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1.
J Neuroimmunol ; 362: 577769, 2022 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-34871864

RESUMO

Cancer-related cognitive decline (CRCD) is a clinically important problem and negatively affects daily functioning and quality of life. We conducted a pilot longitudinal study from pre- to post-chemotherapy in patients with breast cancer to assess changes in inflammation and cognition over time, as well as the impact of baseline cytokine level on post-chemotherapy cognitive scores. We found that concentrations of IL-6, MCP-1, sTNFRI, and sTNFRII significantly increased in patients, while IL-1ß significantly decreased (p < 0.05). After controlling for covariates, increases in IL-6 and MCP-1 were associated with worse executive function and verbal fluency in patients from pre- to post-chemotherapy (p < 0.05). Higher baseline IL-6 was associated with better performance on executive function and verbal fluency post chemotherapy (p < 0.05). Overall, these results suggest that chemotherapy-associated increases in cytokines/receptors is associated with worse cognitive function. Larger studies are needed to confirm these findings.


Assuntos
Antineoplásicos/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Disfunção Cognitiva/induzido quimicamente , Disfunção Cognitiva/imunologia , Citocinas/imunologia , Adulto , Idoso , Estudos de Coortes , Citocinas/sangue , Feminino , Humanos , Inflamação/induzido quimicamente , Inflamação/imunologia , Estudos Longitudinais , Pessoa de Meia-Idade , Projetos Piloto
2.
J Cancer Educ ; 35(2): 292-300, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-30612315

RESUMO

To examine whether (a) non-minority participants differed from racial minority participants in the understanding of biospecimens collected for research purposes, (b) patients differed from comparison group in their understanding of the ways their biospecimens could be used by researchers, and (c) participants received adequate information before consenting to donate blood for research studies. We analyzed cross-sectional data from female breast cancer patients scheduled to receive chemotherapy at the National Cancer Institute (NCI) Community Oncology Research Program (NCORP) clinical sites and a healthy comparison group. After reading a consent form related to biospecimens and consenting to participate in a clinical trial, participants' understanding of biospecimen collection was evaluated. Linear models were used to compare scores between non-minority and racial minority participants as well as cancer and non-cancer comparisons adjusting for possible confounding factors. A total of 650 participants provided evaluable data; 592 were non-minority (Caucasian) and 58 participants were a racial minority (71% Black and 29% other). There were 427 cancer patients and 223 comparisons. Non-minority participants scored higher than racial minorities on relevance-to-care items (diff. = 0.48, CI 0.13-0.80, p = 0.001). Comparison group scored higher than cancer patients on relevance-to-care items (diff. = 0.58, CI 0.37-0.78). A moderate number of the participants exhibited a poor understanding of biospecimen collection across all racial/ethnic backgrounds, but racial minority participants' scores remained lower in the relevance-to-care subscale even after adjusting for education and reading level. Differences were also noted among the patients and comparison group. Researchers should facilitate comprehension of biospecimen collection for all study participants, especially racial minority participants.


Assuntos
Bancos de Espécimes Biológicos/estatística & dados numéricos , Neoplasias da Mama/etnologia , Ensaios Clínicos como Assunto/estatística & dados numéricos , Compreensão , Etnicidade/educação , Etnicidade/psicologia , Disparidades nos Níveis de Saúde , Adulto , Negro ou Afro-Americano/educação , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/psicologia , Estudos de Casos e Controles , Estudos Transversais , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Pessoa de Meia-Idade , Participação do Paciente , Manejo de Espécimes , População Branca/educação , Adulto Jovem
3.
Am J Physiol Regul Integr Comp Physiol ; 297(5): R1532-45, 2009 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-19759333

RESUMO

During the brain's innate immune response microglia, astroglia and ependymal cells resolve/repair damaged tissue and control infection. Released interleukin-1beta (IL-1beta) reaching cerebroventricles stimulates circumventricular organs (CVOs; subfornical organ, SFO; organum vasculosum lamina terminalis, OVLT), the median preoptic nucleus (MePO), and magnocellular and parvocellular neurons in the supraoptic (SON) and paraventricular (PVN) nuclei. Hypertonic saline (HS) also activates these osmosensory CVOs and neuroendocrine systems, but, in contrast to IL-1beta, inhibits the peripheral immune response. To examine whether the brain's innate immune response is attenuated by osmotic stimulation, sterile acidic perfusion fluid was microdialyzed (2 microl/min) in the SON area of conscious rats for 6 h with sterile HS (1.5 M NaCl) injected subcutaneously (15 ml/kg) at 5 h. Immunohistochemistry identified cytokine sources (IL-1beta(+); OX-42(+) microglia) and targets (IL-1R(+); inducible cyclooxygenase, COX-2(+); c-Fos(+)) near the probe, in CVOs, MePO, ependymal cells, periventricular hypothalamus, SON, and PVN. Inserting the probe stimulated magnocellular neurons (c-Fos(+); SON; PVN) via the MePO (c-Fos(+)), a response enhanced by HS. Microdialysis activated microglia (OX-42(+); amoeboid/hypertrophied; IL-1beta(+)) in the adjacent SON and bilaterally in perivascular areas of the PVN, periventricular hypothalamus and ependyma, coincident with c-Fos expression in ependymal cells and COX-2 in the vasculature. These microglial responses were attenuated by HS, coincident with activating parvocellular and magnocellular neuroendocrine systems and elevating circulating IL-1beta, oxytocin, and vasopressin. Acidosis-induced cellular injury from microdialysis activated the brain's innate immune response by a mechanism inhibited by peripheral osmotic stimulation.


Assuntos
Encéfalo/imunologia , Imunidade Inata/fisiologia , Osmose/fisiologia , Solução Salina Hipertônica/farmacologia , Núcleo Supraóptico/efeitos dos fármacos , Núcleo Supraóptico/metabolismo , Acidose/metabolismo , Acidose/fisiopatologia , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Modelos Animais de Doenças , Epêndima/efeitos dos fármacos , Epêndima/metabolismo , Imunidade Inata/efeitos dos fármacos , Interleucina-1beta/metabolismo , Masculino , Microdiálise , Microglia/efeitos dos fármacos , Microglia/fisiologia , Núcleos da Linha Média do Tálamo/efeitos dos fármacos , Núcleos da Linha Média do Tálamo/metabolismo , Ocitocina/metabolismo , Ratos , Ratos Sprague-Dawley , Solução Salina Hipertônica/administração & dosagem , Vasopressinas/metabolismo
4.
Brain Res ; 983(1-2): 162-73, 2003 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-12914977

RESUMO

We tested the hypothesis that in spontaneously hypertensive rat (SHR) NO produced centrally influences the resting arterial blood pressure by attenuating mechanisms involving prostaglandins, angiotensin II, endothelin and sympathetic nervous system. L-NAME (200 micro g/5 micro l), an inhibitor of NO synthase, administered intracerebroventricularly (i.c.v.) to awake and freely moving rats increased mean arterial blood pressure (MABP) in a biphasic pattern: an early transient increase within 1 min and a late prolonged response starting at 45 min and persisting for the duration of experiment (180 min). The two pressor responses involve different neurochemical mechanisms and, based on their latencies, they appear to reflect different anatomical sites of action of L-NAME. The late, but not the early pressor response, was prevented by pretreatment with chlorisondamine (2.5 mg/kg, i.v.), a ganglionic blocker, indicating its dependence on the sympathetic nervous system. Both pressor responses were abolished by i.c.v. pretreatment with indomethacin (200 micro g/5 micro l, i.c.v.), an inhibitor of cyclo-oxygenase, showing that they are mediated by prostaglandin(s). In contrast, losartan (25 micro g/5 micro l), an angiotensin II AT(1) receptor antagonist, had no effect. The initial pressor response was also attenuated by pretreatment with the endothelin ET(A)/ET(B) receptor antagonist, PD 145065 (48 micro g/2 micro l, i.c.v.). Intravenous pretreatment with another ET(A)/ET(B) receptor antagonist, L-754,142 (15 mg/kg as a bolus+15 mg/kg/h for 180 min), however, attenuated both responses to L-NAME. It is possible that L-754,142 crossed the blood-brain barrier and blocked, in addition, central ET(A)/ET(B) receptors. These studies show that NO synthesized in the brain attenuates pressor mechanisms involving prostaglandin, endothelin and sympathetic nervous system, but not angiotensin II, to modulate resting arterial blood pressure.


Assuntos
Pressão Sanguínea/efeitos dos fármacos , Endotelinas/fisiologia , Inibidores Enzimáticos/farmacologia , NG-Nitroarginina Metil Éster/farmacologia , Óxido Nítrico Sintase/antagonistas & inibidores , Óxido Nítrico/fisiologia , Prostaglandinas/fisiologia , Sistema Nervoso Simpático/fisiologia , Acetamidas/farmacologia , Angiotensina II/metabolismo , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Animais , Clorisondamina/farmacologia , Inibidores de Ciclo-Oxigenase/farmacologia , Antagonistas dos Receptores de Endotelina , Inibidores Enzimáticos/administração & dosagem , Bloqueadores Ganglionares/farmacologia , Frequência Cardíaca/efeitos dos fármacos , Indometacina/farmacologia , Injeções Intraventriculares , Losartan/farmacologia , Masculino , NG-Nitroarginina Metil Éster/administração & dosagem , Óxido Nítrico Sintase Tipo I , Oligopeptídeos/farmacologia , Ratos , Ratos Endogâmicos SHR
5.
Mol Endocrinol ; 17(11): 2251-67, 2003 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-12907752

RESUMO

Previous studies have suggested that upstream stimulatory factors (USFs) regulate genes involved with cell cycle progression. Because of the relationship of USFs to an important oncogene in breast cancer, c-myc, we chose to determine the importance of USF to normal mammary gland development in the mouse. Expression of USF in the mammary gland throughout development demonstrated only modest changes. Mutation of the Usf2 gene was associated with reduced fertility in females, but had no effect on prepartum mammary gland development. However, lactation performance in Usf2-/- females was only half of that observed in Usf2+/+ females, and both lactose and nitrogen were decreased in milk from Usf2-/- dams. This decrease was associated with diminished mammary tissue wet weight and luminal area by d 9 of lactation and with a decreased protein-DNA ratio. This decrease was associated with reduced abundance of the eukaryotic initiation factors eIF4E and eIF4G. Blood oxytocin concentrations on d 9 postpartum were also lower in Usf2-/- mice than Usf2+/+ mice. In contrast, the mutation had no effect on blood prolactin concentrations, mammary cell proliferation or apoptosis, mammary tissue oxytocin receptors, or milk protein gene expression. The mutation had only modest effects on maternal behavior. These data support the idea that USF is important to physiological processes necessary for the establishment and maintenance of normal lactation and suggest that USF-2 may impact lactation through both systemic and mammary cell-specific mechanisms.


Assuntos
Proteínas de Ligação a DNA/deficiência , Proteínas de Ligação a DNA/genética , Fator de Iniciação 4E em Eucariotos/metabolismo , Fator de Iniciação Eucariótico 4G/metabolismo , Glândulas Mamárias Animais/metabolismo , Leite/metabolismo , Ocitocina/sangue , Fatores de Transcrição/deficiência , Fatores de Transcrição/genética , Animais , Proteínas de Ligação a DNA/metabolismo , Feminino , Lactação , Comportamento Materno , Camundongos , Camundongos Transgênicos , Leite/química , Proteínas do Leite/genética , Mutação/genética , Tamanho do Órgão , Gravidez , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Fatores de Transcrição/metabolismo , Fatores Estimuladores Upstream
6.
Brain Res ; 940(1-2): 10-20, 2002 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-12020869

RESUMO

Magnocellular neurons are innervated by an excitatory histaminergic pathway. They also express neuronal NO synthase, interleukin-1beta (IL-1beta) and cyclo-oxygenase (COX). In normally hydrated rats when NO synthase activity is inhibited with N(G)-nitro-L-arginine methyl ester (L-NAME), administered intracerebroventricularly (i.c.v.), OT concentration in plasma increases. In the present study, the increase in hormone after L-NAME is attenuated by indomethacin, an inhibitor of COX, as well as by antagonists of histamine receptors at H1 (pyrilamine) and H2 (cimetidine) subtypes injected i.c.v. Moreover, enhanced OT secretion induced by centrally administered IL-1beta, but not naloxone (opiate receptor antagonist), is prevented by indomethacin. PGE2 and PGD2 (i.c.v.) stimulate OT release, but only PGD2 affects circulating vasopressin levels. Thus, NO inhibits release of OT stimulated by: (1) a COX-dependent mechanism, i.e. NO-->-(COX-->+PG-->+OT release); (2) histamine, i.e. NO-->-(histamine-->H1 and H2 receptors-->+OT release); and possibly (3) IL-1beta, i.e. NO-->-(IL-1beta-->+COX-->+PG-->+OT release). These interactions of NO, cytokine and histamine may be important for management of stress-induced activation of neuroendocrine systems.


Assuntos
Interleucinas/metabolismo , Neurônios/metabolismo , Sistemas Neurossecretores/metabolismo , Óxido Nítrico/metabolismo , Prostaglandinas/metabolismo , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Relação Dose-Resposta a Droga , Ativação Enzimática/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Feminino , Antagonistas dos Receptores Histamínicos H1/administração & dosagem , Antagonistas dos Receptores H2 da Histamina/administração & dosagem , Injeções Intraventriculares , Interleucina-1/administração & dosagem , Masculino , NG-Nitroarginina Metil Éster/farmacologia , Antagonistas de Entorpecentes/farmacologia , Neurônios/efeitos dos fármacos , Sistemas Neurossecretores/efeitos dos fármacos , Óxido Nítrico Sintase/antagonistas & inibidores , Óxido Nítrico Sintase/metabolismo , Óxido Nítrico Sintase Tipo I , Concentração Osmolar , Ocitocina/sangue , Prostaglandina-Endoperóxido Sintases/metabolismo , Ratos , Ratos Sprague-Dawley , Vasopressinas/sangue , Privação de Água/fisiologia
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