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1.
Nanotechnology ; 31(18): 185401, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-31935698

RESUMO

In this work, we have a demonstrated zinc oxide (ZnO) polymer-based ecofriendly piezoelectric nanogenerator (PENG) on a paper substrate for an energy harvesting application. The ZnO thin film is developed on the paper substrate, where different doping concentrations of Sn have been investigated systematically to validate the effect of doping towards enhancing the device performance. The piezoelectric potential of the fabricated device is evaluated by applying three different loads (4 N, 8 N, 22 N), where the source of the corresponding mechanical loads is based on the object of a musical drum stick. The results suggest that the pristine ZnO PENG device can generate a maximum output voltage and current of 2.15 V and 17 nA respectively. Moreover, the ZnO PENG device doped with 2.5% Sn achieved an even higher voltage (4.15 V) and current (36 nA) compared to pristine ZnO devices. In addition, the hydrothermal growth technique used to develop Sn-doped ZnO has the benefits of high scalability and low cost. Hence, the Sn-doped PENG device is a suitable candidate for energy harvesting applications operating in both uniform and non-uniform loading conditions.

2.
Nanotechnology ; 29(10): 105406, 2018 03 09.
Artigo em Inglês | MEDLINE | ID: mdl-29388558

RESUMO

Zinc oxide (ZnO) is a remarkable inorganic semiconductor with exceptional piezoelectric properties compared to other semiconductors. However, in comparison to lead-based hazardous piezoelectric materials, its properties have undesired limitations. Here we report a 5∼6 fold enhancement in piezoelectric features via chemical doping of copper matched to intrinsic ZnO. A flexible piezoelectric nanogenerator (F-PENG) device was fabricated using an unpretentious solution process of spin coating, with other advantages such as robustness, low-weight, improved adhesion, and low cost. The device was used to demonstrate energy harvesting from a standard weight as low as 4 gm and can work as a self-powered mass sensor in a broad range of 4 to 100 gm. The device exhibited a novel energy harvesting technique from a wind source due to its inherent flexibility. At three different velocities (10∼30 m s-1) and five different angles of attack (0∼180 degrees), the device validated the ability to discern different velocities and directions of flow. The device will be useful for mapping the flow of air apart from harvesting the energy. The simulation was done to verify the underlining mechanism of aerodynamics involved.

3.
Br J Psychiatry ; 202(1): 50-5, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23284150

RESUMO

BACKGROUND: Hippocampal shrinkage is commonly reported in schizophrenia, but its role in the illness is still poorly understood. In particular, it is unclear how clinical and psychosocial variables relate to hippocampal volumes. AIMS: To investigate neuroanatomic differences in the hippocampus using three-dimensional (3D) computational image analysis. METHOD: We used high-resolution magnetic resonance imaging and surface-based modelling to map the 3D profile of hippocampal differences in adults with schizophrenia (n = 67) and a healthy control group (n = 72). Manual tracings were used to create 3D parametric mesh models of the hippocampus. Regression models were used to relate diagnostic measures to maps of radial distance, and colour-coded maps were generated to show the profile of associations. RESULTS: There was no detectable difference between the schizophrenia and control groups in hippocampal radial distance. In the schizophrenia group, however, bilateral shape deflation was associated with greater illness severity (length of illness, positive and negative symptoms) and with poorer social functioning (educational level, quality of life and health status), which survived Bonferroni correction. CONCLUSIONS: Illness severity and poor social functioning may be associated with hippocampal deflation in schizophrenia. As a structural sign of poor outcome, imaging measures might help to identify a subgroup of patients who may need specific treatment to resist hippocampal shrinkage, such as cognitive rehabilitation or physical exercise.


Assuntos
Hipocampo/patologia , Imageamento Tridimensional/métodos , Esquizofrenia/patologia , Psicologia do Esquizofrênico , Atividades Cotidianas/psicologia , Adulto , Mapeamento Encefálico/métodos , Estudos de Casos e Controles , Estudos Transversais , Feminino , Nível de Saúde , Humanos , Processamento de Imagem Assistida por Computador/métodos , Imageamento Tridimensional/estatística & dados numéricos , Entrevista Psicológica , Imageamento por Ressonância Magnética/métodos , Masculino , Qualidade de Vida , Índice de Gravidade de Doença
4.
Nanoscale ; 13(48): 20615-20624, 2021 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-34874984

RESUMO

Efficaciously scavenging waste mechanical energy from the environment is an emerging field in the self-powered and self-governing electronics systems which solves battery limitations. It demonstrates enormous potential in various fields such as wireless devices, vesture, and portable electronic devices. Different surface textured PET triboelectric nanogenerators (TENGs) were developed by the laser pattern method in the previous work, with the line textured TENG device showing improved performance due to a larger surface contact area. Here, a polyethylene oxide (PEO) and polyvinyl alcohol (PVA) coated line patterned PET-based TENG was developed for the conversion of mechanical energy into useful electric energy. The PEO layer boosted the TENG output to 4 times higher than that of the PA6-laser patterned PET TENG device (our previous report) and 2-fold higher than that of a pristine line patterned TENG. It generated an open-circuit voltage, short circuit current, and instantaneous power density of 131 V, 2.32 µA, and 41.6 µW cm-2, respectively. The as-fabricated device was tested for 10 000 cycles for reliability evaluation, which shows no significant performance degradation. In addition, the device was deployed to power 10 LEDs with high intensity. Thus, this device can be used for ambient mechanical energy conversion and to power micro and nano-electronic devices.

5.
Arch Virol ; 155(7): 1047-57, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20443030

RESUMO

Two isolates of Capsicum chlorosis virus (CaCV, genus Tospovirus) from tomato (CaCV-To-Ind) and chilli (CaCV-Ch-Pan), collected from Haryana and Uttar Pradesh states of northern India respectively, were compared. A comparison of the amino acid sequences of their N genes revealed more than 96% identity, confirming that the virus isolates in India have a high degree of sequence conservation and are closely related to Australian isolates. Analysis of the host range of CaCV revealed no biological difference between the isolates, but they differed from CaCV-Australia. The nucleotide sequences of S, M and L RNA of CaCV-Ch-Pan were determined. The S RNA contains 3,105 nucleotides (nt), with NSs and N genes of 1,320 and 828 nt, respectively. The M RNA consists of 4,821 nt, with an NSm gene of 927 nt and a Gn/Gc gene of 3,366 nt. The intergenic regions of S and M RNA contain 824 and 425 nt, respectively. The L RNA consists of 8,912 nt, with an RNA-dependent RNA polymerase gene of 8,634 nt.


Assuntos
Capsicum/virologia , Doenças das Plantas/virologia , Solanum lycopersicum/virologia , Tospovirus/fisiologia , Sequência de Bases , Variação Genética , Interações Hospedeiro-Patógeno , Índia , Dados de Sequência Molecular , Filogenia , Folhas de Planta/virologia , RNA Viral/genética , Tospovirus/genética
6.
Nefrologia (Engl Ed) ; 40(3): 287-298, 2020.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-32417009

RESUMO

BACKGROUND: Diabetic Nephropathy (DN) is a major complication of Type 2 Diabetes Mellitus (T2DM) with high morbidity rates worldwide. OBJECTIVE: To determine the association of PPARγ rs1801282 polymorphism in T2DM and DN in south Indian population. METHODS: We have conducted a case-control study to test the association of rs1801282 polymorphism with T2DM and DN in 424 subjects (DN=128; T2DM=148 and controls=148) belonging to the south Indian population using ARMS-PCR and Sanger sequencing method. Further, a meta-analysis was performed for rs1801282 polymorphism from the published literature retrieved from various electronic databases to determine the susceptibility among T2DM and DN across various ethnic populations under five genetic models. RESULTS: The genotyping of rs1801282 polymorphism showed significant (p-value<0.05) association with DN and T2DM compared to controls. In the meta-analysis, no significant association (p-value>0.05) was noticed for rs1801282 with DN vs. controls in homozygote, heterozygote, allelic, recessive and dominant genetic models. However, a significant association was observed between rs1801282 SNP and T2DM under heterozygote (Jj vs JJ) genetic model with OR=0.56, (95%CI [0.43-0.74]), p≤0.0001 of Asian and Caucasian populations. CONCLUSION: Overall analysis suggests that the rs1801282 polymorphism might be associated with DN and T2DM. More case-control studies on the PPARγ gene with a larger sample size including all the confounding factors are required to corroborate the findings from this meta-analysis.


Assuntos
Diabetes Mellitus Tipo 2/genética , Nefropatias Diabéticas/genética , PPAR gama/genética , Polimorfismo de Nucleotídeo Único , Idoso , Estudos de Casos e Controles , Fatores de Confusão Epidemiológicos , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/etnologia , Nefropatias Diabéticas/epidemiologia , Nefropatias Diabéticas/etnologia , Etnicidade/genética , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Humanos , Índia/epidemiologia , Pessoa de Meia-Idade , Modelos Genéticos , Grupos Raciais/genética , Tamanho da Amostra
7.
Clin Transplant ; 23(5): 589-99, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19719728

RESUMO

This exploratory, multicenter, open-label study evaluated the efficacy and safety of FTY720, as a part of an immunosuppressive regimen, in combination with everolimus and steroids in de novo renal transplant recipients at increased risk of delayed graft function (DGF). Patients received FTY720 (5 mg) and everolimus (4 mg) 2-12 h pre-transplantation, followed by 2.5 mg/d FTY720 and concentration-controlled everolimus (4-8 ng/mL) post-transplant for 12 months. Induction therapy was prohibited. After enrollment of 56 of the planned 200 patients between 2000 and 2002, the recruitment was terminated. The primary endpoint, rate of graft loss, or death at three months was 15.4% and the biopsy-confirmed acute rejection was 42.3%. Death or graft loss at 12 months in the DGF and non-DGF arms was 36.0% and 25.9%, respectively. The mean estimated creatinine clearance at three months was 63 and 55 mL/min in the non-DGF and DGF groups, respectively, while at 12 months it was 56 mL/min in both the groups. Although there was no comparator arm, the results from this exploratory study (compared with data from other phases II and III trials) indicated no apparent benefits of FTY720-based regimens for prevention of acute rejection and preservation of renal function in renal transplant recipients at high risk of DGF.


Assuntos
Função Retardada do Enxerto/prevenção & controle , Rejeição de Enxerto/prevenção & controle , Imunossupressores/uso terapêutico , Transplante de Rim , Propilenoglicóis/uso terapêutico , Sirolimo/análogos & derivados , Esfingosina/análogos & derivados , Adulto , Função Retardada do Enxerto/etiologia , Quimioterapia Combinada , Everolimo , Feminino , Cloridrato de Fingolimode , Rejeição de Enxerto/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Sirolimo/uso terapêutico , Esfingosina/uso terapêutico , Taxa de Sobrevida , Resultado do Tratamento
10.
Bioorg Med Chem Lett ; 19(15): 4480-3, 2009 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-19500983
11.
Br J Cancer ; 99(10): 1579-85, 2008 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-19002179

RESUMO

Telatinib (BAY 57-9352) is an orally available, small-molecule inhibitor of vascular endothelial growth factor receptors 2 and 3 (VEGFR-2/-3) and platelet-derived growth factor receptor beta tyrosine kinases. In this multicentre phase I dose escalation study, 71 patients with refractory solid tumours were enroled into 14 days on/7 days off (noncontinuous dosing) or continuous dosing groups to receive telatinib two times daily (BID). Hypertension (23%) and diarrhoea (7%) were the most frequent study drug-related adverse events of CTC grade 3. The maximum-tolerated dose was not reached up to a dose of 1500 mg BID continuous dosing. Telatinib was rapidly absorbed with median t(max) of 3 hours or less. Geometric mean C(max) and AUC(0-12) increased in a less than dose-proportional manner and plateaued in the 900-1500 mg BID dose range. Two renal cell carcinoma patients reached a partial response. Tumour blood flow measured by contrast-enhanced magnetic resonance imaging and sVEGFR-2 plasma levels decreased with increasing AUC(0-12) of telatinib. Telatinib is safe and well tolerated up to a dose of 1500 mg BID continuous dosing. Based on pharmacokinetic and pharmacodynamic criteria, 900 mg telatinib BID continuously administered was selected as the recommended phase II dose.


Assuntos
Inibidores da Angiogênese/administração & dosagem , Antineoplásicos/administração & dosagem , Neoplasias/tratamento farmacológico , Piridazinas/administração & dosagem , Piridinas/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
12.
Antimicrob Agents Chemother ; 52(12): 4432-41, 2008 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-18824605

RESUMO

Future treatments for chronic hepatitis C virus (HCV) infection are likely to include agents that target viral components directly. Here, the preclinical characteristics of ITMN-191, a peptidomimetic inhibitor of the NS3/4A protease of HCV, are described. ITMN-191 inhibited a reference genotype 1 NS3/4A protein in a time-dependent fashion, a hallmark of an inhibitor with a two-step binding mechanism and a low dissociation rate. Under preequilibrium conditions, 290 pM ITMN-191 half-maximally inhibited the reference NS3/4A protease, but a 35,000-fold-higher concentration did not appreciably inhibit a panel of 79 proteases, ion channels, transporters, and cell surface receptors. Subnanomolar biochemical potency was maintained against NS3/4A derived from HCV genotypes 4, 5, and 6, while single-digit nanomolar potency was observed against NS3/4A from genotypes 2b and 3a. Dilution of a preformed enzyme inhibitor complex indicated ITMN-191 remained bound to and inhibited NS3/4A for more than 5 h after its initial association. In cell-based potency assays, half-maximal reduction of genotype 1b HCV replicon RNA was afforded by 1.8 nM; 45 nM eliminated the HCV replicon from cells. Peginterferon alfa-2a displayed a significant degree of antiviral synergy with ITMN-191 and reduced the concentration of ITMN-191 required for HCV replicon elimination. A 30-mg/kg of body weight oral dose administered to rats or monkeys yielded liver concentrations 12 h after dosing that exceeded the ITMN-191 concentration required to eliminate replicon RNA from cells. These preclinical characteristics compare favorably to those of other inhibitors of NS3/4A in clinical development and therefore support the clinical investigation of ITMN-191 for the treatment of chronic hepatitis C.


Assuntos
Antivirais , Proteínas de Transporte/antagonistas & inibidores , Hepacivirus/efeitos dos fármacos , Hepacivirus/enzimologia , Inibidores de Proteases , Proteínas não Estruturais Virais/antagonistas & inibidores , Proteínas Virais/antagonistas & inibidores , Animais , Antivirais/química , Antivirais/metabolismo , Antivirais/farmacologia , Linhagem Celular Tumoral , Avaliação Pré-Clínica de Medicamentos , Sinergismo Farmacológico , Hepacivirus/genética , Hepacivirus/fisiologia , Humanos , Interferon alfa-2 , Interferon-alfa/farmacologia , Peptídeos e Proteínas de Sinalização Intracelular , Fígado/metabolismo , Macaca fascicularis , Polietilenoglicóis/farmacologia , Inibidores de Proteases/química , Inibidores de Proteases/metabolismo , Inibidores de Proteases/farmacologia , Ratos , Proteínas Recombinantes , Replicação Viral/efeitos dos fármacos
13.
Acta Biomater ; 4(4): 827-37, 2008 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-18178532

RESUMO

Ionic elastin-like polypeptide (ELP) conjugates are a new class of biocompatible, self-assembling biomaterials. ELPs composed of the repeat unit (GVGVP)(n) are derived from the primary sequence of mammalian elastin and produced in Escherichia coli. These biopolymers exhibit an inverse transition temperature that renders them extremely useful for applications in cell-sheet engineering. Cationic and anionic conjugates were synthesized by the chemical coupling of ELP to polyethyleneimine (PEI) and polyacrylic acid (PAA). The self-assembly of ELP-PEI and ELP-PAA using the layer-by-layer deposition of alternately charged polyelectrolytes is a simple, versatile technique to generate bioactive and biomimetic surfaces with the ability to modulate cell-substratum interactions. Our studies are focused on cellular response to self-assembled multilayers of ionic (GVGVP)(40) incorporated within the polymeric sequence H(2)N-MVSACRGPG-(GVGVP)(40)-WP-COOH. Angle-dependent XPS studies indicated a difference in the chemical composition at the surface ( approximately 10A below the surface) and subsurface regions. These studies provided additional insight into the growth of the nanoscale multilayer assembly as well as the chemical environment that the cells can sense. Overall, cellular response was enhanced on glass substrata coated with ELP conjugates compared with uncoated surfaces. We report significant differences in cell proliferation, focal adhesions and cytoskeletal organization as a function of the number of bilayers in each assembly. These multilayer assemblies have the potential to be successfully utilized in the rational design of coatings on biomaterials to elicit a desired cellular response.


Assuntos
Elastina/farmacologia , Eletrólitos/farmacologia , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Nanoestruturas , Peptídeos/farmacologia , Células 3T3 , Animais , Carbono/metabolismo , Adesão Celular/efeitos dos fármacos , Contagem de Células , Proliferação de Células/efeitos dos fármacos , Citoesqueleto/efeitos dos fármacos , Adesões Focais/efeitos dos fármacos , Camundongos , Nitrogênio/metabolismo , Espectroscopia de Infravermelho com Transformada de Fourier , Análise Espectral
14.
Transplantation ; 82(12): 1689-97, 2006 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-17198261

RESUMO

BACKGROUND: Phase II trials of FTY720, a novel immunomodulator, have shown promise in preventing rejection with both standard and reduced cyclosporine exposure. This study was designed to confirm those findings. METHODS: This one-year, multicenter, randomized, phase III study in 696 de novo renal transplant patients compared FTY720 5 mg plus reduced-dose cyclosporine (RDC) or FTY720 2.5 mg plus full-dose cyclosporine (FDC) with mycophenolate mofetil (MMF) plus FDC. All patients received concomitant corticosteroid therapy without antibody induction. The primary efficacy composite endpoint was the incidence of first treated biopsy-proven acute rejection (treated BPAR), graft loss, death or premature study discontinuation at month 12. RESULTS: FTY720 2.5 mg plus FDC was demonstrated to be non-inferior to MMF plus FDC as the primary efficacy endpoint (30.8% and 30.6%) was comparable. The FTY720 5 mg plus RDC treatment regimen was discontinued due to an increased incidence of acute rejection episodes (primary endpoint 43.3%). FTY720 was associated with significantly lower creatinine clearance with a mean difference at 12 months between FTY720 2.5 mg plus FDC and MMF plus FDC of 8 ml/min. CONCLUSIONS: While FTY720 2.5 mg plus FDC yielded similar efficacy to MMF plus FDC, the FTY720 5 mg plus RDC did not allow a 50% reduction in cyclosporine exposure. The associated lower creatinine clearance indicated that FTY720 combined with cyclosporine provided no benefit over standard care.


Assuntos
Rejeição de Enxerto/prevenção & controle , Imunossupressores/uso terapêutico , Transplante de Rim , Propilenoglicóis/uso terapêutico , Esfingosina/análogos & derivados , Adulto , Creatinina/urina , Ciclosporina/administração & dosagem , Quimioterapia Combinada , Feminino , Cloridrato de Fingolimode , Humanos , Imunossupressores/administração & dosagem , Masculino , Pessoa de Meia-Idade , Ácido Micofenólico/administração & dosagem , Ácido Micofenólico/análogos & derivados , Ácido Micofenólico/uso terapêutico , Propilenoglicóis/administração & dosagem , Esfingosina/administração & dosagem , Esfingosina/uso terapêutico
15.
J Med Chem ; 48(23): 7468-76, 2005 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-16279806

RESUMO

As bacteria continue to develop resistance toward current antibiotics, we find ourselves in a continual battle to identify new antibacterial agents and targets. We report herein a class of boron-containing compounds termed borinic esters that have broad spectrum antibacterial activity with minimum inhibitory concentrations (MIC) in the low microgram/mL range. These compounds were identified by screening for inhibitors against Caulobacter crescentus CcrM, an essential DNA methyltransferase from gram negative alpha-proteobacteria. In addition, we demonstrate that borinic esters inhibit menaquinone methyltransferase in gram positive bacteria using a new biochemical assay for MenH from Bacillus subtilis. Our data demonstrate the potential for further development of borinic esters as antibacterial agents as well as leads to explore more specific inhibitors against two essential bacterial enzymes.


Assuntos
Antibacterianos/síntese química , Ácidos Borínicos/síntese química , Metilases de Modificação do DNA/antagonistas & inibidores , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Antibacterianos/química , Antibacterianos/farmacologia , Bacillus subtilis/efeitos dos fármacos , Bacillus subtilis/enzimologia , Ácidos Borínicos/química , Ácidos Borínicos/farmacologia , Caulobacter crescentus/efeitos dos fármacos , Caulobacter crescentus/enzimologia , Metilases de Modificação do DNA/química , Ésteres/síntese química , Ésteres/química , Ésteres/farmacologia , Bactérias Gram-Negativas/enzimologia , Bactérias Gram-Negativas/crescimento & desenvolvimento , Bactérias Gram-Positivas/enzimologia , Bactérias Gram-Positivas/crescimento & desenvolvimento , Cinética , Testes de Sensibilidade Microbiana , Proteobactérias/enzimologia , Relação Estrutura-Atividade
16.
Transplantation ; 80(11): 1633-5, 2005 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-16371936

RESUMO

Neoral was replaced with a generic cyclosporine formulation on our hospital formulary. We compared outcomes for de novo kidney transplant recipients who either received Gengraf (n=88) or Neoral (n=100) in a single-center, retrospective review. As compared to patients who received Neoral, patients who received Gengraf were significantly more likely to have an acute rejection episode (39% vs. 25%, P=0.04), more likely to have a second rejection episode (13% vs. 4%; P=0.03), or to have received an antibody preparation to treat acute rejection (19% vs. 8%; P=0.02). Patients treated with Gengraf had a higher degree of intrapatient variability for cyclosporine trough concentrations as determined by %CV (P<0.05). The incidence of acute rejection at 6 months posttransplant was significantly higher in patients who received Gengraf compared to Neoral. A larger, prospective analysis is warranted to compare these formulations of cyclosporine in de novo kidney transplant recipients.


Assuntos
Química Farmacêutica , Ciclosporina/farmacocinética , Ciclosporina/uso terapêutico , Rejeição de Enxerto/epidemiologia , Biópsia , Feminino , Rejeição de Enxerto/patologia , Humanos , Imunossupressores/farmacocinética , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Estudos Retrospectivos , Equivalência Terapêutica , Resultado do Tratamento
17.
Transplantation ; 80(2): 244-52, 2005 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-16041270

RESUMO

BACKGROUND: This 36-month, randomized, parallel-group study compared safety and efficacy of two doses of everolimus with mycophenolate mofetil (MMF) in de novo renal-transplant recipients. METHODS: Renal-allograft recipients received 1.5 mg/day or 3 mg/day of everolimus or 2 g/day of MMF, plus full-dose cyclosporine (CsA) and corticosteroids after randomization. For at least their first year, patients received study medication according to a double-blinded, double-dummy design. Concerns over nephrotoxicity led to a protocol amendment to an open-label design with reduced CsA troughs. RESULTS: Incidences of primary efficacy failure at 36 months (biopsy-proven acute rejection, graft loss, death, or loss to follow-up) were everolimus 1.5 mg/day, 33.7% (65/193); everolimus 3 mg/day, 34.0% (66/194); and MMF, 31.1% (61/196) (P=0.810). Antibody-treated acute rejection at 36 months was significantly lower with everolimus 1.5 mg (9.8%) than MMF (18.4%, P=0.014). Discontinuation for adverse events was more frequent with everolimus and hemolytic uremic syndrome, lymphoproliferative disease, and proteinuria, and higher serum creatinine occurred at increased frequency relative to the MMF arm. Creatinine levels in the everolimus arms were stable in follow-up: the mean rise in creatinine over the first 6 months of the open-label phase was 3 micromol/L or greater with everolimus and 7 micromol/L with MMF. However, serum creatinine levels were lower in the MMF group throughout. Death and graft loss were higher in the everolimus arms (not significant). CONCLUSIONS: As part of triple-drug immunosuppression, everolimus (1.5 or 3 mg/day) was as efficacious as MMF, although the side-effect profile featured increased adverse events. Nephrotoxicity/calcineurin-inhibitor-related adverse events will require judicious lowering of CsA exposure with monitoring of everolimus troughs.


Assuntos
Rejeição de Enxerto/prevenção & controle , Imunossupressores/uso terapêutico , Transplante de Rim/imunologia , Ácido Micofenólico/análogos & derivados , Sirolimo/análogos & derivados , Adolescente , Adulto , Idoso , Quimioterapia Combinada , Everolimo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ácido Micofenólico/uso terapêutico , Segurança , Sirolimo/uso terapêutico , Doadores de Tecidos/estatística & dados numéricos
18.
Diabetes Care ; 20(8): 1310-4, 1997 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-9250460

RESUMO

OBJECTIVE: The racial impact on graft outcome is not well defined in diabetic recipients. The purpose of this study is to analyze our experience with kidney-alone (A) and kidney-pancreas (KP) transplantation in type 1 diabetic recipients and evaluate the impact of racial disparity on outcome. RESEARCH DESIGN AND METHODS: The records of 217 kidney transplants (118 KA, 99 KP) performed on type 1 diabetic patients between 1985 and 1995 at the Medical University of South Carolina and the University of Texas Medical Branch were reviewed. RESULTS: A total of 53 (31%) white patients and 15 (33%) black patients experienced at least one episode of biopsy-proven acute rejection of the renal graft (NS). Patient survival at 1, 2, and 5 years was similar in white (92, 87, 69%) and black (91, 91, 69%) patients (NS). Kidney graft survival at 1, 2, and 5 years in the KA group was 72, 62, and 42% in blacks, compared with 79, 76, and 53% in whites (NS). Kidney graft survival at 1, 2, and 5 years in the KP group was 92, 92, and 74% in blacks, compared with 83, 77, and 58% in whites (NS). Pancreas graft survival at 1, 2, and 5 years was 81, 81, and 81% in blacks, compared with 81, 75, and 62% in whites (NS). Cox regression analysis revealed that donor age > or = 40 years increased the risk of renal graft failure 6.2-fold (P = 0.0001), whereas the addition of a pancreas transplant to a kidney and a living-related transplant decreased the risk of failure of the kidney graft 0.2 (P = 0.005) and 0.1 times (P = 0.005). CONCLUSIONS: Our results suggest that when compared with whites, there may be a trend toward an improved kidney and pancreas graft outcome in blacks undergoing KP transplants. These findings suggest that diabetes may override the risk factors that account for the pronounced disparity in outcome observed between nondiabetic white and black recipients.


Assuntos
População Negra , Diabetes Mellitus Tipo 1/cirurgia , Rejeição de Enxerto/genética , Sobrevivência de Enxerto/genética , Transplante de Rim , Transplante de Pâncreas , População Branca , Adulto , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/mortalidade , Feminino , Seguimentos , Sobrevivência de Enxerto/imunologia , Humanos , Transplante de Rim/mortalidade , Masculino , Transplante de Pâncreas/mortalidade , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , Doadores de Tecidos , Resultado do Tratamento
19.
Diabetes Care ; 6(1): 71-4, 1983.
Artigo em Inglês | MEDLINE | ID: mdl-6220878

RESUMO

In a large series of patients with insulin-dependent diabetes mellitus who were screened for autoantibodies, two patients were positive for antinuclear antibodies. Both of these patients developed severe renal disease with the renal biopsy findings of membranoproliferative glomerulonephritis. Multiple autoantibodies and circulating immune complexes were demonstrated in their sera. There was evidence suggesting complement consumption. This article illustrates that immune complex glomerulonephritis can occur in some patients with IDDM, particularly in those with antinuclear antibody and polyendocrine involvement, and that renal biopsy in such cases may have prognostic and therapeutic importance.


Assuntos
Anticorpos Antinucleares/análise , Autoanticorpos/análise , Diabetes Mellitus/imunologia , Glomerulonefrite/imunologia , Adulto , Complicações do Diabetes , Diabetes Mellitus/patologia , Feminino , Glomerulonefrite/patologia , Humanos , Doenças do Complexo Imune/imunologia , Doenças do Complexo Imune/patologia , Rim/patologia , Masculino
20.
Nefrología (Madrid) ; 40(3): 287-298, mayo-jun. 2020.
Artigo em Inglês | IBECS (Espanha) | ID: ibc-201529

RESUMO

ANTECEDENTES: La nefropatía diabética (ND) es una complicación importante de la diabetes mellitus de tipo 2 (DMT2) con altas tasas de morbilidad mundial. OBJETIVO: Determinar la asociación del polimorfismo rs1801282 de PPAR en la DMT2 y la ND en la población del sur de India. MÉTODOS: Hemos llevado a cabo un estudio de casos y controles para analizar la asociación del polimorfismo rs1801282 con la DMT2 y la ND en 424 sujetos (ND = 128; DMT2 = 148 y controles = 148) pertenecientes a la población del sur de India mediante RCP-ARMS y método de secuenciación de Sanger. Además, se realizó un metaanálisis para el polimorfismo de rs1801282 a partir de la literatura publicada en varias bases de datos electrónicas para determinar la sensibilidad entre la DMT2 y la ND en varias poblaciones étnicas con 5 modelos genéticos. RESULTADOS: El genotipado de polimorfismo rs1801282 demostró una asociación significativa (valor de p < 0,05) con la ND y la DMT2 en comparación con los controles. En el metaanálisis no se observó asociación significativa (valor de p > 0,05) de rs1801282 con la ND frente a los controles en modelos genéticos homocigóticos, heterocigóticos, alélicos, recesivos y dominantes. Sin embargo, se observó una asociación significativa entre el polimorfismo de nucleótido único (PNU) rs1801282 SNP y la DMT2 en el modelo genético heterocigótico (Jj frente a JJ) con OR = 0,56, (IC del 95%: 0,43-0,74; p ≤ 0,0001 de poblaciones asiáticas y caucásicas. CONCLUSIÓN: El análisis general sugiere que el polimorfismo rs1801282 puede asociarse a ND y a DMT2. Se precisan más estudios de casos y controles sobre el gen PPAR con un taman˜ o de la muestra mayor que incluya todos los factores de confusión para corroborar los resultados de este metaanálisis


BACKGROUND: Diabetic Nephropathy (DN) is a major complication of Type 2 Diabetes Mellitus (T2DM) with high morbidity rates worldwide. OBJECTIVE: To determine the association of PPAR rs1801282 polymorphism in T2DM and DN in south Indian population. METHODS: We have conducted a case-control study to test the association of rs1801282 polymorphism with T2DM and DN in 424 subjects (DN = 128; T2DM = 148 and controls = 148) belonging to the south Indian population using ARMS-PCR and Sanger sequencing method. Further, a meta-analysis was performed for rs1801282 polymorphism from the published literature retrieved from various electronic databases to determine the susceptibility among T2DM and DN across various ethnic populations under five genetic models. RESULTS: The genotyping of rs1801282 polymorphism showed significant (p-value < 0.05) association with DN and T2DM compared to controls. In the meta-analysis, no significant association (p-value > 0.05) was noticed for rs1801282 with DN vs. controls in homozygote, heterozygote, allelic, recessive and dominant genetic models. However, a significant association was observed between rs1801282 SNP and T2DM under heterozygote (Jj vs JJ) genetic model with OR = 0.56, (95%CI [0.43-0.74]), p ≤ 0.0001 of Asian and Caucasian populations. CONCLUSION: Overall analysis suggests that the rs1801282 polymorphism might be associated with DN and T2DM. More case-control studies on the PPAR gene with a larger sample size including all the confounding factors are required to corroborate the findings from this meta-analysis


Assuntos
Humanos , Pessoa de Meia-Idade , Idoso , Diabetes Mellitus Tipo 2/genética , Nefropatias Diabéticas/genética , PPAR gama/genética , Polimorfismo de Nucleotídeo Único , Estudos de Casos e Controles , Fatores de Confusão Epidemiológicos , Grupos Raciais/genética , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/etnologia , Nefropatias Diabéticas/epidemiologia , Nefropatias Diabéticas/etnologia , Etnicidade/genética , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Índia/epidemiologia , Modelos Genéticos , Tamanho da Amostra
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