RESUMO
Objective: The aim of the study was to investigate endothelial function in treatment-naïve polymyalgia rheumatica (PMR) patients and its modification during steroid therapy, in relation to changes in clinical and laboratory parameters.Method: This prospective observational study involved patients with a new diagnosis of PMR according to provisional American College of Rheumatology/European League Against Rheumatism 2012 criteria, who were naïve to steroid therapy, and control subjects matched for age, gender, and comorbidities. All participants underwent clinical and vascular ultrasound evaluations at baseline and after 1, 3, 6, and 12 months of steroid therapy. For the study of endothelial function, we evaluated the brachial artery reactivity, which has emerged as the most well-established technique used in adults, by assessing flow-mediated dilatation (FMD), which measures the endothelium-dependent vasodilatation.Results: Sixteen newly diagnosed PMR patients were compared with a population of 16 matched controls. FMD values in all subjects showed an inverse correlation with the values of erythrocyte sedimentation rate and C-reactive protein. At baseline, the FMD of PMR patients was significantly lower than controls and remained significantly lower with respect to controls until the sixth month of therapy, despite a clinical improvement already being evident after 1 month of therapy.Conclusions: PMR is characterized by an important chronic subclinical inflammatory component. This pilot study demonstrates that affected patients show endothelial dysfunction that slowly responds to steroid therapy. Further studies are needed to investigate the clinical relevance of these observations and, in particular, to monitor the cardiovascular risk profile of PMR patients.
Assuntos
Aterosclerose/etiologia , Artéria Braquial/fisiopatologia , Endotélio Vascular/fisiopatologia , Polimialgia Reumática/complicações , Vasodilatação/fisiologia , Idoso , Aterosclerose/diagnóstico , Aterosclerose/fisiopatologia , Artéria Braquial/diagnóstico por imagem , Endotélio Vascular/diagnóstico por imagem , Feminino , Seguimentos , Glucocorticoides/uso terapêutico , Humanos , Masculino , Projetos Piloto , Polimialgia Reumática/tratamento farmacológico , Polimialgia Reumática/fisiopatologia , Estudos Prospectivos , Ultrassonografia Doppler em CoresRESUMO
The aims of the study were to determine (1) whether the presence of High blood pressure (HBP) states in the youth associate a steeper rate of age-related change in arterial geometrical and wall properties with respect to subjects with no previous cardiovascular risk factor (CRF) exposure, (2) in which parameters and in what magnitude, and (3) the existence of a gender-related difference in the impact of this condition on arterial properties. 300 individuals (mean/range: 15/4-29 years; 133 females) were included. Two groups were assembled: (1) Reference: nonprevious exposure to traditional CRF and (2) HBP: subjects with arterial hypertension and/or elevated blood pressure (BP) levels during the study. Additionally, HBP subjects were separated in BP-related subgroups. Measured parameters were (1) central (aortic) arterial BP and aortic pulse wave analysis parameters, (2) carotid and femoral artery local (pressure-strain elastic modulus) and regional (pulse wave velocity; PWV) stiffness, and (3) arterial diameters and carotid intima-media thickness (CIMT). Age-related changes in these parameters (absolute values and z-scores) were explored by obtaining simple linear regression models for each group. HBP presented a steeper rate of change (accelerated vascular aging; VA) for most of the parameters assessed, mainly in central (aortic) hemodynamics. VA increased as the HBP level got higher. Both males' and females' aging rates were affected by this condition, but females presented a more marked relative age-related increase with HBP exposure. HBP states in the youth gradually associate accelerated VA, with a progressive hemodynamic-structural-functional onset of damage, with females presenting a more marked relative HBP-associated arterial repercussion.
Assuntos
Envelhecimento , Artérias/fisiopatologia , Hipertensão/fisiopatologia , Doenças Vasculares/fisiopatologia , Adolescente , Adulto , Aorta/fisiopatologia , Pressão Arterial , Artérias Carótidas/fisiopatologia , Espessura Intima-Media Carotídea , Criança , Pré-Escolar , Feminino , Artéria Femoral/fisiopatologia , Hemodinâmica , Humanos , Masculino , Análise de Onda de Pulso , Fluxo Sanguíneo Regional , Fatores de Risco , Fatores Sexuais , Rigidez Vascular , Adulto JovemAssuntos
COVID-19 , Psoríase , Sinovite , Vacinas contra COVID-19 , Edema , Humanos , Psoríase/complicações , SARS-CoV-2 , VacinaçãoRESUMO
OBJECTIVE: To investigate the role of the HS1,2 enhancer polymorphisms as a new candidate marker for rheumatoid arthritis (RA) and to define the possible association with autoantibody positivity and clinical outcome. METHODS: Genomic DNA was obtained from two cohorts of patients with RA (100 with early RA (ERA) and 114 with longstanding RA (LSRA)) and from 248 gender-matched controls from the same geographical area. Clinical and immunological characteristics were recorded for all the patients. RESULTS: The percentage of the 2/2 genotype was higher in patients with ERA (27.0%), and in patients with LSRA (34.2%), than in controls (14.9%) (ERA: OR = 2.11 (95% CI 1.20 to 3.70) vs controls; LSRA: OR = 2.96 (95% CI 1.76 to 5.00) vs controls). A lower representation of allele *3 was present in patients with ERA (2.0%) than in controls (6.0%; OR = 0.32 (95% CI 0.11 to 0.91)). No significant associations were found between polymorphisms and autoantibodies positivity. CONCLUSION: The HS1,2A allele *2 associates with early and longstanding RA.
Assuntos
Alelos , Artrite Reumatoide/genética , Cadeias Pesadas de Imunoglobulinas/genética , Adulto , Idoso , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/imunologia , Autoanticorpos/sangue , Estudos de Coortes , Elementos Facilitadores Genéticos , Feminino , Marcadores Genéticos , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Sequências Reguladoras de Ácido Nucleico , Fator Reumatoide/sangue , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
The shortage of organs leads to the need for utilizing suboptimal kidneys for transplantation. The distinction between optimal, marginal, and suboptimal kidneys leads surgeons to face not only technical problems but also ethical and legal issues related to clinical advantages offered by the transplant of a nonstandard kidney and the acquisition of consent. Between 1999 and 2015, we performed 658 transplants, 49 (7.5%) using suboptimal kidneys. All patients were alive and with vital graft throughout follow-up. We did not encounter any major surgical complications. From a technical point of view, our experience and literature review confirm that transplant of suboptimal kidney leads to good clinical results but exposes patients to a increased risks of surgical complications. Therefore, these interventions must take place in hospitals fully prepared for this type of surgery and performed by experienced transplant surgeons with proper matching between organ and recipient. Considering the insufficient resources available, from an ethical and legal point of view, doctors play an essential role in optimizing the use of these kidneys by avoiding wastage of organs, ensuring that transplants are done in suitable patients, and that patients are fully informed and aware of the risks and benefits associated with the specific suboptimal kidney being transplanted. We believe that, in highly specialized centers, the number of suboptimal kidney transplants should be increased, as their use has shown good clinical results and carries fewer ethical issues compared with marginal kidneys. Further, suboptimal kidneys may also be proposed for use in young patients with end-stage renal disease.
Assuntos
Transplante de Rim/ética , Transplante de Rim/métodos , Rim/anormalidades , Transplantes/anormalidades , Transplantes/provisão & distribuição , Adulto , Sobrevivência de Enxerto , Humanos , Itália , Falência Renal Crônica/cirurgia , Transplante de Rim/mortalidade , Doadores de Tecidos/legislação & jurisprudênciaRESUMO
BACKGROUND: Patients on peritoneal dialysis treatment represent 15% of the global dialysis population. The major complication of peritoneal dialysis is catheter and peritoneal infection. Peritoneal dialysis patients who receive kidney transplants are at increased risk of infection because of immunosuppressive therapy. AIM: The purpose of this study is to show our ideal timing to remove peritoneal catheter after kidney transplant, which gives adequate security on renal function recovery and reduction of septic risk. METHOD OF STUDY: We analyzed the outcomes of 65 patients on peritoneal dialysis who underwent kidney transplant between 2000 and 2016. RESULTS: In 61 cases there was an immediate graft functional recovery. In 4 cases there was a delayed graft function (DGF), and we performed a hemodialysis with temporary placement of a venous catheter. In all patients we removed peritoneal dialysis catheter 30 to 45 days after transplant. There has been 1 case of catheter infection, which was treated with antibiotic therapy. DISCUSSION: Our average time to remove the peritoneal dialysis catheter was shorter than times in previous studies, between the 30th and 45th postoperative day. In the 4 cases in which there has been a DGF, we performed hemodialysis treatment to avoid, in the immediate postoperative period, direct insults to the peritoneum by local dialysis procedures. CONCLUSION: Our experience show that the 30th to 45th postoperative day is a good time frame, better yet a good watershed between the safe removal of peritoneal catheter when patients have a stabilized renal function and the possibility of leaving it in situ, to resume peritoneal dialysis in case of persistent DGF.
Assuntos
Transplante de Rim , Diálise Peritoneal , Adulto , Cateteres de Demora , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Diálise Peritoneal/métodos , Estudos Retrospectivos , Fatores de TempoRESUMO
Neurodegenerative diseases (NDs) and brain tumors are severe, disabling, and incurable disorders that represent a critical problem regarding human suffering and the economic burden on the healthcare system. Because of the lack of effective therapies to treat NDs and brain tumors, the challenge for physicians is to discover new drugs to improve their patients' quality of life. In addition to risk factors such as genetics and environmental influences, increased cellular oxidative stress has been reported as one of the potential common etiologies in both disorders. Given their antioxidant and anti-inflammatory potential, dietary polyphenols are considered to be one of the most bioactive natural agents in chronic disease prevention and treatment. Despite the protective activity of polyphenols, their inefficient delivery systems and poor bioavailability strongly limit their use in medicine and functional food. A potential solution lies in polymeric nanoparticle-based polyphenol delivery systems that are able to enhance their absorption across the gastrointestinal tract, improve their bioavailability, and transport them to target organs. In the present manuscript, we provide an overview of the primary polyphenols used for ND and brain tumor prevention and treatment by focusing on recent findings, the principal factors limiting their application in clinical practice, and a promising delivery strategy to improve their bioavailability.
Assuntos
Neoplasias Encefálicas/prevenção & controle , Sistemas de Liberação de Medicamentos/métodos , Nanopartículas/administração & dosagem , Doenças Neurodegenerativas/prevenção & controle , Compostos Fitoquímicos/administração & dosagem , Polifenóis/administração & dosagem , Animais , Antioxidantes/administração & dosagem , Antioxidantes/química , Antioxidantes/metabolismo , Neoplasias Encefálicas/metabolismo , Ensaios Clínicos como Assunto/métodos , Humanos , Nanopartículas/química , Nanopartículas/metabolismo , Doenças Neurodegenerativas/metabolismo , Fármacos Neuroprotetores/administração & dosagem , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/metabolismo , Compostos Fitoquímicos/química , Compostos Fitoquímicos/metabolismo , Polifenóis/química , Polifenóis/metabolismoRESUMO
BACKGROUND: Fatigue is common in celiac disease. L-Carnitine blood levels are low in untreated celiac disease. L-Carnitine therapy was shown to improve muscular fatigue in several diseases. AIM: To evaluate the effect of L-carnitine treatment in fatigue in adult celiac patients. METHODS: Randomised double-blind versus placebo parallel study. Thirty celiac disease patients received 2 g daily, 180 days (L-carnitine group) and 30 were assigned to the placebo group (P group). The patients underwent clinical investigation and questionnaires (Scott-Huskisson Visual Analogue Scale for Asthenia, Verbal Scale for Asthenia, Zung Depression Scale, SF-36 Health Status Survey, EuroQoL). OCTN2 levels, the specific carnitine transporter, were detected in intestinal tissue. RESULTS: Fatigue measured by Scott-Huskisson Visual Analogue Scale for Asthenia was significantly reduced in the L-carnitine group compared with the placebo group (p=0.0021). OCTN2 was decreased in celiac patients when compared to normal subjects (-134.67% in jejunum), and increased after diet in both celiac disease treatments. The other scales used did not show any significant difference between the two celiac disease treatment groups. CONCLUSION: L-Carnitine therapy is safe and effective in ameliorating fatigue in celiac disease. Since L-carnitine is involved in muscle energy production its decreased absorption due to OCTN2 reduction might explain muscular symptoms in celiac disease patients. The diet-induced OCTN2 increase, improving carnitine absorption, might explain the L-carnitine treatment efficacy.
Assuntos
Carnitina/uso terapêutico , Doença Celíaca/complicações , Fadiga/tratamento farmacológico , Complexo Vitamínico B/uso terapêutico , Administração Oral , Adulto , Biomarcadores/metabolismo , Biópsia , Carnitina/administração & dosagem , Carnitina/farmacocinética , Doença Celíaca/diagnóstico , Doença Celíaca/tratamento farmacológico , Cromatografia Líquida de Alta Pressão , Relação Dose-Resposta a Droga , Método Duplo-Cego , Eletroforese em Gel de Poliacrilamida , Fadiga/sangue , Fadiga/etiologia , Feminino , Seguimentos , Humanos , Jejuno/metabolismo , Jejuno/patologia , Masculino , Proteínas de Transporte de Cátions Orgânicos/metabolismo , Projetos Piloto , Qualidade de Vida , Membro 5 da Família 22 de Carreadores de Soluto , Inquéritos e Questionários , Resultado do Tratamento , Complexo Vitamínico B/administração & dosagem , Complexo Vitamínico B/farmacocinéticaRESUMO
AIM: It has been established that antiphospholipid antibodies (aPL) are associated with recurrent abortions, but the pathophysiologic mechanisms that characterize thrombosis and recurrent pregnancy losses are still not clear.However, it is known that they are associated with the presence of antibodies directed against anionic phospholipids and putative cofactors. In this study the pathogenetic role of annexin A5, a potent anticoagulant cofactor protein for its anticoagulant property in recurrent abortions, was investigated. METHODS: Endothelial cells of human umbilical veins ''EAHY2936 Line'' in culture were used, incubated with antiphospholipid anticardiolipin (ACA) antibodies purified from plasma of patients with recurrent abortions. The expression of annexin A5 on the cells with ACA was investigated by immunofluorescence and by confocal microscope. The negative control was also carried out: EAHY cells in cultivation medium without ACA. RESULTS: Confocal analysis revealed a uniform distribution of annexin A5 on the cellular membranes in the negative control. Instead, in EAHY cells with ACA, the annexin A5 appears distributed in irregular manners on the cellular membranes (cytoplasmic and nuclear). CONCLUSION: The results of an irregular ''cluster'' distribution of annexin A5 on the EAHY cells in presence of aPL, and in agreement with the literature, demonstrated that aPL, inhibiting annexin A5 ability to protect anionic phospholipid, promote the coagulation factors to diffuse laterally against phospholipids.
Assuntos
Aborto Habitual/imunologia , Anexina A5/imunologia , Anticorpos Antifosfolipídeos/imunologia , Inibidores Enzimáticos/imunologia , Fatores Imunológicos/imunologia , Microscopia Confocal , Adulto , Síndrome Antifosfolipídica/imunologia , Feminino , Humanos , Imuno-Histoquímica , GravidezRESUMO
Hyperspectral Raman images of human prostatic cells have been collected and analysed with several approaches to reveal differences among normal and tumor cell lines. The objective of the study was to test the potential of different chemometric methods in providing diagnostic responses. We focused our analysis on the ν(CH) region (2800-3100cm-1) owing to its optimal Signal-to-Noise ratio and because the main differences between the spectra of the two cell lines were observed in this frequency range. Multivariate analysis identified two principal components, which were positively recognized as due to the protein and the lipid fractions, respectively. The tumor cells exhibited a modified distribution of the cytoplasmatic lipid fraction (mainly localized alongside the cell boundary) which may result very useful for a preliminary screening. Principal Component analysis was found to provide high contrast and to be well suited for image-processing purposes. Self-Modelling Curve Resolution made available meaningful spectra and relative-concentration values; it revealed a 97% increase of the lipid fraction in the tumor cell with respect to the control. Finally, a univariate approach confirmed significant and reproducible differences between normal and tumor cells.
Assuntos
Próstata/citologia , Neoplasias da Próstata/patologia , Análise de Célula Única/métodos , Análise Espectral Raman/métodos , Linhagem Celular , Linhagem Celular Tumoral , Humanos , Processamento de Imagem Assistida por Computador/métodos , Análise dos Mínimos Quadrados , Masculino , Análise Multivariada , Análise de Componente Principal , Próstata/química , Processamento de Sinais Assistido por Computador , Razão Sinal-RuídoRESUMO
Cancer cells reprogram their metabolism to maintain both viability and uncontrolled proliferation. Although an interplay between the genetic, epigenetic and metabolic rewiring in cancer is beginning to emerge, it remains unclear how this metabolic plasticity occurs. Here, we report that in prostate cancer cells (PCCs) microRNAs (miRNAs) greatly contribute to deregulation of mitochondrial fatty acid (FA) oxidation via carnitine system modulation. We provide evidence that the downregulation of hsa-miR-124-3p, hsa-miR-129-5p and hsa-miR-378 induced an increase in both expression and activity of CPT1A, CACT and CrAT in malignant prostate cells. Moreover, the analysis of human prostate cancer and prostate control specimens confirmed the aberrant expression of miR-124-3p, miR-129-5p and miR-378 in primary tumors. Forced expression of the miRNAs mentioned above affected tumorigenic properties, such as proliferation, migration and invasion, in PC3 and LNCaP cells regardless of their hormone sensitivity. CPT1A, CACT and CrAT overexpression allow PCCs to be more prone on FA utilization than normal prostate cells, also in the presence of high pyruvate concentration. Finally, the simultaneous increase of CPT1A, CACT and CrAT is fundamental for PCCs to sustain FA oxidation in the presence of heavy lipid load on prostate cancer mitochondria. Indeed, the downregulation of only one of these proteins reduces PCCs metabolic flexibility with the accumulation of FA-intermediate metabolites in the mitochondria. Together, our data implicate carnitine cycle as a primary regulator of adaptive metabolic reprogramming in PCCs and suggest new potential druggable pathways for prevention and treatment of prostate cancer.
Assuntos
Carnitina O-Palmitoiltransferase/genética , Proteínas de Membrana Transportadoras/genética , MicroRNAs/genética , Neoplasias da Próstata/genética , Carcinogênese/genética , Carnitina/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/genética , Ácidos Graxos/genética , Ácidos Graxos/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Oxirredução , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologiaRESUMO
Recent studies suggest a close relationship between cell metabolism and apoptosis. We have evaluated changes in lipid metabolism on permeabilized hepatocytes treated with truncated Bid (tBid) in the presence of caspase inhibitors and exogenous cytochrome c. The measurement of beta-oxidation flux by labeled palmitate demonstrates that tBid inhibits beta-oxidation, thereby resulting in the accumulation of palmitoyl-coenzyme A (CoA) and depletion of acetyl-carnitine and acylcarnitines, which is pathognomonic for inhibition of carnitine palmitoyltransferase-1 (CPT-1). We also show that tBid decreases CPT-1 activity by a mechanism independent of both malonyl-CoA, the key inhibitory molecule of CPT-1, and Bak and/or Bax, but dependent on cardiolipin decrease. Overexpression of Bcl-2, which is able to interact with CPT-1, counteracts the effects exerted by tBid on beta-oxidation. The unexpected role of tBid in the regulation of lipid beta-oxidation suggests a model in which tBid-induced metabolic decline leads to the accumulation of toxic lipid metabolites such as palmitoyl-CoA, which might become participants in the apoptotic pathway.
Assuntos
Carnitina O-Palmitoiltransferase/antagonistas & inibidores , Proteínas de Transporte/farmacologia , Ácidos Graxos/metabolismo , Mitocôndrias Hepáticas/metabolismo , Proteína Agonista de Morte Celular de Domínio Interatuante com BH3 , Cardiolipinas/metabolismo , Carnitina O-Palmitoiltransferase/metabolismo , Proteínas de Transporte/metabolismo , Inibidores de Caspase , Caspases/metabolismo , Permeabilidade da Membrana Celular/efeitos dos fármacos , Células Cultivadas , Citocromos c/metabolismo , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Humanos , Malonil Coenzima A/metabolismo , Potenciais da Membrana/efeitos dos fármacos , Proteínas de Membrana/genética , Mitocôndrias Hepáticas/genética , Oxirredução/efeitos dos fármacos , Ligação Proteica , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteína Killer-Antagonista Homóloga a bcl-2RESUMO
Metabolic profiling is defined as the simultaneous assessment of substrate fluxes within and among the different pathways of metabolite synthesis and energy production under various physiological conditions. The use of stable-isotope tracers and the analysis of the distribution of labeled carbons in various intermediates, by both mass spectrometry and NMR spectroscopy, allow the role of several metabolic processes in cell growth and death to be defined. In the present paper we describe the metabolic profiling of Jurkat cells by isotopomer analysis using (13)C-NMR spectroscopy and [1,2-(13)C(2)]glucose as the stable-isotope tracer. The isotopomer analysis of the lactate, alanine, glutamate, proline, serine, glycine, malate and ribose-5-phosphate moiety of nucleotides has allowed original integrated information regarding the pentose phosphate pathway, TCA cycle, and amino acid metabolism in proliferating human leukemia T cells to be obtained. In particular, the contribution of the glucose-6-phosphate dehydrogenase and transketolase activities to phosphoribosyl-pyrophosphate synthesis was evaluated directly by the determination of isotopomers of the [1'-(13)C], [4',5'-(13)C(2)]ribosyl moiety of nucleotides. Furthermore, the relative contribution of the glycolysis and pentose cycle to lactate production was estimated via analysis of lactate isotopomers. Interestingly, pyruvate carboxylase and pyruvate dehydrogenase flux ratios measured by glutamate isotopomers and the production of isotopomers of several metabolites showed that the metabolic processes described could not take place simultaneously in the same macrocompartments (cells). Results revealed a heterogeneous metabolism in an asynchronous cell population that may be interpreted on the basis of different metabolic phenotypes of subpopulations in relation to different cell cycle phases.
Assuntos
Glucose/metabolismo , Espectroscopia de Ressonância Magnética/métodos , Isótopos de Carbono , Ciclo Celular/fisiologia , Proliferação de Células , Ciclo do Ácido Cítrico/fisiologia , Glutamina/metabolismo , Glicina/metabolismo , Humanos , Células Jurkat , Ácido Láctico/metabolismo , Leucemia de Células T/metabolismo , Leucemia de Células T/patologia , Leucemia de Células T/fisiopatologia , Modelos Biológicos , Nucleotídeos/metabolismo , Via de Pentose Fosfato/fisiologia , Pentoses/metabolismo , Serina/metabolismoRESUMO
SV-IV, a 9.8-kd protein isolated from rat seminal vesicle secretion, has been shown to have strong non-species-specific immunosuppressive, anti-inflammatory, antithrombotic, and antiphospholipase A2 properties. The present investigation was undertaken to determine the mechanism of action of its immunosuppressive effects. It was found that SV-IV is a potent inhibitor of interleukin-1 (IL-1) release from lipopolysaccharide (LPS)-activated human adherent monocytes and an effective inhibitor of IL-1-induced thymocyte proliferation. The ability of SV-IV to form a noncovalent dimeric association with IL-1 alpha but not with IL-1 beta, its ability to induce a marked decrease of IL-1 binding to its own receptors on the thymocyte surface, and its capacity to bind specifically to the macrophage plasma membrane might play an important role in the molecular mechanism of these inhibitory effects.
Assuntos
Interleucina-1/antagonistas & inibidores , Interleucina-1/metabolismo , Proteínas Secretadas pela Próstata , Proteínas/farmacologia , Animais , Sítios de Ligação/efeitos dos fármacos , Adesão Celular/efeitos dos fármacos , HIV-1/fisiologia , Humanos , Interleucina-6/metabolismo , Lipopolissacarídeos/farmacologia , Ativação Linfocitária/fisiologia , Monócitos/citologia , Ratos , Proteínas de Plasma Seminal , Dióxido de Silício/farmacologiaRESUMO
The effect of SV-IV, one of the major proteins secreted from the rat seminal vesicle epithelium, on phagocytosis and chemotaxis of human polymorphonuclear leukocytes (PMNs) has been studied. Various cytological, biochemical, metabolic, and physical correlates of both biological activities have been found to be markedly reduced by the presence in the medium of micromolar concentrations of protein SV-IV. Moreover, the Scatchard analysis of the labeled SV-IV binding to PMN cell surface has demonstrated that such binding is specific. The binding sites contain only saturable components, completely displaceable by unlabeled SV-IV. The number of the specific sites has been calculated to be 87,000/cell, with a Kd of 1.72 X 10(-7) M. The molecular mechanism of the inhibitory effect is discussed along with the possible biological and clinical implications of the experimental findings.
Assuntos
Quimiotaxia de Leucócito/efeitos dos fármacos , Neutrófilos/efeitos dos fármacos , Fagocitose/efeitos dos fármacos , Proteínas Secretadas pela Próstata , Proteínas/farmacologia , Glândulas Seminais/metabolismo , Animais , Adesão Celular/efeitos dos fármacos , Epitélio/metabolismo , Humanos , Masculino , Neutrófilos/imunologia , Consumo de Oxigênio/efeitos dos fármacos , Ratos , Ratos Endogâmicos , Receptores de Formil Peptídeo , Receptores Imunológicos/análise , Proteínas de Plasma SeminalRESUMO
After about 10 years of experience, laparoscopic adrenalectomy has become the gold standard for the treatment of adrenal lesions. Here, we describe the presenting features, imaging methods, and current surgical approaches to diseases of the adrenal gland. There is general agreement on the suitability of the laparoscopic approach for benign adrenal lesions, but controversy exists about using laparoscopy for suspected adrenal malignancy, metastasis, and partial adrenalectomy. This article reviews the literature on laparoscopic adrenalectomy. In particular, we focus our attention on the new surgical approaches to the gland. We evaluate the indications, operative techniques, and tools for partial adrenalectomy, and we discuss new surgical strategies such as cryosurgery and radiofrequency ablation.
Assuntos
Neoplasias das Glândulas Suprarrenais/diagnóstico , Neoplasias das Glândulas Suprarrenais/cirurgia , Adrenalectomia/métodos , Ablação por Cateter/métodos , Criocirurgia/métodos , Laparoscopia/métodos , Neoplasias do Córtex Suprarrenal/diagnóstico , Neoplasias do Córtex Suprarrenal/cirurgia , Doenças das Glândulas Suprarrenais/diagnóstico , Doenças das Glândulas Suprarrenais/cirurgia , Ablação por Cateter/efeitos adversos , Criocirurgia/efeitos adversos , Síndrome de Cushing/etiologia , Síndrome de Cushing/cirurgia , Feminino , Seguimentos , Humanos , Hiperaldosteronismo/etiologia , Hiperaldosteronismo/cirurgia , Laparoscopia/efeitos adversos , Masculino , Procedimentos Cirúrgicos Minimamente Invasivos/efeitos adversos , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Feocromocitoma/diagnóstico , Feocromocitoma/cirurgia , Complicações Pós-Operatórias , Fatores de Risco , Sensibilidade e Especificidade , Resultado do TratamentoRESUMO
Fluoride-releasing restorative dental materials can be beneficial to remineralize dentin and help prevent secondary caries. However, the effects of fluoride release from dental materials on the activity of dental pulp stem cells are not known. Here we investigate whether different fluoride release kinetics from dental resins supplemented with modified hydrotalcite (RK-F10) or fluoride-glass filler (RK-FG10) could influence the behavior of a human dental pulp stem cell subpopulation (STRO-1(+) cells) known for its ability to differentiate toward an odontoblast-like phenotype. The 2 resins, characterized by similar physicochemical properties and fluoride content, exhibited different long-term fluoride release kinetics. Our data demonstrate that long-term exposure of STRO-1(+) cells to a continuous release of a low amount of fluoride by RK-F10 increases their migratory response to transforming growth factor ß1 (TGF-ß1) and stromal cell-derived factor 1 (SDF-1), both important promoters of pulp stem cell recruitment. Moreover, the expression patterns of dentin sialoprotein (dspp), dentin matrix protein 1 (dmp1), osteocalcin (ocn), and matrix extracellular phosphoglycoprotein (mepe) indicate a complete odontoblast-like cell differentiation only when STRO-1(+) cells were cultured on RK-F10. On the contrary, RK-FG10, characterized by an initial fluoride release burst and reduced lifetime of the delivery, did not elicit any significant effect on both STRO-1(+) cell migration and differentiation. Taken together, our results highlight the importance of taking into account fluoride release kinetics in addition to fluoride concentration when designing new fluoride-restorative materials.
Assuntos
Cariostáticos/farmacocinética , Materiais Dentários/química , Polpa Dentária/citologia , Fluoretos/farmacocinética , Odontogênese/efeitos dos fármacos , Células-Tronco/efeitos dos fármacos , Hidróxido de Alumínio/química , Diferenciação Celular/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Células Cultivadas , Quimiocina CXCL12/farmacologia , Proteínas da Matriz Extracelular/metabolismo , Glicoproteínas/metabolismo , Humanos , Cinética , Hidróxido de Magnésio/química , Osteocalcina/metabolismo , Fenótipo , Fosfoproteínas/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Saliva Artificial/química , Sialoglicoproteínas/metabolismo , Células-Tronco/citologia , Fator de Crescimento Transformador beta1/farmacologiaRESUMO
Three-dimensional (3D) volumetric ultrasonography (US) is an interesting tool that could improve the traditional approach to musculoskeletal US in rheumatology, due to its virtual operator independence and reduced examination time. The aim of this study was to investigate the performance of 3DUS in the detection of bone erosions in hand and wrist joints of early rheumatoid arthritis (ERA) patients, with computed tomography (CT) as the reference method. Twenty ERA patients without erosions on standard radiography of hands and wrists underwent 3DUS and CT evaluation of eleven joints: radiocarpal, intercarpal, ulnocarpal, second to fifth metacarpo-phalangeal (MCP), and second to fifth proximal interphalangeal (PIP) joints of dominant hand. Eleven (55.0%) patients were erosive with CT and ten of them were erosive also at 3DUS evaluation. In five patients, 3DUS identified cortical breaks that were not erosions at CT evaluation. Considering CT as the gold standard to identify erosive patients, the 3DUS sensitivity, specificity, PPV, and NPV were 0.9, 0.55, 0.71, and 0.83, respectively. A total of 32 erosions were detected with CT, 15 of them were also observed at the same sites with 3DUS, whereas 17 were not seen on 3DUS evaluation. The majority of these 3DUS false-negative erosions were in the wrist joints. Furthermore, 18 erosions recorded by 3DUS were false positive. The majority of these 3DUS false-positive erosions were located at PIP joints. This study underlines the limits of 3DUS in detecting individual bone erosion, mostly at the wrist, despite the good sensitivity in identifying erosive patients.
Assuntos
Artrite Reumatoide/diagnóstico por imagem , Artrite Reumatoide/fisiopatologia , Sinovite/diagnóstico por imagem , Sinovite/fisiopatologia , Ultrassonografia/métodos , Adulto , Artrite Reumatoide/tratamento farmacológico , Ensaio de Imunoadsorção Enzimática , Feminino , Ácido Fólico/administração & dosagem , Mãos/diagnóstico por imagem , Humanos , Processamento de Imagem Assistida por Computador/métodos , Imageamento Tridimensional/métodos , Masculino , Metotrexato/administração & dosagem , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Sensibilidade e Especificidade , Sinovite/tratamento farmacológico , Sinovite/radioterapia , Tomografia Computadorizada por Raios X , Articulação do Punho/diagnóstico por imagemRESUMO
In summary, the present study documents that platelet aggregation triggered by thrombin, ADP, collagen and PAF both in vivo and in vitro, was prevented by SV-IV in a dose-dependent manner. Only platelet aggregation by AA was not affected by the protein, thus suggesting a possible involvement of PLA2 inhibition in the molecular mechanism at the basis of SV-IV anti-thrombotic effect.