RESUMO
OBJECTIVE: A small percentage of patients do not develop any evidence of diabetic retinopathy (DR) even after many years of diabetes. Vascular endothelial growth factor (VEGF) has been implicated in the development of DR. Therefore, we sought to determine if the regulation of VEGF differs in those patients who develop DR after many years of diabetes compared with those who do not develop DR. RESEARCH DESIGN AND METHODS: We performed standard 7-field stereoscopic fundus photography on 95 consecutive patients with type 1 and type 2 diabetes. Patients were categorized into 3 groups according to the presence or absence of DR and the duration of diabetes: group 1 was defined by presence of DR, group 2 was defined by absence of DR after >10 years duration of diabetes, and group 3 was defined by absence of DR with long-standing diabetes (> or =20 years for type 1 diabetes and > or =15 years for type 2 diabetes). Monocytes from 40 ml peripheral blood were isolated from all patients, and the hypoxic induction of VEGF was determined in vitro. RESULTS: We found no significant difference in the basal level of VEGF in patients with and without DR. However, we did find a markedly significant difference in the hypoxic induction of VEGF between patients from group 1 and group 3 (4.35+/-0.55 vs. 1.87+/-0.3, P<0.00013). CONCLUSIONS: This study suggests that 1 mechanism for the absence of DR in patients with long-standing diabetes is a decreased hypoxic induction of VEGF.
Assuntos
Hipóxia Celular/fisiologia , Diabetes Mellitus Tipo 1/fisiopatologia , Diabetes Mellitus Tipo 2/fisiopatologia , Retinopatia Diabética/fisiopatologia , Fatores de Crescimento Endotelial/sangue , Fundo de Olho , Linfocinas/sangue , Monócitos/fisiologia , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 2/sangue , Fatores de Crescimento Endotelial/biossíntese , Feminino , Humanos , Técnicas In Vitro , Linfocinas/biossíntese , Masculino , Fotografação , Fatores de Tempo , Fator A de Crescimento do Endotélio Vascular , Fatores de Crescimento do Endotélio VascularRESUMO
Increasing evidence suggests that endothelin, a potent vasoconstrictor, is implicated in cyclosporin A (CsA)-induced nephrotoxicity. Increased levels of urinary and circulating endothelin have been described in CsA-treated humans and animals. The exact mechanisms by which CsA induces these increases are still unknown, and no data indicate whether these elevated levels reflect increased synthesis or decreased clearance of endothelin. In the present study, we investigated the effects of CsA administration (50 mg/kg per day i.p. for 6 days) to rats on plasma and urinary levels of endothelin; expression of endothelin-1 (ET-1), ET-3, and endothelin-converting enzyme in renal tissue; clearance of infused 125I-ET-1; and degradation of 125I-ET-1 by recombinant neutral endopeptidase. Rats given CsA for 6 days developed severe renal insufficiency, as shown by a 74% decrease in creatinine clearance rate (Ccr) (P < .006). Ccr was remarkably improved in CsA-treated rats that received bosentan, the combined antagonist of both endothelin A and endothelin B receptors. Urinary excretion of endothelin increased from an undetectable level to 31.7 +/- 6.0 pg/24 h (P < .001), and plasma levels of endothelin were unchanged (2.8 +/- 0.2 to 3.1 +/- 0.2 pg/mL). Reverse transcription followed by quantitative polymerase chain reaction revealed that ET-1 mRNA in the renal medulla increased by 59% (P < .006), whereas the expression of both ET-3 and endothelin-converting enzyme was unchanged. In other rats, neither acute nor chronic treatment with CsA affected either the clearance of 125I-ET-1 from the blood or the renal and pulmonary uptake of the peptide. Moreover, CsA did not affect the degradation of 125I-ET-1 by highly purified recombinant neutral endopeptidase, a well-known endothelinase. Taken together, these data suggest that the elevated urinary endothelin levels obtained after CsA treatment originate from the kidney and reflect increased renal synthesis of ET-1. Moreover, the production of endothelin appears to be regulated at the mRNA transcription level, and expressions of ET-1 and ET-3 are regulated independently.
Assuntos
Ciclosporina/farmacologia , Endotelinas/metabolismo , Rim/metabolismo , Animais , Ácido Aspártico Endopeptidases/genética , Ácido Aspártico Endopeptidases/metabolismo , Sequência de Bases , Bosentana , Creatinina/metabolismo , Enzimas Conversoras de Endotelina , Endotelinas/genética , Endotelinas/urina , Rim/efeitos dos fármacos , Masculino , Metaloendopeptidases/genética , Metaloendopeptidases/metabolismo , Sondas Moleculares/genética , Dados de Sequência Molecular , Neprilisina/metabolismo , Ratos , Ratos Sprague-Dawley , Proteínas Recombinantes , Sulfonamidas/farmacologiaRESUMO
A number of important themes emerge from our compartmental analyses of Na,K-ATPase biosynthesis in response to ionic stimuli. The ubiquitous alpha 1 beta 1 type sodium pump evolved to generate and maintain transmembrane Na+ and K+ gradients, and there are cell-type specific mechanisms of increasing synthesis and decreasing degradation to control surface expression of this important "housekeeping" enzyme. Expression of alpha 2 beta-type sodium pumps may have evolved in cells designated as K+ storehouses to facilitate maintenance of extracellular K+ in the presence of K+ restriction. Finally, the specialized distribution of Na,K-ATPase (and related E1-E2 type pumps) along the renal epithelia allows for monitoring and fine control of extracellular K+ and Na+ (volume). Many interesting questions remain to be answered, and we now have the probes and techniques needed to answer them.
Assuntos
Isoenzimas/metabolismo , Potássio/metabolismo , ATPase Trocadora de Sódio-Potássio/metabolismo , ATPase Trocadora de Sódio-Potássio/fisiologia , Animais , Homeostase , Rim/fisiologia , Modelos Biológicos , Potássio/farmacologiaRESUMO
We report a patient with reversible acute oligoanuric renal failure. Intravenous mannitol 25% was infused to treat intracranial edema, during chronic administration of ACE inhibitors for arterial hypertension. Serum creatinine level rose to 5.6 mg/dl from a previous value of 1.2 mg/dl. Measured and calculated serum osmolalities were 310 and 280 mosm/kg respectively. We postulate that the association of afferent arteriolar constriction due to mannitol induced tubulo-glomerular imbalance and efferent dilatation due to ACE inhibitors provoked a sharp reduction in glomerular filtration rate. Alternatively, mannitol infusion may have caused tubular cell swelling with luminal obstruction.
Assuntos
Injúria Renal Aguda/induzido quimicamente , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Diuréticos Osmóticos/efeitos adversos , Enalapril/efeitos adversos , Manitol/efeitos adversos , Injúria Renal Aguda/diagnóstico , Quimioterapia Combinada , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Influenza vaccination is a widely accepted practice, particularly among the elderly and high-risk individuals. Minor and transitory side effects following the vaccination are common, while systemic complications are infrequently reported. We describe here a case of a patient who presented to the emergency room with arthralgia, myalgias and purpura, following influenza vaccination. Necrotizing vasculitis associated with pauci-immune glomerulonephritis was observed on kidney biopsy. With increasing use of influenza vaccination, attention should be drawn to the possible expression of systemic adverse effects such as vasculitis and glomerulonephritis.
Assuntos
Glomerulosclerose Segmentar e Focal/etiologia , Vacinas contra Influenza/efeitos adversos , Vasculite Leucocitoclástica Cutânea/etiologia , Glomerulosclerose Segmentar e Focal/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Vasculite Leucocitoclástica Cutânea/patologiaRESUMO
A 63-year-old man presented to our department with dyspnea and peripheral edema. A cystic mass in the right upper abdomen, consistent with echinococcal disease was discovered. Proteinuria was also present, and a nephrotic syndrome was diagnosed. The kidney biopsy revealed minimal change glomerulonephritis. Treatment with the antiechinococcal drug albendazole induced complete remission of the nephrotic syndrome, suggesting an etiopathogenic role for a hydatid antigen in the development of an immune-mediated glomerulonephritis.
Assuntos
Equinococose Hepática/complicações , Nefrose Lipoide/etiologia , Albendazol/administração & dosagem , Anticestoides/administração & dosagem , Biópsia , Equinococose Hepática/diagnóstico , Equinococose Hepática/tratamento farmacológico , Humanos , Testes Imunológicos , Rim/patologia , Fígado/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Nefrose Lipoide/diagnóstico , Nefrose Lipoide/tratamento farmacológico , Síndrome Nefrótica/diagnóstico , Síndrome Nefrótica/tratamento farmacológico , Síndrome Nefrótica/etiologia , Cintilografia , UltrassonografiaRESUMO
The authors report two cases of renovascular hypertension associated with neurofibromatosis. A 19-year-old woman was admitted to our hospital with a complaint of abdominal pain and blood pressure of 180/120 mmHg. Examination revealed café-au-lait spots over her chest and extremities. Peripheral plasma renin activity (PRA) under basal conditions was 2.8 ng/ml/h and increased to 12.6 ng/ml/h after administration of 50 mg captopril. Plasma and urinary catecholamines were normal. Selective renal angiography showed left aneurysmal dilatation of the segmentary branch and right renal artery stenosis with multiple aneurysmal affecting different branches. Blood pressure was controlled by multiple drugs, including beta-blockers and angiotensin-converting enzyme inhibitor. Another patient, a 20-year-old woman, was admitted because of severe arterial hypertension, numerous café-au-lait spots, scoliosis, and mass over the right arm. PRA from the right renal vein was extremely elevated, and selective angiography demonstrated bilateral renal artery stenosis. Aortorenal bypass was performed successfully.
Assuntos
Hipertensão Renovascular/complicações , Neurofibromatoses/complicações , Adulto , Aneurisma/complicações , Aneurisma/diagnóstico por imagem , Feminino , Humanos , Hipertensão Renovascular/diagnóstico por imagem , Artéria Renal/diagnóstico por imagem , Obstrução da Artéria Renal/complicações , Obstrução da Artéria Renal/diagnóstico por imagem , Tomografia Computadorizada por Raios XAssuntos
Hiperpotassemia/etiologia , Potássio/sangue , Mielofibrose Primária/cirurgia , Esplenectomia/efeitos adversos , Trombocitose/cirurgia , Diagnóstico Diferencial , Eletrocardiografia , Feminino , Seguimentos , Humanos , Hiperpotassemia/sangue , Hiperpotassemia/diagnóstico , Pessoa de Meia-Idade , Mielofibrose Primária/complicações , Trombocitose/complicaçõesAssuntos
Transplante de Rim , Rim/patologia , Mucormicose/etiologia , Infecções Oportunistas/etiologia , Adulto , Evolução Fatal , Feminino , Humanos , Rim/microbiologia , Falência Renal Crônica/cirurgia , Doadores Vivos , Masculino , Pessoa de Meia-Idade , Mucormicose/patologia , Infecções Oportunistas/patologiaAssuntos
Síndrome de Secreção Inadequada de HAD/diagnóstico , Síndrome de Secreção Inadequada de HAD/etiologia , Neoplasias Hipofisárias/complicações , Prolactinoma/complicações , Sódio/metabolismo , Idoso , Diagnóstico Diferencial , Humanos , Hiponatremia/etiologia , Síndrome de Secreção Inadequada de HAD/tratamento farmacológico , Masculino , Neoplasias Hipofisárias/diagnóstico , Prolactinoma/diagnóstico , Desequilíbrio Hidroeletrolítico/diagnóstico , Desequilíbrio Hidroeletrolítico/tratamento farmacológico , Desequilíbrio Hidroeletrolítico/etiologiaAssuntos
Aquaporinas/fisiologia , Rim/fisiologia , Animais , Aquaporinas/genética , Doença , Humanos , Rim/fisiopatologiaRESUMO
We describe a patient who presented dramatically with life-threatening hypokalemic flaccid paralysis. Following resuscitation, extensive investigation showed that the patient had lupus erythematosus (SLE) and Sjogren's syndrome (SS) of which she was unaware. A search for the cause of the profound hypokalemia led to the finding of obligatory renal potassium wasting due to distal renal tubular acidosis (RTA), secretory type. The acid base status of the patient showed hyperchloremic metabolic acidosis compatible with distal renal tubular acidosis. Our case is a further proof that patients with "overlap syndrome" (SLE-SS) may have RTA, which may lead to life-threatening hypokalemia. Others have shown that the SLE-SS complex may occasionally be complicated by hyperkalemia. Thus, an autoimmune disease that is relatively common may present with devastating electrolyte abnormalities.
Assuntos
Hipopotassemia/etiologia , Lúpus Eritematoso Sistêmico/complicações , Nefrite Intersticial/etiologia , Quadriplegia/etiologia , Síndrome de Sjogren/complicações , Adulto , Feminino , Humanos , Lúpus Eritematoso Sistêmico/metabolismo , Hipotonia Muscular , Quadriplegia/metabolismo , Síndrome de Sjogren/metabolismo , SíndromeRESUMO
Hyponatremic encephalopathy is a well-known complication of surgical procedures. This syndrome has not been described in the cardiology literature. We report three patients who developed acute hyponatremia with life-threatening encephalopathy following an invasive cardiac procedure. Diagnosis and treatment were delayed because of a lack of awareness for the syndrome among the cardiology staff. The diagnosis of hyponatremia should be suspected in any patient who develops behavioral or neurological manifestations following an invasive cardiac procedure. Prompt diagnosis and treatment are essential to avoid permanent neurological damage or death.
Assuntos
Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Hiponatremia/etiologia , Doença Aguda , Adulto , Idoso , Feminino , HumanosRESUMO
Renal Na,K-ATPase drives active reabsorption of sodium and cotransported solutes along the nephron. There is a large increase in net Na(+) reabsorption in the postnatal rat kidney. It has previously been established that the postnatal increase in expression of sodium pump isoforms in the brain, but not the heart, is blunted in the hypothyroid neonate. The aims of this study were to establish whether the developmental increase in renal sodium transport is associated with coordinate increases in the abundance of the sodium pump alpha(1) catalytic and beta(1) glycoprotein subunits and Na,K-ATPase activity, and to determine whether thyroid status influences the postnatal increase in renal Na,K-ATPase expression. Pregnant rats were made hypothyroid with low iodine diet, propylthiouracil and perchlorate. Offspring were hypothyroid assessed by triiodothyronine/thyroxine RIA. Renal cortical membranes were prepared from euthyroid and hypothyroid rats from 6 to 24 days of age. There was no change in Na,K-ATPase activity or expression between 6 and 15 days. Between 15 and 24 days, Na,K-ATPase activity increased 1.35-fold while sodium pump alpha(1) and beta(1) subunit abundance increased coordinately to 1.7- and 2-fold over the previous period, respectively. In hypothyroid neonates, kidney weight was less than in euthyroids, and Na,K-ATPase activity, alpha(1) and beta(1) subunit pool sizes did not significantly increase as a function of age between 6 and 24 days. We conclude that the postnatal increase in sodium pump activity can be accounted for by coordinate increases in the pool sizes of alpha(1) and beta(1) subunits and that, like in brain, this increased Na,K-ATPase expression is dependent on normal thyroid status.
Assuntos
Hipotireoidismo/enzimologia , Córtex Renal/enzimologia , ATPase Trocadora de Sódio-Potássio/metabolismo , Análise de Variância , Animais , Animais Recém-Nascidos , Feminino , Córtex Renal/crescimento & desenvolvimento , Gravidez , Radioimunoensaio , Ratos , Ratos Sprague-DawleyRESUMO
A 66-year-old woman presented with acute-onset rapid atrial fibrillation and right upper quadrant pain which had appeared 24 h prior to admission. The patient also manifested acute oliguric renal failure (serum creatinine 6.9 mg/dl). Selective renal angiography revealed total occlusion of the right renal artery with normal visualization of the left kidney vasculature. The patient was treated with intra-arterial urokinase and intravenous heparin, with no response. Intravenous administration of the prostacyclin analogue, iloprost, resulted in rapid resolution (within hours) of the oliguric acute renal failure, in spite of the continuing presence of a nonfunctioning right kidney. We conclude that the etiology of the acute renal insult in this patient is probably related to unilateral renal arterial embolization accompanied by arterial spasm of the unaffected kidney. The contralateral vasospasm can be reversed by iloprost, which then leads to a rapid recovery from acute renal failure. We are unaware of prior reports documenting the beneficial effect of iloprost in a clinical setting as described here.
Assuntos
Injúria Renal Aguda/etiologia , Embolia/complicações , Iloprosta/uso terapêutico , Oligúria/etiologia , Obstrução da Artéria Renal/complicações , Vasodilatadores/uso terapêutico , Idoso , Fibrilação Atrial/complicações , Feminino , Humanos , Cardiopatia Reumática/complicaçõesRESUMO
In rapidly growing neonatal rats, the intestine is insensitive to vitamin D, and Ca absorption is solely mediated through a non-energy-dependent process. Changes in Ca absorption associated with pregnancy and lactation are qualitatively similar in vitamin D-replete and vitamin D-deplete rats. Moreover, in vivo studies in man and the rat have demonstrated that the bulk of Ca absorption is accomplished in the ileum, a segment with limited capacity for active Ca absorption and is relatively insensitive to the action of 1,25-dihydroxyvitamin D. In patients with intestinal bypass operations the degree of Ca malabsorption and bone mineral loss is proportional to the length of ileum, not duodenum or proximal intestine, removed. Bile salts and lactose are examples of agents which can augment vitamin D-independent ileal Ca absorption through the intercellular pathway.
Assuntos
Cálcio/metabolismo , Absorção Intestinal/efeitos dos fármacos , Animais , Ácidos e Sais Biliares/farmacologia , Humanos , Íleo/metabolismo , Lactose/farmacologia , Vitamina D/farmacologiaRESUMO
A 69-year-old woman presented with persistent dyspnea and continuous coughing and mediastinal mass. The mass was found to be a malignant thymoma and was resected incompletely. A full-blown nephrotic syndrome appeared 1 year after removal of the thymoma. Renal biopsy revealed minimal-change glomerulonephritis. There was no evidence of other autoimmune diseases or causes of the minimal-change glomerulonephritis.
Assuntos
Nefrose Lipoide/complicações , Timoma/complicações , Neoplasias do Timo/complicações , Idoso , Feminino , Humanos , Rim/patologia , Nefrose Lipoide/patologia , Timoma/patologia , Neoplasias do Timo/patologiaRESUMO
The clinical and laboratory data, and histologic, electron microscopic and immunocytochemical findings of a carcinoid tumor of the lung associated with parathyroid hyperplasia and persistent hypercalcemia are described. The carcinoid tumor consists of uniform cuboidal cells with regular round vesicular nuclei and eosinophilic granular cytoplasm. The tumor cells were chromogranin and neuron-specific enolase positive. The CAT scan of the abdomen revealed an adrenal mass, 3 cm in diameter, and an enlarged body in the pancreas. Our patient is still suffering from hypercalcemia and renal colic, despite repeated parathyroid gland removal, and enucleation of the lung mass. Recent parathyroid scintigraphy with Tc revealed an enlarged parathyroid gland. The thoracic CAT scan is normal. We believe that our patient is suffering from multiple endocrine neoplasia type-1 with persistent hypercalcemia due to hyperparathyroidism.