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1.
J Viral Hepat ; 25(2): 180-186, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-28783247

RESUMO

The aim of the study was to evaluate whether bacterial translocation (BT) predicts the clinical outcome in HIV/HCV-coinfected patients with compensated cirrhosis. A cohort of 282 HIV/HCV-coinfected patients with cirrhosis and no previous liver decompensation (LD) was recruited. Serum levels of the DNA sequences encoding the well-conserved 16S rRNA subunit (16S rDNA), the lipopolysaccharide (LPS) and soluble CD14 (sCD14) at diagnosis of cirrhosis were measured. Primary endpoint was the emergence of the first LD and/or death of any cause. Secondary endpoints were LD, liver-related death (LRD) and death of any cause. After a median (Q1-Q3) follow-up of 51 (27-72) months, 67 patients (24%; 95% CI: 19-29) developed their first LD or died during follow-up. Baseline levels of 16S rDNA, LPS and sCD14 were not associated with the probability of developing the primary endpoint of the study. The mean (SD) survival time free of LD and/or death according to levels of 16S rDNA (<83, 83-196, 197-355, >355 [copies/µL]) was 78 (5), 72 (5), 81 (4) and 82 (4) months, respectively (P = .5). The corresponding figures for LPS (<0.1, 0.1-0.6, 0.6-1.5, > 1.5 [IU/mL]) were 76 (5), 71 (5), 77 (5) and 81 (4) months, respectively (P = .4). Baseline levels of BT serum markers were not associated with any of the secondary endpoints analysed in the study. Thus, BT does not seem to be a relevant predictor of clinical outcome in HIV/HCV-coinfected patients with compensated cirrhosis.


Assuntos
Translocação Bacteriana , Biomarcadores/sangue , Coinfecção/virologia , Infecções por HIV/complicações , Hepatite C/microbiologia , Cirrose Hepática/virologia , Adulto , Infecções Bacterianas/sangue , Coinfecção/microbiologia , Feminino , Hepacivirus , Hepatite C/complicações , Hepatite C/mortalidade , Humanos , Receptores de Lipopolissacarídeos/sangue , Lipopolissacarídeos/sangue , Cirrose Hepática/mortalidade , Masculino , Pessoa de Meia-Idade , Peritonite/microbiologia , Estudos Prospectivos , RNA Ribossômico 16S/sangue , Estudos Retrospectivos
2.
Ann Hematol ; 96(10): 1699-1705, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28770277

RESUMO

Chromosome 1q gains and 13q deletions are common cytogenetic aberrations in multiple myeloma (MM) that confer a poor prognosis. There are several techniques for the targeted study of these alterations, but interphase fluorescence in situ hybridization (FISH) is the current gold standard. The aim of the present study was to validate quantitative PCR (qPCR) as an alternative to FISH studies in CD138+-enriched plasma cells (PCs) from MM patients at diagnosis. We analyzed 1q gains and 13q deletions by qPCR in 57 and 60 MM patients, respectively. qPCR applicability was 84 and 88% for 1q and 13q, respectively. The qPCR and FISH methods had a sensitivity and specificity of 88 and 71% for 1q gains, and 79 and 100% for 13q deletions. A second qPCR assay for each region was carried out to confirm the previous results. Paired qPCR (two assays) and FISH results were available from 53 MM patients: 26 for 1q amplification and 27 for 13q deletion. qPCR assays gave concordant results (qPCR-consistent) in 20 of the 26 (77%) 1q gains and 25 of the 27 (93%) 13q deletions. Considering only the consistent data, the overall concordance among qPCR and FISH was 85 and 100% for 1q gains and 13q deletions, respectively. Our results show a substantial agreement between qPCR and the gold standard FISH technique, indicating the potential of qPCR as an alternative approach, particularly when the starting material is too scarce or cells are too damaged to obtain accurate results from FISH studies.


Assuntos
Deleção Cromossômica , Cromossomos Humanos Par 13/genética , Cromossomos Humanos Par 1/genética , Mieloma Múltiplo/genética , Reação em Cadeia da Polimerase em Tempo Real , Feminino , Humanos , Hibridização in Situ Fluorescente , Masculino , Mieloma Múltiplo/patologia
3.
Eur J Clin Microbiol Infect Dis ; 34(2): 385-93, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25236396

RESUMO

Interleukin-7 (IL-7) is a critical factor in maintaining or inducing effective antiviral CD4+ and CD8+ T-cell responses. The aim of this study was to examine the association of interleukin-7 receptor-α (IL7RA) polymorphisms with a sustained virologic response (SVR) after hepatitis C virus (HCV) therapy with pegylated interferon-alpha plus ribavirin (pegIFNα/ribavirin) in 177 human immunodeficiency virus (HIV)/HCV-coinfected patients. We performed a retrospective study in 177 naïve patients who started HCV treatment. The IL7RA rs6897932, rs987106, and rs3194051 polymorphisms were genotyped by the GoldenGate® assay. An SVR was defined as undetectable HCV viral load through 24 weeks after the end of HCV treatment. The highest SVR rate was found in patients with the rs6897932 CC (p = 0.029) and rs3194051 GG (p = 0.002) genotypes, and HCV genotypes 2/3 (GT2/3) infected patients with the rs987106 AA genotype (p = 0.048). Additionally, carriers of the rs3194051 GG genotype had a higher likelihood of achieving an SVR [adjusted odds ratio (aOR) = 5.32; 95 % confidence interval (CI) = 1.07-26.94; p = 0.040] than patients with the rs3194051 AA/AG genotype, while rs6897932 CC (aOR = 0.63; p = 0.205) and rs987106 AA (aOR = 0.60; p = 0.213) were not significant. Moreover, three major haplotypes were found: 46.6 % for CTA, 32.4 % for CAG, and 20.7 % for TAA haplotypes. Patients infected with GT2/3 and carriers of the CTA haplotype had lower odds of achieving an SVR (aOR = 0.08; p = 0.004) and the CAG haplotype (favorable alleles) had higher odds of achieving an SVR than other haplotypes (aOR = 21.96; p < 0.001). IL7RA polymorphisms seem to play a significant role in the virological response to pegIFNα/ribavirin therapy in HIV/HCV-coinfected patients, in particular among patients infected with HCV GT2/3.


Assuntos
Antivirais/uso terapêutico , Infecções por HIV/tratamento farmacológico , Hepacivirus/efeitos dos fármacos , Hepatite C/tratamento farmacológico , Interleucina-7/genética , Polimorfismo Genético , Adulto , Alelos , Coinfecção , Quimioterapia Combinada , Feminino , Genótipo , Infecções por HIV/virologia , Haplótipos , Hepatite C/virologia , Humanos , Interferon alfa-2 , Interferon-alfa/uso terapêutico , Masculino , Razão de Chances , Polietilenoglicóis/uso terapêutico , Proteínas Recombinantes/uso terapêutico , Estudos Retrospectivos , Ribavirina/uso terapêutico
4.
Org Biomol Chem ; 13(10): 3144-54, 2015 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-25634805

RESUMO

Some hybrids of vinca alkaloids and phomopsin A, linked by a glycine pattern, have been synthesized in one or two steps, by an insertion reaction and shown to inhibit microtubule assembly. These compounds have been elaborated in order to interact with both the "vinca site" and the "peptide site" of the vinca domain in tubulin. Two out of three hybrids are potent inhibitors of microtubules assembly and they present good cytotoxicity against different cell lines. Molecular modelling studies show that they could bind, within the vinca domain, in similar spatial regions as those of vinca and phomopsin thanks to the flexibility provided by the glycine linker used to elaborate these hybrids.


Assuntos
Glicina/química , Micotoxinas/síntese química , Tubulina (Proteína)/química , Alcaloides de Vinca/síntese química , Alcaloides/química , Apoptose , Sítios de Ligação , Linhagem Celular , Guanosina Trifosfato/química , Humanos , Células K562 , Microtúbulos/metabolismo , Modelos Moleculares , Micotoxinas/química , Peptídeos/química , Estrutura Terciária de Proteína , Transdução de Sinais , Vimblastina/análogos & derivados , Vimblastina/química , Alcaloides de Vinca/química , Vinorelbina
5.
Epidemiol Infect ; 143(3): 653-62, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24762978

RESUMO

An observational study was conducted to describe the epidemiology of bacteriuria and candiduria in the intensive care unit (ICU), and the occurrence of blood stream infection (BSI) associated with ICU-acquired positive urine culture. Between 2006 and 2011, 444 episodes of either bacteriuria or candiduria defined by positive urine culture (microorganisms ⩾105 c.f.u./ml) occurred in 406 patients. Three hundred and seventy-seven (85%) were hospital-acquired including 221 which were ICU-acquired (6·4 ± 0·8 episodes/1000 ICU days). Escherichia coli was the most common bacteria of both community- and ICU-acquired bacteriuria/candiduria (49·2% and 29%, respectively). Candida spp. represented 55% (129/236) of pathogens responsible for ICU-acquired positive urine cultures. Patients with ICU-acquired candiduria had greater illness severity at ICU admission than those with ICU-acquired bacteriuria (APACHE III score 79 ± 25 vs. 66 ± 31, P = 0·0015). BSI associated with ICU-acquired positive urine culture occurred in 0·15/1000 ICU days and was more often due to Candida. In this study, Candida was the most common pathogen responsible for ICU-acquired positive urine cultures and illness severity was a risk factor for candiduria in the study population.


Assuntos
Bactérias/isolamento & purificação , Candida/isolamento & purificação , Infecções Urinárias/epidemiologia , Infecções Urinárias/microbiologia , Urina/microbiologia , Adolescente , Adulto , Idoso , Bacteriemia/epidemiologia , Bacteriemia/microbiologia , Bactérias/classificação , Candidemia/epidemiologia , Candidemia/microbiologia , Estado Terminal , Feminino , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Índice de Gravidade de Doença , Infecções Urinárias/complicações , Adulto Jovem
6.
HIV Med ; 15(7): 425-30, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24580757

RESUMO

OBJECTIVES: Mitochondria are multifunctional organelles with a key role in the innate immune response against viral infections. Mitochondrial DNA (mtDNA) haplogroups have been related to AIDS progression and CD4 T-cell recovery in HIV-infected patients, and to a delay in the development of liver fibrosis in HIV/hepatitis C virus (HCV)-coinfected patients. We performed a study to investigate whether mtDNA haplogroups may be associated with HCV treatment response in HIV/HCV-coinfected patients on pegylated interferon (pegIFN) plus ribavirin (RBV). METHODS: We performed a retrospective study in 304 patients who completed a course of HCV therapy. mtDNA polymorphisms were genotyped using Sequenom's MassARRAY platform. The interleukin-28B (IL-28B) polymorphism (rs12980275) was genotyped using the GoldenGate® assay. Sustained virological response (SVR) was defined as an undetectable HCV viral load at week 24 after the end of treatment. The statistical analysis was carried out using on-treatment data. RESULTS: The SVR rates were 52.6% (160 of 304) for all patients, and 37.8% (46 of 201) for patients with HCV genotype 1 or 4 vs. 81.4% (83 of 102) for patients with HCV genotype 2 or 3 (P < 0.001). No significant associations were found between mtDNA haplogroup and SVR when all patients were included in the analysis and when patients were stratified by HCV genotype (i.e. those with genotypes 1/4 and 2/3 analysed separately) or IL-28B rs12980275 genotype. CONCLUSIONS: European mtDNA haplogroups were not related to HCV treatment response in HIV/HCV-coinfected patients on pegIFN-α/RBV therapy.


Assuntos
Antivirais/uso terapêutico , DNA Mitocondrial/genética , Infecções por HIV/complicações , Haplótipos , Hepatite C/tratamento farmacológico , Interferon-alfa/uso terapêutico , Polietilenoglicóis/uso terapêutico , Ribavirina/uso terapêutico , Adulto , Coinfecção/tratamento farmacológico , Feminino , Genótipo , Hepatite C/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético , Proteínas Recombinantes/uso terapêutico , Estudos Retrospectivos , Espanha , População Branca
7.
J Viral Hepat ; 21(3): 189-97, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24438680

RESUMO

Hepatitis C virus (HCV) infection is associated with insulin resistance (IR), although mechanisms leading to IR in these patients are not completely understood. The aim of this study was to evaluate the association of interleukin 28B (IL28B) and interleukin 28 receptor alpha (IL28RA) polymorphisms with IR among human immunodeficiency virus (HIV)/HCV-coinfected patients. We carried out a cross-sectional study on 203 patients. IL28B (rs8099917) and IL28RA (rs10903035) polymorphisms were genotyped by GoldenGate(®) assay. IR was defined as homeostatic model assessment (HOMA) values ≥3.00. Univariate and multivariate generalized linear models (GLM) were used to compare HOMA values and the percentage of patients with IR according to IL28B and IL28RA genotypes. In total, 32% (n = 65/203) of the patients had IR. IL28B rs8099917 TT was not significantly associated with HOMA values and IR. In contrast, rs10903035 AA was significantly associated with high HOMA values taking into account all patients (P = 0.024), as well as the subgroups of patients with significant fibrosis (P = 0.047) and infected with HCV genotype 3 (P = 0.024). Additionally, rs10903035 AA was significantly associated with IR (HOMA ≥3.00) in all patients (adjusted odds ratio (aOR) = 2.02; P = 0.034), in patients with significant fibrosis (aOR = 2.86; P = 0.039) and HCV genotype 3 patients (aOR = 4.89; P = 0.031). In conclusions, IL28RA polymorphism (rs10903035) seems to be implicated in the glucose homeostasis because AA genotype increases the likelihood of IR, but this association was different depending on hepatic fibrosis and HCV genotype.


Assuntos
Coinfecção , Infecções por HIV/genética , Hepatite C Crônica/genética , Resistência à Insulina/genética , Polimorfismo Genético , Receptores de Citocinas/genética , Adulto , Contagem de Linfócito CD4 , Estudos Transversais , Feminino , Estudos de Associação Genética , Genótipo , Infecções por HIV/tratamento farmacológico , Infecções por HIV/metabolismo , HIV-1/genética , Hepacivirus/genética , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/metabolismo , Humanos , Interferons , Interleucinas/genética , Masculino , Razão de Chances , Carga Viral
9.
J Viral Hepat ; 20(5): 358-66, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23565619

RESUMO

Due to the poor rate of response to hepatitis C virus (HCV) with pegylated interferon and ribavirin treatment in HCV/HIV coinfected patients, key factors for predicting failure would be useful. We performed a retrospective study on 291 patients on HCV treatment, who had early virological response (EVR) data. IL28B and IL28RA polymorphisms were performed using the GoldenGate(®) assay. Unfavourable genotypes at IL28B (rs12980275 AG/GG and rs8099917 GT/GG) and an unfavourable allele at IL28RA (rs10903035 G) were associated with early treatment failure. However, only the rs12980275 AG/GG genotype and rs10903035 G allele remained independently associated with early failure in the overall population (OR = 4.15 (95% CI = 1.64-10.54) and OR = 2.00 (95% CI = 1.19-3.36), respectively) as well as in GT1/4 patients (OR = 5.07 (95% CI = 1.81-14.22) and OR = 2.03 (95% CI = 1.13-3.66), respectively). Next, a decision tree showed early treatment failure increased from 37.1% to 65.5% when the unfavourable rs12980275 AG/GG and rs10903035 AG/GG genotypes and HCV-RNA≥ 500.000 IU/mL were taken into account in GT1/4 patients. In contrast, the failure rate decreased from 37.1% to 11.9% when the favourable rs12980275 AA and rs10903035 AA genotypes were detected. The percentage of patients correctly classified was 78.4%, and AUROC was 0.802 ± 0.028. Regarding GT3 patients, the presence of the GCGCA haplotype (all unfavourable alleles) was associated with early treatment failure, while no association was observed for the IL28B polymorphisms. In conclusion, the IL28RA polymorphism was associated with early treatment failure independently of the IL28B SNPs. The combination of IL28B and IL28RA polymorphisms might be a valuable tool for predicting early treatment failure before starting HCV treatment.


Assuntos
Antivirais/uso terapêutico , Infecções por HIV/complicações , Hepatite C Crônica/complicações , Interferons/uso terapêutico , Polimorfismo Genético , Receptores de Citocinas/genética , Ribavirina/uso terapêutico , Adulto , Feminino , Infecções por HIV/tratamento farmacológico , Hepatite C Crônica/tratamento farmacológico , Humanos , Interleucinas/genética , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Falha de Tratamento
10.
Eur J Clin Microbiol Infect Dis ; 32(2): 289-97, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22983402

RESUMO

Torque teno virus (TTV) and torque teno mini virus (TTMV) have been potentially related to liver diseases. The aim of the study was to quantify TTV and TTMV in human immunodeficiency virus (HIV)/hepatitis C virus (HCV)-coinfected patients to study the relationship between the TTV and TTMV viral loads and the severity of liver disease. We carried out a cross-sectional study in 245 patients coinfected with HIV and HCV (HIV/HCV-group), 114 patients monoinfected with HIV (HIV-group), and 100 healthy blood donors (Control-group). Plasma samples were tested for TTV and TTMV by quantitative real-time polymerase chain reaction (PCR). The prevalences of TTV and TTMV infections in the HIV/HCV-group and the HIV-group were significantly higher than the Control-group (p < 0.05). Furthermore, TTV and TTMV coinfections were found in 92.2 % (226/245) in the HIV/HCV-group, 84.2 % (96/114) in the HIV-group, and 63 % (63/100 %) in the Control-group (p ≤ 0.05). HIV/HCV-coinfected patients with HIV viral load ≥50 copies/mL and patients with severe activity grade had the highest viral loads of TTV and TTMV (p ≤ 0.05). HIV/HCV-coinfected patients with high TTV load (>2.78 log copies/µL) had increased odds of having advanced fibrosis or severe necroinflammatory activity grade in the liver biopsy. Moreover, HIV/HCV-coinfected patients with high TTMV load (>1.88 log copies/µL) had decreased odds of having no/minimal fibrosis and no/mild activity grade, and increased odds of having a high fibrosis progression rate. In conclusion, TTV and TTMV might play a role in the development of liver disease in immunodeficiency patients, such as the patients coinfected with HIV and HCV.


Assuntos
Infecções por Vírus de DNA/epidemiologia , Infecções por Vírus de DNA/virologia , Infecções por HIV/complicações , Hepatite C Crônica/complicações , Fígado/patologia , Plasma/virologia , Torque teno virus/isolamento & purificação , Adulto , Estudos Transversais , Feminino , Humanos , Masculino , Prevalência , Reação em Cadeia da Polimerase em Tempo Real , Estudos Retrospectivos , Carga Viral
11.
Eur J Clin Microbiol Infect Dis ; 30(10): 1213-21, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21442358

RESUMO

The aim of this study was to evaluate the influence of clinical and epidemiological characteristics of 183 HIV/HCV coinfected patients and HCV clearance after antiviral treatment on serum sFas and sFasL levels. Thirty out of 183 patients underwent HCV antiviral therapy with IFN-α + RBV for a duration of 48 weeks. HCV genotype 1 and homeostasis model assessment for insulin resistance (HOMA-IR) had a significant positive relationship, and CD4+/µL had a significant negative relationship with sFas (R-square = 0.582; p < 0.001) and sFasL (R-square = 0.216; p < 0.001) in multivariate linear regression analysis. HCV genotype 1 was the only significant variable associated with the sFas/sFasL ratio (R-square = 0.201; p < 0.001). sFas and sFasL levels had positive significant correlations with serum sICAM-1, sVCAM-1, and HOMA levels (p < 0.05). Among patients on IFN-α + RBV therapy, 15 patients showed a sustained virologic response (SVR), while 15 patients were non-responders (NR). Patients with SVR had significant decreases in sFas (p = 0.008) and sFas/sFasL ratio (p = 0.002), while non-responders had a significant increase in sFasL values (p = 0.013). In conclusion, HCV genotype 1, high HOMA, and low CD4+/µL were associated with high serum levels of sFas and sFasL, which indicate higher levels of inflammation and, possibly, increased cardiovascular risk. Moreover, response to HCV antiviral therapy is known to reduce inflammation.


Assuntos
Antivirais/administração & dosagem , Proteína Ligante Fas/sangue , Infecções por HIV/complicações , Infecções por HIV/patologia , Hepatite C/complicações , Hepatite C/patologia , Receptor fas/sangue , Adulto , Contagem de Linfócito CD4 , Estudos Transversais , Feminino , Genótipo , Hepacivirus/classificação , Hepacivirus/genética , Hepatite C/tratamento farmacológico , Humanos , Interferon-alfa/administração & dosagem , Masculino , Ribavirina/administração & dosagem , Resultado do Tratamento
12.
Blood Cancer J ; 7(8): e591, 2017 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-28841204

RESUMO

Transformation of Waldenström's macroglobulinemia (WM) to diffuse large B-cell lymphoma (DLBCL) occurs in up to 10% of patients and is associated with an adverse outcome. Here we performed the first whole-exome sequencing study of WM patients who evolved to DLBCL and report the genetic alterations that may drive this process. Our results demonstrate that transformation depends on the frequency and specificity of acquired variants, rather than on the duration of its evolution. We did not find a common pattern of mutations at diagnosis or transformation; however, there were certain abnormalities that were present in a high proportion of clonal tumor cells and conserved during this transition, suggesting that they have a key role as early drivers. In addition, recurrent mutations gained in some genes at transformation (for example, PIM1, FRYL and HNF1B) represent cooperating events in the selection of the clones responsible for disease progression. Detailed comparison reveals the gene abnormalities at diagnosis and transformation to be consistent with a branching model of evolution. Finally, the frequent mutation observed in the CD79B gene in this specific subset of patients implies that it is a potential biomarker predicting transformation in WM.


Assuntos
Biomarcadores Tumorais/genética , Antígenos CD79/genética , Transformação Celular Neoplásica/genética , Exoma , Linfoma Difuso de Grandes Células B/genética , Mutação , Proteínas de Neoplasias/genética , Macroglobulinemia de Waldenstrom/genética , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
13.
Ann Pharm Fr ; 63(6): 371-84, 2005 Nov.
Artigo em Francês | MEDLINE | ID: mdl-16292231

RESUMO

Type II diabetes is a serious, insidious disease which is growing at an impressive rate, with 200 million diabetics worldwide and as many who ignore their state. Having been seriously studied over more than a century and a half, an enormous quantity of knowledge regarding this disease has been accumulated. The research we are conducting has allowed us to identify the most important actors responsible for diabetes. These are glucose which leads to glyoxal and to methylglyoxal which in turn reacts with innumerable targets in the organism (including insulin) unless prevented from doing so by detoxifying mechanisms (e.g., glyoxalases). The role of microorganisms in the occurrence and development of diabetes has also to be seriously examined.


Assuntos
Diabetes Mellitus/fisiopatologia , Animais , Diabetes Mellitus/enzimologia , Diabetes Mellitus/genética , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/fisiopatologia , Glucose/farmacologia , Humanos , Aldeído Pirúvico/farmacologia
14.
Transplant Proc ; 47(6): 1998-2002, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26293088

RESUMO

With the limitations of surgical reconstructive procedures, the growing number of gunshot wounds, burns, and work accidents in Mexico that result in complex facial deformities leaves only 1 option-face transplantation. The National Institute of Medical Sciences and Nutrition "Salvador Zubiran" (INCMNSZ) has performed transplants since 1971. We at INCMNSZ undertook the 1st bilateral upper-limb transplantation in Latin America in 2012. We are willing to continue in this manner toward conducting face transplantation at our institute. To this end, we identified and solved various challenges. The 1st challenge was acceptance and inclusion of vascularized composite allotransplantation (VCA) within general Mexican health law and approval of the face transplantation procedure. Subsequently, the health ministry provided a license to INCMNSZ to perform the procedure. The 2nd challenge concerned who would pay for the procedure. The costs will be paid by the patient (1st-party payer), social security institutions (2nd-party payers), and the health ministry (3rd-party payer). The 3rd challenge was to maintain ongoing surgical training of the team using cadavers. The fourth challenge was to locate donors; toward this end, we developed a campaign for promoting face donation in social media, making a comic book, and training organ and tissue coordinators to further VCA. Thus, INCMNSZ has the legal, administrative, medical, and surgical wherewithal to accomplish face transplantation.


Assuntos
Face/cirurgia , Traumatismos Faciais/cirurgia , Transplante de Face/métodos , Doadores de Tecidos , Cadáver , Traumatismos Faciais/epidemiologia , Humanos , Incidência , México/epidemiologia , Alotransplante de Tecidos Compostos Vascularizados/métodos
15.
Neurology ; 59(8): 1197-202, 2002 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-12391347

RESUMO

BACKGROUND: The mitochondrial DNA (mtDNA) depletion syndrome (MDS) is an autosomal recessive disorder of early childhood characterized by decreased mtDNA copy number in affected tissues. Recently, MDS has been linked to mutations in two genes involved in deoxyribonucleotide (dNTP) metabolism: thymidine kinase 2 (TK2) and deoxy-guanosine kinase (dGK). Mutations in TK2 have been associated with the myopathic form of MDS, and mutations in dGK with the hepatoencephalopathic form. OBJECTIVES: To further characterize the frequency and clinical spectrum of these mutations, the authors screened 20 patients with myopathic MDS. RESULTS: No patient had dGK gene mutations, but four patients from two families had TK2 mutations. Two siblings were compound heterozygous for a previously reported H90N mutation and a novel T77M mutation. The other siblings harbored a homozygous I22M mutation, and one of them had evidence of lower motor neuron disease. The pathogenicity of these mutations was confirmed by reduced TK2 activity in muscle (28% to 37% of controls). CONCLUSIONS: These results show that the clinical expression of TK2 mutations is not limited to myopathy and that the myopathic form of MDS is genetically heterogeneous.


Assuntos
DNA Mitocondrial/genética , DNA Mitocondrial/metabolismo , Atrofia Muscular Espinal/genética , Doenças Musculares/genética , Mutação/genética , Timidina Quinase/genética , Pré-Escolar , Feminino , Humanos , Masculino , Músculos/patologia , Atrofia Muscular Espinal/enzimologia , Atrofia Muscular Espinal/patologia , Doenças Musculares/enzimologia , Doenças Musculares/patologia , Linhagem , Fosfotransferases (Aceptor do Grupo Álcool)/genética , Fosfotransferases (Aceptor do Grupo Álcool)/metabolismo , Timidina Quinase/química , Timidina Quinase/metabolismo
16.
Pediatr Neurol ; 14(4): 328-34, 1996 May.
Artigo em Inglês | MEDLINE | ID: mdl-8962591

RESUMO

We report 7 patients with pyruvate dehydrogenase (PDH) deficiency caused by mutations of the PDH-E1 alpha subunit. Each patient had a different mutation; 4 with duplicate insertions, 1 with a deletion of tandem repeat, and 2 with point mutations. Five of the mutations were novel, thus confirming allelic heterogeneity. Immunoblot analysis revealed decreased immunoreactivity for the E1 alpha and E1 beta subunits in every patient. Pulse-labeling and chase study for the E1 alpha and E1 beta subunits revealed that initial synthesis of the mutant E1 alpha subunit was normal and posttranslational degradation was complete by 48 hours. However, the post-translational degradation rate of the E1 beta subunit varied from one patient to another. Factors other than instability of the E1 beta monomer must contribute to the degradation rate of this subunit in the presence of an E1 alpha subunit mutation. Including this series, 3 patients with the S312 deletion and 5 with the R302C point mutation have been reported, and all of these patients are female. These findings suggest that these two loci are hot spots for gene mutations, and may be lethal in the male fetus.


Assuntos
Fragmentos de Peptídeos/genética , Doença da Deficiência do Complexo de Piruvato Desidrogenase/genética , Adolescente , Sequência de Bases , Northern Blotting , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Dados de Sequência Molecular , Mutação , Fragmentos de Peptídeos/deficiência , Biossíntese de Proteínas , Transcrição Gênica
17.
J Agric Food Chem ; 50(3): 419-25, 2002 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-11804506

RESUMO

NIR transflectance spectroscopy was used to determine polarimetric parameters (direct polarization, polarization after inversion, specific rotation in dry matter, and polarization due to nonmonosaccharides) and sucrose in honey. In total, 156 honey samples were collected during 1992 (45 samples), 1995 (56 samples), and 1996 (55 samples). Samples were analyzed by NIR spectroscopy and polarimetric methods. Calibration (118 samples) and validation (38 samples) sets were made up; honeys from the three years were included in both sets. Calibrations were performed by modified partial least-squares regression and scatter correction by standard normal variation and detrend methods. For direct polarization, polarization after inversion, specific rotation in dry matter, and polarization due to nonmonosaccharides, good statistics (bias, SEV, and R(2)) were obtained for the validation set, and no statistically (p = 0.05) significant differences were found between instrumental and polarimetric methods for these parameters. Statistical data for sucrose were not as good as those of the other parameters. Therefore, NIR spectroscopy is not an effective method for quantitative analysis of sucrose in these honey samples. However, NIR spectroscopy may be an acceptable method for semiquantitative evaluation of sucrose for honeys, such as those in our study, containing up to 3% of sucrose. Further work is necessary to validate the uncertainty at higher levels.


Assuntos
Mel/análise , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Calibragem , Reprodutibilidade dos Testes , Sacarose/análise
18.
J Agric Food Chem ; 48(11): 5154-8, 2000 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-11087451

RESUMO

NIR transflectance spectroscopy was used to analyze fructose, glucose, and moisture in honey. A total of 161 honey samples were collected during 1992 (46), 1995 (58), and 1996 (57). Samples were analyzed by instrumental, enzymatic (fructose and glucose), and refractometric (moisture) methods. Initially, different calibrations were performed for each of the 3 years of sampling. Good predictions were obtained for all three components with equations of the particular year. But good predictions were not always obtained when the equations calculated one year were applied to samples from another year. To perform a lasting calibration, unique calibration (121 samples) and validation (40 samples) sets were built; honeys of the 3 years were included in both sets. Good statistics (bias, standard error of validation (SEV), and R(2)) were obtained for all three components of the validation set. No statistically significant differences (p = 0.05) were found between instrumental and reference methods.


Assuntos
Mel/análise , Calibragem , Frutose/análise , Glucose/análise , Reprodutibilidade dos Testes , Espectrofotometria Infravermelho/métodos , Água/análise
19.
Rev Esp Cardiol ; 44(6): 379-82, 1991.
Artigo em Espanhol | MEDLINE | ID: mdl-1833799

RESUMO

To reduce problems during percutaneous transluminal angioplasties and valvuloplasties in the catheterization laboratory, percutaneous cardiopulmonary bypass was used in 6 patients (three aortic, two mitral and one coronary). Percutaneous 21 F (venous) and 17 F (arterial) cannulas were placed through the femoral vessels. Mean flows of 3 l/min were achieved with a roller pump, with a mean blood pressure of 60 mmHg. Bypass time ranged between 22 and 55 minutes (mean 39). Light intravenous sedations and spontaneous breathing was maintained in all cases. Maximum inflation time of balloons were 4 minutes for the aortic valvuloplasty patients and 50 seconds for the mitral. Two patients developed groin hematomas, and one of them required surgical exploration. Percutaneous bypass is a simple and easily achieved technique to ensure safety in the high-risk patient.


Assuntos
Angioplastia com Balão/métodos , Ponte Cardiopulmonar/métodos , Cateterismo/métodos , Anestesia Local/métodos , Estenose da Valva Aórtica/terapia , Doença das Coronárias/terapia , Artéria Femoral , Veia Femoral , Humanos , Estenose da Valva Mitral/terapia , Fatores de Tempo
20.
J Ethnopharmacol ; 149(3): 676-84, 2013 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-23906782

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Based on ethnobotanical data obtained from Nigerien and Senegalese traditional healers, two Euphorbiaceae plants, Sebastiania chamaelea and Chrozophora senegalensis, traditionally used to treat malaria, were selected for further investigations. MATERIALS AND METHODS: Plant extracts were prepared with different solvents and tested both in vitro on several strains of Plasmodium falciparum, and in vivo to evaluate their antiplasmodial properties and isolate their active principles. RESULTS: With IC50 values around 6.5µg/ml and no significant cytotoxicity (>50µg/ml), the whole plant aqueous extract from S. chamaelea showed the best in vitro results. In vitro potentiation assays showed strong synergistic activity of S. chamaelea extract with the antiplasmodial drug chloroquine on the chloroquine-resistant P. falciparum strain W2-Indochina. In other respects, the aqueous crude extract of C. senegalensis leaves showed the most significant antiplasmodial activity in vitro (IC50 values less than 2µg/ml). We also demonstrated the prophylactic activity of C. senegalensis in vivo in a murine malaria model. Bioassay-guided fractionation of aqueous extracts of these plants enabled the isolation and identification of ellagic acid (EA, 1) as the main compound responsible for their antiplasmodial activity. Together with EA, other derivatives belonging to different chemical groups were isolated but showed moderate antimalarial activity: gallic acid (2), brevifolin carboxylic acid (3), protocatechuic acid (4), corillagin (5), rutin (6) and 3,4,8,9,10-pentahydroxy-dibenzo(b,d)pyran-6-one (7). The structures were determined by the usual spectroscopic methods and by comparison with published data. Furthermore, we report here the quantification of compound 1 (EA) by RP-HPLC in the dried extracts of these plants, reported for the first time in both these species, and possessing the highest in vitro antiplasmodial activity with IC50 values from 180 to 330nm. CONCLUSIONS: These in vitro and in vivo results support the traditional use in Africa of crude extracts of both S. chamaelea and C. senegalensis as an antimalarial treatment and prove the significant antiplasmodial property of EA.


Assuntos
Antimaláricos/uso terapêutico , Euphorbiaceae/química , Malária/tratamento farmacológico , Medicinas Tradicionais Africanas , Extratos Vegetais/uso terapêutico , Plasmodium/efeitos dos fármacos , Animais , Antimaláricos/isolamento & purificação , Antimaláricos/toxicidade , Sobrevivência Celular/efeitos dos fármacos , Ácido Elágico/isolamento & purificação , Feminino , Células Endoteliais da Veia Umbilical Humana , Humanos , Malária/parasitologia , Malária Falciparum/tratamento farmacológico , Malária Falciparum/parasitologia , Camundongos , Níger , Testes de Sensibilidade Parasitária , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/toxicidade , Plasmodium falciparum/efeitos dos fármacos , Senegal
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