RESUMO
Fat transplantation experiments have previously shown regulatory properties of lean adipose tissue on glucose homeostasis in the whole animal. In the current study, we addressed whether obese visceral white adipose tissue grafted in lean mice could alter glucose homeostasis. Obese visceral fat (VF) tissue was effective in increasing body weight gain and energy efficiency but not energy intake, when transplanted into the epididymal VF depot in lean recipient mice. These changes were accompanied by impaired glucose and insulin tolerance tests, showing altered glucose homeostasis. None of these effects were observed when transplants were grafted subcutaneously. These effects show that both physiologic state of donor VF (obese vs lean) and graft location (epididymal vs subcutaneous) in the recipient animal are critical to express deleterious effects of VF on glucose homeostasis in the whole organism.
Assuntos
Metabolismo Energético , Glucose/metabolismo , Homeostase , Resistência à Insulina , Gordura Intra-Abdominal/metabolismo , Gordura Intra-Abdominal/transplante , Animais , Camundongos , Transplante HomólogoRESUMO
Since the discovery of nuclear factor-kappa B (NF-kappaB) in 1986, many studies have been conducted showing the link between the NF-kappaB signalling pathway and control of the inflammatory response. Today it is well known that control of the inflammatory response and apoptosis is closely related to the activation of NF-kappaB. Three NF-kappaB activation pathways exist. The first (the classical pathway) is normally triggered in response to microbial and viral infections or exposure to pro-inflammatory cytokines that activate the tripartite IKK complex, leading to phosphorylation-induced IkappaB degradation and depends mainly on IKKbeta activity. The second (the alternative pathway), leads to selective activation of p52:RelB dimers by inducing the processing of the NF-kappaB2/p100 precursor protein, which mostly occurs as a heterodimer with RelB in the cytoplasm. This pathway is triggered by certain members of the tumour necrosis factor cytokine family, through selective activation of IKKalpha homodimers by the upstream kinase NIK. The third pathway is named CK2 and is IKK independent. NF-kappaB acts through the transcription of anti-apoptotic proteins, leading to increased proliferation of cells and tumour growth. It is also known that some drugs act directly in the inhibition of NF-kappaB, thus producing regulation of apoptosis; some examples are aspirin and corticosteroids. Here we review the role of NF-kappaB in the control of apoptosis, its link to oncogenesis, the evidence of several studies that show that NF-kappaB activation is closely related to different cancers, and finally the potential target of NF-kappaB as cancer therapy.
Assuntos
Apoptose , Núcleo Celular/metabolismo , NF-kappa B/metabolismo , Neoplasias/metabolismo , Humanos , NF-kappa B/genética , Neoplasias/genética , Transdução de Sinais , Transcrição GênicaRESUMO
Wernicke encephalopathy, due to the depletion of thiamine, can be a complication of chronic hemodialysis. We report a 43 years old diabetic male in chronic hemodialysis, who two weeks after an infra-condyleal amputation of his left leg, was admitted to the hospital due to an episode of vomiting and abdominal pain lasting 5 days, where confusion and ocular motor signs appeared. Parenteral thiamine administration was started and the confusional state abated. Dialysis can be a predisposing factor for Wernicke encephalopathy and this diagnosis must be considered in confused patients.
Assuntos
Diálise Renal/efeitos adversos , Encefalopatia de Wernicke/etiologia , Adulto , Humanos , Masculino , Tiamina/uso terapêutico , Deficiência de Tiamina/complicações , Deficiência de Tiamina/tratamento farmacológicoRESUMO
BACKGROUND: Microemulsion cyclosporine is a new pharmaceutical form whose intestinal absorption is more constant, resulting in a better bioavailability. AIM: To assess dose adjustments and variability of blood levels after the conversion of cyclosporine to microemulsion cyclosporine in renal transplant recipients function receiving cyclosporine-ketoconazole. PATIENTS AND METHODS: Thirty four patients with more than one year after the transplantation, with stable renal function and receiving triple immunosuppression were studied. Conventional cyclosporine was changed to the microemulsion form maintaining the same daily dose. Drug serum levels, serum creatinine and blood pressure were measured within two to eight months after the conversion. Doses of microemulsion cyclosporine were adjusted to achieve serum levels of 150 +/- 40 ng/ml. RESULTS: Microemulsion cyclosporine induced a slight initial increase in blood cyclosporine levels. Afterwards, levels were more stable than with conventional cyclosporine (165-185 and 145-210 ng/ml respectively) and the dispersion of values were lower (standard deviations of 70 and 100 ng/ml respectively). Twenty three patients did not require dose adjustments, in four it was reduced and in five it was increased. There were no changes in serum creatinine or blood pressure after the conversion. CONCLUSION: More stable serum levels without adverse reactions were obtained with microemulsion cyclosporine. Doses of cyclosporine need not to be changed during the conversion.
Assuntos
Antifúngicos/sangue , Ciclosporina/sangue , Imunossupressores/sangue , Cetoconazol/sangue , Transplante de Rim , Adolescente , Adulto , Antifúngicos/administração & dosagem , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Creatinina/sangue , Ciclosporina/administração & dosagem , Ciclosporina/farmacologia , Emulsões , Feminino , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/farmacologia , Cetoconazol/administração & dosagem , Cetoconazol/farmacologia , Cetoconazol/uso terapêutico , Transplante de Rim/fisiologia , Masculino , Pessoa de Meia-IdadeRESUMO
Delayed imaging may help detect viable myocardium after stress Thallium scintigraphy. In 22 patients who had sustained myocardial infarction we performed a stress Thallium test followed by imaging after 24 hr. Delayed reperfusion was observed in 57% of segments showing no reperfusion at 4 hr, which is similar to findings reported in the literature. We proposed that delayed imaging should be performed in all patients showing perfusion defects at 4 hr. Even though a better image may be obtained using reinjection of Thallium, delayed imaging may be the technique of choice to reduce the cost of the test.