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1.
Phys Rev Lett ; 121(20): 204502, 2018 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-30500232

RESUMO

Bubbles reside at the water surface before bursting, emitting droplets that can contain chemicals and pathogens linked to disease and contamination. We discover that bacterial secretions enhance the lifetime of bubbles. We also reveal and elucidate two distinct regimes of thinning for such contaminated bubbles. Initially, marginal regeneration governs their thinning rate, similarly to clean water bubbles. However, due to their enhanced lifetime, it is eventually evaporation that governs their thinning, thus also dramatically decreasing their thickness at burst. We derive and experimentally validate the expression for the critical timescale at which the transition between the two regimes occurs. The shift in thinning law makes the droplets produced by contaminated bubbles smaller, faster, and more numerous than those produced by clean bubbles. Our findings suggest that microorganisms can manipulate the aging physics of surface bubbles to enhance their own water-to-air dispersal.


Assuntos
Ar , Bactérias/química , Tensoativos/química , Água/química
2.
Phys Rev Lett ; 120(20): 204503, 2018 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-29864348

RESUMO

Unsteady fragmentation of a fluid bulk into droplets is important for epidemiology as it governs the transport of pathogens from sneezes and coughs, or from contaminated crops in agriculture. It is also ubiquitous in industrial processes such as paint, coating, and combustion. Unsteady fragmentation is distinct from steady fragmentation on which most theoretical efforts have been focused thus far. We address this gap by studying a canonical unsteady fragmentation process: the breakup from a drop impact on a finite surface where the drop fluid is transferred to a free expanding sheet of time-varying properties and bounded by a rim of time-varying thickness. The continuous rim destabilization selects the final spray droplets, yet this process remains poorly understood. We combine theory with advanced image analysis to study the unsteady rim destabilization. We show that, at all times, the rim thickness is governed by a local instantaneous Bond number equal to unity, defined with the instantaneous, local, unsteady rim acceleration. This criterion is found to be robust and universal for a family of unsteady inviscid fluid sheet fragmentation phenomena, from impacts of drops on various surface geometries to impacts on films. We discuss under which viscous and viscoelastic conditions the criterion continues to govern the unsteady rim thickness.


Assuntos
Modelos Biológicos , Modelos Químicos , Fenômenos Biomecânicos
3.
Oncogene ; 35(4): 479-90, 2016 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-25893290

RESUMO

Waldenström macroglobulinemia (WM) is a proliferative disorder of IgM-secreting, lymphoplasmacytoid cells that inhabit the lymph nodes and bone marrow. The disease carries a high prevalence of activating mutations in MyD88 (91%) and CXCR4 (28%). Because signaling through these pathways leads to Bcl-xL induction, we examined Bcl-2 family expression in WM patients and cell lines. Unlike other B-lymphocyte-derived malignancies, which become dependent on expression of anti-apoptotic proteins to counter expression of pro-apoptotic proteins, WM samples expressed both pro- and anti-apoptotic Bcl-2 proteins at low levels similar to their normal B-cell and plasma cell counterparts. Three WM cell lines expressed pro-apoptotic Bcl-2 family members Bim or Bax and Bak at low levels, which determined their sensitivity to inducers of intrinsic apoptosis. In two cell lines, miR-155 upregulation, which is common in WM, was responsible for the inhibition of FOXO3a and Bim expression. Both antagonizing miR-155 to induce Bim and proteasome inhibition increased the sensitivity to ABT-737 in these lines indicating a lowering of the apoptotic threshold. In this manner, treatments that increase pro-apoptotic protein expression increase the efficacy of agents treated in combination in addition to direct killing.


Assuntos
Proteínas Reguladoras de Apoptose/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Macroglobulinemia de Waldenstrom/metabolismo , Macroglobulinemia de Waldenstrom/patologia , Apoptose/efeitos dos fármacos , Apoptose/fisiologia , Proteínas Reguladoras de Apoptose/genética , Proteína 11 Semelhante a Bcl-2 , Compostos de Bifenilo/farmacologia , Bortezomib/farmacologia , Linhagem Celular Tumoral/efeitos dos fármacos , Proteína Forkhead Box O3 , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Mieloma Múltiplo/genética , Mieloma Múltiplo/metabolismo , Mieloma Múltiplo/patologia , Nitrofenóis/farmacologia , Piperazinas/farmacologia , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/genética , Sulfonamidas/farmacologia , Macroglobulinemia de Waldenstrom/tratamento farmacológico , Macroglobulinemia de Waldenstrom/genética , Proteína Killer-Antagonista Homóloga a bcl-2/genética , Proteína Killer-Antagonista Homóloga a bcl-2/metabolismo , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismo
4.
Orthop Traumatol Surg Res ; 101(8 Suppl): S297-303, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26514849

RESUMO

BACKGROUND: The primary objective was to evaluate correlations linking anatomical to functional outcomes after endoscopically assisted repair of acute acromioclavicular joint dislocation (ACJD). HYPOTHESIS: Combined acromioclavicular and coracoclavicular stabilisation improves radiological outcomes compared to coracoclavicular stabilisation alone. MATERIAL AND METHODS: A prospective multicentre study was performed. Clinical outcome measures were pain intensity on a visual analogue scale (VAS), subjective functional impairment (QuickDASH score), and Constant's score. Anatomical outcomes were assessed on standard radiographs (anteroposterior view of the acromioclavicular girdle and bilateral axillary views) obtained preoperatively and postoperatively and on postoperative dynamic radiographs taken as described by Tauber et al. RESULTS: Of 116 patients with acute ACJD included in the study, 48% had type III, 30% type IV, and 22% type V ACJD according to the Rockwood classification. Coracoclavicular stabilisation was achieved using a double endobutton in 93% of patients, and concomitant acromioclavicular stabilisation was performed in 50% of patients. The objective functional outcome was good, with an unweighted Constant's score ≥ 85/100 and a subjective QuickDASH functional disability score ≤ 10 in 75% of patients. The radiographic analysis showed significant improvements from the preoperative to the 1-year postoperative values in the vertical plane (decrease in the coracoclavicular ratio from 214 to 128%, p=10(-6)) and in the horizontal plane (decrease in posterior displacement from 4 to 0mm, p=5×10(-5)). The anatomical outcome correlated significantly with the functional outcome (absolute R value=0.19 and p=0.045). We found no statistically significant differences across the various types of constructs used. Intra-operative control of the acromioclavicular joint did not improve the result. Implantation of a biological graft significantly improved both the anatomical outcome in the vertical plane (p=0.04) and acromioclavicular stabilisation in the horizontal plane (p=0.02). The coracoclavicular ratio on the anteroposterior radiograph was adversely affected by a longer time from injury to surgery (p=0.02) and by a higher body mass index (BMI) (p=0.006). High BMI also had a negative effect on the difference in the distance separating the anterior edge of the acromion from the anterior edge of the clavicle between the injured and uninjured sides, as assessed on the axillary views (p=0.009). CONCLUSION: This study demonstrates that acute ACJD requires stabilisation in both planes, i.e., at the coracoclavicular junction and at the acromioclavicular joint. Coracoclavicular stabilisation alone is not sufficient, regardless of the type of implant used. Implantation of a biological graft should be considered when the time from injury to surgery is longer than 10days. The weight of the upper limb should be taken into account, with 6weeks of immobilisation to unload the construct in patients who have high BMI values. LEVEL OF EVIDENCE: II, prospective non-randomised comparative study.


Assuntos
Articulação Acromioclavicular/lesões , Luxações Articulares/diagnóstico por imagem , Luxações Articulares/cirurgia , Articulação Acromioclavicular/diagnóstico por imagem , Articulação Acromioclavicular/fisiopatologia , Articulação Acromioclavicular/cirurgia , Acrômio/diagnóstico por imagem , Acrômio/cirurgia , Doença Aguda , Adulto , Idoso , Artroscopia/efeitos adversos , Artroscopia/métodos , Índice de Massa Corporal , Clavícula/diagnóstico por imagem , Clavícula/cirurgia , Feminino , Humanos , Fixadores Internos , Luxações Articulares/classificação , Masculino , Pessoa de Meia-Idade , Dor Pós-Operatória/etiologia , Período Pós-Operatório , Período Pré-Operatório , Estudos Prospectivos , Radiografia , Tempo para o Tratamento , Adulto Jovem
5.
Orthop Traumatol Surg Res ; 101(8 Suppl): S305-11, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26470802

RESUMO

INTRODUCTION: Treatment of chronic acromioclavicular joint dislocation (ACJD) remains a poorly known and controversial subject. Given the many surgical options, it is not always easy to determine which steps are indispensable. METHODS: This article reports a multicenter prospective study. The clinical and radiological follow-up involved a comparative analysis of the preoperative and postoperative data at 1 year, including pain (visual analogue scale), subjective functional incapacity (QuickDASH), and the objective Constant score, as well as a comparative analysis of vertical and horizontal movements measured on simple x-rays. RESULTS: Based on a series of 140 operated ACJDs, we included 24 chronic ACJDs. The mean time to surgery was 46 weeks (range, 1 month to 4 years). The patients' mean age was 41 years, with a majority of males (75%), 72% of whom participated in recreational sports. Professionally, 40% of the subjects had jobs involving manual labor. We noted 40% grade III, 24% grade IV, and 36% grade V injury according to the Rockwood classification. In 92% of cases, coracoclavicular stabilization was provided by a double button implant, reinforced with a biological graft in 88% of the cases. In 29%, millimeters to centimeters of the distal clavicle were resected and acromioclavicular stabilization was associated in 54%. We observed complications in 33% of the cases. At 1 year postoperative, 21 patients underwent clinical and radiological follow-up (87.5%). Only 35% of the patients were satisfied or very satisfied, whereas 100% of them would recommend the operation. Full-time work was resumed in 91% of the cases and all sports could be resumed in 86%. The pre- and postoperative values at 1 year changed as follows: the mean Constant score improved from 61 to 87 (p=0.00002); the subjective QuickDASH score decreased from 41 to 9 (p=0.00002); and radiologically significant reduction of the initial displacement was observed in the vertical plane (p<10(-3)) and the horizontal plane (p=0.022). CONCLUSION: In this study, the favorable prognostic factors found were: time to surgery less than 3 months (p=0.02), associated acromioclavicular stabilization, and postoperative immobilization with a sling extended to 6 weeks. However, resection of the distal clavicle did not influence the final result. LEVEL OF PROOF: Level II prospective non-randomized comparative study.


Assuntos
Articulação Acromioclavicular/lesões , Luxações Articulares/cirurgia , Articulação Acromioclavicular/diagnóstico por imagem , Articulação Acromioclavicular/cirurgia , Adulto , Doença Crônica , Clavícula/cirurgia , Feminino , Humanos , Fixadores Internos , Luxações Articulares/diagnóstico por imagem , Luxações Articulares/fisiopatologia , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente , Período Pós-Operatório , Período Pré-Operatório , Estudos Prospectivos , Radiografia , Volta ao Esporte , Retorno ao Trabalho , Dor de Ombro/etiologia , Tempo para o Tratamento , Adulto Jovem
6.
J Sports Med Phys Fitness ; 51(2): 255-9, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21681160

RESUMO

AIM: The aim of this study was to assess the functional outcome of patients who had undergone elbow arthroscopy, evaluating the correlation between three elbow scoring systems and the patients' subjective perception of satisfaction METHODS: Fourteen patients who had undergone elbow arthroscopy were retrospective reviewed to evaluate the correlation between three elbow scoring systems and the patients' subjective perception of satisfaction at a mean follow-up time of 24 months (range 12-64 months). Two independent orthopedic surgeons evaluated all patients using three elbow scoring systems, a simple satisfaction question and a visual analogue scale. RESULTS: The three scoring systems showed significant correlation with each other (P<0.05). There was no correlation between the results of the three scoring systems and patients' satisfaction: patients with the same level of satisfaction could perform differently at the scoring systems. CONCLUSION: Although the three scoring systems used to evaluate the patients showed significant correlation with each other, they failed to correlate to patients' satisfaction. In reporting the results of arthroscopic elbow procedures, emphasis should be placed on individual variables, rather than on global elbow ratings. Further studies are needed to develop a single outcome evaluation system which is reliable, valid and sensitive to changes of clinical importance, which takes into account both patients' and physicians perspective, and which is short and practical to use.


Assuntos
Articulação do Cotovelo/cirurgia , Medição da Dor , Satisfação do Paciente , Adolescente , Adulto , Idoso , Artroscopia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
7.
Rev Med Interne ; 31(5): 385-94, 2010 May.
Artigo em Francês | MEDLINE | ID: mdl-20363537

RESUMO

Waldenström's macroglobulinemia (WM) is a B-cell disorder characterized primarily by bone marrow infiltration with lymphoplasmacytic cells, along with the presence of an IgM monoclonal gammopathy in the blood. WM remains incurable with a median of 8-year of overall survival for patients with symptomatic WM. Treatment is postponed for asymptomatic patients and progressive anemia is the most common indication for initiation of treatment. The main therapeutic options include alkylating agents, nucleoside analogues, and rituximab, either alone or in combination. Studies involving new combination chemotherapy are ongoing and preliminary results are encouraging. However, there are several limitations to these approaches. The complete response rate is low and the treatment free survival is short in many patients, no specific agent or regimen has been shown to be superior to another, and no treatment has been specifically approved for WM. As such, new therapeutic agents are needed for the treatment of WM. In ongoing efforts, we and others have sought to exploit advances made in the understanding of the biology of WM so as to better target therapeutics for this malignancy. These efforts have led to the development of proteasome inhibitors as bortezomib, several Akt/mTor inhibitors, such as perifosine and Rad001. Many other agents and monoclonal antibodies are currently being tested in clinical trials and seem promising. This article provides an update of the current preclinical studies and clinical efforts for the development of novel agents in the treatment of WM.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Macroglobulinemia de Waldenstrom/diagnóstico , Macroglobulinemia de Waldenstrom/tratamento farmacológico , Idoso , Anemia/etiologia , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais Murinos , Antineoplásicos Alquilantes/administração & dosagem , Ácidos Borônicos/administração & dosagem , Bortezomib , Diagnóstico Diferencial , Humanos , Masculino , Nucleosídeos/administração & dosagem , Fosforilcolina/administração & dosagem , Fosforilcolina/análogos & derivados , Prognóstico , Inibidores de Proteases/administração & dosagem , Pirazinas/administração & dosagem , Rituximab , Macroglobulinemia de Waldenstrom/complicações
8.
Water Sci Technol ; 59(4): 673-85, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19237761

RESUMO

Reverse Osmosis is the most widely used method for treating municipal solid waste landfill leachates, since it produces a permeate in compliance with reject requirements. However, the efficiency of this process at the industrial scale is limited mainly because of membrane fouling and the high osmotic pressures involved. Although lime precipitation is traditionally used to eliminate the temporary hardness of water by decarbonation, it has also been shown to be highly efficient in removing humic substances which are known to have strong fouling potential towards membranes. Our objective is to study the lime/leachate physico-chemistry, in order to determine the potential of the lime precipitation as pre-treatment for reverse osmosis. The results show that the lime treatment makes it possible (i) to act efficiently on the inorganic fraction of leachates through a decarbonation mechanism which entails massive precipitation of the carbonates under the form of CaCO(3), (ii) to eliminate by co-precipitation the high Molecular Weight (MW) organic macromolecules (>50,000 g.mol(-1)) such as humic acids, and (iii) to generate a stable residue that can be easily stored at a landfill. The reverse osmosis step will be facilitated through significant reduction of the osmotic pressures and prevention of membrane fouling.


Assuntos
Compostos de Cálcio/química , Óxidos/química , Eliminação de Resíduos Líquidos/métodos , Carbonato de Cálcio/química , Cristalização , Concentração de Íons de Hidrogênio , Microscopia Eletrônica de Varredura , Esgotos
9.
J Hazard Mater ; 150(3): 468-93, 2008 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-17997033

RESUMO

In most countries, sanitary landfilling is nowadays the most common way to eliminate municipal solid wastes (MSW). In spite of many advantages, generation of heavily polluted leachates, presenting significant variations in both volumetric flow and chemical composition, constitutes a major drawback. Year after year, the recognition of landfill leachate impact on environment has forced authorities to fix more and more stringent requirements for pollution control. This paper is a review of landfill leachate treatments. After the state of art, a discussion put in light an opportunity and some results of the treatment process performances are given. Advantages and drawbacks of the various treatments are discussed under the items: (a) leachate transfer, (b) biodegradation, (c) chemical and physical methods and (d) membrane processes. Several tables permit to review and summarize each treatment efficiency depending on operating conditions. Finally, considering the hardening of the standards of rejection, conventional landfill leachate treatment plants appear under-dimensioned or do not allow to reach the specifications required by the legislator. So that, new technologies or conventional ones improvements have been developed and tried to be financially attractive. Today, the use of membrane technologies, more especially reverse osmosis (RO), either as a main step in a landfill leachate treatment chain or as single post-treatment step has shown to be an indispensable means of achieving purification.


Assuntos
Eliminação de Resíduos , Eliminação de Resíduos Líquidos/métodos , Poluentes Químicos da Água
11.
Rev Chir Orthop Reparatrice Appar Mot ; 91(5): 423-31, 2005 Sep.
Artigo em Francês | MEDLINE | ID: mdl-16350999

RESUMO

PURPOSE OF THE STUDY: We conducted a prospective multicentric study of 203 consecutive patients who underwent hemi-arthroplasty for femoral neck fracture between May 1999 and August 2001. The purpose of the study was to assess quality-of-life among these patients one year after their surgery. MATERIAL AND METHODS: Mean patient age was 79.6 +/- 8.6 years; 71.2% were women. Most fractures were Garden type III and IV (87.4%) and 90.9% were recent (< 21 d). The hemiarthroplasty was performed with the Intermedia implant via a posterolateral approach in 73.9% of patients with acetabular reaming for 13.7%; a skirted head was used in only 20.8%. The Robinson score (19/26 < or = 6.89) for joint motion, lifestyle, degree of osteoporosis (Singh score), and history (ASA score), as well as a psychomotor indicator (Hodkinson score) were noted preoperatively. Quality-of-life was measured at one year in the same patients using the Postel Merle d'Aubigne (PMA) score and a quality-of-life score. RESULTS: Among the 203 patients, 38 (18.7%) were lost to follow-up and 37 died (18.2%). Eleven posterior dislocations (5.4%) were noted and four were reduced orthopedically. The PMA score was 84.7% satisfactory results (excellent, very good, good). Preoperatively 58.8% of the patients were independent and 7% were in nursing homes; one year postoperatively, these proportions were 54% and 4.8%. There was a significant difference in the PMA score between two populations defined by the preoperative Robinson score less than or greater than 20. Outcome was better for patients with a Robinson score > 20 pre-operatively. For these two populations, change in lifestyle was highly significant one year postoperatively. However, for the overall population, changes in lifestyle and joint motion were not significantly different between the pre- and postoperative evaluations. Paradoxically, 29.1% of the patients who were dependent preoperatively were not one year after surgery, which indicates that certain patients also had a better quality-of-life after their hemiarthroplasty. CONCLUSION: Mortality after fracture of the femoral neck remains high (18.2% at one year). There were no infections requiring revision in this series, but there were eleven cases of dislocation (5.4%). The difference in joint motion and quality-of-life between the pre- and postoperative assessment was not significant for the whole population, but one third of the patients who were independent preoperatively were not at last follow-up.


Assuntos
Fraturas do Colo Femoral/cirurgia , Prótese de Quadril , Qualidade de Vida , Idoso , Idoso de 80 Anos ou mais , Feminino , Prótese de Quadril/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Estudos Prospectivos , Desenho de Prótese
12.
J Chromatogr A ; 976(1-2): 123-34, 2002 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-12462603

RESUMO

Liquid chromatography coupled to tandem mass spectrometry has been used for the detection and the structural characterization of T-rich model oligonucleotides covalently modified by estradiol-2,3-quinone. After separation by gradient elution, adducts were analyzed by negative electrospray mass spectrometry, enabling to evidence and localize the modifications in the oligonucleotide sequence. Modifications by one molecule of estrogen were evidenced on purines (A, G) whereas no reaction was observed on pyrimidic bases (T). Isomeric adducts were differentiated using tandem mass spectrometry, and energy resolved mass spectrometry allowed to underline differences in the behavior of the adducts towards collisional excitation into an ion trap device.


Assuntos
Cromatografia Líquida/métodos , Estradiol/análogos & derivados , Estradiol/química , Oligonucleotídeos/química , Espectrometria de Massas por Ionização por Electrospray/métodos , Sequência de Bases
13.
Clin Nephrol ; 56(2): 162-8, 2001 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-11522094

RESUMO

Chronic hypotension, infrequent though possible in chronic renal failure patients on hemodialysis, has harmful consequences on their physical state and hence general well-being. These patients often experience acute intradialytic manifestations while non-pharmacologic interventions as pharmacologic agents are sometimes insufficient to improve symptoms. Well tolerated, midodrine appears to be a suitable and effective agent as it raises blood pressure significantly via its effect on peripheral alpha-adrenergic receptors. The authors describe their use of midodrine in a dialysis patient for the longest period of time reported up to now, documented by a pharmacokinetic study, confirming long-term both clinical efficacy and safety of the drug.


Assuntos
Hipotensão/tratamento farmacológico , Midodrina/uso terapêutico , Diálise Renal/efeitos adversos , Vasoconstritores/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Relação Dose-Resposta a Droga , Humanos , Hipotensão/etiologia , Falência Renal Crônica/terapia , Masculino , Pessoa de Meia-Idade , Midodrina/farmacocinética , Vasoconstritores/farmacocinética
14.
Br J Haematol ; 110(3): 591-8, 2000 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-10997969

RESUMO

In the myelodysplastic syndromes (MDS), P-glycoprotein (P-gp) expression is clinically associated with drug resistance, whereas the clinical significance of multidrug resistance-associated protein (MRP1) is uncertain. Bone marrow from 56 patients with MDS, including six with refractory anaemia (RA)/RA with ringed sideroblasts (RARS), 23 cases of RA with excess blasts/in transformation (RAEB/T), four patients with chronic myelomonocytic leukaemia (CMML) and 23 cases of MDS having progressed to acute myeloid leukaemia (MDS-AML), were studied. MRP1 expression was investigated by immunocytochemistry (ICC) and by flow cytometry using MRPm6 monoclonal antibody. The efflux test using calcein-AM (CAM) +/- probenecid to evaluate MRP1 activity was performed in ten of the 56 patients. Twenty-eight of the 56 cases (50%) expressed MRP1. MRP1 expression was more frequent in MDS-AML than in MDS (70% vs. 36%). The efflux test using CAM was positive in three out of the ten patients tested. The results were in agreement with expression of MRP1 in six cases, and were discordant in four cases (1 MRP-/CAM+, 3 MRP+/CAM-). No correlation was observed between MRP1 expression and P-gp, lung resistance-associated protein (LRP) or CD34 expression, although there was a trend for more frequent MRP1 expression in P-gp-positive cases in MDS-AML (P = 0.08). Ten of the 26 patients treated with intensive chemotherapy achieved complete remission including six out of 16 MRP1+ and four out of ten MRP1- cases (P = NS). In conclusion, MRP1 expression was correlated with disease stage in MDS in our study. As for P-gp, discordant expression/function of MRP1 could be found in some cases, suggesting the existence of non-functional transport proteins in MDS. MRP1 expression did not seem to be a prognostic factor in MDS in our experience.


Assuntos
Transportadores de Cassetes de Ligação de ATP/análise , Síndromes Mielodisplásicas/metabolismo , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/análise , Adulto , Animais , Antígenos CD34/análise , Linhagem Celular , Distribuição de Qui-Quadrado , Aberrações Cromossômicas/metabolismo , Transtornos Cromossômicos , Citometria de Fluxo , Humanos , Imuno-Histoquímica/métodos , Leucemia Mieloide/tratamento farmacológico , Leucemia Mieloide/metabolismo , Pessoa de Meia-Idade , Proteínas Associadas à Resistência a Múltiplos Medicamentos , Síndromes Mielodisplásicas/tratamento farmacológico , Proteínas de Neoplasias/análise , Resultado do Tratamento , Partículas de Ribonucleoproteínas em Forma de Abóbada
15.
Nephrologie ; 21(4): 179-83, 2000.
Artigo em Francês | MEDLINE | ID: mdl-10976433

RESUMO

Chronic hypotension, although unfrequent in uremic patients on hemodialysis, accentuates the deterioration of patients physical state and thus, their general well-being. These patients often experience acute intradialytic symptoms and respond very poorly to conventional therapies. Well tolerated, midodrine is a suitable and effective choice as it raises blood pressure significantly through its effect on peripheral alpha-adrenergic receptors. The authors report observing the use of midodrine by a dialysis patient during the longest time period published to date, documented by a pharmacokinetic study, and that confirms the excellent results and proves long term tolerance for that drug.


Assuntos
Agonistas alfa-Adrenérgicos/uso terapêutico , Hipotensão/tratamento farmacológico , Midodrina/uso terapêutico , Diálise Renal , Agonistas alfa-Adrenérgicos/farmacocinética , Doença Crônica , Insuficiência Cardíaca/complicações , Humanos , Hipertrofia Ventricular Esquerda/complicações , Hipotensão/etiologia , Falência Renal Crônica/complicações , Falência Renal Crônica/terapia , Masculino , Pessoa de Meia-Idade , Midodrina/farmacocinética
16.
Phytochemistry ; 52(4): 567-73, 1999 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-10570826

RESUMO

In a non aerated incubation medium, the oxidation of the tested thiaoleic acids by C. vulgaris was regioselective. Moreover the non oxidised 14-thiaoleic acid had no influence on the endogenous fatty acid pattern whereas the 13-thiaoleic acid, readily oxidised by the microalgae, caused a significant 18:1 accumulation in phospholipids. Examination of the 13-thiaoleic acid metabolism revealed that up to 15% of the substrate was specifically oxidised in the phospholipids before being transferred into the neutral lipids class of C. vulgaris. Confirmation of the monooxygenase-like delta 12-desaturase intervention in this biotransformation was obtained by the stereochemical analysis of the optically active sulfoxide isolated from the endoplasmic phospholipids.


Assuntos
Chlorella/enzimologia , Ácidos Oleicos/metabolismo , Estearoil-CoA Dessaturase/metabolismo , Acil Coenzima A/metabolismo , Biotransformação , Células Cultivadas , Chlorella/metabolismo , Metabolismo dos Lipídeos , Oxirredução , Fosfolipídeos/metabolismo , Estereoisomerismo , Especificidade por Substrato , Sulfóxidos/metabolismo
17.
Ann Biol Clin (Paris) ; 57(5): 595-600, 1999.
Artigo em Francês | MEDLINE | ID: mdl-10518062

RESUMO

UNLABELLED: P glycoprotein (Pgp) expression is associated with failure of anticancer chemotherapy in acute myeloid leukemia (AML). However, a consensus has been difficult to reach, due to the variable results obtained by different methods. Samples of 27 patients with AML were studied here according to international recommendations (Beck, et al. , Cancer Research 1996; 56: 3010-20). Pgp expression was performed by immunocytochemistry (ICC) using the avidin-biotin peroxidase technique with JSB1 and UIC2 monoclonal antibodies. Flow cytometry (FCM) analysis of Pgp was investigated using UIC2 in an indirect immunofluorescent assay. UIC2 staining was measured by the Kolmogorov-Smirnov statistical test and fluorescence intensity ratio. Finally, the rhodamine 123 test (Rh 123) with or without verapamil was performed to detect functional activity. RESULTS: by ICC, results of JSB1 and UIC2 were consistent in 94% of the cases. In 74% of the cases, concordant conclusions were observed by ICC and FCM. Overall, Pgp expression was detected in 67% of the cases (ICC/JSB1+ and ICC/UIC2+ or FCM/UIC2+). Functional activity of Pgp was shown in 59% of the patients. Rh 123 efflux was correlated with Pgp expression in 70% of the 27 studied cases but 3 cases were Pgp-/Rh 123+ and 5 Pgp+/Rh 123-. In conclusion, assessment of Pgp expression by ICC and FCM using two different monoclonal antibodies coupled with functional efflux test is required to identify discordant expression/function cases suggesting a non functional Pgp or another alteration of drug transport.


Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Leucemia Mieloide/tratamento farmacológico , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/análise , Doença Aguda , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais , Bloqueadores dos Canais de Cálcio , Criança , Pré-Escolar , Citometria de Fluxo , Fluoresceína-5-Isotiocianato , Técnica Indireta de Fluorescência para Anticorpo , Corantes Fluorescentes , Regulação Neoplásica da Expressão Gênica , Humanos , Técnicas Imunoenzimáticas , Imuno-Histoquímica , Pessoa de Meia-Idade , Rodamina 123 , Estatísticas não Paramétricas , Falha de Tratamento , Verapamil
18.
Adv Exp Med Biol ; 457: 57-63, 1999.
Artigo em Inglês | MEDLINE | ID: mdl-10500780

RESUMO

Drug resistance often results in failure of anticancer chemotherapy in leukemias. A large number of studies have been published on the effect of P-glycoprotein (Pgp) expression on prognosis in AML. However, a consensus has been difficult to reach, due to the variable results obtained by different laboratories. Pgp expression was investigated here in bone marrow samples from 34 patients with AML including 19 newly diagnosed cases and 15 relapsing patients. Pgp expression was performed by immunocytochemistry (ICC) using the aviding-biotin-peroxydase technique with JSB1 and UIC2 MoAbs. Flow cytometry (FCM) analysis of Pgp expression was performed using UCI2 MoAbs in an indirect immunofluorescent assay without cell permeabilization. Rhodamine 123 (Rh 123) uptake was measured in the presence or absence of verapamil. Result was discordant in only 1/20 samples studied with both JSB1 and UIC2 by ICC. Results of Pgp expression were consistent on FCM and ICC in 23 of the 28 (82%) samples tested. Overall, Pgp expression was observed by ICC or FCM in 23 (67%) patients, including 11 (58%) newly diagnosed patients and 12 (80%) patients in relapse. Functional Rh123 efflux (Rh123+) was observed in 20 cases (59%): 10 de novo AML (53%) vs 10 AML in relapse (67%). The functional efflux was correlated with Pgp expression in 25 of the 34 cases analyzed (p = 0.013). 3 (9%) and 6 (18%) samples were Pgp-/Rh123+ and Pgp+/Rh123- respectively. Nine of the 14 pts (64%) treated with intensive anthracyclin-Ara C chemotherapy achieved complete remission, including 5/5 (100%) Pgp- cases vs 4/9 (44%) Pgp+ cases (p = 0.04) and 4/6 (67%) Rh 123- vs 4/7 (57%) Rh123+ cases (p = 0.5). In conclusion, assessment of Pgp expression by ICC and FMC using 2 different MoAbs coupled with functional efflux analysis confirms that Pgp expression is correlated with disease stage and response to treatment in AML. Discordant Pgp/Rh123 cases suggest a non functional Pgp or another alteration of drug transport.


Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/análise , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patologia , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Adolescente , Adulto , Idoso , Anticorpos Monoclonais , Antígenos CD34/análise , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biópsia por Agulha , Células da Medula Óssea/patologia , Criança , Pré-Escolar , Citometria de Fluxo/métodos , Humanos , Imuno-Histoquímica/métodos , Leucemia Mieloide Aguda/tratamento farmacológico , Pessoa de Meia-Idade , Recidiva
19.
Cancer Genet Cytogenet ; 108(2): 158-61, 1999 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-9973946

RESUMO

We report on a 67-year-old woman with acute lymphoblastic leukemia (ALL) who was supposed to have a variant Philadelphia (Ph) translocation identified by conventional cytogenetic techniques. Fluorescence in situ hybridization (FISH) analysis demonstrated the presence of an amplification of BCR-ABL rearrangement at locus 22q11. This is the first observation, to our knowledge, of a duplicated BCR-ABL chimeric gene within the derived chromosome 22 in ALL. Our observation supports the possibility of detecting a variant Ph chromosome at the single-cell level by FISH analysis.


Assuntos
Proteínas de Fusão bcr-abl/genética , Rearranjo Gênico , Cromossomo Filadélfia , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Feminino , Humanos , Hibridização in Situ Fluorescente , Cariotipagem , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico
20.
Leuk Lymphoma ; 29(5-6): 547-51, 1998 May.
Artigo em Inglês | MEDLINE | ID: mdl-9643568

RESUMO

The major vault lung resistance protein LRP is a cytoplasmic protein involved in drug resistance, especially in acute myeloid leukemia. We looked for LRP overexpression, using immunocytochemistry with LRP 56 monoclonal antibody, on marrow slides from 41 cases of myelodysplastic syndromes (MDS). LRP overexpression (LRP+) was defined by expression of LRP 56 in at least 20% of marrow blasts. LRP overexpression was seen in 19 (46%) cases. Concordant results between LRP overexpression and P-glycoprotein (PGP) expression were seen in 66% of the cases (p = 0.03), and discordant results (LRP+ and PGP-, or LRP- and PGP+) in 33% of the cases. No correlation was seen between LRP overexpression and FAB type, karyotype, CD34, p53 expression and bcl2 overexpression in blasts. Furthermore, in the 18 cases treated with anthracycline-AraC intensive chemotherapy and the 7 cases treated with low dose AraC, the response rate was not significantly different in LRP+ and LRP- patients. Survival was also similar in LRP+ and LRP- patients. In conclusion, LRP overexpression is probably more frequent in MDS than in de novo AML and, as in AML, is only partially correlated with PGP expression. In our experience, however, LRP was not a prognostic factor for response to chemotherapy and survival in MDS.


Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/biossíntese , Resistência a Múltiplos Medicamentos/genética , Resistencia a Medicamentos Antineoplásicos/genética , Células-Tronco Hematopoéticas/metabolismo , Síndromes Mielodisplásicas/metabolismo , Proteínas de Neoplasias/biossíntese , Partículas de Ribonucleoproteínas em Forma de Abóbada , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Doença Aguda , Antibióticos Antineoplásicos/administração & dosagem , Antibióticos Antineoplásicos/farmacologia , Antígenos CD34/análise , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Citarabina/administração & dosagem , Citarabina/farmacologia , Danazol/administração & dosagem , Progressão da Doença , Regulação da Expressão Gênica , Células-Tronco Hematopoéticas/patologia , Humanos , Cariotipagem , Leucemia Mieloide/genética , Leucemia Mieloide/metabolismo , Leucemia Mielomonocítica Crônica/genética , Leucemia Mielomonocítica Crônica/metabolismo , Leucemia Mielomonocítica Crônica/patologia , Tábuas de Vida , Síndromes Mielodisplásicas/tratamento farmacológico , Síndromes Mielodisplásicas/genética , Síndromes Mielodisplásicas/patologia , Proteínas de Neoplasias/genética , Proteínas Proto-Oncogênicas c-bcl-2/análise , Quinina/farmacologia , Análise de Sobrevida , Resultado do Tratamento , Proteína Supressora de Tumor p53/análise
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