: Larger proportions of chronic obstructive pulmonary disease (COPD) patients are currently overweight or with obesity than underweight, and the combination of COPD and obesity is increasing. The purpose of this study was to investigate differences in the body composition, pulmonary function tests, exercise capacity, and health-related quality of life among normal weight, overweight, and obese patients with COPD. STUDY DESIGN: A total of 514 patients with COPD were included in the study. According to the World Health Organization criteria for body mass index, the patients were classified as normal weight, overweight, and obese. Evaluations included fat-free mass, fat-free mass index, phase angle, pulmonary function tests, and 6-minute walk test. Dyspnea was assessed using the modified Medical Research Council dyspnea scale, and the health-related quality of life was evaluated using COPD Assessment Test and St. George's Respiratory Questionnaire. Values were compared among the three groups. RESULTS: There were 315 male and 199 female patients, with a mean age of 66.7 ± 8.4 years. Fat-free mass, fat-free mass index, and phase angle values were significantly higher in COPD patients with obesity than in other patients (P < .001, P < .001, P < .001). Forced expiratory volume in 1 s, forced expiratory volume in 1 s/forced vital capacity, and diffusing capacity of lung for carbon monoxide value in pulmonary function tests were significantly higher in COPD patients with obesity than in other patients (P = .046, P < .001, P < .001), while the forced vital capacity values were similar in all groups. Exercise capacity (6-min walk test distance), dyspnea symptoms (modified Medical Research Council scale), and health-related quality of life (COPD Assessment Test and St. George's Respiratory Questionnaire) did not differ significantly between groups. CONCLUSIONS: According to our study, obesity has no negative effect on pulmonary function tests, dyspnea perception, exercise capacity, and health-related quality of life.


Assuntos
Composição Corporal , Índice de Massa Corporal , Tolerância ao Exercício , Obesidade , Doença Pulmonar Obstrutiva Crônica , Qualidade de Vida , Testes de Função Respiratória , Humanos , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Doença Pulmonar Obstrutiva Crônica/psicologia , Doença Pulmonar Obstrutiva Crônica/complicações , Masculino , Feminino , Idoso , Obesidade/fisiopatologia , Obesidade/complicações , Obesidade/psicologia , Tolerância ao Exercício/fisiologia , Pessoa de Meia-Idade , Teste de Caminhada , Dispneia/fisiopatologia , Dispneia/etiologia
2.
Int J Mol Sci ; 25(7)2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38612680

RESUMO

The central exacerbating factor in the pathophysiology of ischemic-reperfusion acute kidney injury (AKI) is oxidative stress. Lipid peroxidation and DNA damage in ischemia are accompanied by the formation of 3-nitrotyrosine, a biomarker for oxidative damage. DNA double-strand breaks (DSBs) may also be a result of postischemic AKI. γH2AX(S139) histone has been identified as a potentially useful biomarker of DNA DSBs. On the other hand, hypoxia-inducible factor (HIF) is the "master switch" for hypoxic adaptation in cells and tissues. The aim of this research was to evaluate the influence of hyperbaric oxygen (HBO) preconditioning on antioxidant capacity estimated by FRAP (ferric reducing antioxidant power) and ABTS (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)) assay, as well as on oxidative stress parameter 3-nitrotyrosine, and to assess its effects on γH2AX(S139), HIF-1α, and nuclear factor-κB (NF-κB) expression, in an experimental model of postischemic AKI induced in spontaneously hypertensive rats. The animals were divided randomly into three experimental groups: sham-operated rats (SHAM, n = 6), rats with induced postischemic AKI (AKI, n = 6), and group exposed to HBO preconditioning before AKI induction (AKI + HBO, n = 6). A significant improvement in the estimated glomerular filtration rate, eGFR, in AKI + HBO group (p < 0.05 vs. AKI group) was accompanied with a significant increase in plasma antioxidant capacity estimated by FRAP (p < 0.05 vs. SHAM group) and a reduced immunohistochemical expression of 3-nitrotyrosine and γH2AX(S139). Also, HBO pretreatment significantly increased HIF-1α expression (p < 0.001 vs. AKI group), estimated by Western blot and immunohistochemical analysis in kidney tissue, and decreased immunohistochemical NF-κB renal expression (p < 0.01). Taking all of these results together, we may conclude that HBO preconditioning has beneficial effects on acute kidney injury induced in spontaneously hypertensive rats.


Assuntos
Injúria Renal Aguda , Oxigenoterapia Hiperbárica , Traumatismo por Reperfusão , Animais , Ratos , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/terapia , Antioxidantes , Biomarcadores , Dano ao DNA , Rim , NF-kappa B , Estresse Oxidativo , Oxigênio , Ratos Endogâmicos SHR
3.
Medicina (Kaunas) ; 60(4)2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38674308

RESUMO

Background and Objectives: Differentiating between a high-grade glioma (HGG) and solitary cerebral metastasis presents a challenge when using standard magnetic resonance imaging (MRI) alone. Magnetic resonance spectroscopy (MRS), an advanced MRI technique, may assist in resolving this diagnostic dilemma. N-acetylaspartate (NAA), an amino acid found uniquely in the central nervous system and in high concentrations in neurons, typically suggests HGG over metastatic lesions in spectra from ring-enhancing lesions. This study investigates exceptions to this norm. Materials and Methods: We conducted an MRS study on 49 histologically confirmed and previously untreated patients with brain metastases, employing single-voxel (SVS) techniques with short and long echo times, as well as magnetic resonance spectroscopic imaging (MRSI). Results: In our cohort, 44 out of 49 (90%) patients demonstrated a typical MR spectroscopic profile consistent with secondary deposits: a Cho peak, very low or absent Cr, absence of NAA, and the presence of lipids. A peak at approximately 2 ppm, termed the "NAA-like peak", was present in spectra obtained with both short and long echo times. Among the MRS data from 49 individuals, we observed a peak at 2.0 ppm in five brain metastases from mucinous carcinoma of the breast, mucinous non-small-cell lung adenocarcinoma, two metastatic melanomas, and one metastatic non-small-cell lung cancer. Pathohistological verification of mucin in two of these five cases suggested this peak likely represents N-acetyl glycoproteins, indicative of mucin expression in cancer cells. Conclusions: The identification of a prominent peak at 2.0 ppm could be a valuable diagnostic marker for distinguishing single ring-enhancing lesions, potentially associated with mucin-expressing metastases, offering a new avenue for diagnostic specificity in challenging cases.


Assuntos
Ácido Aspártico , Ácido Aspártico/análogos & derivados , Neoplasias Encefálicas , Espectroscopia de Ressonância Magnética , Humanos , Ácido Aspártico/análise , Ácido Aspártico/metabolismo , Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/metabolismo , Espectroscopia de Ressonância Magnética/métodos , Feminino , Pessoa de Meia-Idade , Masculino , Idoso , Adulto , Glioma/diagnóstico por imagem , Glioma/metabolismo , Estudos de Coortes
4.
Int J Mol Sci ; 24(15)2023 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-37569620

RESUMO

Renal cell carcinoma (RCC) is the deadliest urological neoplasm. Up to date, no validated biomarkers are included in clinical guidelines for the screening and follow up of patients suffering from RCC. Slug (Snail2) and Snail (Snail1) belong to the Snail superfamily of zinc finger transcriptional factors that take part in the epithelial-mesenchymal transition, a process important during embryogenesis but also involved in tumor progression. We examined Slug and Snail immunohistochemical expression in patients with different stages of renal cell carcinomas with the aim to investigate their potential role as staging and prognostic factors. A total of 166 samples of malignant renal cell neoplasms were analyzed using tissue microarray and immunohistochemistry. Slug and Snail expressions were evaluated qualitatively (presence or absence), in nuclear and cytoplasmic cell compartments and compared in relation to clinical parameters. The Kaplan-Meier survival analysis showed the impact of the sarcomatoid component and Slug expression on the survival longevity. Cox regression analysis separated Slug as the only independent prognostic factor (p = 0.046). The expression of Snail was associated with higher stages of the disease (p = 0.004), especially observing nuclear Snail expression (p < 0.001). All of the tumors that had metastasized showed nuclear immunoreactivity (p < 0.001). In clear cell RCC, we showed a significant relationship between a high nuclear grade and nuclear Snail expression (p = 0.039). Our results suggest that Slug and Snail could be useful immunohistochemical markers for staging and prognosis in patients suffering from various RCCs, representing potential targets for further therapy strategies of renal cancer.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Humanos , Carcinoma de Células Renais/patologia , Fatores de Transcrição da Família Snail , Estadiamento de Neoplasias , Neoplasias Renais/metabolismo , Biomarcadores , Transição Epitelial-Mesenquimal , Biomarcadores Tumorais/análise
5.
Int J Mol Sci ; 24(9)2023 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-37175793

RESUMO

Ischemia-reperfusion injury (IRI) is a frequent cause of AKI, resulting in vasoconstriction, cellular dysfunction, inflammation and the induction of oxidative stress. DNA damage, including physical DNA strand breaks, is also a potential consequence of renal IRI. The histone H2A variants, primary H2AX and H2AZ participate in DNA damage response pathways to promote genome stability. The aim of this study was to evaluate the immunohistochemical pattern of histone H2A variants' (H2AX, γH2AX(S139), H2AXY142ph and H2AZ) expression in an experimental model of ischemia-reperfusion-induced acute kidney injury in spontaneously hypertensive rats. Comparing the immunohistochemical nuclear expression of γH2AX(S139) and H2AXY142ph in AKI, we observed that there is an inverse ratio of these two histone H2AX variants. If we follow different regions from the subcapsular structures to the medulla, there is an increasing extent gradient in the nuclear expression of H2AXY142ph, accompanied by a decreasing nuclear expression of γH2AX. In addition, we observed that different structures dominated when γH2AX and H2AXY142ph expression levels were compared. γH2AX was expressed only in the proximal tubule, with the exception of when they were dilated. In the medulla, H2AXY142ph is predominantly expressed in the loop of Henle and the collecting ducts. Our results show moderate sporadic nuclear H2AZ expression mainly in the cells of the distal tubules and the collecting ducts that were surrounded by dilated tubules with PAS (periodic acid-Schiff stain)-positive casts. These findings may indicate the degree of DNA damage, followed by postischemic AKI, with potential clinical and prognostic implications regarding this condition.


Assuntos
Injúria Renal Aguda , Traumatismo por Reperfusão , Ratos , Animais , Histonas/metabolismo , Rim/metabolismo , Injúria Renal Aguda/genética , Injúria Renal Aguda/metabolismo , Traumatismo por Reperfusão/complicações , Traumatismo por Reperfusão/genética , Traumatismo por Reperfusão/metabolismo , Reperfusão , Isquemia/metabolismo , Modelos Teóricos
6.
Artigo em Inglês | MEDLINE | ID: mdl-37702707

RESUMO

The nutritional status of patients with chronic obstructive pulmonary disease (COPD) is a significant factor that influences the prognosis of the disease. This observational study aimed to analyse the nutritional status of COPD patients and assess the associations between nutritional status, disease severity, and exercise capacity in four different regions of Croatia. In this multicentre study, 534 COPD patients were recruited and evaluated concerning fat-free mass (FFM), fat-free mass index (FFMI), skeletal muscle mass index (SMMI), phase angle (PhA), pulmonary function tests, and the 6-minute walk test (6MWT). There were 325 (60.9%) male and 209 (39.1%) female patients with a mean age of 66.7±8.4 years. Most patients (73.2%) exhibited a moderate to severely abnormal obstructive pattern and had a reduced 6MWT distance (396.5±110.8 m). Among the participants, 32.8% were overweight and 22.3% were obese, and they had satisfactory values for nutritional status variables (FFM, FFMI, SMMI, PhA). There were no statistical differences between the centres in terms of nutritional status variables. There was a significantly positive correlation of FEV1 with BMI (r=0.148, p=0.001), PhA (r=0.256, p=0.00), FFM (r=0.365, p=0.00), and SMMI (r=0.238, p=0.00). However, there was no significant correlation of the 6MWT with BMI (r=-0.049, p=0.254), FFM (r=0.065, p=0.133), and SMMI (r=-0.007, p=0.867). The data analysis demonstrated that our patients were not underweight and that there was no significant difference between the centres in terms of BMI, FFM, FFMI, SMMI, and PhA. This lack of significant difference was observed even though one of the regions studied was Mediterranean.

7.
Exp Mol Pathol ; 128: 104820, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35908617

RESUMO

INTRODUCTION: ST2 is the receptor for interleukin (IL)-33, the last discovered member of the IL-1 cytokine family. Acute inflammation is an early response of vascularized tissue to injury, in which alteration of micro- and macro-elements occurs. This study aimed to examine the alteration of cobalt, sodium, potassium, and calcium concentration at the site of acute inflammation and the role of ST2 in these alterations. MATERIAL AND METHODS: Wild-type (WT) and ST2 knockout (ST2-/-) mice were divided into groups: WT control group (WT-C), ST2 knockout control group (KO-C), WT inflammatory group (WT-I), and ST2 knockout inflammatory group (KO-I). We induced acute inflammation by intramuscular injection of turpentine oil or saline in the case of the control group. After 12 h, we anesthetized mice and collected treated tissues for histopathological analysis and determination of cobalt, sodium, potassium, and calcium concentration by atomic absorption spectrometer. RESULTS: Histopathological analysis showed the inflammatory infiltrate and cell necrosis in the treated tissue in WT-I and KO-I. The concentration of sodium was significantly lower in WT-I than in WT-C. The concentration of potassium and cobalt was significantly lower in WT-I and KO-I when compared to WT-C and KO-C, respectively. However, the concentration of potassium and cobalt in the tissue was significantly lower in WT-I than in KO-I. The concentration of calcium in the tissue did not significantly differ between groups. CONCLUSION: We reported, to our knowledge for the first time, that ST2 is involved in decreasing sodium, potassium, and cobalt concentration at the site of acute inflammation.


Assuntos
Cálcio , Proteína 1 Semelhante a Receptor de Interleucina-1 , Animais , Camundongos , Cobalto , Citocinas , Inflamação/induzido quimicamente , Inflamação/patologia , Interleucina-1 , Interleucina-33 , Camundongos Knockout , Potássio , Sódio , Terebintina
8.
Int J Mol Sci ; 22(3)2021 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-33573145

RESUMO

Renal ischemia and reperfusion (I/R) injury is the most common cause of acute kidney injury (AKI). Pathogenesis of postischemic AKI involves hemodynamic changes, oxidative stress, inflammation process, calcium ion overloading, apoptosis and necrosis. Up to date, therapeutic approaches to treat AKI are extremely limited. Thus, the aim of this study was to evaluate the effects of hyperbaric oxygen (HBO) preconditioning on citoprotective enzyme, heme oxygenase-1 (HO-1), pro-apoptotic Bax and anti-apoptotic Bcl-2 proteins expression, in postischemic AKI induced in normotensive Wistar and spontaneously hypertensive rats (SHR). The animals were randomly divided into six experimental groups: SHAM-operated Wistar rats (W-SHAM), Wistar rats with induced postischemic AKI (W-AKI) and Wistar group with HBO preconditioning before AKI induction (W-AKI + HBO). On the other hand, SHR rats were also divided into same three groups: SHR-SHAM, SHR-AKI and SHR-AKI + HBO. We demonstrated that HBO preconditioning upregulated HO-1 and anti-apoptotic Bcl-2 protein expression, in both Wistar and SH rats. In addition, HBO preconditioning improved glomerular filtration rate, supporting by significant increase in creatinine, urea and phosphate clearances in both rat strains. Considering our results, we can also say that even in hypertensive conditions, we can expect protective effects of HBO preconditioning in experimental model of AKI.


Assuntos
Injúria Renal Aguda/prevenção & controle , Heme Oxigenase (Desciclizante)/metabolismo , Oxigenoterapia Hiperbárica/métodos , Hipertensão/complicações , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Traumatismo por Reperfusão/prevenção & controle , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/patologia , Injúria Renal Aguda/urina , Animais , Creatinina/metabolismo , Creatinina/urina , Modelos Animais de Doenças , Humanos , Hipertensão/fisiopatologia , Hipertensão/terapia , Rim/irrigação sanguínea , Rim/patologia , Rim/fisiopatologia , Masculino , Oxigênio/administração & dosagem , Fosfatos/metabolismo , Fosfatos/urina , Ratos , Ratos Endogâmicos SHR , Ratos Wistar , Eliminação Renal/fisiologia , Traumatismo por Reperfusão/etiologia , Traumatismo por Reperfusão/patologia , Traumatismo por Reperfusão/urina , Regulação para Cima , Ureia/metabolismo , Ureia/urina
9.
Microsc Microanal ; 26(4): 717-730, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32588793

RESUMO

Occasionally, Hashimoto's thyroiditis (HT) and papillary thyroid carcinoma (PTC) share similar nuclear features. The current study aims to quantify the differences between the investigated specimens of HT-associated PTC versus the HT alone, to reduce the subjective experience of an observer, by the use of fractal parameters as well as gray-level co-occurrence matrix (GLCM) textural parameters. We have analyzed 250 segmented nuclei per group (nn = 25 per patient and np = 10 patients per group) using the ImageJ software (NIH, Bethesda, MD, USA) as well as an in-house written code for the GLCM analysis. The mean values of parameters were calculated for each patient. The results demonstrated that the malignant cells from the HT-associated PTC specimens showed lower chromatin fractal dimension (p = 0.0321) and higher lacunarity (p = 0.0038) compared with the corresponding cells from the HT specimens. Also, there was a statistically significant difference between the investigated specimens, in the contrast, correlation, angular second moment, and homogeneity, of the GLCM corresponding to the visual texture of follicular cell chromatin. The differences in chromatin fractal and GLCM parameters could be integrated with other diagnostic methods for the improved evaluation of distinctive features of the HT-associated PTC versus the HT in cytology and surgical pathology specimens.


Assuntos
Cromatina/metabolismo , Fractais , Doença de Hashimoto/diagnóstico , Câncer Papilífero da Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/diagnóstico , Diagnóstico Diferencial , Doença de Hashimoto/genética , Doença de Hashimoto/patologia , Humanos , Processamento de Imagem Assistida por Computador , Estudos Retrospectivos , Câncer Papilífero da Tireoide/genética , Câncer Papilífero da Tireoide/patologia , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/patologia
10.
Microsc Microanal ; 25(3): 762-768, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30813976

RESUMO

Previous evidence suggested that lymphocytic thyroiditis (LT) was a variant of Hashimoto's thyroiditis (HT), thus the aim of the current study is to quantify structural changes in histological specimens taken from HT and LT patients. A total of 600 images containing a single lymphocyte nucleus (300 nuclei per group) were obtained from 20 patients with HT and LT. In order to quantify changes in the nuclear architecture of investigated lymphocytes, the fractal dimension (FD) and some gray-level co-occurrence matrix texture parameters (angular second moment, inverse difference moment, contrast, entropy, and correlation) were calculated for each nucleus. A statistically significant difference in the FD of the "binary-outlined" nucleus and that of the corresponding "black-and-white" nucleus was detected between HT and LT lymphocyte nuclei. In addition, there was also a statistically significant difference in contrast and correlation between HT and LT lymphocyte nuclei. In conclusion, the results of this study suggested that there was a difference in structural complexity between investigated lymphocyte nuclei; additionally, LT lymphocytes possessed probably more complex texture and larger variations as well as more asymmetrical nuclei compared with HT lymphocytes. Accordingly, these findings indicate that LT is probably not a variant of HT; however, more complex studies are necessary to estimate differences between these types of thyroiditis.


Assuntos
Núcleo Celular/patologia , Cromatina/patologia , Fractais , Doença de Hashimoto/patologia , Linfócitos/citologia , Tireoidite Autoimune/patologia , Adulto , Idoso , Algoritmos , Gráficos por Computador , Feminino , Doença de Hashimoto/diagnóstico por imagem , Doença de Hashimoto/terapia , Humanos , Processamento de Imagem Assistida por Computador/métodos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Glândula Tireoide/diagnóstico por imagem , Glândula Tireoide/patologia , Tireoidite Autoimune/diagnóstico por imagem , Tireoidite Autoimune/terapia
11.
Eur J Nutr ; 57(8): 3003-3005, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29255931

RESUMO

We conducted a secondary analysis of a previously completed trial to determine the effects of 8-week guanidinoacetic acid (GAA) loading on brain GAA levels in five healthy men. Brain magnetic resonance spectroscopy (1H-MRS) was taken at baseline and post-administration, with spectra additionally analyzed for brain GAA and glutamate concentrations using TARQUIN 4.3.10 software. Brain GAA levels remained essentially unchanged at follow-up (an increase of 7.7% from baseline levels; 95% confidence interval, - 24.1% to 39.5%; P = 0.88) when averaged across 12 white and grey matter voxel locations. No significant changes were found for brain glutamate levels during the study (P = 0.64). Supplemental GAA appears to be safe intervention concerning brain GAA deposition, at least with GAA dosages used.


Assuntos
Encéfalo/efeitos dos fármacos , Dieta , Glicina/análogos & derivados , Adulto , Índice de Massa Corporal , Encéfalo/metabolismo , Suplementos Nutricionais , Relação Dose-Resposta a Droga , Exercício Físico , Seguimentos , Glicina/administração & dosagem , Glicina/farmacocinética , Humanos , Espectroscopia de Ressonância Magnética , Masculino , Substâncias para Melhoria do Desempenho/administração & dosagem , Substâncias para Melhoria do Desempenho/farmacocinética , Adulto Jovem
12.
Nucleic Acids Res ; 44(12): 5785-97, 2016 07 08.
Artigo em Inglês | MEDLINE | ID: mdl-27257059

RESUMO

Mitochondria have their own translation machinery that produces key subunits of the OXPHOS complexes. This machinery relies on the coordinated action of nuclear-encoded factors of bacterial origin that are well conserved between humans and yeast. In humans, mutations in these factors can cause diseases; in yeast, mutations abolishing mitochondrial translation destabilize the mitochondrial DNA. We show that when the mitochondrial genome contains no introns, the loss of the yeast factors Mif3 and Rrf1 involved in ribosome recycling neither blocks translation nor destabilizes mitochondrial DNA. Rather, the absence of these factors increases the synthesis of the mitochondrially-encoded subunits Cox1, Cytb and Atp9, while strongly impairing the assembly of OXPHOS complexes IV and V. We further show that in the absence of Rrf1, the COX1 specific translation activator Mss51 accumulates in low molecular weight forms, thought to be the source of the translationally-active form, explaining the increased synthesis of Cox1. We propose that Rrf1 takes part in the coordination between translation and OXPHOS assembly in yeast mitochondria. These interactions between general and specific translation factors might reveal an evolutionary adaptation of the bacterial translation machinery to the set of integral membrane proteins that are translated within mitochondria.


Assuntos
DNA Mitocondrial/genética , Complexo IV da Cadeia de Transporte de Elétrons/genética , Regulação Fúngica da Expressão Gênica , Mitocôndrias/genética , Proteínas Mitocondriais/genética , Proteínas de Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/genética , Citocromos b/genética , Citocromos b/metabolismo , DNA Mitocondrial/metabolismo , Complexo IV da Cadeia de Transporte de Elétrons/metabolismo , Genoma Mitocondrial , Mitocôndrias/metabolismo , Proteínas Mitocondriais/química , Proteínas Mitocondriais/metabolismo , ATPases Mitocondriais Próton-Translocadoras/genética , ATPases Mitocondriais Próton-Translocadoras/metabolismo , Modelos Moleculares , Fosforilação Oxidativa , Biossíntese de Proteínas , Ribossomos/genética , Ribossomos/metabolismo , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/química , Proteínas de Saccharomyces cerevisiae/metabolismo , Schizosaccharomyces/genética , Schizosaccharomyces/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
13.
Eur Radiol ; 27(10): 4218-4236, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28293774

RESUMO

OBJECTIVES: The aim of this study was to test neurobiochemical changes in normal appearing brain tissue in HIV+ patients receiving and not receiving combined antiretroviral therapy (cART) and healthy controls, using multivoxel MR spectroscopy (mvMRS). METHODS: We performed long- and short-echo 3D mvMRS in 110 neuroasymptomatic subjects (32 HIV+ subjects on cART, 28 HIV+ therapy-naïve subjects and 50 healthy controls) on a 3T MR scanner, targeting frontal and parietal supracallosal subcortical and deep white matter and cingulate gyrus (NAA/Cr, Cho/Cr and mI/Cr ratios were analysed). The statistical value was set at p < 0.05. RESULTS: Considering differences between HIV-infected and healthy subjects, there was a significant decrease in the NAA/Cr ratio in HIV+ subjects in all observed locations, an increase in mI/Cr levels in the anterior cingulate gyrus (ACG), and no significant differences in Cho/Cr ratios, except in ACG, where the increase showed trending towards significance in HIV+ patients. There were no significant differences between HIV+ patients on and without cART in all three ratios. CONCLUSION: Neuronal loss and dysfunction affects the whole brain volume in HIV-infected patients. Unfortunately, cART appears to be ineffective in halting accelerated neurodegenerative process induced by HIV but is partially effective in preventing glial proliferation. KEY POINTS: • This is the first multivoxel human brain 3T MRS study in HIV. • All observed areas of the brain are affected by neurodegenerative process. • Cingulate gyrus and subcortical white matter are most vulnerable to HIV-induced neurodegeneration. • cART is effective in control of inflammation but ineffective in preventing neurodegeneration.


Assuntos
Complexo AIDS Demência/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Infecções por HIV/complicações , Espectroscopia de Ressonância Magnética/métodos , Doenças Neurodegenerativas/diagnóstico por imagem , Adulto , Ácido Aspártico/análise , Biomarcadores/análise , Encéfalo/metabolismo , Estudos de Casos e Controles , Colina/análise , Creatina/análise , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doenças Neurodegenerativas/etiologia , Estudos Retrospectivos , Substância Branca/diagnóstico por imagem , Adulto Jovem
14.
Molecules ; 22(7)2017 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-28678191

RESUMO

In this study, boroxine derivative (K2[B3O3F4OH]) was tested as an inhibitor of horseradish peroxidase (HRP) by spectrophotometric and electrochemical methods. The activity of horseradish peroxidase was first studied under steady-state kinetic conditions by a spectrophotometric method which required the use of guaiacol as a second substrate to measure guaiacol peroxidation. The results of this method have shown that, by changing the concentration of guaiacol as the literature suggests, a different type of inhibition is observed than when changing the concentration of hydrogen peroxide as the substrate. This suggests that guaiacol interferes with the reaction in some way. The electrochemical method involves direct electron transfer of HRP immobilized in Nafion nanocomposite films on a glassy carbon (GC) electrode, creating a sensor with an electro-catalytic response to the reduction of hydrogen peroxide. The electrochemical method simplifies kinetic assays by removing the requirement of reducing substrates.


Assuntos
Compostos de Boro/farmacologia , Técnicas Eletroquímicas/métodos , Inibidores Enzimáticos/farmacologia , Peroxidase do Rábano Silvestre/antagonistas & inibidores , Carbono/química , Eletrodos , Transporte de Elétrons , Enzimas Imobilizadas , Cinética , Nanocompostos/química , Espectrofotometria
16.
Ophthalmologica ; 235(1): 49-56, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26540208

RESUMO

We are presenting two Leber's hereditary optic neuropathy (LHON) pedigrees with abnormal magnetic resonance imaging (MRI) and proton magnetic resonance spectroscopy (H-MRS) findings but without neurological manifestation associated with LHON. The study included 14 LHON patients and 41 asymptomatic family members from 12 genealogically unrelated families. MRI showed white matter involvement and H-MRS exhibited metabolic anomalies within 12 LHON families. Main outcome measures were abnormal MRI and H-MRS findings in two pedigrees. MRI of the proband of the first pedigree showed a single demyelinating lesion in the right cerebellar hemisphere, while the proband of the second family displayed multiple supratentorial and infratentorial lesions, compatible with the demyelinating process, and both the absolute choline (Cho) concentration and Cho/creatinine ratio were increased. MRI and H-MRS profiles of both affected and unaffected mitochondrial DNA mutation carriers suggest more widespread central nervous involvement in LHON. Although even after 12 years our patients did not develop neurological symptoms, MRI could still be used to detect possible changes during the disease progression.


Assuntos
Doenças Desmielinizantes/diagnóstico , Atrofia Óptica Hereditária de Leber/diagnóstico , Substância Branca/patologia , Adulto , Idoso , Colina , Creatinina , DNA Mitocondrial/genética , Doenças Desmielinizantes/tratamento farmacológico , Doenças Desmielinizantes/genética , Feminino , Glucocorticoides/administração & dosagem , Humanos , Imageamento por Ressonância Magnética , Masculino , Doenças Mitocondriais/diagnóstico , Doenças Mitocondriais/tratamento farmacológico , Doenças Mitocondriais/genética , Atrofia Óptica Hereditária de Leber/tratamento farmacológico , Atrofia Óptica Hereditária de Leber/genética , Linhagem , Mutação Puntual , Espectroscopia de Prótons por Ressonância Magnética , Pulsoterapia , Acuidade Visual/fisiologia
17.
Folia Biol (Krakow) ; 64(3): 183-188, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-29847078

RESUMO

TASK2 (K2P5. 1, KCNK5) is a two-pore domain K⁺ channel belonging to the TALK subgroup of the K2P family of proteins. TASK2 expression has been reported in a variety of cells and tissues ranging from kidney to immune cells and including specific neurons, its proposed functions spanning from involvement in the regulation of cell volume to control of excitability. The purpose of this study was to determine the tubule location ofthe TASK2 K⁺ channel protein in frog kidney applying polyclonal antibody against the carboxyl terminus of human TASK2 (KCNK5) protein. Immunohistochemical analysis revealed that TASK2 is expressed on distal tubules and proximal epithelial cells. TASK2 is strongly expressed predominantly on the luminal part ofthe proximal epithelial cells and slightly cytoplasmatic staining is expressed. Distal tubules showed diffuse cytoplasmatic staining as well as slight staining on the apical parts ofthe cells. These findings suggest that the TASK2 K⁺ channel has cell-specific roles in renal potassium ion transport.


Assuntos
Rim/metabolismo , Canais de Potássio de Domínios Poros em Tandem/metabolismo , Rana esculenta/metabolismo , Animais , Imuno-Histoquímica
18.
BMC Neurol ; 15: 22, 2015 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-25868523

RESUMO

BACKGROUND: Pol III-related leukodystrophies, including 4H leukodystrophy, are recently recognized disorders that comprise hypomyelination and various neurologic and non-neurologic clinical manifestations. We report the unique neurologic presentation of the micturition dysfunction in Pol III-related leukodystrophy and describe the novel endocrine abnormalities in this entity. CASE PRESENTATION: A 32-year-old Caucasian female exhibited chronic urinary incontinence that commenced at the age of 7 years and remained the unexplained symptom more than two decades before the onset of progressive neurologic decline. A transient growth failure and absent sexual development with hypoprolactinemia appeared in the meanwhile. Neurologic, endocrine, neuroradiologic, and genetic evaluation performed only in the patient's thirties, confirmed the diagnosis of 4H leukodystrophy as the only cause of the micturition disturbance. CONCLUSION: The report shows for the first time that an unexplained chronic bladder dysfunction should be evaluated also as a possible 4H leukodystrophy, thus alerting to the unexpected neurologic and endocrine features in 4H leukodystrophy.


Assuntos
Anodontia/complicações , Ataxia/complicações , Encéfalo/patologia , Hipogonadismo/complicações , Leucoencefalopatias/complicações , Bexiga Urinaria Neurogênica/etiologia , Incontinência Urinária/etiologia , Adulto , Anodontia/diagnóstico , Anodontia/metabolismo , Ataxia/diagnóstico , Ataxia/metabolismo , Estradiol/metabolismo , Feminino , Hormônio Foliculoestimulante/metabolismo , Humanos , Hipogonadismo/diagnóstico , Hipogonadismo/metabolismo , Leucoencefalopatias/diagnóstico , Leucoencefalopatias/metabolismo , Hormônio Luteinizante/metabolismo , Imageamento por Ressonância Magnética , Prolactina/metabolismo
19.
J Enzyme Inhib Med Chem ; 30(3): 354-9, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24939106

RESUMO

Dipotassium-trioxohydroxytetrafluorotriborate K2[B3O3F4OH] was listed as a promising new therapeutic for cancer diseases. For in vitro and in vivo investigation of its antitumor effects 4T1 mammary adenocarcinoma, B16F10 melanoma and squamous cell carcinoma SCCVII were used. The detailed in vitro investigation undoubtedly showed that K2[B3O3F4OH] affects the growth of cancer cells. The proliferation of cells depends on the concentration so that aqueous solution of K2[B3O3F4OH], the concentrations of 10(-4) M and less, does not affect cell growth, but the concentrations of 10(-3) M or more, significantly slows cells growth. B16F10 and SCCVII cells show higher sensitivity to the cytotoxic effects of K2[B3O3F4OH] compared to 4T1 cells. Under in vivo conditions, K2[B3O3F4OH] slows the growth of all three tumors tested compared to the control, and the inhibitory effect was most pronounced during the application of the substance. There is almost no difference if K2[B3O3F4OH] was applied intraperitoneally, intratumor, peroral or as ointment. Addition of 5-FU did not further increase the antitumor efficacy of K2[B3O3F4OH].


Assuntos
Antineoplásicos/farmacologia , Compostos de Boro/farmacologia , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Compostos de Boro/síntese química , Compostos de Boro/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Halogenação , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C3H , Camundongos Endogâmicos C57BL , Estrutura Molecular , Relação Estrutura-Atividade
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