RESUMEN
Visceral leishmaniasis (VL) due to Leishmania infantum is an endemic parasitic infection in the Mediterranean area. It most commonly affects immunosuppressed individuals, especially HIV patients and less frequently organ transplant recipients. Renal involvement seems to be frequent and is mostly associated with tubulointerstitial nephritis, as described in autopsy reports. In the 61 cases of renal transplant recipients with VL reported in the literature, renal dysfunction was noted at clinical presentation and was more frequently observed as a complication of antiparasitic therapy. However, no pathological analysis of the allograft lesions was reported. We present the case of a Swiss renal transplant recipient who developed VL after vacations in Spain and Tunisia, complicated by acute parasitic nephritis in the renal allograft 3 months after a well-conducted treatment of liposomal amphotericin B.
Asunto(s)
Leishmaniasis Visceral/tratamiento farmacológico , Leishmaniasis Visceral/etiología , Síndrome de Inmunodeficiencia Adquirida/complicaciones , Síndrome de Inmunodeficiencia Adquirida/etiología , Síndrome de Inmunodeficiencia Adquirida/parasitología , Anciano , Anfotericina B , Resultado Fatal , Infecciones por VIH/complicaciones , Infecciones por VIH/etiología , Infecciones por VIH/parasitología , Humanos , Riñón/parasitología , Leishmania infantum/parasitología , Leishmaniasis Visceral/parasitología , Masculino , Nefritis Intersticial/complicaciones , Nefritis Intersticial/etiología , Nefritis Intersticial/parasitología , España , TúnezRESUMEN
Hemolytic uremic syndrome (HUS) in children is classically associated with diarrheas related to the production of a shiga-toxin. HUS occurs among oncologic patients, in relation with the cancer itself, or as a complication of the cytostatic treatment. The physician should be familiar with the triad of HUS (microangiopathic hemolytic anemia, thrombocytopenia and renal failure) and search actively for this pathology in oncologic patient. The treatment is essentially empirical. It includes plasma exchanges, control of blood pressure, hydro-electrolytic balance control with dialysis, if necessary. Blood transfusion should be avoided. Potential mortal complications associated with HUS can be prevented by a rapid diagnosis and a prompt initiation of adequate therapy.
Asunto(s)
Antimetabolitos Antineoplásicos/efectos adversos , Desoxicitidina/análogos & derivados , Síndrome Hemolítico-Urémico/inducido químicamente , Desoxicitidina/efectos adversos , Femenino , Humanos , Persona de Mediana Edad , GemcitabinaAsunto(s)
Enfermedades Renales/complicaciones , Linfocitosis/etiología , Linfocitos T CD8-positivos , Diagnóstico Diferencial , Infecciones por VIH/complicaciones , Infecciones por VIH/patología , Humanos , Enfermedades Renales/virología , Linfocitosis/diagnóstico , Linfocitosis/virología , Masculino , Persona de Mediana EdadRESUMEN
Chondroid syringoma is a rare benign skin tumor of the head and neck. Only 15 cases presenting on the eyelid have been described in the literature. An 84-year-old patient presented with an 8-mm nodule on the right inferior eyelid that had grown over 5 years. The lesion was surgically removed, and the histopathological examination showed a chondroid syringoma. Knowledge of this disease is important because malignant transformations do occur.
Asunto(s)
Adenoma Pleomórfico/diagnóstico , Neoplasias de los Párpados/diagnóstico , Adenoma Pleomórfico/patología , Adenoma Pleomórfico/cirugía , Anciano de 80 o más Años , Diagnóstico Diferencial , Neoplasias de los Párpados/diagnóstico por imagen , Neoplasias de los Párpados/cirugía , Femenino , Humanos , RadiografíaRESUMEN
BACKGROUND: 'Anaesthetic post-conditioning', that is administration of anaesthetics during early reperfusion, is known to have positive effects on several organs. For the kidney, however, the effects of post-conditioning by volatile anaesthetics are not well researched. We examined renal function and morphology after post-conditioning by desflurane. METHODS: Anaesthetized rats were subjected to 30 or 45 min of renal ischaemia 14 days after contralateral nephrectomy. Post-conditioning was achieved by administration of 1 MAC desflurane (6.7 vol%) for 15 min during early reperfusion (all groups n=8). Cystatin C (CyC), creatinine clearance (Cl(Cr)) and fractional sodium excretion (FE(Na)) were measured in the awake rats over 3 days. Cell damage was graded from 1 to 4 in histological sections. Functional variables [mean (SD)] were compared statistically by a one-way anova followed by Bonferroni's multiple comparison test and histological scores (median and range) by Kruskal-Wallis test followed by Dunn's multiple comparison test. RESULTS: Pre-ischaemia function did not differ between the groups, but was markedly reduced after ischaemia. After 30 min ischaemia, the area under the curve (AUC) for Cl(Cr) was smaller in the desflurane than in the control group [21.5 (5.0) vs 31.6 (5.1) ml min(-1) h, P<0.05]. After 45 min desflurane reduced the AUC compared with the control group for both CyC [15 (4) vs 21 (3) mg litre(-1) h] and FE(Na) [1054 (221) vs 1570 (572)% h, both P<0.05). Morphological differences were greater between the 30 min groups [control: 2.75 (2.0-3.5) vs desflurane: 1.5 (1.0-2.5); P<0.05] than between the 45 min groups [control: 3.5 (3.0-4.0) vs desflurane: 3.0 (1.5-4.0)]. CONCLUSION: Desflurane post-conditioning protects renal function and tissue. This protection was greater after the short episode than after the long episode of ischaemia.
Asunto(s)
Anestésicos por Inhalación/uso terapéutico , Isoflurano/análogos & derivados , Riñón/irrigación sanguínea , Daño por Reperfusión/prevención & control , Animales , Creatinina/orina , Cistatina C , Cistatinas/sangre , Desflurano , Ectodisplasinas/metabolismo , Isoflurano/uso terapéutico , Riñón/patología , Riñón/fisiopatología , Macrófagos/patología , Masculino , Natriuresis , Ratas , Ratas Wistar , Daño por Reperfusión/patología , Daño por Reperfusión/fisiopatología , Factores de TiempoRESUMEN
BACKGROUND AND OBJECTIVE: Whereas the protective effect of anaesthetic and ischaemic preconditioning has been described for several organs, it is uncertain whether this mechanism is also effective in the kidney. We compared the effect of preconditioning with sevoflurane and preconditioning with short episodes of ischaemia on renal ischaemia/reperfusion injury in the rat in vivo. METHODS: Fourteen days after right-sided nephrectomy, anaesthetized male Wistar rats were randomly assigned to a sham-operated group (no arterial occlusion, n = 5) or underwent 45 min of left renal artery occlusion (control group, n = 9) followed by 3 days of reperfusion. Two further experimental groups of animals were preconditioned prior to ischaemia either by administering 1 MAC sevoflurane for 15 min followed by 10 min of washout (sevoflurane group, n = 10) or by subjecting the animals to three short episodes of renal ischaemia (ischaemia-preconditioned group, n = 8). Blood creatinine was measured during reperfusion and morphological damage was assessed by histological examination. RESULTS: Baseline creatinine values were similar in all four groups (0.7 +/- 0.2 mg dL-1; mean +/- SD) and remained unchanged in the sham-operated animals after 3 days (0.8 +/- 0.2 mg dL-1). Creatinine levels increased in the ischaemic preconditioning group (3.3 +/- 1.2 mg dL-1) and sevoflurane preconditioning group (4.0 +/- 1.1 mg dL-1) compared to the control group (1.6 +/- 0.6 mg dL-1). Morphological damage was less severe in the control group, i.e. in animals without preconditioning, than in both preconditioning groups. CONCLUSION: Neither sevoflurane nor ischaemic preconditioning preserves renal function or attenuates cell damage in the rat in vivo.
Asunto(s)
Precondicionamiento Isquémico/métodos , Riñón/irrigación sanguínea , Riñón/patología , Éteres Metílicos/administración & dosificación , Daño por Reperfusión/patología , Animales , Riñón/fisiología , Masculino , Ratas , Ratas Wistar , Daño por Reperfusión/sangre , Daño por Reperfusión/fisiopatología , SevofluranoRESUMEN
BACKGROUND: Volatile anaesthetics precondition the heart against infarction, an effect partly mediated by activation of the epsilon isoform of protein kinase C (PKCepsilon). We investigated whether cardioprotection by activation of PKCepsilon depends on the isoflurane concentration. METHODS: Anaesthetized rats underwent 25 min of coronary artery occlusion followed by 120 min of reperfusion and were randomly assigned to the following groups (n=10 in each group): isoflurane preconditioning induced by 15 min administration of 0.4 minimal alveolar concentration (MAC) (0.4MAC), 1 MAC (1MAC) or 1.75 MAC (1.75MAC) followed by 10 min washout before ischaemia. Each protocol was repeated in the presence of the PKC inhibitor staurosporine (10 microg kg(-1)): 0.4MAC+S, 1MAC+S and 1.75MAC+S. Controls were untreated (CON) and additional hearts received staurosporine without isoflurane (S). In a second set of experiments (n=6 in each group) hearts were excised before the infarct inducing ischaemia, and phosphorylation and translocation of PKCepsilon were determined by western blot analysis. RESULTS: Isoflurane reduced infarct size from a mean of 61(SEM 2)% of the area at risk in controls to 20(1)% (0.4MAC), 26(3)% (1MAC) and 30(1)% (1.75MAC) (all P<0.01 vs CON or S). This protection was partially reversed by administration of staurosporine in the 0.4MAC+S group (30[2]%; P<0.05 vs 0.4MAC) group, but not after administration of 1 MAC or 1.75 MAC isoflurane (26[2]% and 31[2]%, respectively). Thus 0.4MAC increased PKCepsilon phosphorylation, and this effect was blocked by staurosporine. Higher concentrations of isoflurane did not change PKCepsilon phosphorylation. PKCepsilon was translocated to the membrane fraction after administration of 0.4 MAC isoflurane, but not after 1.0 or 1.75 MAC. CONCLUSIONS: Although isoflurane preconditioning resulted in a reduction in infarct size at all concentrations used, the protection was mediated by phosphorylation and translocation of PKCepsilon only at 0.4 MAC.
Asunto(s)
Cardiotónicos/farmacología , Precondicionamiento Isquémico Miocárdico/métodos , Isoflurano/farmacología , Daño por Reperfusión Miocárdica/prevención & control , Proteína Quinasa C/efectos de los fármacos , Anestésicos por Inhalación/farmacología , Animales , Membrana Celular/enzimología , Citosol/enzimología , Relación Dosis-Respuesta a Droga , Activación Enzimática/efectos de los fármacos , Inhibidores Enzimáticos/farmacología , Hemodinámica/efectos de los fármacos , Masculino , Infarto del Miocardio/enzimología , Infarto del Miocardio/patología , Infarto del Miocardio/prevención & control , Daño por Reperfusión Miocárdica/enzimología , Daño por Reperfusión Miocárdica/patología , Fosforilación , Proteína Quinasa C/antagonistas & inhibidores , Proteína Quinasa C/fisiología , Proteína Quinasa C-epsilon , Ratas , Ratas Wistar , Estaurosporina/farmacologíaRESUMEN
The parvovirus minute virus of mice NS1 protein is a multifunctional protein involved in a variety of processes during virus propagation, ranging from viral DNA replication to promoter regulation and cytotoxic action to the host cell. Since NS1 becomes phosphorylated during infection, it was proposed that the different tasks of this protein might be regulated in a coordinated manner by phosphorylation. Indeed, comparing biochemical functions of native NS1 with its dephosphorylated counterpart showed that site-specific nicking of the origin and the helicase and ATPase activities are remarkably reduced upon NS1 dephosphorylation while site-specific affinity of the protein to the origin became enhanced. As a consequence, the dephosphorylated polypeptide is deficient for initiation of DNA replication. By adding fractionated cell extracts to a kinase-free in vitro replication system, the combination of two protein components containing members of the protein kinase C (PKC) family was found to rescue the replication activity of the dephosphorylated NS1 protein upon addition of PKC cofactors. One of these components, termed HA-1, also stimulated NS1 helicase function in response to acidic lipids but not phorbol esters, indicating the involvement of atypical PKC isoforms in the modulation of this NS1 function (J. P. F. Nüesch, S. Dettwiler, R. Corbau, and J. Rommelaere, J. Virol. 72:9966-9977, 1998). The present study led to the identification of atypical PKClambda/iota as the active component of HA-1 responsible for the regulation of NS1 DNA unwinding and replicative functions. Moreover, a target PKClambda phosphorylation site was localized at S473 of NS1. By site-directed mutagenesis, we showed that this residue is essential for NS1 helicase activity but not promoter regulation, suggesting a possible modulation of NS1 functions by PKClambda phosphorylation at residue S473.
Asunto(s)
ADN Helicasas/metabolismo , Virus Diminuto del Ratón/enzimología , Proteína Quinasa C/metabolismo , Proteínas no Estructurales Virales/metabolismo , Animales , Línea Celular , Chlorocebus aethiops , ADN/metabolismo , ADN Helicasas/genética , Replicación del ADN , Células HeLa , Humanos , Isoenzimas , Ratones , Proteína Quinasa C/genética , Proteínas no Estructurales Virales/genéticaRESUMEN
NS1, the major nonstructural protein of the parvovirus minute virus of mice, is a multifunctional phosphoprotein which is involved in cytotoxicity, transcriptional regulation, and initiation of viral DNA replication. For coordination of these various functions during virus propagation, NS1 has been proposed to be regulated by posttranslational modifications, in particular phosphorylation. Recent in vitro studies (J. P. F. Nüesch, R. Corbau, P. Tattersall, and J. Rommelaere, J. Virol. 72:8002-8012, 1998) provided evidence that distinct NS1 activities, notably the intrinsic helicase function, are modulated by the phosphorylation state of the protein. In order to study the dependence of the initiation of viral DNA replication on NS1 phosphorylation and to identify the protein kinases involved, we established an in vitro replication system that is devoid of endogenous protein kinases and is based on plasmid substrates containing the minimal left-end origins of replication. Cellular components necessary to drive NS1-dependent rolling-circle replication (RCR) were freed from endogenous serine/threonine protein kinases by affinity chromatography, and the eukaryotic DNA polymerases were replaced by the bacteriophage T4 DNA polymerase. While native NS1 (NS1(P)) supported RCR under these conditions, dephosphorylated NS1 (NS1(O)) was impaired. Using fractionated HeLa cell extracts, we identified two essential protein components which are able to phosphorylate NS1(O), are enriched in protein kinase C (PKC), and, when present together, reactivate NS1(O) for replication. One of these components, containing atypical PKC, was sufficient to restore NS1(O) helicase activity. The requirement of NS1(O) reactivation for characteristic PKC cofactors such as Ca2+/phosphatidylserine or phorbol esters strongly suggests the involvement of this protein kinase family in regulation of NS1 replicative functions in vitro.
Asunto(s)
Replicación del ADN/fisiología , Virus Diminuto del Ratón/fisiología , Proteína Quinasa C/metabolismo , Proteínas no Estructurales Virales/fisiología , Replicación Viral/fisiología , Animales , Secuencia de Bases , Línea Celular , ADN Helicasas/química , ADN Helicasas/fisiología , Replicación del ADN/genética , Células HeLa , Humanos , Ratones , Virus Diminuto del Ratón/genética , Fosforilación , Plásmidos/genética , Procesamiento Proteico-Postraduccional , Proteínas no Estructurales Virales/química , Replicación Viral/genéticaRESUMEN
The inhibition of pentagastrin-stimulated-(3 micrograms kg-1 h-1) gastric acid secretion by various doses of intravenous and subcutaneous SMS 201-995, a somatostatin analogue, was investigated in healthy volunteers by means of gastric aspiration, using phenol red as a volume marker. The intravenous doses were compared with the standard dose of somatostatin-14, 3.5 micrograms kg-1 h-1. Similarly, SMS 201-995-induced inhibition of gastric acid secretion was compared with that of exocrine pancreatic secretion assessed by gastroduodenal aspiration. The results can be summarized as follows: SMS 201-995 is a potent inhibitor of gastric acid secretion, exerting near maximal inhibition at a dose of greater than or equal to 0.56 micrograms kg-1 h-1. Near maximal inhibition equals that achieved with SST-14 (3.5 micrograms kg-1 h-1). Pancreatic enzyme secretion appears to be strongly inhibited by lower doses of SMS 201-995 than gastric secretion. Single subcutaneous injections of SMS 201-995 produce an inhibition of gastric acid secretion lasting for many hours. Near maximal inhibition was obtained with a dose of 100 micrograms.
Asunto(s)
Ácido Gástrico/metabolismo , Somatostatina/análogos & derivados , Adulto , Humanos , Octreótido , Páncreas/efectos de los fármacos , Páncreas/metabolismo , Pentagastrina/farmacología , Somatostatina/administración & dosificación , Somatostatina/farmacología , Tripsina/metabolismoRESUMEN
We studied the effect of four graded doses of SMS 201-995, a synthetic octapeptide somatostatin analogue (27, 80, 240, and 720 ng/kg/h) on the basal and secretin-plus-cerulein-stimulated exocrine pancreatic function and pancreatic polypeptide (PP) release in five healthy volunteers. Duodenal fluid secretion and bicarbonate output under basal and stimulated conditions were not significantly affected by any dose of SMS. The basal and stimulated enzyme secretion were decreased in a non-dose-dependent manner by all SMS doses used in the study and showed a 75% inhibition of the secretin-plus-cerulein-stimulated trypsin and amylase output. The cerulein-stimulated PP release was significantly suppressed by all four SMS doses. SMS appears to be a strong inhibitor of pancreatic enzyme secretion, at the same time affecting the PP release.