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1.
Exp Oncol ; 44(2): 137-141, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35964641

RESUMO

BACKGROUND: Chemokine (C-C motif) receptor 7 (CCR7) is a chemokine receptor involved in the carcinogenesis of several types of tumors due to its promoting action in epithelial-mesenchymal transition events, invasion, angiogenesis and metastasis. However, its role in prostate cancer (PCa) remains unclear. AIM: To evaluate CCR7 expression by immunohistochemistry in prostate tumors from young patients and to determine the possible relationship with the clinicopathological characteristics. MATERIALS AND METHODS: We analyzed retrospectively paraffin-embedded tissue sections from 23 young PCa (≤ 55 years old) patients and evaluated the transcriptomic expression in the TCGA database. RESULTS: Expression of CCR7 was observed in 15 cases (65%). The tissue samples from younger patients (≤ 50 years) were mostly positive in 72.7% (8/11) of cases. High grade GS (≥ 3) tumors were CCR7-positive in 71% cases. The malignant cells present in lymph nodes were CCR7 positive in 100% cases. The bioinformatic analysis showed a high CCR7 expression associated with the presence of metastasis (FC = 2.6, p = 0.03) in the Cancer Genome Atlas (TCGA) PCa cohort (PRAD). CONCLUSION: We showed that CCR7 expression in tumors from young patients is associated with the early onset of the disease and could also be related to lymph node metastasis.


Assuntos
Neoplasias da Próstata , Receptores CCR7/metabolismo , Quimiocinas/genética , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Receptores CCR7/genética , Estudos Retrospectivos
2.
mSystems ; 6(2)2021 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-33879498

RESUMO

A growing body of data suggests that the microbiome of a species can vary considerably from individual to individual, but the reasons for this variation-and the consequences for the ecology of these communities-remain only partially explained. In mammals, the emerging picture is that the metabolic state and immune system status of the host affect the composition of the microbiome, but quantitative ecological microbiome studies are challenging to perform in higher organisms. Here, we show that these phenomena can be quantitatively analyzed in the tractable nematode host Caenorhabditis elegans Mutants in innate immunity, in particular the DAF-2/insulin growth factor (IGF) pathway, are shown to contain a microbiome that differs from that of wild-type nematodes. We analyzed the underlying basis of these differences from the perspective of community ecology by comparing experimental observations to the predictions of a neutral sampling model and concluded that fundamental differences in microbiome ecology underlie the observed differences in microbiome composition. We tested this hypothesis by introducing a minor perturbation into the colonization conditions, allowing us to assess stability of communities in different host strains. Our results show that altering host immunity changes the importance of interspecies interactions within the microbiome, resulting in differences in community composition and stability that emerge from these differences in host-microbe ecology.IMPORTANCE Here, we used a Caenorhabditis elegans microbiome model to demonstrate how genetic differences in innate immunity alter microbiome composition, diversity, and stability by changing the ecological processes that shape these communities. These results provide insight into the role of host genetics in controlling the ecology of the host-associated microbiota, resulting in differences in community composition, successional trajectories, and response to perturbation.

3.
Actas Urol Esp (Engl Ed) ; 44(8): 523-528, 2020 Oct.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-32684296

RESUMO

Male urethritis is an inflammation of the urethra and the periurethral glands; it is widely classified as gonococcal or non-gonococcal. The most frequent microorganisms responsible are Chlamydia trachomatis, Neisseria gonorrhoeae, Mycoplasma genitalium, Mycoplasma hominis, Ureaplasma urealyticum, and Ureaplasma parvum. In the last three decades, the diagnosis of sexually transmitted diseases depended almost exclusively on traditional methods, such as culture, enzyme immunoassay, fluorescent antibody staining, and hybridization, until the appearance of molecular techniques. Clinical syndromes such as urethritis are rarely specific for a single microorganism, so screening strategies should allow multiple agents to be considered. Multiplex PCR is the fastest and most sensitive technique for the diagnosis of gonococcal and non-gonococcal urethritis. Male urethritis without treatment is one of the main health problems related to reproductive and sexual function, constituting one of the main causes of infertility. The objective of this mini-review was to analyze the epidemiology, causes, diagnosis, and complications of male urethritis.


Assuntos
Uretrite/diagnóstico , Técnicas de Diagnóstico Urológico , Humanos , Masculino , Uretrite/complicações , Uretrite/epidemiologia , Uretrite/microbiologia
4.
Nanotechnology ; 28(27): 275702, 2017 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-28525395

RESUMO

The room temperature photoluminescence from ZnO/MgO core/shell nanowires (NWs) grown by a simple two-step vapor transport method was studied for various MgO shell widths (w). Two distinct effects induced by the MgO shell were clearly identified. The first one, related to the ZnO/MgO interface formation, is evidenced by strong enhancements of the zero-phonon and first phonon replica of the excitonic emission, which are accompanied by a total suppression of its second phonon replica. This effect can be explained by the reduction of the band bending within the ZnO NW core that follows the removal of atmospheric adsorbates and associated surface traps during the MgO growth process on one hand, and a reduced exciton-phonon coupling as a result of the mechanical stabilization of the outermost ZnO NW monolayers by the MgO shell on the other hand. The second effect is the gradual increase of the excitonic emission and decrease in the defect related emission by up to two and one orders of magnitude, respectively, when w is increased in the ∼3-17 nm range. Uniaxial strain build-up within the ZnO NW core with increasing w, as detected by x-ray diffraction measurements, and photocarrier tunneling escape from the ZnO core through the MgO shell enabled by defect-states are proposed as possible mechanisms involved in this effect. These findings are expected to be of key significance for the efficient design and fabrication of ZnO/MgO NW heterostructures and devices.

5.
Skin Res Technol ; 23(2): 243-248, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-27796065

RESUMO

BACKGROUND/PURPOSE: Facial lipoatrophy in HIV patients, secondary to antiretroviral therapy (ART) with thymidine analogs, has been related to important psychosocial alterations and poor adherence to treatment. Polyacrylamide gel (PAAG) is a filler that has been used for treating facial lipoatrophy in HIV patients. The aim was to assess the clinical and sonographic anatomical changes after injection of PAAG in HIV patients with facial lipoatrophy secondary to ART. METHODS: HIV patients receiving ART and suffering from severe facial lipoatrophy were recruited and underwent clinical and color Doppler ultrasound evaluation prior to PAAG application (AQUAMID® ) and sonographically monitored at 18 months and clinically followed up for 36 months after the procedure. Adverse effects were recorded based on occurrence and complexity. RESULTS: A total of 33 patients were evaluated, 30 men (91%) and 3 women (9%) with an average age of 49.6 years (±8.4). Clinical improvement assessed by a dermatologist had an average score of 5.9 (±0.7) on a scale of 1-7. On color Doppler ultrasound there was a significant increase of the thickness of the subcutaneous tissue (SCT) in both nasofold lines when comparing before and after PAAG injection (P < 0.01) and no signs of inflammation (hypervascularity). User satisfaction was qualified as excellent or good in all cases. Only two patients experienced adverse effects (hematoma and puncture site infection), which was successfully managed without consequences. CONCLUSION: Treatment of facial lipoatrophy with PAAG seems to be effective in HIV patients and no signs of complications were observed in the monitoring at 36 months after injection. Color Doppler ultrasound can identify the filler deposits and the anatomical changes of the SCT non-invasively.


Assuntos
Resinas Acrílicas/administração & dosagem , Antirretrovirais/efeitos adversos , Dermatoses Faciais/diagnóstico por imagem , Dermatoses Faciais/terapia , Síndrome de Lipodistrofia Associada ao HIV/diagnóstico por imagem , Síndrome de Lipodistrofia Associada ao HIV/terapia , Ultrassonografia Doppler em Cores/métodos , Adulto , Preenchedores Dérmicos/administração & dosagem , Dermatoses Faciais/induzido quimicamente , Feminino , Síndrome de Lipodistrofia Associada ao HIV/induzido quimicamente , Humanos , Masculino , Resultado do Tratamento
6.
Clin Exp Immunol ; 180(3): 442-51, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25639560

RESUMO

We analysed the proportions of different microparticles (MPs) in plasma from patients with rheumatoid arthritis (RA), and assessed their relationship with disease activity/therapy and their in-vitro effect on proinflammatory cytokine release. Blood and urine samples were obtained from 55 patients with RA (24 untreated and 31 under conventional therapy) and 20 healthy subjects. Fourteen patients with systemic lupus erythematosus (SLE) were also studied. The proportions of CD3(+) , CD14(+) , CD19(+) , CD41(+) and CD62E(+) MPs were determined by flow cytometry analysis. The in-vitro effect of plasma MPs on the release of interleukin (IL)-1, IL-6, IL-17 and tumour necrosis factor (TNF)-α was also analysed. We detected that the proportions of different types of annexin-V(+) MPs were enhanced in plasma (CD3(+) , CD14(+) , CD19(+) , CD41(+) and CD62E(+) MPs) and urine (CD14(+) , CD3(+) and CD19(+) MPs) from RA patients with high disease activity (DAS28 index > 5·1). Accordingly, a significant positive correlation was observed between the levels of MPs and DAS28 score, and these levels diminished significantly at week 4 of immunosuppressive therapy. Finally, MPs isolated from patients with high disease activity induced, in vitro, an enhanced release of IL-1, IL-17 and TNF-α. In SLE, enhanced levels of different types of plasma MPs were also detected, with a tight correlation with disease activity. Our data further support that MPs have a relevant role in the pathogenesis of RA and suggest that the analysis of the proportions of these microvesicles in plasma could be useful to monitor disease activity and therapy response in patients with RA.


Assuntos
Artrite Reumatoide/imunologia , Artrite Reumatoide/metabolismo , Micropartículas Derivadas de Células/imunologia , Micropartículas Derivadas de Células/metabolismo , Adulto , Artrite Reumatoide/sangue , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/urina , Biomarcadores/metabolismo , Estudos de Casos e Controles , Citocinas/biossíntese , Citocinas/sangue , Feminino , Humanos , Imunofenotipagem , Imunossupressores/farmacologia , Imunossupressores/uso terapêutico , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/metabolismo , Masculino , Pessoa de Meia-Idade , Fenótipo , Adulto Jovem
7.
Oncogene ; 32(1): 1-14, 2013 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-22349816

RESUMO

In this study, we show that interfering with the splicing machinery results in activation of the tumour-suppressor p53. The spliceosome was targeted by small interfering RNA-mediated knockdown of proteins associated with different small nuclear ribonucleoprotein complexes and by using the small-molecule splicing modulator TG003. These interventions cause: the accumulation of p53, an increase in p53 transcriptional activity and can result in p53-dependent G(1) cell cycle arrest. Mdm2 and MdmX are two key repressors of p53. We show that a decrease in MdmX protein level contributes to p53 activation in response to targeting the spliceosome. Interfering with the spliceosome also causes an increase in the rate of degradation of Mdm2. Alterations in splicing are linked with tumour development. There are frequently global changes in splicing in cancer. Our study suggests that p53 activation could participate in protection against potential tumour-promoting defects in the spliceosome. A number of known p53-activating agents affect the splicing machinery and this could contribute to their ability to upregulate p53. Preclinical studies indicate that tumours can be more sensitive than normal cells to small-molecule spliceosome inhibitors. Activation of p53 could influence the selective anti-tumour activity of this therapeutic approach.


Assuntos
Precursores de RNA/genética , Splicing de RNA , RNA Mensageiro/genética , Proteína Supressora de Tumor p53/metabolismo , Proteínas de Ciclo Celular , Dano ao DNA , Regulação para Baixo , Técnicas de Silenciamento de Genes , Humanos , Proteínas Nucleares/genética , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas c-mdm2/genética , Transcrição Gênica
8.
Nanotechnology ; 23(27): 275602, 2012 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-22706726

RESUMO

Vertically aligned ZnO nanowires (NWs) were grown on Au-nanocluster-seeded amorphous SiO(2) films by the advective transport and deposition of Zn vapours obtained from the carbothermal reaction of graphite and ZnO powders. Both the NW volume and visible-to-UV photoluminescence ratio were found to be strong functions of, and hence could be tailored by, the (ZnO+C) source-SiO(2) substrate distance. We observe C flakes on the ZnO NWs/SiO(2) substrates which exhibit short NWs that developed on both sides. The SiO(2) and C substrates/NW interfaces were studied in detail to determine growth mechanisms. NWs on Au-seeded SiO(2) were promoted by a rough ZnO seed layer whose formation was catalysed by the Au clusters. In contrast, NWs grew without any seed on C. A correlation comprising three orders of magnitude between the visible-to-UV photoluminescence intensity ratio and the NW volume is found, which results from a characteristic Zn partial pressure profile that fixes both O deficiency defect concentration and growth rate.


Assuntos
Carbono/química , Cristalização/métodos , Nanotubos/química , Nanotubos/ultraestrutura , Dióxido de Silício/química , Óxido de Zinco/química , Gases/química , Temperatura Alta , Substâncias Macromoleculares/química , Teste de Materiais , Conformação Molecular , Oxirredução , Tamanho da Partícula , Propriedades de Superfície
9.
Nefrologia ; 31(2): 174-84, 2011.
Artigo em Espanhol | MEDLINE | ID: mdl-21461011

RESUMO

INTRODUCTION: Important differences in patient survival exist between peritoneal dialysis (PD) and haemodialysis (HD). Several different studies have shown that PD yields a better survival rate than HD in the first and second years of treatment, especially in younger patients and non-diabetic patients with low comorbidity, whereas HD produces better results in diabetic patients, elderly patients, and in patients with greater comorbidity. In recent years, interesting changes have occurred in PD units in the Canary Islands, such as the introduction of peritoneal dialysis solutions with bicarbonate dialysate and low content of glucose degradation products, extended use of automated dialysis, and continuity of physicians and nurses in PD units, in addition to enhancing visits for advanced chronic kidney disease (ACKD). OBJECTIVE: This situation led us to perform our study with the primary objective of comparing medium-term survival among incident dialysis patients on HD versus PD in recent years in the Canary Islands, and as a secondary objective, to compare survival between these two types of dialysis by subgroups as defined by age, sex and diabetes. MATERIAL AND METHODS: This was a retrospective cohort study comparing survival between HD and PD patients starting dialysis in the Canary Islands between 01/01/2006 and 31/12/2009, with adjustment based on the propensity score analysis. We analysed data from the RERCAN database, which collects data on demographic variables, changes in type of dialysis, province and hospital of the patient, and mortality and its causes. We calculated Kaplan-Meier estimates of survival based on the overall population and stratified by age, sex and diabetes. We applied a Cox proportional hazards model for survival to estimate the relative mortality risk of PD compared with HD, using as independent variables: age, sex, quartiles of propensity score, the province of the patient, and diabetes. Finally, we applied a Cox model with time-dependent effects, using as a fixed risk factor the initial type of dialysis in order to assess the effect of PD versus HD on short and medium-term survival. RESULTS: The cohort included 1469 patients (173 PD and 1296 HD), with a mean age of 62.5 years, 65% male. Mean follow-up was 16.2±12.4 months. Factors associated with greater probability of choosing PD were younger age and living in the province of Las Palmas. The cumulative mortality in the intention to treat (ITT) analysis was 27.1% in the HD group and 8.7% in the PD group, P<.0001. The cumulative probability of survival by ITT using PD vs HD was 96.6% versus 89% at 6 months (P<.001), 96% versus 80% at 12 months (P<.001), 90% versus 65% at 24 months (P<.001), 82% versus 58% at 36 months (P<.001) and 73% versus 45% at 46 months (P<.001). In the subgroup analysis, survival was also higher in PD patients compared to HD patients both over and under 65 years old, in both diabetic and non-diabetic patients, and in both genders. The same analysis from the 90th day onward produced similar results. In the ITT analysis, the Cox-adjusted mortality risk for PD was 61% lower than for HD (RR: 0.398, 95% CI 0.237-0.669, P=.001), adjusted for age, diabetes, sex, patient's province and propensity score. Broken down by years of survival on the technique used, the relative risk of death for PD compared with HD in the first year was also significantly lower (RR 0.509, 95% CI: 0.259-0.999, P=.049). From year 2 onwards, only age was a risk factor for mortality (RR: 2.785, 95% CI: 1.525-5.086, P=.001) and no differences were shown between the two dialysis techniques. CONCLUSION: In the Canary Islands, PD has demonstrated survival advantages over HD in the short and medium term. It is remarkable that this benefit was found in young and old patients, men and women, and diabetic and non-diabetic patients, and that this advantage was maintained even after years of being on dialysis.


Assuntos
Falência Renal Crônica/terapia , Diálise Peritoneal , Adulto , Fatores Etários , Idoso , Doenças Cardiovasculares/mortalidade , Causas de Morte , Estudos de Coortes , Nefropatias Diabéticas/mortalidade , Nefropatias Diabéticas/terapia , Feminino , Humanos , Infecções/mortalidade , Estimativa de Kaplan-Meier , Falência Renal Crônica/mortalidade , Transplante de Rim/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Neoplasias/mortalidade , Diálise Peritoneal/estatística & dados numéricos , Modelos de Riscos Proporcionais , Sistema de Registros , Diálise Renal/estatística & dados numéricos , Estudos Retrospectivos , Fatores de Risco , Espanha/epidemiologia , Resultado do Tratamento
10.
Scand J Rheumatol ; 39(1): 50-7, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20132071

RESUMO

OBJECTIVES: Systemic lupus erythematosus (SLE) is characterized by the production of multiple autoantibodies and also by T-cell dysfunction. CD43 is expressed by most immune cells, is involved in lymphocyte adhesion and activation, and interacts with galectin-1 (Gal-1). The aim of this work was to evaluate the plasma levels of autoantibodies against CD43 and Gal-1 as well as the levels of soluble Gal-1 in SLE Mexican mestizo patients, with the aim of establishing a correlation between these parameters and the clinical profile. METHODS: Serum levels of immunoglobulin (Ig)G autoantibodies against CD43 and Gal-1 and levels of soluble Gal-1 were measured by enzyme-linked immunosorbent assay (ELISA) in 55 patients with SLE and 71 healthy controls. RESULTS: We found significantly enhanced titres of anti-CD43 and anti-Gal-1 antibodies in sera from SLE patients compared to controls. In addition, the serum levels of Gal-1 were significantly higher in SLE patients than in healthy individuals. However, we could detect no correlation of these parameters with disease activity [using the Mexican Systemic Lupus Erythematosus Disease Activity Index (MEX-SLEDAI)], age, or a variety of different clinical or laboratory features. Similarly, no significant correlation with immunosuppressive or glucocorticoid therapy was observed. By contrast, a significant association was found between anti-CD43 titres and time of disease evolution, complement levels, and the presence of anti-Gal-1 antibodies. CONCLUSIONS: As CD43 and Gal-1 participate in modulating the immune system, we suggest that the presence of autoantibodies against these molecules may contribute to the immune deregulation observed in SLE.


Assuntos
Autoanticorpos/sangue , Galectina 1/imunologia , Leucossialina/imunologia , Lúpus Eritematoso Sistêmico/imunologia , Adolescente , Adulto , Fatores Etários , Biomarcadores/sangue , Estudos de Casos e Controles , Ensaio de Imunoadsorção Enzimática , Feminino , Galectina 1/sangue , Humanos , Leucossialina/sangue , Lúpus Eritematoso Sistêmico/diagnóstico , Masculino , Prognóstico , Valores de Referência , Medição de Risco , Índice de Gravidade de Doença , Fatores Sexuais , Adulto Jovem
12.
Oncogene ; 29(3): 432-41, 2010 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-19838211

RESUMO

It has previously been shown that ubiquitin-specific protease 2a (USP2a) is a regulator of the Mdm2/p53 pathway. USP2a binds to Mdm2 and can deubiquitinate Mdm2 without reversing Mdm2-mediated p53 ubiquitination. Overexpression of USP2a causes accumulation of Mdm2 and promotes p53 degradation. We now show that MdmX is also a substrate for USP2a. MdmX associates with USP2a independently of Mdm2. Ectopic expression of wild-type USP2a but not a catalytic mutant prevents Mdm2-mediated degradation of MdmX. This correlates with the ability of wild-type USP2a to deubiquitinate MdmX. siRNA-mediated knockdown of USP2a in NTERA-2 testicular embryonal carcinoma cells and MCF7 breast cancer cells causes destabilization of MdmX and results in a decrease in MdmX protein levels, showing that endogenous USP2a participates in the regulation of MdmX stability. The therapeutic drug, cisplatin decreases MdmX protein expression. USP2a mRNA and protein levels were also reduced after cisplatin exposure. The magnitude and time course of USP2a downregulation suggests that the reduction in USP2a levels could contribute to the decrease in MdmX expression following treatment with cisplatin. Knockdown of USP2a increases the sensitivity of NTERA-2 cells to cisplatin, raising the possibility that suppression of USP2a in combination with cisplatin may be an approach for cancer therapy.


Assuntos
Endopeptidases/metabolismo , Proteínas Nucleares/metabolismo , Proteínas Proto-Oncogênicas c-mdm2/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Antineoplásicos/farmacologia , Western Blotting , Domínio Catalítico/genética , Proteínas de Ciclo Celular , Linhagem Celular Tumoral , Cisplatino/farmacologia , Regulação para Baixo/efeitos dos fármacos , Endopeptidases/genética , Humanos , Imunoprecipitação , Mutação , Proteínas Nucleares/genética , Ligação Proteica , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas c-mdm2/genética , Interferência de RNA , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Especificidade por Substrato , Transfecção , Ubiquitina Tiolesterase , Ubiquitinação
14.
Transplant Proc ; 41(6): 2334-6, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19715912

RESUMO

INTRODUCTION: The presence of hepatitis C virus (HCV) in renal transplant recipients is an independent risk factor for death and graft failure. Chronic allograft nephropathy (CAN) favored by the use of calcineurin inhibitors (CNI) is one of the main causes of graft loss, whereas sirolimus (SRL) has proven to maintain better graft function with lower rates of CAN. OBJECTIVES AND METHODS: We developed a protocol to evaluate the safety of SRL in transplant recipients with respect to HCV. We studied 5 patients (3 men) of mean age 52 +/- 9.2 years with HCV who had not received antiviral treatment. The viral genotypes were 1b in 4 cases and 2a/2c in 1 case. Basic immunosuppression was mycophenolate mofetil (MMF) and corticosteroids in all patients, cyclosporine (CsA) in 4 cases, and tacrolimus (Tac) in 1 case. Before the switch, a renal biopsy was performed and viral replication and cryoglobulins determined. RESULTS: Biopsy provided a diagnosis of CAN in 1 case, CNI toxicity-associated CAN in 2 cases, CNI toxicity in 1 case, and no renal damage in the remaining case. We observed a nonsignificant decrease in the number (log) of viral copies with a stabilization of renal function but with a slight to moderate increase in proteinuria. CONCLUSIONS: The switch seemed to be safe with no increase in viral copies. Graft renal function remained stable with increased proteinuria that must be supervised, even though it did not reach statistical significance.


Assuntos
Hepatite C/complicações , Imunossupressores/uso terapêutico , Transplante de Rim/imunologia , Sirolimo/uso terapêutico , Corticosteroides/uso terapêutico , Adulto , Ciclosporina/uso terapêutico , Eritropoetina/uso terapêutico , Seguimentos , Genótipo , Hepacivirus/genética , Hepatite C/patologia , Humanos , Transplante de Rim/patologia , Pessoa de Meia-Idade , Estudos Prospectivos , Proteínas Recombinantes , Segurança
15.
Rev. chil. endocrinol. diabetes ; 2(1): 5-12, ene. 2009. tab, graf
Artigo em Espanhol | LILACS | ID: lil-612518

RESUMO

Background: Medical treatment of obesity requires a multidisciplinary approach including dietary, exercise and behavioral interventions. Aim: To report the results of a multidisciplinary program for the treatment of obesity in children. Patients and Methods: Three hundred twenty four children (155 males), aged between 5 and 18 year, were treated with diet, exercise and behavioral modification, between 1999 and 2006. At baseline and at the end of follow up, weight, height, z score for body mass index (BMI), blood pressure and features of the metabolic syndrome were assessed. Results: z scores for IMC decreased by 0.28 points (95 percent confidence intervals: -0.31 to -0.25). Sixty percent of patients achieved a weight reduction of 5 percent of more of their initial weight. In a multiple linear regression model, weight loss was directly associated with the follow up time and inversely associated with the initial waist circumference. Patients had a reduction of 0.05 z score points of BMI per month (95 percent confidence intervals –0.07 to –0.025; p < 0.001), while adhering to the program. The overall compliance with the three months treatment period was 59 percent. Conclusions: In children and teenagers, a multidisciplinary management of obesity achieves a sustained weight loss, that ifs proportional to the lapse of adherence to the program.


Assuntos
Humanos , Masculino , Feminino , Pré-Escolar , Criança , Adolescente , Obesidade/terapia , Avaliação de Programas e Projetos de Saúde , Índice de Massa Corporal , Dieta , Exercício Físico , Índice Glicêmico , Resistência à Insulina , Estado Nutricional , Equipe de Assistência ao Paciente , Cooperação do Paciente , Estudos Prospectivos , Apoio Social , Sobrepeso/terapia , Relação Cintura-Quadril , Redução de Peso
16.
Transplant Proc ; 40(9): 3115-6, 2008 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-19010210

RESUMO

von Hippel-Lindau (VHL) disease is a genetic syndrome based on an abnormality of the VHL gene located on the short arm of chromosome 3. Clinically, it presents as multiple tumors at several levels. The VHL gene product (pVHL) acts as a tumor-suppressing protein. In conditions of hypoxia it leads to an increase in several growth factor levels. mTOR inhibitors have proved to have dual properties: immunosuppressive and antitumor effects. Herein we have presented a case in which conversion to sirolimus improved graft function and also caused regression of retinal angioblastomas.


Assuntos
Transplante de Rim/imunologia , Sirolimo/uso terapêutico , Doença de von Hippel-Lindau/cirurgia , Adenocarcinoma/cirurgia , Humanos , Imunossupressores/uso terapêutico , Neoplasias Renais/cirurgia , Masculino , Pessoa de Meia-Idade , Diálise Renal , Resultado do Tratamento
17.
Kidney Int Suppl ; (108): S94-S101, 2008 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-18379556

RESUMO

In order to prevent morbidity and mortality in peritoneal dialysis (PD), sodium and water balance as well as a minimal level of small-solute clearances are needed. The impact of three nocturnal peritoneal ultrafiltration (UF) profiles on UF and small solute clearance in patients on automated PD (APD) was studied: constant glucose concentration of 1.36% (flat) or modifying the glucose concentration of the heater bag (descendant: 3.86-1.36%; ascendant: 1.36-3.86%). Sixty-two patients were enrolled in the study and received each profile within a four-month period, thus serving as their own controls. UF was lower with the flat profile (367+/-420ml; P<0.01), but no difference was seen between the two higher glucose concentration profiles. Peritoneal Kt/V (pKt/V) and peritoneal creatinine clearance (CrpC) showed statistically higher values from the descendant vs ascendant vs flat profiles (pKt/V: 1.54+/-0.30 vs 1.45+/-0.30 vs 1.38+/-0.27, and CrpC: 36.9+/-7.9 vs 33.5+/-7.48 vs 29.92+/-7.5 mlmin(-1)). Multivariate analysis showed statistical significance for the following: in the intrasubject comparisons, the profile for pKt/V (F=9.109, P<0.001) and CrpC (F=11.697, P<0.001), and in the intersubjects comparisons, the effects of both gender (F=14.334, P<0.01) for pKt/V and peritoneal permeability for both parameters (pKt/V: F=4.37, P<0.05; CrpC: F=11.697, P<0.001). In conclusion, the application of ascendant and descendant UF profiles in automated PD is feasible and results in better UF and small solute clearances, thus preventing inadequate dialysis and volume overload..


Assuntos
Glicemia/metabolismo , Ritmo Circadiano/fisiologia , Creatinina/sangue , Nefropatias/sangue , Nefropatias/terapia , Diálise Peritoneal , Adulto , Idoso , Idoso de 80 Anos ou mais , Transporte Biológico/fisiologia , Doença Crônica , Feminino , Humanos , Nefropatias/fisiopatologia , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estudos Prospectivos , Resultado do Tratamento , Ultrafiltração
18.
Oncogene ; 26(29): 4234-42, 2007 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-17237821

RESUMO

The p53 tumour suppressor is regulated mainly by Mdm2, an E3 ubiquitin ligase that promotes the ubiquitylation and proteasome-mediated degradation of p53. Many agents that induce p53 are inhibitors of transcription, suggesting that the p53 pathway can detect a signal(s) arising from transcriptional malfunction. Mdm2 associates with TAFII250, a component of the general transcription factor TFIID. Inactivation of TAFII250 in ts13 cells, which express a temperature-sensitive mutant of TAFII250, leads to the induction of p53 and cell cycle arrest. In the present study, we show that TAFII250 stimulates the ubiquitylation and degradation of p53 in a manner that is dependent upon Mdm2 and requires its acidic domain. Mechanistically, TAFII250 downregulates Mdm2 auto-ubiquitylation, leading to Mdm2 stabilization, and promotes p53-Mdm2 association through a recently defined second binding site in the acidic domain of Mdm2. These data provide a novel route through which TAFII250 can directly influence p53 levels and are consistent with the idea that the maintenance of p53 turnover is coupled to the integrity of RNA polymerase II transcription.


Assuntos
Proteínas Proto-Oncogênicas c-mdm2/fisiologia , Fatores Associados à Proteína de Ligação a TATA/fisiologia , Fator de Transcrição TFIID/fisiologia , Proteína Supressora de Tumor p53/metabolismo , Animais , Sítios de Ligação , Linhagem Celular Tumoral , Histona Acetiltransferases , Humanos , Estrutura Terciária de Proteína , Proteínas Proto-Oncogênicas c-mdm2/metabolismo , Spodoptera , Fatores Associados à Proteína de Ligação a TATA/metabolismo , Fator de Transcrição TFIID/metabolismo , Ubiquitina/metabolismo
19.
Transplant Proc ; 38(8): 2434-7, 2006 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17097959

RESUMO

INTRODUCTION: Osteopenia and osteoporosis after renal transplantation have been associated with factors related to the cause of end-stage renal disease, as well as to clinical events and therapeutic factors in the posttransplant period. We studied the prevalence of low bone density (LBD) according to WHO criteria. METHODS: A cross-sectional study was performed in a cohort of 106 patients (54 men and 52 women) with functioning renal allografts, who underwent bone densitometry (DEXA) of the lumbar spine and femoral neck. Patients were grouped according to DEXA into those with normal bone density (NBD) or LBD. We studied clinical, analytical, and therapeutic variables. RESULTS: Thirtysix patients (34%) had NBD and 70 patients (66%) LBD. Weight was the only parameter showing a significant difference (P = .034), namely, among NBD it was 80.44+/-15.13 versus LBD 73.94 +/- 14.54 kg, respectively. Creatinine clearance (CCr) tended to be lower among patients with LBD 59.62 +/- 22.73 versus 69.59 +/- 28.15 mL/min in patients with NBD (P = .052). PTHi levels were higher in patients with LBD (149.39 +/- 110.75) than those with NBD (110.94 +/- 82.61) (P = .069). In the multivariate analysis the important determinants were weight Exp(ss) = 0.967 [CI = 0.939 to 0.996] (P = .036); CCr Exp(ss) = 0.982 [CI = 0.965 to 1.000] (P = .055); and PTHi levels Exp(ss) = 1.003 [CI = 0.932 to 0.994] (P = .059). CONCLUSIONS: Osteopenia and osteoporosis are frequent among kidney transplant patients (66%), with a similar distribution between the lumbar spine and femoral neck. Excess weight and possibly better renal function may be protective factors. The cumulative steroid dose showed a significant effect on bone density. As expected, secondary hyperparathyroidism in patients with renal impairment seemed to be a risk factor for LBD.


Assuntos
Densidade Óssea/fisiologia , Transplante de Rim/fisiologia , Absorciometria de Fóton , Adulto , Doenças Ósseas Metabólicas/epidemiologia , Estudos de Coortes , Estudos Transversais , Feminino , Fraturas Ósseas/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Osteoporose/epidemiologia , Pós-Menopausa , Complicações Pós-Operatórias/epidemiologia
20.
Scand J Immunol ; 64(6): 668-76, 2006 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17083624

RESUMO

Dendritic cells (DC) play a dual role in the immune response, participating in its induction, and the maintenance of immune tolerance. The aim of this work was to perform a quantitative and phenotypic analysis of DC generated in vitro in the presence of IL-10 in patients with systemic lupus erythematosus (SLE). Blood samples were obtained from 10 active and untreated patients with SLE and six controls. Monocyte-derived DC were generated in vitro in the presence or absence of IL-10, and a quantitative and phenotypic analysis was performed. We found that freshly isolated monocytes from SLE patients had an increased expression of CD11b. On the other hand, the efficiency of in vitro DC generation was diminished in blood samples from SLE patients for conventional DC, but not for IL-10-treated DC. A diminished expression of HLA-DR, CD9 and CD86 was observed in conventional DC from SLE patients compared with controls. In contrast, enhanced levels of HLA-DR, CD80, CD9 and CD151 tetraspanins, FN1 (a class II MHC-tetraspanin epitope), CD85j/ILT2 and CD69 were detected in IL-10-treated DC from SLE patients. Accordingly, the phenotypic profile of IL-10-treated DC was very different in SLE and controls. However, the synthesis of IL-10 and IL-12 was similar in IL-10-treated and conventional cells in both SLE patients and controls. Our findings on the aberrant phenotype of IL-10-treated DC in SLE and their normal efficiency of in vitro generation may be important for the design of future therapies of this condition based on the administration of DC to induce immune tolerance.


Assuntos
Antígenos CD/análise , Células Dendríticas/química , Células Dendríticas/efeitos dos fármacos , Antígenos HLA-DR/análise , Interleucina-10/farmacologia , Lúpus Eritematoso Sistêmico/imunologia , Adulto , Diferenciação Celular , Células Dendríticas/imunologia , Feminino , Citometria de Fluxo , Humanos , Masculino , Pessoa de Meia-Idade , Monócitos/química , Monócitos/citologia , Fenótipo , Receptores de Superfície Celular/análise
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