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1.
Rev Environ Contam Toxicol ; 249: 133-152, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-30879139

RESUMO

Mercury (Hg) is an environmental contaminant that has been reported in many wildlife species worldwide. The organic form of Hg bioaccumulates in higher trophic levels, and thus, long-lived predators are at risk for higher Hg exposure. Although ecological risk assessments for contaminants such as Hg include pertinent receptor species, snakes are rarely considered, despite their high trophic status and potential to accumulate high levels of Hg. Our current knowledge of these reptiles suggests that snakes may be useful novel biomarkers to monitor contaminated environments. The few available studies show that snakes can bioaccumulate significant amounts of Hg. However, little is known about the role of snakes in Hg transport in the environment or the individual-level effects of Hg exposure in this group of reptiles. This is a major concern, as snakes often serve as important prey for a variety of taxa within ecosystems (including humans). In this review, we compiled and analyzed the results of over 30 studies to discuss the impact of Hg on snakes, specifically sources of exposure, bioaccumulation, health consequences, and specific scientific knowledge gaps regarding these moderate to high trophic predators.


Assuntos
Monitoramento Ambiental , Mercúrio/metabolismo , Serpentes/metabolismo , Poluentes Químicos da Água/metabolismo , Animais , Biomarcadores/metabolismo , Ecossistema , Humanos
2.
Adv Exp Med Biol ; 1164: 47-61, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31576539

RESUMO

Stem cell antigen-1 (Sca-1) is the first identified member of mouse Ly6 gene family. We discovered that Sca-1 disrupts TGFß signaling and enhances mammary tumorigenesis in a DMBA-induced mammary tumor model. Sca-1 gene is lost during evolution in humans. Human Ly6 genes Ly6D, LyE, LyH, and LyK on human chromosome 8q24.3 genes are syntenic to the mouse chromosome 15 where Sca-1 is located. We found that Ly6D, E, H, and K are upregulated in human cancer compared to normal tissue and that the increased expression of these genes are associated with poor prognosis of multiple types of human cancer. Several other groups have indicated increased expression of Ly6 genes in human cancer. Here we described the relevance of expression of human Ly6D, LyE, LyH, and LyK in functioning of normal tissues and tumor progression.


Assuntos
Antígenos Ly , Biomarcadores , Regulação Neoplásica da Expressão Gênica , Neoplasias , Animais , Antígenos Ly/genética , Biomarcadores/metabolismo , Transformação Celular Neoplásica , Humanos , Neoplasias/diagnóstico , Neoplasias/genética , Prognóstico
3.
J Assoc Physicians India ; 67(10): 54-56, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31571453

RESUMO

Background: Attention has increasingly turned towards the role of factors, such as inflammation in the development of atherosclerosis and CHD. C-reactive protein (CRP) has emerged as one of the most important novel inflammatory marker. Subsequent risk modification and treatment strategies of CHD keeping on pointer towards inflammation may be the appropriate approach. Aim: The aim of this study was to determine the association of CHD with CRP, a sensitive marker of inflammation. Material and Methods: This is a case control study amongst 300 subjects (150 cases and 150 controls), conducted in the Department of Cardiology at Sri Aurobindo Medical College and P.G Institute, Indore, M.P. Subjects with definite diagnosis of CHD established by coronary angiography (CAG) was taken as cases, subjects matched with age, gender with no conventional risk factor and past history of CHD from the relatives and accompanying persons were enlisted as controls. Results: Estimation of CRP reveals ≥0.6 mg/dl in 88(58.7%) subjects out of 150, compared to 26 (17.3%) control subjects out of 150 which is statistically significant (p value<0.0001) (OR=6.7). Conclusion: CRP as a noble marker of inflammation was significantly higher in subjects of CHD and thus supported adequately the hypothesis of an activation of inflammatory cascade for coronary atheromatous plaque formation and causation of CHD.


Assuntos
Proteína C-Reativa/metabolismo , Doença das Coronárias/metabolismo , Biomarcadores/metabolismo , Estudos de Casos e Controles , Humanos , Inflamação/metabolismo , Fatores de Risco
4.
Adv Exp Med Biol ; 1178: 57-76, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31493222

RESUMO

Aging is a natural process defined by the gradual, time-dependent decline of biological and behavioural functions, for which individuals of the same chronological age show variability. The capacity of biological systems to continuously adjust for optimal functioning despite ever changing environments is essential for healthy aging, and variability in these adaptive homeostatic mechanisms may reflect such heterogeneity in the aging process. With an ever-increasing aging population, interest in biomarkers of aging is growing. Although no universally accepted definition of biomarkers of healthy aging exists, mediators of homeostasis are consistently used as measures of the aging process. As important sex differences are known to underlie many of these systems, it is imperative to consider that this may reflect, to some extent, the sex differences observed in aging and age-related disease states. This chapter aims to outline sex differences in key homeostatic domains thought to be associated with the pathophysiology of aging, often proposed as biomarkers of aging and age-related disease states. This includes considering sex-based differences and hormonal status with regards to the gonadal and adrenal endocrine systems and immune function.


Assuntos
Envelhecimento , Biomarcadores , Homeostase , Biomarcadores/metabolismo , Homeostase/fisiologia , Humanos , Fatores Sexuais
5.
J Assoc Physicians India ; 67(7): 65-69, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31559772

RESUMO

According to International Diabetes Federation, the worldwide prevalence of impaired glucose tolerance (IGT) in adults is 318 million and is expected to reach 482 million by 2040. With increasing burden of prediabetes and their expectant progression in diabetes has compounded the problem. Now question is that how we can identify the subjects at high risk to develop prediabetic state and among them who will rapidly progress into diabetes? Once a person diagnosed to be a diabetic then there are only few marker which can depict development of diabetes related complications and also to help in preventing such diabetes related complication progression. In this article, we will review several biomarkers used to predict the risk of progression to prediabetes, diabetes states in context to their mechanism of action, sensitivity, specificity, advantages, disadvantages and association with dysglycemia. The risk stratification arising due to insulin resistance by novel biomarker will improve clinical outcome both in prediabetics and diabetics.


Assuntos
Biomarcadores/metabolismo , Diabetes Mellitus/metabolismo , Adulto , Glicemia , Diabetes Mellitus Tipo 2 , Intolerância à Glucose , Humanos , Estado Pré-Diabético
6.
Medicine (Baltimore) ; 98(37): e17019, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31517821

RESUMO

The role of cytokines in the systemic inflammatory response (SIR) is now well established. This is in keeping with the role of the SIR in tumorigenesis, malignant spread, and the development of cachexia. However, the relationship between performance status/systemic inflammation frameworks and cytokine profiles is not clear. The aim of the present study was to examine the relationship between the Eastern cooperative oncology group performance status/modified Glasgow prognostic score (ECOG-PS/mGPS) and cooperative oncology group performance status/neutrophil platelet score (ECOG-PS/NPS) frameworks and their cytokine profile in patients with advanced cancer.This was a retrospective interrogation of data already collected as part of a recent clinical trial (NCT00676936). The relationship between the independent variables (ECOG-PS/mGPS and ECOG-PS/NPS frameworks), and dependent variables (cytokine levels) was examined using independent Mann-Whitney U and Kruskal Wallis tests where appropriate.Of the 40 patients included in final analysis the majority had evidence of an SIR assessed by mGPS (78%) or NPS (53%). All patients died on follow-up and the median survival was 91 days (4-933 days). With increasing ECOG-PS there was a higher median value of Interleukin 6 (IL-6, P = .016) and C-reactive protein (CRP, P < .01) and lower albumin (P < .01) and poorer survival (P < .001). With increasing mGPS there was a higher median value of IL-6 (P = .016), Macrophage migration inhibitory factor (MIF, P = .010), erythrocyte sedimentation rate (ESR, P < .01) and poorer survival (P < .01). With increasing NPS there was a higher median value of TGF-ß (P < .001) and C-reactive protein (P = .020) and poor survival (P = .001). When those patients with an ECOG-PS 0/1 and mGPS0 were compared with those patients with an ECOG-PS 2 and mGPS2 there was a higher median value of IL-6 (P = .017) and poorer survival (P < .001). When those patients with an ECOG-PS 0/1 and NPS0 were compared with those patients with an ECOG-PS 2 and NPS1/2 there was a higher median value of IL-6 (P = .002), TGF-ß (P < .001) and poorer survival (P < .01).In patients with advanced cancer IL-6 was associated with the ECOG-PS/mGPS and ECOG-PS/NPS frameworks and survival in patients with advanced cancer. Therefore, the present work provides supporting evidence that agents targeting IL-6 are worthy of further exploration.


Assuntos
Citocinas/imunologia , Inflamação/imunologia , Neoplasias/imunologia , Idoso , Biomarcadores/metabolismo , Feminino , Seguimentos , Humanos , Inflamação/diagnóstico , Inflamação/mortalidade , Masculino , Pessoa de Meia-Idade , Neoplasias/diagnóstico , Neoplasias/mortalidade , Neoplasias/terapia , Estudos Retrospectivos , Índice de Gravidade de Doença , Análise de Sobrevida
7.
Medicine (Baltimore) ; 98(37): e17156, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31517861

RESUMO

This study aims to screen differentially expressed host miRNAs that could be used as diagnostic markers for liver alveolar echinococcosis (LAE).Differentially expressed miRNAs were first screened by miRNA microarray in liver tissues from2 LAE patients and normal liver tissues from 3 LAE patients, followed by qRT-PCR validation in 15 LAE tissues and 15 normal tissues. Target genes of differentially expressed miRNAs were predicted using Targetscan, PITA and microRNAorg database, and the overlapped predicted target genes were analyzed by GO and KEGG.The hsa-miR-1237-3p, hsa-miR-33b-3p, and hsa-miR-483-3p were up-regulated whereas the hsa-miR-4306 was down-regulated in LAE tissues compared with normal controls (P < .05). The expression change of miR-483-3p was further confirmed in both liver tissues and plasma. Several predicted targets of miR-1237-3p, miR-4306, and miR-483-3p were related to DNA-dependent transcriptional regulation, developmental regulation of multicellular organisms, and biological functions such as cellular immune responses (T cell proliferation). The overlapped predicted target genes of the 4 differentially expressed miRNAs were enriched in mRNA surveillance, cancer signaling pathway, intestinal immune network, and other signal pathways.Our results indicate that miR-483-3p is a potential marker for the diagnosis of LAE, and targets of this miRNA could be the focus of further studies.


Assuntos
Equinococose Hepática/metabolismo , Fígado/metabolismo , MicroRNAs/metabolismo , Adulto , Biomarcadores/metabolismo , Feminino , Expressão Gênica , Humanos , Masculino , Análise em Microsséries , Pessoa de Meia-Idade
8.
Toxicol Lett ; 314: 172-180, 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31404593

RESUMO

Vesicants cause a multitude of cutaneous reactions like erythema, blisters and ulcerations. After exposure to sulfur mustard (SM) and related compounds, patients present dermal symptoms typically known for chemicals categorized as skin sensitizer (e.g. hypersensitivity and flare-up phenomena). However, although some case reports led to the assumption that SM and other alkylating compounds represent sensitizers, a comprehensive investigation of SM-triggered immunological responses has not been conducted so far. Based on a well-structured system of in chemico and in vitro test methods, the Organization for Economic Co-operation and Development (OECD) established procedures to categorize agents on their skin sensitizing abilities. In this study, the skin sensitizing potential of SM and three related alkylating agents (AAs) was assessed following the OECD test guidelines. Besides SM, investigated AAs were chlorambucil (CHL), nitrogen mustard (HN3) and 2-chloroethyl ethyl sulfide (CEES). The methods are described in detail in the EURL ECVAM DataBase service on ALternative Methods to animal experimentation (DB-ALM). In accordance to OECD recommendations, skin sensitization is a pathophysiological process starting with a molecular initiating step and ending with the in vivo outcome of an allergic contact dermatitis. This concept is called adverse outcome pathway (AOP). An AOP links an adverse outcome to various key events which can be assayed by established in chemico and in vitro test methods. Positive outcome in two out of three key events indicates that the chemical can be categorized as a skin sensitizer. In this study, key event 1 "haptenation" (covalent modification of epidermal proteins), key event 2 "activation of epidermal keratinocytes" and key event 3 "activation of dendritic cells" were investigated. Covalent modification of epidermal proteins measured by using the DPRA-assay provided distinct positive results for all tested substances. Same outcome was seen in the KeratinoSens assay, investigating the activation of epidermal keratinocytes. The h-CLAT assay performed to determine the activation of dendritic cells provided positive results for SM and CEES but not for CHL and HN3. Altogether, following OECD requirements, our results suggest the classification of all investigated substances as skin sensitizers. Finally, a tentative AOP for SM-induced skin sensitization is suggested.


Assuntos
Substâncias para a Guerra Química/toxicidade , Irritantes/toxicidade , Gás de Mostarda/toxicidade , Testes de Irritação da Pele/normas , Pele/efeitos dos fármacos , Biomarcadores/metabolismo , Substâncias para a Guerra Química/classificação , Clorambucila/classificação , Clorambucila/toxicidade , Guias como Assunto , Humanos , Irritantes/classificação , Queratinócitos/efeitos dos fármacos , Queratinócitos/imunologia , Queratinócitos/metabolismo , Células de Langerhans/efeitos dos fármacos , Células de Langerhans/imunologia , Células de Langerhans/metabolismo , Mecloretamina/classificação , Mecloretamina/toxicidade , Gás de Mostarda/análogos & derivados , Gás de Mostarda/classificação , Medição de Risco , Pele/imunologia , Pele/metabolismo
9.
Int J Nanomedicine ; 14: 4911-4929, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31456637

RESUMO

Background: Apocynin (APO) is a bioactive phytochemical with prominent anti-inflammatory and anti-oxidant activities. Designing a nano-delivery system targeted to potentiate the gastric antiulcerogenic activity of APO has not been investigated yet. Chitosan oligosaccharide (COS) is a low molecular weight chitosan and its oral nanoparticulate system for potentiating the antiulcerogenic activity of the loaded APO has been described here. Methods: COS-nanoparticles (NPs) loaded with APO (using tripolyphosphate [TPP] as a cross-linker) were prepared by ionic gelation method and fully characterized. The chosen formula was extensively evaluated regarding in vitro release profile, kinetic analysis, and stability at refrigerated and room temperatures. Ultimately, the in vivo antiulcerogenic activity against ketoprofen (KP)-induced gastric ulceration in rats was assessed by macroscopic parameters including Paul's index and antiulcerogenic activity, histopathological examination, immunohistochemical (IHC) evaluation of cyclooxygenase-2 (COX-2) expression level in ulcerated gastric tissue, and biochemical measurement of oxidative stress markers and nitric oxide (NO) levels. Results: The selected NPs formula with COS (0.5 % w/v) and TPP (0.1% w/v) was the most appropriate one with drug entrapment efficiency percentage of 35.06%, particle size of 436.20 nm, zeta potential of +38.20 mV, and mucoadhesive strength of 51.22%. It exhibited a biphasic in vitro release pattern as well as high stability at refrigerated temperature for a 6-month storage period. APO-loaded COS-NPs provoked marvelous antiulcerogenic activity against KP-induced gastric ulceration in rats compared with free APO treated group, which was emphasized by histopathological, IHC, and biochemical studies. Conclusion: In conclusion, APO-loaded COS-NPs could be considered as a promising oral phytopharmaceutical nanoparticulate system for management of gastric ulceration.


Assuntos
Acetofenonas/administração & dosagem , Acetofenonas/farmacologia , Quitosana/química , Mucosa Gástrica/efeitos dos fármacos , Nanopartículas/química , Oligossacarídeos/química , Compostos Fitoquímicos/administração & dosagem , Compostos Fitoquímicos/farmacologia , Acetofenonas/uso terapêutico , Administração através da Mucosa , Animais , Biomarcadores/metabolismo , Varredura Diferencial de Calorimetria , Ciclo-Oxigenase 2/metabolismo , Liberação Controlada de Fármacos , Cinética , Masculino , Nanopartículas/ultraestrutura , Óxido Nítrico/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Tamanho da Partícula , Ratos Wistar , Espectroscopia de Infravermelho com Transformada de Fourier , Eletricidade Estática , Estômago/efeitos dos fármacos , Estômago/patologia , Úlcera Gástrica/tratamento farmacológico , Úlcera Gástrica/patologia , Suínos , Difração de Raios X
10.
BMC Ophthalmol ; 19(1): 170, 2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31382918

RESUMO

BACKGROUND: To assess bioactive transforming growth factor-ß2 (TGFß2) and secreted frizzled-related protein-1 (SFRP1) levels in aqueous humor (AH) of different types of glaucoma. METHODS: AH samples were obtained immediately before ophthalmic surgery with a 27-gauge needle attached to a microsyringe from 126 eyes (105 patients) divided into five groups: cataract (control), primary open-angle glaucoma (POAG), chronic angle-closure glaucoma (CACG), primary angle-closure suspects (PACS), and acute angle-closure glaucoma (AACG). Bioactive TGFß2 and SFRP1 levels were assayed by ELISA. RESULTS: The concentration of TGFß2 in AH of POAG patients, but not CACG, PACS, or AACG patients, was significantly higher than control eyes. However, within the AACG group, although the TGFß2 levels in AH did not differ significantly from the control level when all AACG patients were grouped together, there were differences when the AACG patients were divided into high and normal intraocular pressure (IOP); TGFß2 of AACG patients with high IOP (> 21 mmHg) was significantly higher than those with normal IOP. AH levels of SFRP1 were not significantly different among the groups. However, a statistical significant, negative correlation between SFRP1 and IOP existed in the POAG group. POAG patients with high IOP had lower levels of SFRP1 than those with normal IOP. In contrast, a significant, positive correlation between SFRP1 level and IOP was detected in the AACG group. AACG patients with high IOP had a higher level of SFRP1 than those with normal IOP. Concentrations of TGFß2 and SFRP1 did not correlate significantly with each other, or with age. CONCLUSIONS: These results indicate that AH levels of TGFß2 and SFRP1 showed different profiles in different types of glaucomas.


Assuntos
Humor Aquoso/metabolismo , Glaucoma de Ângulo Fechado/metabolismo , Glaucoma de Ângulo Aberto/metabolismo , Pressão Intraocular/fisiologia , Proteínas/metabolismo , Fator de Crescimento Transformador beta2/metabolismo , Idoso , Biomarcadores/metabolismo , Ensaio de Imunoadsorção Enzimática , Feminino , Glaucoma de Ângulo Fechado/fisiopatologia , Glaucoma de Ângulo Aberto/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade
11.
Biochem Med (Zagreb) ; 29(3): 030501, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31379458

RESUMO

The complex process of biological aging, as an intrinsic feature of living beings, is the result of genetic and, to a greater extent, environmental factors and time. For many of the changes taking place in the body during aging, three factors are important: inflammation, immune aging and senescence (cellular aging, biological aging). Senescence is an irreversible form of long-term cell-cycle arrest, caused by excessive intracellular or extracellular stress or damage. The purpose of this cell-cycles arrest is to limit the proliferation of damaged cells, to eliminate accumulated harmful factors and to disable potential malignant cell transformation. As the biological age does not have to be in accordance with the chronological age, it is important to find specific hallmarks and biomarkers that could objectively determine the rate of age of a person. These biomarkers might be a valuable measure of physiological, i.e. biological age. Biomarkers should meet several criteria. For example, they have to predict the rate of aging, monitor a basic process that underlies the aging process, be able to be tested repeatedly without harming the person. In addition, biomarkers have to be indicators of biological processes, pathogenic processes or pharmacological responses to therapeutic intervention. It is considered that the telomere length is the weak biomarker (with poor predictive accuracy), and there is currently no reliable biomarker that meets all the necessary criteria.


Assuntos
Envelhecimento , Senescência Celular , Biomarcadores/metabolismo , Dano ao DNA , Humanos , Sistema Imunitário/metabolismo , Estresse Oxidativo , Espécies Reativas de Oxigênio/metabolismo , Homeostase do Telômero
12.
Bone Joint J ; 101-B(8): 970-977, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31362542

RESUMO

AIMS: The aim of this study was to evaluate the diagnostic accuracy of the synovial alpha-defensin enzyme-linked immunosorbent assay (ELISA) for the diagnosis of prosthetic joint infection (PJI) in the work-up prior to revision of total hip (THA) and knee arthroplasty (TKA). PATIENTS AND METHODS: Inclusion criteria for this prospective cohort study were acute or chronic symptoms of the index joint without specific exclusion criteria. Synovial fluid aspirates of 202 patients were analyzed and semiquantitative laboratory alpha-defensin ELISA was performed. Final diagnosis of PJI was established by examination of samples obtained during revision surgery. RESULTS: Sensitivity and specificity of the alpha-defensin ELISA for PJI were 78.2% (95% confidence interval (CI) 66.7 to 88.5) and 96.6% (95% CI 93.0 to 99.3). Positive and negative predictive values were 89.6% (95% CI 80.6 to 97.8) and 92.2% (95% CI 87.5 to 96.1). The test remained false-negative in 22% of septic revisions, most of which were due to coagulase-negative staphylococci all occurring in either late-chronic or early-postoperative PJI. CONCLUSION: The routine use of synovial fluid alpha-defensin laboratory ELISA in the preoperative evaluation of symptomatic THAs and TKAs is insufficient to accurately diagnose PJI. Particularly in cases involving low-virulence organisms, such as coagulase-negative staphylococci, there remains a need for tests with a higher sensitivity. Cite this article: Bone Joint J 2019;101-B:970-977.


Assuntos
Artroplastia de Quadril , Artroplastia do Joelho , Ensaio de Imunoadsorção Enzimática/métodos , Prótese de Quadril/efeitos adversos , Prótese do Joelho/efeitos adversos , Infecções Relacionadas à Prótese/diagnóstico , alfa-Defensinas/metabolismo , Biomarcadores/metabolismo , Reações Falso-Negativas , Feminino , Infecções por Bactérias Gram-Negativas/diagnóstico , Infecções por Bactérias Gram-Positivas/diagnóstico , Humanos , Masculino , Estudos Prospectivos , Reoperação , Sensibilidade e Especificidade , Líquido Sinovial/metabolismo
13.
Bone Joint J ; 101-B(8): 915-921, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31362550

RESUMO

AIMS: Altered alignment and biomechanics are thought to contribute to the progression of osteoarthritis (OA) in the native compartments after medial unicompartmental knee arthroplasty (UKA). The aim of this study was to evaluate the bone activity and remodelling in the lateral tibiofemoral and patellofemoral compartment after medial mobile-bearing UKA. PATIENTS AND METHODS: In total, 24 patients (nine female, 15 male) with 25 medial Oxford UKAs (13 left, 12 right) were prospectively followed with sequential 99mTc-hydroxymethane diphosphonate single photon emission CT (SPECT)/CT preoperatively and at one and two years postoperatively, along with standard radiographs and clinical outcome scores. The mean patient age was 62 years (40 to 78) and the mean body mass index (BMI) was 29.7 kg/m2 (23.6 to 42.2). Mean osteoblastic activity was evaluated using a tracer localization scheme with volumes of interest (VOIs). Normalized mean tracer values were calculated as the ratio between the mean tracer activity in a VOI and background activity in the femoral diaphysis. RESULTS: Significant reduction of normalized tracer activity was observed one year postoperatively in tibial and femoral VOIs adjacent to the joint line in the lateral compartment. Patellar VOIs and remaining femoral VOIs demonstrated a significant, diminished normalized tracer activity at final follow-up. CONCLUSION: The osteoblastic bone activity in the native compartments decreased significantly after treatment of medial end-stage OA with a UKA, implying reduced stress to the subchondral bone in the retained compartments after a UKA. Cite this article: Bone Joint J 2019;101-B:915-921.


Assuntos
Artroplastia do Joelho/efeitos adversos , Fêmur/metabolismo , Hemiartroplastia/efeitos adversos , Articulação do Joelho/metabolismo , Osteoartrite do Joelho/cirurgia , Osteoblastos/metabolismo , Tíbia/metabolismo , Adulto , Idoso , Artroplastia do Joelho/instrumentação , Artroplastia do Joelho/métodos , Biomarcadores/metabolismo , Remodelação Óssea , Feminino , Fêmur/diagnóstico por imagem , Seguimentos , Hemiartroplastia/instrumentação , Hemiartroplastia/métodos , Humanos , Articulação do Joelho/diagnóstico por imagem , Articulação do Joelho/cirurgia , Prótese do Joelho , Masculino , Pessoa de Meia-Idade , Osteoartrite do Joelho/fisiopatologia , Estudos Prospectivos , Tomografia Computadorizada com Tomografia Computadorizada de Emissão de Fóton Único , Tíbia/diagnóstico por imagem , Resultado do Tratamento
14.
Oncology ; 97(4): 236-244, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31412345

RESUMO

INTRODUCTION: On a global scale, the malignant growth of mammary gland is the most common type of cancer in women. In the progress of mammary carcinoma, osseous metastatic invasion has a pivotal significance because it is a frequent complication occurring at an early stage of the disease. BACKGROUND: Bone metastases in breast cancer patients lead to increased mortality and decreased health-related quality of life. Therefore, early diagnostic assessment and treatment is requested. Meanwhile the progress of the disease should be monitored closely. Regarding health-related quality of life and lifetime prolongation, osseous metastases should be early diagnosed, therapied, and monitored. Up to date the gold standard is the whole-body scintigraphy. This kind of bone imaging features has high sensitivity but shows loss of specificity. AIM: This study aims to investigate the diagnostic versatility of bone markers in its resorption and formation function to detect bone metastases in patients with breast cancer. PATIENTS, MATERIALS, AND METHODS: For this purpose, the concentration of competing bone processing tumor markers in serums of 78 patients was detected and analyzed. Two groups of women with mammary carcinoma with and without osseous metastases were built to examine the presence (or absence) of statistically significant disparity of tumor marker concentration. The tumor markers employed in this study were the carboxyterminal collagen type I telopeptid (CTX), known as beta-crosslaps (ß-CTx), the alkaline phosphatase (AP), and its isoenzymes (especially the bone-specific AP [B-AP]). Additionally, the tumor markers for breast cancer (CA 15-3 and CEA) were analyzed in both groups. RESULTS: Our results provide evidence that in both groups, tumor markers such as ß-CTx and B-AP were a promising tool for the detection and exclusion of bone metastases in breast cancer. This comprehensive investigation shows both ß-CTx and B-AP are able to fulfill the conditions of a competent appliance to detect osseous metastases of patients with mammary carcinoma. CONCLUSION: Concerning the urgency of early and frequent detection, staging, and disease monitoring of mammary carcinoma with osseous metastases, this study renewed and underlined the importance of biochemical tumor markers - especially ß-CTx and B-AP - and laid a clinical-based cornerstone to build up on a prospective research.


Assuntos
Biomarcadores/metabolismo , Neoplasias Ósseas/metabolismo , Osso e Ossos/metabolismo , Neoplasias da Mama/metabolismo , Fosfatase Alcalina/metabolismo , Biomarcadores Tumorais , Neoplasias Ósseas/secundário , Neoplasias da Mama/patologia , Colágeno Tipo I/metabolismo , Feminino , Humanos , Mucina-1/metabolismo , Metástase Neoplásica , Qualidade de Vida , Curva ROC , Cintilografia , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Imagem Corporal Total
15.
Clin Exp Rheumatol ; 37 Suppl 118(3): 240-248, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31464680

RESUMO

In the era of personalised medicine new biomarkers are required to early diagnose Sjögren's syndrome (SS), to define different disease subsets and to direct patients' clinical management and therapeutic intervention. In the last few years, several efforts have evaluated saliva proteome to detect and monitor primary SS. Although clinically valuable, these studies presented some limitations that have partially prevented the use of salivary biomarkers in clinical practice. Nowadays, proteomic of extracellular vesicle (EV) represents an emerging and promising field in the discovery of -omic biomarkers for pSS. EV is a relatively new term that includes exosomes, microvesicles and apoptotic body. EVs are packed with proteins, growth factors, cytokines, bioactive lipids, but also nucleic acids and in particular: mRNA, microRNA, long non-coding RNA, tRNA and rRNA. Therefore, they may represent a useful source for diagnostic, prognostic and therapeutic biomarkers in several conditions. In this review we will specifically focus on EV proteomics as a tool for the identification of novel biomarkers for pSS. In the first part we focused on the state of the art of the studies on proteomics in SS existing in the literature. In the second part we provided a definition of EV with an update on biological sample collection and processing for EV proteomic studies. Finally, we summarised the state of the art of EV -omics in SS highlighting the potential advantages of this novel approach compared to the overall traditional concept of analysing the proteome of blood or saliva.


Assuntos
Vesículas Extracelulares , Proteômica/métodos , Síndrome de Sjogren , Biomarcadores/metabolismo , Vesículas Extracelulares/metabolismo , Humanos , Proteoma/metabolismo , Saliva/metabolismo , Síndrome de Sjogren/metabolismo
16.
Clin Exp Rheumatol ; 37(5): 715-722, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31376267

RESUMO

Systemic lupus erythematosus (SLE) is an autoimmune connective-tissue disorder with a wide range of clinical manifestations that predominantly affect women. Many aspects of its pathogenesis are still unclear, and new therapeutic strategies are progressively emerging. Thus, in this review we aim to summarise the most relevant data on SLE that emerged during 2018, following the previous annual review of this series. In particular, the review will focus on new insights in SLE regarding new pathogenetic pathways, new biomarkers, new data on clinical manifestations, clinical outcomes and comorbidities and what has emerged on new drugs and new therapeutic strategies.


Assuntos
Biomarcadores , Lúpus Eritematoso Sistêmico , Autoimunidade , Biomarcadores/metabolismo , Comorbidade , Feminino , Humanos , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/imunologia , Lúpus Eritematoso Sistêmico/terapia , Masculino , Prognóstico , Fatores de Risco
17.
Pan Afr Med J ; 33: 37, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31384352

RESUMO

Introduction: Osteoporosis is characterized by low bone mass and density, as well as change in microarchitecture of bone tissue leading to decreased bone strength. In vitro research shows nicotine can increase osteoblast activity and proliferation, also suppress osteoclast activity. Therefore we explore nicotine anti-resorptive property by in vivo true experimental and randomized posttest only controlled group research that was conducted in 18-20 weeks old Rattus norvegicus. Methods: Twenty-five female rats were divided into five groups, with 5 rats per group. The first group represented normal rats (Sham), while the second to fifth group underwent bilateral ovariectomy. The second group serves as positive control group (ovariectomy-only/OVX). The third to fifth group serve as dose 1 (P1-0.25mg/kg), dose 2 (P2-0.5 mg/kg), and Dose 3 (P3-0.75 mg/kg) treatment group receiving daily per-oral nicotine for 28 days, started 3 weeks post- ovariectomy. After 28 days treatment, the serum was checked. Results: Nicotine has dose-dependent manner on serum osteocalcin and serum DPD level. Level of osteocalcin in P2 group was significantly lower (Mann-Whitney, p = 0.008) compared to OVX group (59.4% lower). Level of DPD in all group was not significantly different (ANOVA, p < 0.05) but shows lowest level in P2 group. For serum calcitonin level, there's no significant different between groups. Conclusion: Nicotine at right low-dose might be able to inhibit osteoclast activity, thus open a possibility of anti-resorptive property of nicotine.


Assuntos
Densidade Óssea/efeitos dos fármacos , Nicotina/farmacologia , Osteoclastos/efeitos dos fármacos , Osteoporose/prevenção & controle , Aminoácidos/sangue , Animais , Biomarcadores/metabolismo , Remodelação Óssea/efeitos dos fármacos , Osso e Ossos/efeitos dos fármacos , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Feminino , Nicotina/administração & dosagem , Osteoblastos/efeitos dos fármacos , Osteoblastos/metabolismo , Osteocalcina/sangue , Osteoclastos/metabolismo , Osteoporose/patologia , Ovariectomia , Ratos , Ratos Wistar
18.
Gene ; 720: 144056, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31437466

RESUMO

Repeated implantation failure (RIF) was mainly due to poor endometrium receptivity. Long noncoding RNAs (lncRNAs) could regulate endometrium receptivity and act in competing endogenous RNA (ceRNA) theory. However, the regulatory mechanism of the lncRNA-miRNA-mRNA network in repeated implantation failure (RIF) is unclear. We obtained RIF-related expression profiles of lncRNAs, mRNAs, and miRNAs using mid-secretory endometrial tissue samples from 5 women with RIF and 5 controls by RNA-sequencing. Co-expression analysis revealed that three functional modules were enriched in immune response/inflammation process; two functional modules were enriched in metabolic/ biosynthetic process, and one functional module were enriched in cell cycle pathway. By adding the miRNA data, ceRNA regulatory relationship of each module was reconstructed. The ceRNA network of the whole differentially expressed RNAs revealed 10 hub lncRNAs. Among them, TRG-AS1, SIMM25, and NEAT1 were involved in the module1, module2, and module3, respectively; LNC00511 and SLC26A4-AS1 in the module4; H19 in the module5. The real-time polymerase chain reaction (RT-PCR) results of 15 randomly selected RNAs were consistent with our sequencing data. These can be used as novel potential biomarkers for RIF. Furthermore, they might be involved in endometrium receptivity by acting as ceRNA.


Assuntos
Biomarcadores/metabolismo , Endométrio/metabolismo , Redes Reguladoras de Genes , Genoma Humano , MicroRNAs/genética , RNA Longo não Codificante/genética , RNA Mensageiro/genética , Adulto , Estudos de Casos e Controles , Implantação do Embrião , Endométrio/patologia , Feminino , Fertilização In Vitro , Regulação da Expressão Gênica , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos
20.
Medicine (Baltimore) ; 98(26): e15947, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31261500

RESUMO

To assess the hypothesis if tocilizumab (TCZ) is effective on disease activity, and also its effect in fatigue and other clinical and psychological disease-related factors in patients with rheumatoid arthritis (RA) treated with TCZ.A 24-week, multicenter, prospective, observational study in patients with moderate to severe RA receiving TCZ after failure or intolerance to disease-modifying antirheumatic drugs or tumor necrosis factor-alpha was conducted.Of the 122 patients included, 85 were evaluable for effectiveness (85% female, 51.9 ±â€Š12.5 years, disease duration 8.7 ±â€Š7.4 years). Mean change in C-reactive protein level from baseline to week 12 was -11.2 ±â€Š4.0 (P < .001). Mean Disease Activity Index score (DAS28) decreased from 5.5 ±â€Š1.0 at baseline to 2.7 ±â€Š1.3 (P < .001) at week 24. Mean change in Functional Assessment of Chronic Illness Therapy score was -5.4 ±â€Š11.2 points at week 24. Multiple regression analysis showed that the improvement in DAS28, sleep, and depression explained 56% and 47% of fatigue variance at week 12 and 24, respectively.Tocilizumab is effective in reducing disease activity and results in a clinically significant improvement in fatigue, pain, swollen joint count, morning stiffness, sleepiness, depression, and DAS28; the last 3 were specifically identified as factors explaining fatigue variance with the use of TCZ in RA patients.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Artrite Reumatoide/psicologia , Artrite Reumatoide/terapia , Fadiga/psicologia , Fadiga/terapia , Antirreumáticos/uso terapêutico , Artrite Reumatoide/fisiopatologia , Biomarcadores/metabolismo , Proteína C-Reativa/metabolismo , Depressão/fisiopatologia , Depressão/terapia , Fadiga/etiologia , Fadiga/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Retratamento , Sono , Resultado do Tratamento , Fator de Necrose Tumoral alfa/uso terapêutico
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