Role of leucocyte caspase-1 activity in epidural-related maternal fever: a single-centre, observational, mechanistic cohort study.

BACKGROUND: Epidural-related maternal fever (ERMF) has been reported in ∼26% of labouring women. The underlying mechanisms remain unclear. We hypothesised that ERMF is promoted by bupivacaine disrupting cytokine production/release from mononuclear leucocytes [mononuclear fraction (MNF)]. We examined whether bupivacaine (i) reduces caspase-1 activity and release of the anti-pyrogenic cytokine interleukin (IL)-1 receptor antagonist (IL-1ra), and (ii) is pro-inflammatory through mitochondrial injury/IL-1ß. METHODS: In labouring women, blood samples were obtained before/after epidural analgesia was implemented. Maternal temperature was recorded hourly for the first 4 h of epidural analgesia. Time-matched samples/temperatures were obtained from labouring women without epidural analgesia, pregnant non-labouring, and non-pregnant women. The primary clinical outcome was change in maternal temperature over 4 h after the onset of siting epidural catheter/enrolment. The secondary clinical outcome was development of ERMF (temperature ≥ 38°C). The effect of bupivacaine/saline on apoptosis, caspase-1 activity, intracellular IL-1ra, and plasma IL-1ra/IL-1ß ratio was quantified in MNF from labouring women or THP-1 monocytes (using flow cytometry, respirometry, or enzyme-linked immunosorbent assay). RESULTS: Maternal temperature increased by 0.06°C h-1 [95% confidence interval (CI): 0.03-0.09; P=0.003; n=38] after labour epidural placement. ERMF only occurred in women receiving epidural analgesia (five of 38; 13.2%). Bupivacaine did not alter MNF or THP-1 apoptosis compared with saline control, but reduced caspase-1 activity by 11% (95% CI: 5-17; n=10) in MNF from women in established labour. Bupivacaine increased intracellular MNF IL-1ra by 25% (95% CI: 10-41; P<0.001; n=10) compared with saline-control. Epidural analgesia reduced plasma IL-1ra/IL-1ß ratio (mean reduction: 14; 95% CI: 7-30; n=30) compared with women without epidural analgesia. CONCLUSIONS: Impaired release of anti-pyrogenic IL-1ra might explain ERMF mechanistically. Immunomodulation by bupivacaine during labour could promote ERMF.

[Microalbuminuria in pediatric patients diagnosed with hemolytic uremic syndrome]. / Microalbuminuria en Pacientes Pediátricos Con Diagnóstico de síndrome Hemolítico Urémico.

INTRODUCTION: Hemolytic uremic syndrome (HUS) is characterized by the presence of microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney failure. It is the leading cause of acute kidney failure in children under 3 years of age. A variable number of patients develop proteinuria, hypertension, and chronic renal failure. OBJECTIVE: To evaluate the renal involvement in pediatric patients diagnosed with HUS using the microalbumin/creatinine ratio. PATIENTS AND METHODS: Descriptive concurrent cohort study that analyzed the presence of microalbuminuria in patients diagnosed with HUS between January 2001 and March 2012, who evolved without hypertension and normal renal function (clearance greater than 90ml/min using Schwartz formula). Demographic factors (age, sex), clinical presentation at time of diagnosis, use of antibiotics prior to admission, and need for renal replacement therapy were evaluated. RESULTS: Of the 24 patients studied, 54% were male. The mean age at diagnosis was two years. Peritoneal dialysis was required in 45%, and 33% developed persistent microalbuminuria. Antiproteinuric treatment was introduce in 4 patients, with good response. The mean follow-up was 6 years (range 6 months to 11 years). The serum creatinine returned to normal in all patients during follow up. CONCLUSIONS: The percentage of persistent microalbuminuria found in patients with a previous diagnosis of HUS was similar in our group to that described in the literature. Antiproteinuric treatment could delay kidney damage, but further multicenter prospective studies are necessary.

Microalbuminuria en pacientes pediátricos con diagnóstico de síndrome hemolítico urémico / Microalbuminuria in pediatric patients diagnosed with hemolytic uremic syndrome

Introducción: El síndrome hemolítico urémico (SHU) se caracteriza por la presencia de anemia hemolítica microangiopática, trombocitopenia y afectación renal aguda. Es la principal causa de falla renal aguda en niños menores de 3 años. Un número variable de pacientes evoluciona con afectación renal a largo plazo con proteinuria, hipertensión arterial e insuficiencia renal crónica. Objetivo: Evaluar la afectación renal mediante el índice microalbuminuria/creatininuria en pacientes pediátricos con diagnóstico de SHU. Pacientes y Método: Estudio descriptivo de cohorte concurrente que analizó la presencia de microalbuminuria en pacientes diagnosticados de SHU entre enero de 2001 y marzo de 2012, que evolucionaron sin hipertensión y con función renal normal (clearance mayor de 90 ml/min medido por fórmula de Schwartz). Se evaluaron factores demográficos (edad, sexo), presentación clínica en el momento del diagnóstico, uso de antibióticos previo al ingreso y requerimiento de terapia de reemplazo renal. Resultados: Se estudiaron 24 pacientes, el 54% varones; la edad promedio en el momento del diagnóstico fue de 2 años; un 45% requirió diálisis peritoneal; un 33% evolucionó con microalbuminuria persistente; cuatro pacientes recibieron tratamiento antiproteinúrico con buena respuesta. El promedio de seguimiento fue de 6 años (rango: 6 meses a 11 años); todos los pacientes durante el seguimiento evolucionaron con creatinina plasmática normal. Conclusiones: En nuestro grupo, el porcentaje de microalbuminuria persistente en pacientes con diagnóstico previo de SHU fue similiar a lo descrito en la literatura; el tratamiento con antiproteinúricos podría retrasar el daño renal, pero es necesario realizar estudios prospectivos multicéntricos.

Introduction: Hemolytic uremic syndrome (HUS) is characterized by the presence of microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney failure. It is the leading cause of acute kidney failure in children under 3 years of age. A variable number of patients develop proteinuria, hypertension, and chronic renal failure. Objective: To evaluate the renal involvement in pediatric patients diagnosed with HUS using the microalbumin/creatinine ratio. Patients and Methods: Descriptive concurrent cohort study that analyzed the presence of microalbuminuria in patients diagnosed with HUS between January 2001 and March 2012, who evolved without hypertension and normal renal function (clearance greater than 90 ml/min using Schwartz formula). Demographic factors (age, sex), clinical presentation at time of diagnosis, use of antibiotics prior to admission, and need for renal replacement therapy were evaluated. Results: Of the 24 patients studied, 54% were male. The mean age at diagnosis was two years. Peritoneal dialysis was required in 45%, and 33% developed persistent microalbuminuria. Antiproteinuric treatment was introduce in 4 patients, with good response. The mean follow-up was 6 years (range 6 months to 11 years). The serum creatinine returned to normal in all patients during follow up. Conclusions: The percentage of persistent microalbuminuria found in patients with a previous diagnosis of HUS was similar in our group to that described in the literature. Antiproteinuric treatment could delay kidney damage, but further multicenter prospective studies are necessary.

Development of a low-cost, insect larvae-derived recombinant subunit vaccine against RHDV.

Vaccine antigens against rabbit hemorrhagic disease virus (RHDV) are currently derived from inactivated RHDV obtained from livers of experimentally infected rabbits. Several RHDV-derived recombinant immunogens have been reported. However, their application in vaccines has been restricted due to their high production costs. In this paper, we describe the development of an inexpensive, safe, stable vaccine antigen for RHDV. A baculovirus expressing a recombinant RHDV capsid protein (VP60r) was used to infect Trichoplusia ni insect larvae. It reached an expression efficiency of 12.5% of total soluble protein, i.e. approximately 2 mg of VP60r per larva. Preservation of the antigenicity and immunogenicity of the VP60r was confirmed by immunological and immunization experiments. Lyophilized crude larvae extracts, containing VP60r, were stable, at room temperature, for at least 800 days. In all cases, rabbits immunized with a single dose of VP60r by the intramuscular route were protected against RHDV challenge. Doses used were as low as 2 microg of VP60r in the presence of adjuvant or 100 microg without one. Orally administered VP60r in the absence of an adjuvant gave no protection. The potential costs of an RHDV vaccine made using this technology would be reduced considerably compared with producing the same protein in insect cells maintained by fermentation. In conclusion, the larva expression system may provide a broad-based strategy for production of recombinant subunit antigens (insectigens) for human or animal medicines, especially when production costs restrain their use.