RESUMO
CASE REPORT: A 54 year-old woman with diabetes mellitus type two and end-stage renal disease on hemodialysis presented to the emergency department with a four day history of generalized malaise, fever, and chills. Her symptoms were also associated with occasional dyspnea without a cough. She reported intermittent chronic diarrhea with hemodialysis which was currently unchanged. On the day of admission, she could not tolerate hemodialysis due to her symptoms. Over the past year she admitted to night sweats and a 40 pound weight loss. She denied having palpitations, chest pain, hemoptysis, lymph node swelling, sick contacts, or recent travel. The remainder of the review of systems was negative.
Assuntos
Aggregatibacter aphrophilus/isolamento & purificação , Endocardite Bacteriana/diagnóstico por imagem , Endocardite Bacteriana/terapia , Insuficiência da Valva Mitral/cirurgia , Infecções por Pasteurellaceae/diagnóstico , Antibacterianos/uso terapêutico , Ceftriaxona/uso terapêutico , Calafrios/etiologia , Diabetes Mellitus Tipo 2/complicações , Diagnóstico Diferencial , Ecocardiografia , Feminino , Febre/etiologia , Humanos , Falência Renal Crônica/complicações , Falência Renal Crônica/terapia , Pessoa de Meia-Idade , Diálise RenalRESUMO
Appropriate laboratory animal facility lighting and lighting protocols are essential for maintaining the health and wellbeing of laboratory animals and ensuring the credible outcome of scientific investigations. Our recent experience in relocating to a new laboratory facility illustrates the importance of these considerations. Previous studies in our laboratory demonstrated that animal room contamination with light-at-night (LAN) of as little as 0.2 lx at rodent eye level during an otherwise normal dark-phase disrupted host circadian rhythms and stimulated the metabolism and proliferation of human cancer xenografts in rats. Here we examined how simple improvements in facility design at our new location completely eliminated dark-phase LAN contamination and restored normal circadian rhythms in nontumor-bearing rats and normal tumor metabolism and growth in host rats bearing tissue-isolated MCF7(SR(-)) human breast tumor xenografts or 7288CTC rodent hepatomas. Reducing LAN contamination in the animal quarters from 24.5 ± 2.5 lx to nondetectable levels (complete darkness) restored normal circadian regulation of rodent arterial blood melatonin, glucose, total fatty and linoleic acid concentrations, tumor uptake of O(2), glucose, total fatty acid and CO(2) production and tumor levels of cAMP, triglycerides, free fatty acids, phospholipids, and cholesterol esters, as well as extracellular-signal-regulated kinase, mitogen-activated protein kinase, serine-threonine protein kinase, glycogen synthase kinase 3ß, γ-histone 2AX, and proliferating cell nuclear antigen.
Assuntos
Academias e Institutos/normas , Ritmo Circadiano/fisiologia , Laboratórios/normas , Iluminação/normas , Neoplasias Experimentais/metabolismo , Neoplasias Experimentais/patologia , Ratos Endogâmicos BUF/fisiologia , Ratos Nus/fisiologia , Animais , Animais de Laboratório/fisiologia , Glicemia/metabolismo , Neoplasias da Mama/irrigação sanguínea , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Carcinoma Hepatocelular/irrigação sanguínea , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Proliferação de Células , Feminino , Humanos , Neoplasias Hepáticas/irrigação sanguínea , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Masculino , Melatonina/sangue , Neoplasias Experimentais/irrigação sanguínea , Ratos , Transplante Heterólogo , Local de TrabalhoRESUMO
Dark-phase light contamination can significantly disrupt chronobiologic rhythms, thereby potentially altering the endocrine physiology and metabolism of experimental animals and influencing the outcome of scientific investigations. We sought to determine whether exposure to low-level light contamination during the dark phase influenced the normally entrained circadian rhythms of various substances in plasma. Male Sprague-Dawley rats (n = 6 per group) were housed in photobiologic light-exposure chambers configured to create 1) a 12:12-h light:dark cycle without dark-phase light contamination (control condition; 123 µW/cm(2), lights on at 0600), 2) experimental exposure to a low level of light during the 12-h dark phase (with 0.02, 0.05, 0.06, or 0.08 µW/cm(2) light at night), or 3) constant bright light (123 µW/cm(2)). Dietary and water intakes were recorded daily. After 2 wk, rats underwent 6 low-volume blood draws at 4-h intervals (beginning at 0400) during both the light and dark phases. Circadian rhythms in dietary and water intake and levels of plasma total fatty acids and lipid fractions remained entrained during exposure to either control conditions or low-intensity light during the dark phase. However, these patterns were disrupted in rats exposed to constant bright light. Circadian patterns of plasma melatonin, glucose, lactic acid, and corticosterone were maintained in all rats except those exposed to constant bright light or the highest level of light during the dark phase. Therefore even minimal light contamination during the dark phase can disrupt normal circadian rhythms of endocrine metabolism and physiology and may alter the outcome of scientific investigations.
Assuntos
Ritmo Circadiano/efeitos da radiação , Luz , Fotoperíodo , Ratos/fisiologia , Animais , Glicemia/metabolismo , Corticosterona/sangue , Sistema Endócrino/efeitos da radiação , Ácidos Graxos/sangue , Abrigo para Animais , Ciência dos Animais de Laboratório , Ácido Láctico/sangue , Masculino , Melatonina/sangue , Ratos/metabolismo , Ratos Sprague-DawleyRESUMO
Melatonin provides a circadian signal that regulates linoleic acid (LA)-dependent tumor growth. In rodent and human cancer xenografts of epithelial origin in vivo, melatonin suppresses the growth-stimulatory effects of linoleic acid (LA) by blocking its uptake and metabolism to the mitogenic agent, 13-hydroxyoctadecadienoic acid (13-HODE). This study tested the hypothesis that both acute and long-term inhibitory effects of melatonin are exerted on LA transport and metabolism, and growth activity in tissue-isolated human leiomyosarcoma (LMS), a rare, mesenchymally-derived smooth muscle tissue sarcoma, via melatonin receptor-mediated inhibition of signal transduction activity. Melatonin added to the drinking water of female nude rats bearing tissue-isolated LMS xenografts and fed a 5% corn oil (CO) diet caused the rapid regression of these tumors (0.17 +/- 0.02 g/day) versus control xenografts that continued to grow at 0.22 +/- 0.03 g/day over a 10-day period. LMS perfused in situ for 150 min with arterial donor blood augmented with physiological nocturnal levels of melatonin showed a dose-dependent suppression of tumor cAMP production, LA uptake, 13-HODE release, extracellular signal-regulated kinase (ERK 1/2), mitogen activated protein kinase (MEK), Akt activation, and [(3)H]thymidine incorporation into DNA and DNA content. The inhibitory effects of melatonin were reversible and preventable with either melatonin receptor antagonist S20928, pertussis toxin, forskolin, or 8-Br-cAMP. These results demonstrate that, as observed in epithelially-derived cancers, a nocturnal physiological melatonin concentration acutely suppress the proliferative activity of mesenchymal human LMS xenografts while long-term treatment of established tumors with a pharmacological dose of melatonin induced tumor regression via a melatonin receptor-mediated signal transduction mechanism involving the inhibition of tumor LA uptake and metabolism.