Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 12 de 12
Filtrar
Mais filtros











Intervalo de ano de publicação
1.
Transplantation ; 106(11): e488-e498, 2022 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-35831929

RESUMO

BACKGROUND: Kidney transplant programs have variable thresholds to accept obese candidates. This study aimed to examine trends and the social context of obesity among United States dialysis patients and implications for kidney transplant access. METHODS: We performed a retrospective cohort study of 1 084 816 adults who initiated dialysis between January 2007 and December 2016 using the United States Renal Data System data. We estimated national body mass index (BMI) trends and 1-y cumulative incidence of waitlisting and death without waitlisting by BMI category (<18.5 kg/m 2 , ≥18.5 and <25 kg/m 2 [normal weight], ≥25 and <30 kg/m 2 [overweight], ≥30 and <35 kg/m 2 [class 1 obesity], ≥35 and <40 kg/m 2 [class 2 obesity], and ≥40 kg/m 2 [class 3 obesity]). We then used Fine-Gray subdistribution hazard regression models to examine associations between BMI category and 1-y waitlisting with death as a competing risk and tested for effect modification by End Stage Renal Disease (ESRD) network, patient characteristics, and neighborhood social deprivation index. RESULTS: The median age was 65 (interquartile range 54-75) y, 43% were female, and 27% were non-Hispanic Black. From 2007 to 2016, the adjusted prevalence of class 1 obesity or higher increased from 31.9% to 38.2%. Class 2 and 3 obesity but not class 1 obesity were associated with lower waitlisting rates relative to normal BMI, especially for younger individuals, women, those of Asian race, or those living in less disadvantaged neighborhoods ( pinteraction < 0.001 for all). CONCLUSIONS: Obesity prevalence is rising among US incident dialysis patients. Relative to normal BMI, waitlisting rates with class 2 and 3 obesity were lower and varied substantially by region, patient characteristics, and socioeconomic context.


Assuntos
Falência Renal Crônica , Diálise Renal , Adulto , Humanos , Estados Unidos/epidemiologia , Feminino , Idoso , Masculino , Diálise Renal/efeitos adversos , Estudos Retrospectivos , Falência Renal Crônica/diagnóstico , Falência Renal Crônica/epidemiologia , Falência Renal Crônica/cirurgia , Índice de Massa Corporal , Obesidade/epidemiologia , Meio Social
2.
Biochem Pharmacol ; 183: 114291, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33075312

RESUMO

Voltage-gated sodium (NaV) channels play crucial roles in a range of (patho)physiological processes. Much interest has arisen within the pharmaceutical industry to pursue these channels as analgesic targets following overwhelming evidence that NaV channel subtypes NaV1.7-NaV1.9 are involved in nociception. More recently, NaV1.1, NaV1.3 and NaV1.6 have also been identified to be involved in pain pathways. Venom-derived disulfide-rich peptide toxins, isolated from spiders and cone snails, have been used extensively as probes to investigate these channels and have attracted much interest as drug leads. However, few peptide-based leads have made it as drugs due to unfavourable physiochemical attributes including poor in vivo pharmacokinetics and limited oral bioavailability. The present work aims to bridge the gap in the development pipeline between drug leads and drug candidates by downsizing these larger venom-derived NaV inhibitors into smaller, more "drug-like" molecules. Here, we use molecular engineering of small cyclic peptides to aid in the determination of what drives subtype selectivity and molecular interactions of these downsized inhibitors across NaV subtypes. We designed a series of small, stable and novel NaV probes displaying NaV subtype selectivity and potency in vitro coupled with potent in vivo analgesic activity, involving yet to be elucidated analgesic pathways in addition to NaV subtype modulation.


Assuntos
Fragmentos de Peptídeos/farmacologia , Venenos de Escorpião/farmacologia , Bloqueadores do Canal de Sódio Disparado por Voltagem/farmacologia , Canais de Sódio Disparados por Voltagem/fisiologia , Animais , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fragmentos de Peptídeos/química , Venenos de Escorpião/química , Bloqueadores do Canal de Sódio Disparado por Voltagem/química , Xenopus laevis
3.
Dalton Trans ; 46(28): 9280-9286, 2017 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-28686272

RESUMO

Reactions of (NBu4)[TcOCl4] or [TcCl3(PPh3)2(CH3CN)] with in situ-prepared lithium arylselenolates and -tellurolates give (NBu4)[TcVO(ArE)4] (E = Se, Te; Ar = phenyl) and [TcIII(ArE)3(PPh3)(CH3CN)] (E = Se, Te; Ar = phenyl, 2,6-Me2phenyl, mesityl) complexes, respectively. The products contain square-pyramidal (TcV compounds) and trigonal bipyramidal (TcIII complexes) coordinated technetium atoms. Density functional theory calculations indicate that the Tc-chalcogen bonds in the TcIII compounds have a greater bond order than those in the TcV compounds.

6.
Rev Med Chil ; 137(2): 200-7, 2009 Feb.
Artigo em Espanhol | MEDLINE | ID: mdl-19543641

RESUMO

BACKGROUND: Health-related quality of life (HRQOL) among patients on chronic hemodialysis (CHD), is associated with mortality, complications and compliance to treatment. AIM: To assess HRQOL in a group of patients on CHD. PATIENTS AND METHODS: A cross-sectional multicenter study was carried out, involving 224 patients from five CHD units (3 private and 2 public) in Bio Bio Region, using the Kidney Disease Quality of Life -36 items (KDQOL-36) questionnaire and Karnofsky scale. Scores range from 0 to 100, with higher values representing a better HRQOL. RESULTS: Physical and Mental scales and subscales of symptoms, effect and the burden of kidney disease subscales rendered scores below 50 (the referential value), in 80%, 61%, 8%, 43% and 80% of evaluations, respectively. The lower scores were observed in patients with diabetes, coronary artery disease, hypoalbuminemia, serum creatinine below 9.4 mg/dL, age >or=55 years and in those with a low economic and educational level (p <0.05). CONCLUSIONS: HRQOL in patients on hemodialysis had values below the referential score in subjects with diabetes and coronary artery disease, poor nutritional status and a low educational and socioeconomic level. The incorporation of support professionals, such as social workers, psychologists, dieticians, covering psychosocial factors, could improve the patients quality of life.


Assuntos
Nível de Saúde , Falência Renal Crônica/terapia , Qualidade de Vida , Diálise Renal , Inquéritos e Questionários/normas , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Distribuição de Qui-Quadrado , Estudos Transversais , Feminino , Humanos , Avaliação de Estado de Karnofsky , Masculino , Pessoa de Meia-Idade , Diálise Renal/efeitos adversos , Fatores Socioeconômicos , Adulto Jovem
7.
Rev. méd. Chile ; 137(2): 200-207, feb. 2009. tab
Artigo em Espanhol | LILACS | ID: lil-516084

RESUMO

patients on chronic hemodialysis Background: Health-related quality of life (HRQOL) among patients on chronic hemodialysis (CHD), is associated with mortality, complications and compliance to treatment. Aim: To assess HRQOL in a group of patients on CHD. Patients andmethods: A cross-sectional multicenter study was carried out, involving 224 patients from five CHD units (3 private and 2 public) in Bio Bio Region, using the Kidney Disease Quality of Life – 36 items (KDQOL-36) questionnaire and Karnofsky scale. Scores range from 0 to 100, with higher values representing a better HRQOL. Results: Physical and Mental scales and subscales of symptoms, effect and the burden of kidney disease subscales rendered scores below 50 (the referential value), in 80%, 61%, 8%, 43% and 80% of evaluations, respectively. The lower scores were observed in patients with diabetes, coronary artery disease, hypoalbuminemia...


Assuntos
Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Nível de Saúde , Falência Renal Crônica/terapia , Qualidade de Vida , Inquéritos e Questionários/normas , Diálise Renal , Distribuição de Qui-Quadrado , Estudos Transversais , Avaliação de Estado de Karnofsky , Diálise Renal/efeitos adversos , Fatores Socioeconômicos , Adulto Jovem
8.
Cell Mol Biol (Noisy-le-grand) ; 53 Suppl: OL954-64, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17695085

RESUMO

Oxidized low density lipoproteins (oxLDL), macrophages and T-lymphocytes are present in atherosclerotic lesions. We and others have shown that oxLDL is cytotoxic for macrophages, endothelial, smooth muscle and activated T-lymphocytes and induce apoptosis. Here we demonstrate that (i) oxidized LDL (oxLDL), oxidized VLDL (oxVLDL) and hydrogen peroxide (H2O2) induce apoptosis in human T-lymphocytes and (ii) mitogen-activated protein kinases are involved in this process. Apoptosis was monitored by immunofluorescence microscopy and flow cytometry for annexin V binding, Apo 2.7 expression, the TUNEL reaction and caspase 3 activity. In the presence of oxLDL (100 microg/ml), oxVLDL (50 microg/ml) and H2O2 (5 mM), the fraction of apoptotic cells increased within 6 hours to more than 70%. Preincubation of lymphocytes with the MAPKK inhibitor PD-98059 and the p38MAPK inhibitor SB-203580 almost completely abolished these effects. Furthermore, oxLDL and H2O2 but not native LDL strongly enhanced phosphorylation of JNK, p38MAPK and p42/44MAPK. The results suggest that in the resting lymphocyte apoptosis triggered by oxidized lipoproteins and oxidative stress depends on the activation of p44/42MAPK and p38MAPK cascades.


Assuntos
Apoptose/efeitos dos fármacos , Lipoproteínas LDL/farmacologia , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Linfócitos T/metabolismo , Anexina A5/metabolismo , Caspase 3/análise , Caspase 3/metabolismo , Células Cultivadas , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/farmacologia , Flavonoides/farmacologia , Humanos , Imidazóis/farmacologia , Proteínas Quinases Ativadas por Mitógeno/antagonistas & inibidores , Oxirredução , Estresse Oxidativo , Piridinas/farmacologia , Fatores de Tempo
9.
Rev Med Chil ; 129(2): 141-8, 2001 Feb.
Artigo em Espanhol | MEDLINE | ID: mdl-11351464

RESUMO

BACKGROUND: Advanced glycation end products are associated with chronic complications of diabetes mellitus. This glycation process renders many proteins immunogenic. AIM: To detect the presence of antibodies against albumin, collagen and low density lipoprotein glycation products in boys and teenagers with diabetes mellitus. PATIENTS AND METHODS: Thirty one patients with diabetes mellitus type I, aged 11 +/- 3.8 years and with a mean duration of disease of 3.7 +/- 2.7 years and 31 healthy controls aged 12.4 +/- 5.3 years were studied. Antibodies against glycation end products were detected by ELISA and results were expressed as a ratio of the optical density of the glycated protein/optical density of the native protein. RESULTS: Diabetic patients and healthy controls did not have antibodies against albumin glycation end products. Diabetics had higher levels of antibodies than controls for collagen glycation end products (2.6 +/- 0.4 and 1.8 +/- 0.2 respectively, p < 0.01) and low density lipoprotein glycation end products (3.07 +/- 0.92 and 2.2 +/- 0.72 respectively, p < 0.05). CONCLUSIONS: The biological role of these antibodies is not clear. They could be a depuration mechanism for glycation end products or contribute to chronic complications of diabetes mellitus.


Assuntos
Autoanticorpos/sangue , Diabetes Mellitus Tipo 1/imunologia , Produtos Finais de Glicação Avançada/imunologia , Proteínas/imunologia , Adolescente , Estudos de Casos e Controles , Criança , Pré-Escolar , Diabetes Mellitus Tipo 1/sangue , Produtos Finais de Glicação Avançada/sangue , Humanos , Proteínas/metabolismo
10.
Rev. méd. Chile ; 129(2): 141-8, feb. 2001. ilus, tab
Artigo em Espanhol | LILACS | ID: lil-284979

RESUMO

Background: Advanced glycation end products are associated with chronic complications of diabetes mellitus. This glycation process renders many proteins immunogenic. Aim: To detect the presence of antibodies against albumin, collagen and low density lipoprotein glycation products in boys and teenagers with diabetes mellitus. Patients and methods : Thirty one patients with diabetes mellitus type I, aged 11ñ3.8 years and with a mean duration of disease of 3.7ñ2.7 years and 31 healthy controls aged 12.4ñ5.3 years were studied. Antibodies against glycation end products were detected by ELISA and results were expressed as a ratio of the optical density of the glycated protein/optical density of the native protein. Results : Diabetic patients and healthy controls did not have antibodies against albumin glycation end products. Diabetics had higher levels of antibodies than controls for collagen glycation end products (2.6ñ0.4 and 1.8ñ0.2 respectively, p< 0.01) and low density lipoprotein glycation end products (3.07ñ0.92 and 2.2ñ0.72 respectively, p< 0.05). Conclusions: The biological role of these antibodies is not clear. They could be a depuration mechanism for glycation end products or contribute to chronic complications of diabetes mellitus


Assuntos
Humanos , Masculino , Feminino , Pré-Escolar , Adolescente , Autoanticorpos/sangue , Diabetes Mellitus Tipo 1/imunologia , Produtos Finais de Glicação Avançada/imunologia , Ensaio de Imunoadsorção Enzimática , Estudos de Casos e Controles
11.
Rev. méd. Chile ; 127(11): 1305-11, nov. 1999. tab
Artigo em Espanhol | LILACS | ID: lil-257988

RESUMO

Background: immune cells participate in the formation of atheromatous plate, however little is known about the effects of native or oxidatively modified lipoproteins on these cells. Aim: To study the effects of lipoproteins on in vitro mononuclear cell proliferation. Material and methods: peripheral blood mononuclear cells were obtained from 10 patients with type 2 diabetes mellitus (aged 52 ñ 9 years old with a disease duration of 8.2 ñ 5.7 years and a mean glycosilated hemoglobin of 9.3 ñ 2.2 percent) and 10 non diabetic healthy controls (aged 50.3 ñ 7.1 years old). These were stimulated with phytohemagglutinin (PHA) alone or in the presence of native LDLS, malondialdehyde modified LDLs or glycated LDLs. Proliferation was measured as 3H-thymidine incorporation and expressed as Stimulation Index (SI). Results: SI of patients and healthy subjects, after PHA stimulation were similar: (57.5 ñ 29.8 and 61.1 ñ 23.5) respectively LDLs did not induce proliferation in neither group. Native LDLs produced a 98 percent inhibition of PHA induced proliferation. Malondialdehyde modified and glycated LDLs caused a 50 percent inhibition. The suppressive effect was maintained when lipoproteins were incorporated to culture media 60 min prior or after PHA stimulation. Conclusions: Lipoproteins inhibit in vitro PHA induced peripheral blood mononuclear cell proliferation both in diabetic and in non diabetic subjects


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Diabetes Mellitus Tipo 2/imunologia , Terapia de Imunossupressão , Técnicas In Vitro , Lipoproteínas LDL/imunologia , Fito-Hemaglutininas/farmacologia , Transtornos Linfoproliferativos/imunologia , Ativação Linfocitária
12.
Rev Med Chil ; 127(11): 1305-11, 1999 Nov.
Artigo em Espanhol | MEDLINE | ID: mdl-10835716

RESUMO

BACKGROUND: Immune cells participate in the formation of atheromatous plate, however little is known about the effects of native or oxidatively modified lipoproteins on these cells. AIM: To study the effects of lipoproteins on in vitro mononuclear cell proliferation. MATERIAL AND METHODS: Peripheral blood mononuclear cells were obtained from 10 patients with type 2 diabetes mellitus (aged 52 +/- 9 years old with a disease duration of 8.2 +/- 5.7 years and a mean glycosilated hemoglobin of 9.3 +/- 2.2%) and 10 non diabetic healthy controls (aged 50.3 +/- 7.1 years old). These were stimulated with phytohemagglutinin (PHA) alone or in the presence of native LDLS, malondialdehyde modified LDLs or glycated LDLs. Proliferation was measured as 3H-thymidine incorporation and expressed as Stimulation Index (SI). RESULTS: SI of patients and healthy subjects, after PHA stimulation were similar: (57.5 +/- 29.8 and 61.1 +/- 23.5) respectively LDLs did not induce proliferation in neither group. Native LDLs produced a 98% inhibition of PHA induced proliferation. Malondialdehyde modified and glycated LDLs caused a 50% inhibition. The suppressive effect was maintained when lipoproteins were incorporated to culture media 60 min prior or after PHA stimulation. CONCLUSIONS: Lipoproteins inhibit in vitro PHA induced peripheral blood mononuclear cell proliferation both in diabetic and in non diabetic subjects.


Assuntos
Diabetes Mellitus Tipo 2/imunologia , Lipoproteínas LDL/farmacologia , Linfócitos T/efeitos dos fármacos , Adulto , Idoso , Divisão Celular/efeitos dos fármacos , Células Cultivadas , Diabetes Mellitus Tipo 2/metabolismo , Feminino , Humanos , Ativação Linfocitária/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Fito-Hemaglutininas/farmacologia , Linfócitos T/imunologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA