RESUMO
WHAT IS KNOWN AND OBJECTIVE: Deferasirox has nephrotoxic effects in the context of chronic therapy. This case report illustrates proximal tubular dysfunction (Fanconi syndrome) due to an acute deferasirox overdose. CASE DESCRIPTION: In response, we trialled plasmapheresis to eliminate the drug. Deferasirox levels were obtained in the context of three rounds of plasmapheresis. Given the half-life model of decay, we concluded that plasmapheresis may not have been successful. The patient ultimately recovered normal tubular function after 2 months. WHAT IS NEW AND CONCLUSION: This report is the first to describe acute deferasirox-induced nephrotoxicity, and the application of plasmapheresis that, ultimately, did not change the typical time to recovery.
Assuntos
Benzoatos/intoxicação , Síndrome de Fanconi/induzido quimicamente , Quelantes de Ferro/intoxicação , Plasmaferese/métodos , Triazóis/intoxicação , Deferasirox , Overdose de Drogas , Síndrome de Fanconi/terapia , Meia-Vida , Humanos , Masculino , Adulto JovemRESUMO
OBJECTIVE: The aim of this study was to inform best evidence-based practice by collating and disseminating the experiences of members of the International Pediatric Peritoneal Dialysis Network with children having concurrent ventriculoperitoneal shunts (VPS) and peritoneal dialysis catheters (PDC). METHODS: An online questionnaire was created and distributed to all 135 centers participating in the International Pediatric Peritoneal Dialysis Network; the overall response rate was 56 %. RESULTS: A total of 18 patients with a concurrent VPS and PDC were reported. The children were 0-12 (mean 6.8) years old at the time of placement of the second indwelling device (PDC or VPS). In 15 cases, the PDC was inserted post-VPS. On average, the two catheters were present concurrently for 23 (range 1-60) months. There were 20 episodes of peritonitis observed in 11 of the 18 patients during a period of 392 months at risk, which is a peritonitis rate of 1/19.6 months. Only one patient developed both a VPS infection and an episode of peritonitis, and these events were temporally unrelated. No episodes of an ascending shunt infection or meningitis occurred in association with any episode of peritonitis, and no other complications of catheter dysfunction were described. CONCLUSIONS: The rate of peritonitis, the absence of any documented ascending or descending infections and the lack of catheter dysfunction during the period of observation suggests that the presence of, or need for, a VPS should not preclude PD as a safe option for children requiring renal replacement therapy.
Assuntos
Cateteres de Demora/efeitos adversos , Diálise Peritoneal/efeitos adversos , Peritonite/microbiologia , Derivação Ventriculoperitoneal/efeitos adversos , Cateteres de Demora/microbiologia , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Meningite/microbiologia , Falha de Prótese , Inquéritos e QuestionáriosRESUMO
Although isolated neurons can generate rhythmic activity, they have not yet been shown to generate rhythms with a period in the circadian range (near 24 hours). The eye of the mollusk Bulla gouldiana expresses a circadian rhythm in optic nerve impulses that is generated by electrically coupled cells known as basal retinal neurons (BRNs). Daily fluctuations in the membrane potential of the BRNs appear to be driven by a rhythm in membrane conductance. Isolated BRNs exhibited spontaneous conductance changes similar to those observed in the intact retina. Membrane conductance was high in the late subjective night and decreased approximately twofold near projected dawn during at least two circadian cycles in culture. The persistence of daily conductance changes in isolated BRNs indicates that individual neurons can function as circadian pacemakers.
Assuntos
Membrana Celular/fisiologia , Ritmo Circadiano , Moluscos/fisiologia , Neurônios/fisiologia , Retina/citologia , Potenciais de Ação , Animais , Condutividade Elétrica , Neurônios/ultraestrutura , Canais de Potássio/fisiologiaRESUMO
Basal retinal neurons of the marine mollusc Bulla gouldiana continue to express a circadian modulation of their membrane conductance for at least two cycles in cell culture. Voltage-dependent currents of these pacemaker cells were recorded using the whole-cell perforated patch-clamp technique to characterize outward currents and investigate their putative circadian modulation. Three components of the outward potassium current were identified. A transient outward current (IA) was activated after depolarization from holding potentials greater than -30 mV, inactivated with a time constant of 50 ms, and partially blocked by 4-aminopyridine (1-5 mM). A Ca(2+)-dependent potassium current (IK(Ca)) was activated by depolarization to potentials more positive than -10 mV and was blocked by removing Ca2+ from the bath or by applying the Ca2+ channel blockers Cd2+ (0.1-0.2 mM) and Ni2+ (1-5 mM). A sustained Ca(2+)-independent current component including the delayed rectifier current (IK) was recorded at potentials positive to -20 mV in the absence of extracellular Na+ and Ca2+ and was partially blocked by tetraethylammonium chloride (TEA, 30mM). Whole-cell currents recorded before and after the projected dawn and normalized to the cell capacitance revealed a circadian modulation of the delayed rectifier current (IK). However, the IA and IK(Ca) currents were not affected by the circadian pacemaker.
Assuntos
Ritmo Circadiano/fisiologia , Moluscos/citologia , Neurônios/fisiologia , Canais de Potássio de Abertura Dependente da Tensão da Membrana , Canais de Potássio/fisiologia , Retina/fisiologia , 4-Aminopiridina/farmacologia , Animais , Axônios/fisiologia , Cálcio/metabolismo , Divisão Celular/efeitos dos fármacos , Células Cultivadas , Ritmo Circadiano/efeitos dos fármacos , Canais de Potássio de Retificação Tardia , Ativação do Canal Iônico/efeitos dos fármacos , Potenciais da Membrana/efeitos dos fármacos , Metais/farmacologia , Neurônios/citologia , Neurônios/efeitos dos fármacos , Técnicas de Patch-Clamp , Potássio/metabolismo , Canais de Potássio/efeitos dos fármacos , Retina/citologia , Sódio/metabolismo , Tetraetilamônio/farmacologiaRESUMO
1. Ventricular myocytes demonstrate a steeply inwardly rectifying K(+) current termed I(K1). We investigated the molecular basis for murine I(K1) by removing the genes encoding Kir2.1 and Kir2.2. The physiological consequences of the loss of these genes were studied in newborn animals because mice lacking Kir2.1 have a cleft palate and die shortly after birth. 2. Kir2.1 (-/-) ventricular myocytes lack detectable I(K1) in whole-cell recordings in 4 mM external K(+). In 60 mM external K(+) a small, slower, residual current is observed. Thus Kir2.1 is the major determinant of I(K1). Sustained outward K(+) currents and Ba(2+) currents through L- and T-type channels were not significantly altered by the mutation. A 50 % reduction in I(K1) was observed in Kir2.2 (-/-) mice, raising the possibility that Kir2.2 can also contribute to the native I(K1). 3. Kir2.1 (-/-) myocytes showed significantly broader action potentials and more frequent spontaneous action potentials than wild-type myocytes. 4. In electrocardiograms of Kir2.1 (-/-) neonates, neither ectopic beats nor re-entry arrhythmias were observed. Thus the increased automaticity and prolonged action potential of the mutant ventricular myocytes were not sufficiently severe to disrupt the sinus pacing of the heart. The Kir2.1 (-/-) mice, however, had consistently slower heart rates and this phenotype is likely to arise indirectly from the influence of Kir2.1 outside the heart. 5. Thus Kir2.1 is the major component of murine I(K1) and the Kir2.1 (-/-) mouse provides a model in which the functional consequences of removing I(K1) can be studied at both cellular and organismal levels.
Assuntos
Miocárdio/metabolismo , Canais de Potássio Corretores do Fluxo de Internalização , Canais de Potássio/fisiologia , Potenciais de Ação/fisiologia , Animais , Animais Recém-Nascidos , Cálcio/fisiologia , Condutividade Elétrica , Eletrocardiografia , Deleção de Genes , Ventrículos do Coração , Camundongos , Camundongos Endogâmicos , Camundongos Knockout/genética , Fenótipo , Canais de Potássio/genética , RNA/metabolismo , Tempo de Reação/fisiologia , Valores de ReferênciaRESUMO
The molecular bases of inwardly rectifying K(+) (Kir) currents and K(+)-induced dilations were examined in cerebral arteries of mice that lack the Kir2.1 and Kir2.2 genes. The complete absence of the open reading frame in animals homozygous for the targeted allele was confirmed. Kir2.1(-/-) animals die 8 to 12 hours after birth, apparently due to a complete cleft of the secondary palate. In contrast, Kir2.2(-/-) animals are viable and fertile. Kir currents were observed in cerebral artery myocytes isolated from control neonatal animals but were absent in myocytes from Kir2.1(-/-) animals. Voltage-dependent K(+) currents were similar in cells from neonatal control and Kir2.1(-/-) animals. An increase in the extracellular K(+) concentration from 6 to 15 mmol/L caused Ba(2+)-sensitive dilations in pressurized cerebral arteries from control and Kir2.2 mice. In contrast, arteries from Kir2.1(-/-) animals did not dilate when the extracellular K(+) concentration was increased to 15 mmol/L. In summary, Kir2.1 gene expression in arterial smooth muscle is required for Kir currents and K(+)-induced dilations in cerebral arteries.