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1.
J Endocrinol Invest ; 47(11): 2851-2864, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38733428

RESUMO

PURPOSE: Information on the general health of transgender and gender diverse (TGD) individuals continues to be lacking. To bridge this gap, the National Institute of Health in Italy together with the National Office against Racial Discriminations, clinical centres, and TGD organizations carried out a cross-sectional study to define the sociodemographic profile, health-related behaviours, and experiences of healthcare access in Italian TGD adult population. METHODS: A national survey was conducted by Computer-Assisted Web Interviewing (CAWI) technique. Collected data were compared within the TGD subgroups and between TGD people and the Italian general population (IGP). RESULTS: TGD respondents were 959: 65% assigned female at birth (AFAB) and 35% assigned male at birth (AMAB). 91.8% and 8.2% were binary and non-binary TGD respondents, respectively. More than 20% of the TGD population reported to be unemployed with the highest rate detectable in AMAB and non-binary people. Cigarette smoking and binge drinking were higher in the TGD population compared with IGP (p < 0.05), affecting TGD subgroups differently. A significant lower percentage of AFAB TGD people reported having had screening for cervical and breast cancer in comparison with AFAB IGP (p < 0.0001, in both cases). Over 40% was the percentage of AFAB and non-binary TGD people accessing healthcare who felt discriminated against because of their gender identity. CONCLUSIONS: Our results are a first step towards a better understanding of the health needs of TGD people in Italy in order to plan the best policy choices for a more inclusive public health.


Assuntos
Comportamentos Relacionados com a Saúde , Acessibilidade aos Serviços de Saúde , Pessoas Transgênero , Humanos , Feminino , Masculino , Adulto , Pessoas Transgênero/estatística & dados numéricos , Pessoas Transgênero/psicologia , Itália/epidemiologia , Estudos Transversais , Acessibilidade aos Serviços de Saúde/estatística & dados numéricos , Pessoa de Meia-Idade , Adulto Jovem , Adolescente , Fatores Sociodemográficos , Inquéritos e Questionários , Idoso
2.
Proc Natl Acad Sci U S A ; 113(36): E5308-17, 2016 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-27540115

RESUMO

Despite numerous reports implicating NADPH oxidases (Nox) in the pathogenesis of many diseases, precise regulation of this family of professional reactive oxygen species (ROS) producers remains unclear. A unique member of this family, Nox1 oxidase, functions as either a canonical or hybrid system using Nox organizing subunit 1 (NoxO1) or p47(phox), respectively, the latter of which is functional in vascular smooth muscle cells (VSMC). In this manuscript, we identify critical requirement of ezrin-radixin-moesin-binding phosphoprotein 50 (EBP50; aka NHERF1) for Nox1 activation and downstream responses. Superoxide (O2 (•-)) production induced by angiotensin II (AngII) was absent in mouse EBP50 KO VSMC vs. WT. Moreover, ex vivo incubation of aortas with AngII showed a significant increase in O2 (•-) in WT but not EBP50 or Nox1 nulls. Similarly, lipopolysaccharide (LPS)-induced oxidative stress was attenuated in femoral arteries from EBP50 KO vs. WT. In silico analyses confirmed by confocal microscopy, immunoprecipitation, proximity ligation assay, FRET, and gain-/loss-of-function mutagenesis revealed binding of EBP50, via its PDZ domains, to a specific motif in p47(phox) Functional studies revealed AngII-induced hypertrophy was absent in EBP50 KOs, and in VSMC overexpressing EBP50, Nox1 gene silencing abolished VSMC hypertrophy. Finally, ex vivo measurement of lumen diameter in mouse resistance arteries exhibited attenuated AngII-induced vasoconstriction in EBP50 KO vs. WT. Taken together, our data identify EBP50 as a previously unidentified regulator of Nox1 and support that it promotes Nox1 activity by binding p47(phox) This interaction is pivotal for agonist-induced smooth muscle ROS, hypertrophy, and vasoconstriction and has implications for ROS-mediated physiological and pathophysiological processes.


Assuntos
ATPases Associadas a Diversas Atividades Celulares/metabolismo , DNA Helicases/metabolismo , Hipertrofia/metabolismo , NADPH Oxidase 1/genética , Fosfoproteínas/metabolismo , Proteínas/metabolismo , Trocadores de Sódio-Hidrogênio/metabolismo , ATPases Associadas a Diversas Atividades Celulares/genética , Proteínas Adaptadoras de Transdução de Sinal , Angiotensina II/administração & dosagem , Angiotensina II/efeitos adversos , Animais , DNA Helicases/genética , Artéria Femoral/efeitos dos fármacos , Artéria Femoral/metabolismo , Artéria Femoral/patologia , Humanos , Hipertrofia/induzido quimicamente , Hipertrofia/patologia , Lipopolissacarídeos/toxicidade , Camundongos , Camundongos Knockout , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patologia , NADPH Oxidase 1/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Fosfoproteínas/genética , Proteínas/genética , Espécies Reativas de Oxigênio/metabolismo , Trocadores de Sódio-Hidrogênio/genética , Superóxidos/metabolismo , Vasoconstrição/efeitos dos fármacos , Vasoconstrição/genética
3.
Vox Sang ; 113(3): 268-274, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29359471

RESUMO

BACKGROUND: During massive transfusion, the volume ratio of administered plasma (PL Vol) to red blood cell (RBC Vol) appears to be associated with reduced blood utilization and improved survival. The aim of this study was to evaluate the optimal component ratio in the setting of liver transplantation. METHODS: This is a retrospective chart review of patients who underwent liver transplantation and received at least 500 ml of red blood cells from January 2013 through December 2015. Kernel smoothing analysis determined the proper component ratios to evaluate were a ≥0·85:1 ratio (high) to a ≤0·85:1 ratio (low). Two groups, plasma volume to RBC volume (PL Vol/RBC Vol) and plasma contained in the platelet units added to the plasma calculation [PL + PLT (platelet)] Vol/RBC Vol, were used to evaluate the component ratios. RESULTS: A total of 188 patients were included in the analysis. In the PL Vol/RBC Vol evaluation, a low ratio revealed that 1238 ml (977-1653 ml) (P < 0·0001) and 1178 ml (747-1178) (P < 0·0001) of RBC were used in excess compared to the high ratio, in the univariable and multivariable analysis, respectively. In the PL +PLT Vol/RBC Vol evaluation, a low ratio used 734 ml (193-1275) (P = 0·008) and 886 ml (431-1340) (P < 0·0001) of RBC in excess when compared to high ratio in the univariable and multivariable analysis, respectively. CONCLUSION: In patients undergoing liver transplantation, the transfusion of plasma to RBC ratio ≥0·85 was associated with decreased need of RBC transfusions.


Assuntos
Transfusão de Eritrócitos/métodos , Transplante de Fígado/métodos , Adulto , Contagem de Eritrócitos , Transfusão de Eritrócitos/efeitos adversos , Transfusão de Eritrócitos/normas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Plasma , Estudos Retrospectivos
4.
Vox Sang ; 2018 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-29714029

RESUMO

BACKGROUND AND OBJECTIVES: Blood utilization during liver transplant has decreased, but remains highly variable due to many complex surgical and physiologic factors. Previous models attempted to predict utilization using preoperative variables to stratify cases into two usage groups, usually using entire blood units for measurement. We sought to develop a practical predictive model using specific transfusion volumes (in ml) to develop a data-driven patient blood management strategy. MATERIALS AND METHODS: This is a retrospective evaluation of primary liver transplants at a single institution from 2013 to 2015. Multivariable analysis of preoperative recipient and donor factors was used to develop a model predictive of intraoperative red-blood-cell (pRBC) use. RESULTS: Of 256 adult liver transplants, 207 patients had complete transfusion volume data for analysis. The median intraoperative allogeneic pRBC transfusion volume was 1250 ml, and the average was 1563 ± 1543 ml. Preoperative haemoglobin, spontaneous bacterial peritonitis, preoperative haemodialysis and preoperative international normalized ratio together yielded the strongest model predicting pRBC usage. When it predicted <1250 ml of pRBCs, all cases with 0 ml transfused were captured and only 8·6% of the time >1250 ml were used. This prediction had a sensitivity of 0·91 and a specificity of 0·89. If predicted usage was >2000 ml, 75% of the time blood loss exceeded 2000 ml. CONCLUSION: Patients likely to require low or high pRBC transfusion volumes were identified with excellent accuracy using this predictive model at our institution. This model may help predict bleeding risk for each patient and facilitate optimized blood ordering.

5.
Transfus Med ; 28(6): 405-412, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30325081

RESUMO

OBJECTIVES: Using a multidisciplinary approach and simulation, a massive transfusion process (MTP) was developed to care for patients in need of emergency transfusion. It was then assessed for effectiveness. BACKGROUND: After a series of sentinel emergency bleeding events, a reliable process for hospital staff to deliver appropriate blood products and obtain relevant laboratory tests to guide therapy for patients with emergency bleeding was needed. METHODS: To determine the feasibility of the new MTP, multidisciplinary teams participated in simulation events. Each simulation event helped refine the MTP. A special laboratory testing panel was devised. To judge the effectiveness and timeliness of the MTP, process measures and patient survival was retrospectively evaluated during the time period before and after MTP implementation. RESULTS: A new emergency bleeding panel of laboratory tests significantly decreased the turn-around time for fibrinogen, haematocrit, International normalised ratio (INR) and platelet count. The speed of commencing the first red blood cells transfusion was also improved (2:00 h vs 0:20 min, P = 0·001). Of 78 patients, there was no change in survival before (n = 31, 48·4%) and after (n = 47, 42·6%; P = 0·6478) MTP implementation. However, there was significant improvement in survival associated with MTP events on the weekdays. CONCLUSIONS: A reliable emergency transfusion process consists of an automatic chain of events that keeps decision-making to a minimum and leads to the fast procurement of blood products and salient test results. This work shows that a multidisciplinary iterative process using simulation increases the efficiency of clinical care delivery for bleeding paediatric and neonatal patients.


Assuntos
Serviços Médicos de Emergência , Transfusão de Eritrócitos , Hemorragia/terapia , Qualidade da Assistência à Saúde , Treinamento por Simulação , Pré-Escolar , Feminino , Hemorragia/sangue , Humanos , Lactente , Recém-Nascido , Coeficiente Internacional Normatizado , Masculino
6.
Fish Shellfish Immunol ; 55: 529-34, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27346153

RESUMO

The fan mussel Pinna nobilis (Linnaeus, 1758) is one of the biggest bivalves worldwide. Currently, no updated information is available in the literature concerning the morpho-functional aspects of haemocytes from this bivalve species. Consequently, in this study, we characterised P. nobilis haemocytes from both a morphological and functional point of view. The mean number of haemocytes was about 5 (×10(5)) cells mL haemolymph(-1), and the cell viability was about 92-100%. Two haemocyte types were distinguished under the light microscope: granulocytes (51.6%), with evident cytoplasmic granules, and hyalinocytes (48.4%), with a few granules. The granules of the granulocytes were mainly lysosomes, as indicated by the in vivo staining with Neutral Red. Haemocytes were further distinguished in basophils (83.75%), acidophils (14.75%) and neutrophils (1.5%). After adhesion to slides and fixation, the cell diameter was approximately 10 µm for granulocytes and 7 µm for hyalinocytes. The granulocytes and hyalinocytes were both positive to the Periodic Acid-Schiff reaction for carbohydrates. Only granulocytes were able to phagocytise yeast cells. The phagocytic index (6%) increased significantly up to twofold after preincubation of yeast in cell-free haemolymph, suggesting that haemolymph has opsonising properties. In addition, haemocytes produce superoxide anion and acid and alkaline phosphatases. Summarising, this preliminary study indicates that both the granulocytes and hyalinocytes circulate in the haemolymph of P. nobilis and that they are active immunocytes.


Assuntos
Bivalves/citologia , Bivalves/fisiologia , Fagocitose , Animais , Bivalves/ultraestrutura , Hemócitos/citologia , Hemócitos/fisiologia , Hemócitos/ultraestrutura , Microscopia Eletrônica de Transmissão
7.
Int J Immunogenet ; 42(4): 294-6, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25976429

RESUMO

The new allelic variant HLA-B*38:55Q differs from the closest related B*38:01:01 by one nucleotide substitution at position 373 in exon 3 (TGC>CGC). This results in a difference of one amino acid at residue 101 of the HLA-B heavy chain, from a neutral-polar Cys to a basic-polar Arg, thus impairing disulphide bridge formation in the alpha-2 domain. This alteration of the secondary structure probably affects the maturation of the heavy chain and the level of surface expression, making the HLA-B*38:55Q undetectable by standard serological typing.


Assuntos
Alelos , Substituição de Aminoácidos/genética , Regulação da Expressão Gênica , Antígenos HLA-B/genética , Sequência de Aminoácidos/genética , Éxons , Antígenos HLA-B/biossíntese , Humanos , Dados de Sequência Molecular , Estrutura Secundária de Proteína , Alinhamento de Sequência , População Branca
8.
Neurologia ; 29(9): 567-72, 2014.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-24140159

RESUMO

INTRODUCTION: Epidemiological studies have demonstrated that patients with diabetes mellitus have an increased risk of developing Alzheimer disease, but the relationship between the 2 entities is not clear. DEVELOPMENT: Both diseases exhibit similar metabolic abnormalities: disordered glucose metabolism, abnormal insulin receptor signalling and insulin resistance, oxidative stress, and structural abnormalities in proteins and ß-amyloid deposits. Different hypotheses have emerged from experimental work in the last two decades. One of the most comprehensive relates the microvascular damage in diabetic polyneuritis with the central nervous system changes occurring in Alzheimer disease. Another hypothesis considers that cognitive impairment in both diabetes and Alzheimer disease is linked to a state of systemic oxidative stress. Recently, attenuation of cognitive impairment and normalisation of values in biochemical markers for oxidative stress were found in patients with Alzheimer disease and concomitant diabetes. Antidiabetic drugs may have a beneficial effect on glycolysis and its end products, and on other metabolic alterations. CONCLUSIONS: Diabetic patients are at increased risk for developing Alzheimer disease, but paradoxically, their biochemical alterations and cognitive impairment are less pronounced than in groups of dementia patients without diabetes. A deeper understanding of interactions between the pathogenic processes of both entities may lead to new therapeutic strategies that would slow or halt the progression of impairment.


Assuntos
Doença de Alzheimer/etiologia , Diabetes Mellitus Tipo 2/complicações , Transtornos Cognitivos/etiologia , Demência/etiologia , Diabetes Mellitus Tipo 2/metabolismo , Progressão da Doença , Humanos , Estresse Oxidativo
9.
Epidemiol Infect ; 141(2): 330-3, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22717017

RESUMO

SUMMARY Over the last decade, Acinetobacter baumannii resistant to carbapenems has emerged in many medical centres and is commonly associated with high morbidity and mortality. We investigated potential mechanisms contributing to antimicrobial resistance of 58 clinical isolates of A. baumannii collected during a prolonged city-wide outbreak in five different hospitals in southern Brazil. The integrase gene was detected in 51 (87·9%) isolates of which 36 harboured class 2 integrons alone and 14 had both class 1 and 2 integrons; all carbapenem-resistant isolates displayed class 2 integrons. ISAba1 was found upstream of bla OXA-23-like only in isolates resistant to carbapenems; however, ISAba1 upstream of blaOXA-51-like was present in both susceptible and resistant isolates. This is the first report of a high prevalence of class 2 integrons in A. baumannii in southern Brazil. Moreover, our study suggests that ISAba1/blaOXA-51-like alone is insufficient to confer resistance to carbapenems.


Assuntos
Infecções por Acinetobacter/epidemiologia , Acinetobacter baumannii/genética , Antibacterianos/farmacologia , Carbapenêmicos/farmacologia , Elementos de DNA Transponíveis , Resistência Microbiana a Medicamentos/genética , Integrases/genética , Infecções por Acinetobacter/tratamento farmacológico , Infecções por Acinetobacter/microbiologia , Acinetobacter baumannii/isolamento & purificação , Brasil/epidemiologia , Infecção Hospitalar/epidemiologia , Surtos de Doenças , Eletroforese em Gel de Campo Pulsado , Humanos , Integrons , Testes de Sensibilidade Microbiana , Epidemiologia Molecular/métodos
10.
Ann Nutr Metab ; 63(1-2): 55-9, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23899667

RESUMO

BACKGROUND: Iron deficiency anemia frequently occurs in gastrectomized patients. METHODS: Serum iron levels following the ingestion of a single oral dose of 105 mg elemental iron, taken as ferrous sulfate (FeS) or ferric gluconate (FeG), have been evaluated in 20 gastrectomized patients (and 20 controls). All subjects participated on 2 different test days, 1 month apart: they took a single dose of 105 mg elemental iron as FeS or FeG after a night of fasting. Serum iron concentrations at baseline, 30, 60, 120 and 180 min after the oral dose administration were measured. RESULTS: In patients and controls receiving FeG, serum iron levels did not significantly change. After oral ingestion of FeS, patients' serum iron levels gradually increased. The increase in serum iron levels was 148 and 168% at 120 and 180 min in patients (p < 0.0001 for both evaluations), whilst in controls, it was 216% at 120 min and 234% at 180 min, i.e. significantly higher than in gastrectomized patients (p < 0.001 for both evaluations). CONCLUSIONS: In gastrectomized patients, a single oral dose of FeS shows a significant increase in iron serum concentration, albeit lower than in controls. Further studies on a larger sample of patients will be necessary to confirm these results.


Assuntos
Compostos Férricos/farmacocinética , Compostos Ferrosos/farmacocinética , Gastrectomia/efeitos adversos , Ferro/farmacocinética , Absorção , Administração Oral , Adulto , Anemia Ferropriva/tratamento farmacológico , Anemia Ferropriva/etiologia , Relação Dose-Resposta a Droga , Feminino , Compostos Férricos/administração & dosagem , Compostos Ferrosos/administração & dosagem , Seguimentos , Humanos , Ferro/administração & dosagem , Ferro/sangue , Masculino , Pessoa de Meia-Idade , Método Simples-Cego , Resultado do Tratamento
11.
Eur Rev Med Pharmacol Sci ; 17(13): 1752-9, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23852899

RESUMO

OBJECTIVE: We developed a standardized technique for ultrasound guided intra-articular injection of the hip joint with the purpose of extending routine intra-articular injection of hyaluronans and steroids to the hip, as commonly used in the knee. In this article we report the safety of this technique in an extended series of patients. PATIENTS AND METHODS: Patients were injected supine with an anterosuperior approach under ultrasound guidance. The Us probe is applied with a target device for biopsy. RESULTS: The standardised technique was used to inject 1906 patients with 4002 injections of hyaluronan products over a four-year period. The treatment was well tolerated with few, and exclusively local, side effects. CONCLUSIONS: The administration of hyaluronans under ultrasound-guided intra-articular injection is a safe technique for treatment of rheumatic diseases of the hip.


Assuntos
Articulação do Quadril/diagnóstico por imagem , Ácido Hialurônico/administração & dosagem , Ácido Hialurônico/uso terapêutico , Osteoartrite do Quadril/tratamento farmacológico , Idoso , Análise de Variância , Feminino , Humanos , Ácido Hialurônico/efeitos adversos , Injeções Intra-Articulares , Masculino , Pessoa de Meia-Idade , Dor/epidemiologia , Dor/etiologia , Segurança do Paciente , Estudos Retrospectivos , Ultrassonografia de Intervenção
12.
Mar Pollut Bull ; 196: 115573, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37778243

RESUMO

Pollution is one of the main anthropogenic threats to marine ecosystems. Studies analysing the accumulation and transfer of contaminants in planktonic food webs tend to rely on samples collected in discrete water bodies. Here, we assessed the representativeness of measurements at the chlorophyll-a maximum layer during the MERITE-HIPPOCAMPE cruise for the entire water column by investigating the vertical distribution of particles and plankton obtained by in-situ optical profilers at nine stations across the Mediterranean Sea. We identified specific conditions where the interpretation of results from contaminant analyses can be improved by detailing plankton size structure and vertical distributions. First, the presence of higher than usual plankton concentrations can result in sampling issues that will affect biomass estimation within each size class and therefore bias our understanding of the contaminant dynamics. Secondly, the presence of an unsampled water layer with high zooplankton biomass might imply non-resolved contaminant pathways along the trophic structure. This study lays the basis for optimizing sampling strategy in contaminant studies.


Assuntos
Plâncton , Zooplâncton , Animais , Plâncton/química , Ecossistema , Água , Cadeia Alimentar
13.
Int J Cardiol ; 371: 516-522, 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36130621

RESUMO

INTRODUCTION: Due to their rare prevalence and marked heterogeneity, pediatric cardiomyopathies (CMPs) are little known and scarcely reported. We report the etiology, clinical profile and outcome of a consecutive cohort of children diagnosed with CMP and followed at Meyer Children's Hospital over a decade. PATIENTS AND METHODS: We retrospectively reviewed patients consecutively referred from May 2008 to May 2019 for pediatric onset CMP (<18 years). Heart disease caused by arrhythmic disorders, toxic agents, rheumatic conditions and maternal disease were excluded. RESULTS: We enrolled 110 patients (65 males), diagnosed at a median age of 27 [4-134] months; 35% had an infant onset (<1 year of age). A positive family history was more often associated with childhood-onset (38.8%). Hypertrophic cardiomyopathy (HCM; 48 patients) was the most frequent phenotype, followed by dilated cardiomyopathy (DCM; 35 patients). While metabolic and idiopathic etiologies were preponderant in infants, metabolic and sarcomeric diseases were most frequent in the childhood-onset group. Major adverse cardiac events (MACE) occurred in 31.8% of patients, including hospitalization for acute heart failure in 25.5% of patients, most commonly due to DCM. Overall, the most severe outcomes were documented in patients with metabolic diseases. CONCLUSIONS: In a consecutive cohort of pediatric patients with CMP, those with infantile onset and with a metabolic etiology had the worst prognosis. Overall, MACE occurred in 41% of the entire population, most commonly associated with DCM, inborn errors of metabolism and genetic syndromes. Systematic NGS genetic testing was critical for etiological diagnosis and management.


Assuntos
Cardiomiopatias , Cardiomiopatia Dilatada , Cardiomiopatia Hipertrófica , Humanos , Masculino , Cardiomiopatias/diagnóstico , Cardiomiopatias/epidemiologia , Cardiomiopatias/genética , Cardiomiopatia Dilatada/genética , Cardiomiopatia Hipertrófica/diagnóstico , Cardiomiopatia Hipertrófica/epidemiologia , Cardiomiopatia Hipertrófica/genética , Estudos Retrospectivos
14.
Ann Oncol ; 23(7): 1899-905, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22104576

RESUMO

BACKGROUND: Bone metastatic patients with osteosarcoma have a very poor prognosis. Targeted radiation therapy has been pursued as a valid alternative. The primary end point of this study was progression-free survival (PFS) at 4 months. PATIENTS AND METHODS: Twenty-two osteosarcoma patients were treated with Samarium-153 ethylenediaminetetramethylene phosphonic acid (153Sm-EDTMP) at various dosages. Administered activities ranged from 150 (3 mCi/kg) to 1140 MBq/kg (30 mCi/kg). Autologous hematopoietic stem cell infusion was carried out on day 14 after the (153)Sm-EDTMP infusion. RESULTS: The median PFS was 61 days (18-436 days) and the median overall survival (OS) was 189 days (31-1175 days). PFS and OS for the entire patient population were 32% [95% confidence interval (CI) 16-50] and 76% (95% CI 52-89) at 4 months, respectively. No statistical differences emerged according to 153Sm-EDTMP administered or 24-h retained activity. One-month pain palliation was only observed in a minority of subjects and in none at 4 months. CONCLUSIONS: Based on our series, the PFS is dramatically short even when higher activity of (153)Sm-EDTMP is administered. This would mean that, even at high level, 153Sm-EDTMP is itself ineffective against relapsed osteosarcoma or the residual activity is too low to be active on these particular subsets of patients.


Assuntos
Neoplasias Ósseas/terapia , Compostos Organometálicos/administração & dosagem , Compostos Organofosforados/administração & dosagem , Osteossarcoma/terapia , Compostos Radiofarmacêuticos/administração & dosagem , Adolescente , Adulto , Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/patologia , Criança , Terapia Combinada , Intervalo Livre de Doença , Feminino , Transplante de Células-Tronco Hematopoéticas , Humanos , Estimativa de Kaplan-Meier , Masculino , Compostos Organometálicos/efeitos adversos , Compostos Organometálicos/farmacocinética , Compostos Organofosforados/efeitos adversos , Compostos Organofosforados/farmacocinética , Osteossarcoma/mortalidade , Osteossarcoma/secundário , Doses de Radiação , Compostos Radiofarmacêuticos/efeitos adversos , Compostos Radiofarmacêuticos/farmacocinética , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
15.
J Neurosurg Sci ; 56(3): 221-9, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22854590

RESUMO

AIM: Mesenchymal stem cells (MSCs) migrate in response to chemokines and possess extensive tropism for experimental glioma. Antitumor effects have been reported following intracranial and intravenous administration of gene-modified MSCs. Among the different routes for cell transplant, the intraventricular (IV) approach found very little employment in comparison with intraparenchymal, intratumoral and intravenous administration protocols. Nevertheless, IV transplantation offers advantages in terms of cells viability and distribution toward target sites, opening interesting opportunities for its clinical application. METHODS: Using a rat glioma model, we investigated migratory capacity, tumor tropism, distribution and differentiation of MSCs following IV administration. RESULTS: Transplanted MSCs create niches of viable cells in the subventricular zone and can be stimulated to migrate to sites of tumor infiltration. MSCs seemed not to be involved in tumor growth and angiogenesis. CONCLUSION: We speculate that the IV route can be used to achieve a kind of reservoir of self-renewal cells, potentially active against the spread of cancer cells. Further studies are needed to shed light on MSCs distribution close to the ventricular wall, in order to define their lifespan and their capacity to migrate towards new-enhancing foci time after implantation.


Assuntos
Neoplasias Encefálicas/cirurgia , Glioblastoma/cirurgia , Transplante de Células-Tronco Mesenquimais/métodos , Animais , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Modelos Animais de Doenças , Glioblastoma/patologia , Sobrevivência de Enxerto , Injeções Intravenosas/métodos , Injeções Intraventriculares/métodos , Masculino , Gradação de Tumores , Transplante de Neoplasias , Ratos , Ratos Wistar
16.
Front Physiol ; 13: 920952, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35899021

RESUMO

Pharmaceuticals are now considered to be established contaminants, and their presence in water poses a real risk not only to the marine ecosystem, as they may adversely affect non-target organisms that are exposed to them, but also indirectly to humans. This is particularly true for the model organism considered in this work, Mytilus galloprovincialis (Lamarck, 1819), a suspensivore and bioaccumulating organism that enters the human food chain. Among the most commonly used over-the-counter medicines, anti-inflammatory drugs certainly feature prominently, with acetylsalicylic acid (ASA) at the top. In this work, M. galloprovincialis specimens were exposed to two concentrations of ASA (10 and 100 µg/L) for 10 and 20 days to evaluate possible alterations in the decrease in regulatory volume (RVD) in digestive gland cells and cell viability of both these cells and hemocytes. In addition, the histopathological condition index of the gills and digestive gland was evaluated. The data obtained showed that chronic exposure to ASA did not alter the cell viability of hemocytes and digestive gland cells but alters the physiological mechanisms of volume regulation in the digestive gland and, in addition, a time-dose reaction to ASA in the gills and digestive gland showing numerous alterations such as lipofuscin deposits and hemocyte infiltration was found. These results confirm the potential toxicity to the marine biota, highlighting the necessity to deepen the knowledge regarding the link between over-the-counter pharmaceuticals and non-target organisms.

17.
Nat Cell Biol ; 1(4): 193-9, 1999 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-10559916

RESUMO

Degradation of the mammalian cyclin-dependent kinase (CDK) inhibitor p27 is required for the cellular transition from quiescence to the proliferative state. The ubiquitination and subsequent degradation of p27 depend on its phosphorylation by cyclin-CDK complexes. However, the ubiquitin-protein ligase necessary for p27 ubiquitination has not been identified. Here we show that the F-box protein SKP2 specifically recognizes p27 in a phosphorylation-dependent manner that is characteristic of an F-box-protein-substrate interaction. Furthermore, both in vivo and in vitro, SKP2 is a rate-limiting component of the machinery that ubiquitinates and degrades phosphorylated p27. Thus, p27 degradation is subject to dual control by the accumulation of both SKP2 and cyclins following mitogenic stimulation.


Assuntos
Proteínas de Ciclo Celular/metabolismo , Quinases Ciclina-Dependentes/antagonistas & inibidores , Inibidores Enzimáticos/metabolismo , Proteínas Associadas aos Microtúbulos/metabolismo , Proteínas Supressoras de Tumor , Ubiquitinas/metabolismo , Sequência de Bases , Proteínas de Ciclo Celular/genética , Linhagem Celular , Inibidor de Quinase Dependente de Ciclina p27 , Células HeLa , Humanos , Técnicas In Vitro , Cinética , Oligodesoxirribonucleotídeos Antissenso/genética , Oligodesoxirribonucleotídeos Antissenso/farmacologia , Fosforilação , Ligação Proteica , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Proteínas Quinases Associadas a Fase S
18.
Nat Cell Biol ; 3(3): 321-4, 2001 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-11231585

RESUMO

The cyclin-dependent kinase (CDK) inhibitor p27 is degraded in late G1 phase by the ubiquitin pathway, allowing CDK activity to drive cells into S phase. Ubiquitinylation of p27 requires its phosphorylation at Thr 187 (refs 3, 4) and subsequent recognition by S-phase kinase associated protein 2 (Skp2; refs 5-8), a member of the F-box family of proteins that associates with Skp1, Cul-1 and ROC1/Rbx1 to form an SCF ubiquitin ligase complex. However, in vitro ligation of p27 to ubiquitin could not be reconstituted by known purified components of the SCFSkp2 complex. Here we show that the missing factor is CDK subunit 1 (Cks1), which belongs to the highly conserved Suc1/Cks family of proteins that bind to some CDKs and phosphorylated proteins and are essential for cell-cycle progression. Human Cks1, but not other members of the family, reconstitutes ubiquitin ligation of p27 in a completely purified system, binds to Skp2 and greatly increases binding of T187-phosphorylated p27 to Skp2. Our results represent the first evidence that an SCF complex requires an accessory protein for activity as well as for binding to its phosphorylated substrate.


Assuntos
Proteínas de Transporte/metabolismo , Proteínas de Ciclo Celular/metabolismo , Ligases/metabolismo , Proteínas Associadas aos Microtúbulos/metabolismo , Proteínas Quinases , Proteínas Supressoras de Tumor , Ubiquitinas/metabolismo , Quinases relacionadas a CDC2 e CDC28 , Proteínas de Transporte/isolamento & purificação , Ciclo Celular/fisiologia , Inibidor de Quinase Dependente de Ciclina p27 , Quinases Ciclina-Dependentes , Células HeLa , Humanos , Fosforilação , Ligação Proteica , Proteínas Recombinantes de Fusão/metabolismo , Ubiquitina-Proteína Ligases
19.
Nat Med ; 3(2): 231-4, 1997 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-9018245

RESUMO

The cell-cycle inhibitor p27 is a potential tumor suppressor, but its gene has never been found inactivated in human tumors. Because cell-cycle regulation of p27 cellular abundance occurs at the post-transcriptional level, we analyzed p27 protein expression and degradation in human colorectal carcinomas. Proteasome-mediated degradation activity of p27 was compared with its protein levels in a subset of tumor samples. We found that carcinomas with low or absent p27 protein displayed enhanced proteolytic activity specific for p27, suggesting that low p27 expression can result from increased proteasome-mediated degradation rather than altered gene expression. Patients whose tumors expressed p27 had a median survival of 151 months, whereas patients who lacked p27 (10%) had a median survival of 69 months. By multivariate analysis, p27 was found to be an independent prognostic marker. Lack of p27 was associated with poor prognosis (2.9 risk ratio for death; P = 0.003). The absence of p27 protein expression is thus a powerful negative prognostic marker in colorectal carcinomas, particularly in stage II tumors, and thereby may help in the selection of patients who will benefit from adjuvant therapy. These data suggest that aggressive tumors may result from the selection of a clone or clones that lack p27 due to increased proteasome-mediated degradation.


Assuntos
Adenocarcinoma/metabolismo , Proteínas de Ciclo Celular , Neoplasias Colorretais/metabolismo , Quinases Ciclina-Dependentes/antagonistas & inibidores , Cisteína Endopeptidases/metabolismo , Genes cdc , Proteínas Associadas aos Microtúbulos/metabolismo , Complexos Multienzimáticos/metabolismo , Proteínas Supressoras de Tumor , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Idoso , Biomarcadores Tumorais , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Inibidor de Quinase Dependente de Ciclina p27 , Feminino , Genes Supressores de Tumor , Humanos , Masculino , Proteínas Associadas aos Microtúbulos/genética , Estadiamento de Neoplasias , Prognóstico , Complexo de Endopeptidases do Proteassoma
20.
Eur Rev Med Pharmacol Sci ; 15(1): 25-34, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21381497

RESUMO

INTRODUCTION: Non-steroidal anti-inflammatory drugs (NSAIDs) consumption is strictly related to a high gastrointestinal and cardiovascular mortality and morbidity rate. Osteoarthritis Research Society International (OARSI) recommendations in patients with symptomatic hip or knee OA stated that NSAIDs should be used at the lowest effective dose but their long-term use should be avoided if possible. OARSI guidelines for the treatment of the hip OA include the use of viscosupplementation, which aims to restore physiological and rheological features of the synovial fluid. OBJECTIVE: Aim of this multicentric, open and retrospective study is to investigate if NSAID consumption may be reduced by the use of ultrasound-guided intra-articular injection of several hyaluronic acid (HA) products in hip joint administered in patients affected by symptomatic hip OA. MATERIALS AND METHODS: Patients affected by mono or bilateral symptomatic hip OA according to American Rheumatology Association (ARA) criteria, radiological OA graded II-IV (Kellgren and Lawrence) entered the study and were administered with ultrasound-guided intra-articular injection of hyaluronic acid products. As a primary endpoint, consumption of NSAIDs was evaluated by recording the number of days a month (range 0-30) the patient had used NSAID during the previous month, reported at each visit during the 24 months follow-up period. Secondary endpoints included further analysis for subgroups of patients categorized for Lequesne index score, Kellgren-Lawrence score, pain visual analogue scale (VAS) score, ultrasound pattern, age, hyaluronic acid used. RESULTS: 2343 patients entered the study. Regarding primary endpoint, the consumption of NSAIDs was reduced of 48.2% at the third month when compared with baseline values. This sparing effect increased at 12th and 24th month with a reduction respectively of 50% and 61% in comparison to baseline values. These differences were statistically significant. CONCLUSIONS: These data point out that intraarticular hyaluronan preparations provide OA pain relief and reduce NSAIDs consumption in a large cohort of patients for a long period of follow-up. Multiple courses of viscosupplementation (vs) are required to maintain low dose of NSAID consumption over time. NSAIDs consumption is strictly related to an high gastrointestinal and cardiovascular mortality and morbidity rate, instead HA intra-articular treatment is well tolerated and is associated with a low incidence of adverse effects. For these reasons further studies evaluating cost-effectiveness and cost-utility of VS in the management of hip OA are required.


Assuntos
Anti-Inflamatórios não Esteroides/administração & dosagem , Ácido Hialurônico/administração & dosagem , Osteoartrite do Quadril/tratamento farmacológico , Idoso , Seguimentos , Humanos , Injeções Intra-Articulares , Pessoa de Meia-Idade , Osteoartrite do Quadril/diagnóstico por imagem , Medição da Dor , Sistema de Registros , Estudos Retrospectivos , Ultrassom , Ultrassonografia
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