Relapse rate and renal prognosis in ANCA-associated vasculitis according to long-term ANCA patterns.

Long-term observation of patients with ANCA-associated vasculitis (AAV) allows the identification of different longitudinal patterns of ANCA levels during follow-up. This study aimed to characterize these patterns and to determine their prognostic significance. All ANCA determinations performed in two university hospitals during a 2-year period were retrospectively reviewed. Patients were included in the analysis if they had high titers of anti-myeloperoxidase (anti-MPO) or anti-proteinase 3 (anti-PR3) antibodies at least once, ≥ 5 serial ANCA determinations and AAV diagnosed by biopsy or American College of Rheumatology (ACR) classification criteria. Patients' time-course ANCA patterns were classified as monophasic, remitting, recurrent or persistent. Associations between ANCA patterns and prognostic variables (relapse rate and renal outcome) were analysed by univariate and multivariate statistics. A total of 99 patients [55 with microscopic polyangiitis (MPA), 36 with granulomatosis with polyangiitis (GPA) and eight with eosinophilic granulomatosis with polyangiitis (EGPA)] were included. Median follow-up was 9 years. Among patients diagnosed with MPA or GPA, recurrent or persistent ANCA patterns were associated with a higher risk of clinical relapse [hazard ratio (HR) = 3·7, 95% confidence interval (CI) = 1·5-9·1 and HR = 2·9, 95% CI = 1·1-8·0, respectively], independently of clinical diagnosis or ANCA specificity. In patients with anti-MPO antibodies, the recurrent ANCA pattern was associated with worsening renal function [odds ratio (OR) = 5·7, 95% CI = 1·2-26·0]. Recurrent or persistent ANCA patterns are associated with a higher risk of clinical relapse. A recurrent ANCA pattern was associated with worsening renal function in anti-MPO-associated vasculitis.

Improving cause of death certification in the Philippines: implementation of an electronic verbal autopsy decision support tool (SmartVA auto-analyse) to aid physician diagnoses of out-of-facility deaths.

BACKGROUND: The majority of deaths in the Philippines occur out-of-facility and require a medical certificate of cause of death by Municipal Health Officers (MHOs) for burial. MHOs lack a standardised certification process for out-of-facility deaths and when no medical records are available, certify a high proportion of ill-defined causes of death. We aimed to develop and introduce SmartVA Auto-Analyse, a verbal autopsy (VA) based electronic decision support tool in order to assist the MHOs in certifying out-of-facility deaths. METHOD: We conducted a stakeholder consultation, process mapping and a pre-test to assess feasibility and acceptability of SmartVA Auto-Analyse. MHOs were first asked to conduct an open-ended interview from the family members of the deceased, and if they were not able to arrive at a diagnosis, continue the interview using the standardised SmartVA questionnaire. Auto-Analyse then presented the MHO with the three most likely causes of death. For the pilot, the intervention was scaled-up to 91 municipalities. We performed a mixed-methods evaluation using the cause of death data and group discussions with the MHOs. RESULTS: Of the 5649 deaths registered, Auto-Analyse was used to certify 4586 (81%). For the remaining 19%, doctors believed they could assign a cause of death based on the availability of medical records and the VA open narrative. When used, physicians used the Auto-Analyse diagnosis in 85% of cases to certify the cause of death. Only 13% of the deaths under the intervention had an undetermined cause of death. Group discussions identified two themes: Auto-Analyse standardized the certification of home deaths and assisted the MHOs to improve the quality of death certification. CONCLUSION: Standardized VA combined with physician diagnosis using the SmartVA Auto-Analyse support tool was readily used by MHOs in the Philippines and can improve the quality of death certification of home deaths.

Asymmetrical influence of a standard light/dark cycle and constant light conditions on the alanyl-aminopeptidase activity of the left and right retinas in adult male rats.

The retina acts as an independent clock informing the central pacemaker, the suprachiasmatic nucleus, under environmental light conditions, with consequences of such inputs for the central and peripheral nervous system. Differences in the behavior of the left and right retinas depending on environmental light conditions may influence the information projected to the brain hemispheres. The retina possesses neuropeptides that act as neurotransmitters or neuromodulators. Alanyl-aminopeptidase (AlaAP, EC 3.4.11.2) activity regulates some of these neuropeptides and therefore reflects their function. We analyzed AlaAP activity in the left and right retinas of adult male rats at successive time points under standard (12/12 h light/dark cycle) and nonstandard (constant light) conditions. AlaAP activity was measured fluorometrically using alanyl-beta-naphthylamide as the substrate. Under standard conditions, there were no differences in the left or right retina between time points, with the left retina predominating, particularly in the light period. In contrast, under constant light, no left versus right differences were observed, but significant differences between time points appeared. In comparison with standard conditions, constant conditions led to significantly higher AlaAP activity. Considering all the left retina data in comparison with all the right retina data, no correlation was found between the left and right retinas under standard conditions, but a significant positive correlation was observed under constant light. These results demonstrate an asymmetrical response of retinal AlaAP activity to changes in environmental light conditions, which may affect the functions in which the substrates of AlaAP are involved and the information projected to the brain hemispheres.

Efficacy and safety of bortezomib in refractory lupus nephritis: a single-center experience.

BACKGROUND AND OBJECTIVES: Resistant lupus nephritis (LN) has been associated with the persistence of long-lived plasma cells. Preliminary studies identified bortezomib as a potential treatment option for patients with refractory LN. The aim of this study was to analyze the efficacy and safety of bortezomib in the treatment of severe refractory LN. METHODS: This retrospective study included 12 female patients diagnosed for the first time with class IV or IV/V LN with acute or rapidly progressive kidney injury (n = 11) and/or severe nephrotic syndrome (n = 1) who showed resistance to induction therapy with cyclophosphamide, steroids, mycophenolate, and rituximab, and were treated with either intravenous or subcutaneous bortezomib plus intravenous dexamethasone. RESULTS: All patients with acute or rapidly progressive kidney injury showed a significant reduction in both biochemical and immunological activity after a mean of 6 (minimum 5, maximum 7) weekly cycles of bortezomib regimen, with a significant increase in C3 levels and a significant decrease of anti-ds DNA antibody titers, Systemic Lupus Erythematosus Disease Activity Index score, serum creatinine, and proteinuria. One patient (8.3%) achieved a complete response, and 10 patients (83.4%) achieved a partial response. During follow-up, all these patients maintained partial responses under treatment with mycophenolate and low-dose glucocorticoids. The patient with refractory nephrotic syndrome showed a partial response but relapsed 11 months after the end of bortezomib treatment and was resistant to treatment. A significant decrease in serum IgG levels after initiation of bortezomib treatment was observed in all patients, five of them (41.6%) showed hypogammaglobulinemia (<500 mg/dl), but no patient suffered from opportunistic infections; in only two patients (16.6%) hypogammaglobulinemia persisted at the end of follow-up. Two patients (16.6%) suffered from sensory neuropathy, which led to bortezomib treatment discontinuation. CONCLUSIONS: Bortezomib may be an effective option for refractory LN, but close monitoring must be performed for possible adverse events such as peripheral neuropathy and hypogammaglobulinemia.

[Congenital portosistemic shunt. Importance of early treatment]. / Shunt portosistémico congénito. Importancia del tratamiento precoz.

AIM: Congenital portosistemic shunt (CPSS) is an uncommon condition that can cause serious complications such as encephalopathy and liver tumors at risk of malignant degeneration. Occlusion of the shunt by surgery or interventional radiology can prevent and even improve such complications. In some cases, liver transplantation is the only curative option. We describe our experience with this condition. PATIENTS AND METHODS: Between 1992 and 2013, eight children (four male and four female) were diagnosed with CPSS (four extrahepatic and four intrahepatic) in our center, of which seven were diagnosed after 2007. The mean age at diagnosis was 5.5 years (1 month-15 years). Five patients had associated comorbidities. RESULTS: Five patients had developed hyperammonemia and intellectual impairment, one of those manifested with an onset of coma. Four patients have developed at diagnosis liver tumors, including focal nodular hyperplasia/regenerative nodules (n=3) and adenomas (n=3). One patient with multiple tumors required a hepatectomy owing to compressive symptoms. Two patients, developed malignant degeneration, a child under five years treated with liver transplantation and another in adulthood treated with hepatectomy. In one patient, diagnosed in the neonatal period, the shunt occlusion occurred spontaneously. Direct portography with the occlusion test was performed in five patients, the shunt was occluded with interventional radiology in three cases, surgery in one and liver transplantation in the remaining. CONCLUSIONS: The treatment of the SPSC must be early to prevent and even to reverse its complications, avoiding liver transplantation. Currently, interventional radiology is essential in the strategy to follow and treatment of these patients.

OBJETIVOS: El shunt porto-sistémico congénito (SPSC) es una patología infrecuente que puede producir complicaciones graves, como encefalopatía y tumores hepáticos con riesgo de degeneración maligna. La oclusión del shunt por cirugía o radiología intervencionista puede evitar, e incluso mejorar, las complicaciones. En algunos casos el trasplante hepático es la única opción. Describimos nuestra experiencia con esta patología. PACIENTES Y METODO: Entre 1992 y 2013, ocho pacientes en edad pediátrica (cuatro varones y cuatro mujeres) fueron diagnosticados de un SPSC (cuatro extrahepáticos y cuatro intrahepáticos), de los cuales siete fueron diagnosticados después del año 2007. La mediana de edad al diagnóstico fue 5,5 años (1 mes-15 años). Cinco pacientes tenían patología asociada. RESULTADOS: Cinco pacientes presentaban hiperamoniemia y afectación intelectual. Una niña debutó con coma. Cuatro pacientes presentaron tumoraciones hepáticas, incluyendo hiperplasia nodular focal/nódulos de regeneración (n=3), y adenomas (n=3). Una paciente con tumoraciones múltiples requirió una hepatectomía por síntomas compresivos. En dos pacientes se produjo degeneración a hepatocarcinoma, un niño de 5 años tratado con trasplante y otro en edad adulta tratado con hepatectomía. En un paciente de diagnóstico neonatal, el shunt cerró espontáneamente en seis meses. En cinco pacientes se ha realizado portografía directa con test de oclusión, realizándose cierre del shunt en tres casos por radiología intervencionista, uno con cirugía y en otro, con trasplante. CONCLUSIONES: El tratamiento del SPSC ha de ser precoz para prevenir, e incluso revertir, las complicaciones, evitando el trasplante hepático. En la actualidad la radiología intervencionista juega un papel fundamental en la estrategia y el tratamiento de estos pacientes.

[Rupture of a superior mesenteric artery aneurysm in pediatric age: case report and literature review]. / Rotura de un aneurisma de arteria mesentérica superior en edad pediátrica: caso clínico y revisión de la literatura.

INTRODUCTION: Splanchnic artery aneurysms are rare in children. High mortality from rupture justifies its treatment, with various therapeutic options among which stand out surgery and recently, endovascular treatment. CASE REPORT: A 11 year old girl presented with abdominal pain and sudden drop in hematocrit. The urgent abdominal CT angiography showed a saccular aneurysm of the superior mesenteric artery (SMA) at 4 cm from the ostium with dissection and active bleeding. A selective angiography was performed which confirmed the dissection. A self-expanding stent was placed in the main trunk of the SMA and a transcatheter coil and onyx embolization of the aneurysm was performed. The control angiogram showed no evidence of residual perfusion of the false lumen and demonstrated proper vascularization of the distal jejunum-ileal branches. Dual antiplatelet therapy with aspirin and dipyridamole was begun. After 24 months of follow-up the patient is asymptomatic. COMMENTS: Endovascular treatment of a SMA aneurysm is effective in the pediatric patient, even in emergency situations.

INTRODUCCION: Los aneurismas esplácnicos son excepcionales en la edad pediátrica. La elevada mortalidad por rotura justifica su tratamiento, existiendo diversas opciones terapéuticas entre las que destacan la cirugía y, recientemente, el tratamiento endovascular. CASO CLINICO: Paciente de 11 años que presentó dolor abdominal súbito y caída del hematocrito. La angio-TC abdominal urgente mostró un aneurisma sacular de la arteria mesentérica superior (AMS) a 4 cm del ostium con disección de la luz y signos de sangrado activo. Se realizó una angiografía que confirmó el aneurisma. Se colocó un stent autoexpandible en el tronco principal de la arteria mesentérica superior con repleción del aneurisma con microcoils y Onyx, sin evidenciar perfusión residual de la falsa luz y comprobando una adecuada vascularización tanto distal como de las ramas yeyuno-ileales. Se instauró doble antiagregación con AAS y dipiridamol. Tras 24 meses de seguimiento se encuentra asintomática.. COMENTARIOS: El tratamiento endovascular es efectivo en el paciente pediátrico, incluso en situaciones de emergencia.

Relationship of angiotensinase and vasopressinase activities between hypothalamus, heart, and plasma in L-NAME-treated WKY and SHR.

The renin-angiotensin system (RAS), vasopressin, and nitric oxide (NO) interact to regulate blood pressure at central and peripheral level. To improve our understanding of their interaction and their relationship with the hypothalamus and the cardiovascular system, we analyzed angiotensin- and vasopressin-metabolizing activities in hypothalamus (HT), left ventricle (LV), and plasma, collected from Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) treated or not with L-NAME [N(G)-nitro-L-arginine methyl ester], which inhibits the formation of NO and over-activates the sympathetic nervous system. Previous observations in WKY suggested higher formation of Ang III and Ang IV in the HT and higher availability of Ang II in plasma after L-NAME treatment. Our current results show higher formation of Ang IV and higher metabolism of vasopressin after treatment with L-NAME in the LV of WKY rats. In SHR treated with L-NAME, there is higher availability of Ang III in the HT leading to higher release of vasopressin together with lower formation of Ang 2-10. In their LV, however, there is an increase of vasopressinase. Interestingly, while the enzymatic activities in the HT and LV of WKY rats and control SHR are poorly correlated, they are well but inversely correlated in the L-NAME treated SHR. On the other hand, no significant correlations between enzymatic activities in HT or LV and plasma were noticed. Our results suggest that eNOS inhibition in SHR induces or enhances an inverse reciprocal interaction between HT and LV involving the RAS and vasopressin, which may be mediated by the autonomic nervous system.

Mycophenolate as maintenance therapy for lupus nephritis with impaired renal function.

BACKGROUND: Mycophenolate (MF) is effective as a maintenance therapy after induction therapy in patients with lupus nephritis (LN). However, little is known about its role in patients with impaired renal function. The purpose of this study was to evaluate the efficacy and safety of MF as a maintenance therapy for LN and its association with renal function. METHODS: Data were obtained for 56 Spanish patients who were receiving MF as a maintenance therapy for LN. Patients were classified into two groups according to renal function at the initiation of MF treatment: group 1 [estimated glomerular filtration rate (eGFR) ≥60 ml/min/1.73 m(2)] and group 2 (eGFR <60 ml/min/1.73 m(2)). The primary endpoints of the study were the rates of renal relapse and responses, and their relationship with baseline renal function. Secondary outcomes were the appearance of side effects during treatment. RESULTS: At initiation of MF treatment, the only differences between the groups were for age, hemoglobin levels, anti-DNA antibody titer, proteinuria, and renal function. In group 1 (n = 38), the eGFR was 98 ± 34 ml/min/1.73 m(2) and in group 2 (n = 18) the eGFR was 43 ± 14 ml/min/1.73 m(2). Only 3 cases had an eGFR <30 ml/min/1.73 m(2). No significant differences were observed in the rate of relapse at 6 months (group 1: 20%; group 2: 23%) or at 12 months (group 1: 25%; group 2: 17%). Response rates were also similar in both groups. Side effects were unremarkable. CONCLUSIONS: MF is effective and safe as a maintenance therapy for LN both in patients with normal renal function and in those with renal impairment.

Effects of antihypertensive drugs on angiotensinase activities in the testis of spontaneously hypertensive rats.

Sexual dysfunction is a frequent adverse effect during antihypertensive therapy. However, the mechanisms responsible for these effects are not well understood. The renin-angiotensin system has been identified in testis where it may play a role in testicular function and be involved in the detrimental effects of antihypertensive drugs. Therefore, our objective was to compare the influence of captopril and propranolol on plasma testosterone levels and on hydrolyzing angiotensin's enzymes (angiotensinases) in the testis of spontaneously hypertensive rats (SHRs) and in control animals. Twenty-four adult male SHRs were used in this study; eight were treated with captopril in drinking water, 8 with propranolol, and 8 were controls. At the end of the 4 weeks treatment period, systolic blood pressure (SBP) was recorded, blood samples were collected, and the right testis was dissected after perfusion of the rat with saline. The soluble (Sol) and membrane-bound (MB) fractions were obtained after solubilization and ultracentrifugation. Fluorometric measurement of Sol and MB angiotensinase activities were performed using arylamide derivatives as substrates. Testosterone was measured by enzyme immunoassay. SBP decreased after captopril but did not change with propranolol treatment. Whereas captopril did not affect angiotensinase activities, highly significant reductions in Sol and MB angiotensinase activities, particularly glutamyl- and aspartyl-aminopeptidases, were observed after treatment with propranolol. Plasma testosterone decreased in captopril treated rats but propranolol had a greater effect. The present results support a general functional depression of the RAS cascade in the testis of propranolol-treated SHR, which may influence the sexual function of these animals.

Mycophenolate as induction therapy in lupus nephritis with renal function impairment.

BACKGROUND: Mycophenolate (MF) is effective as induction therapy for lupus nephritis (LN) in patients with normal renal function; however, little is known about its role in patients with impaired renal failure. The purpose of this study was to evaluate the response to MF in LN and its association with baseline renal function. METHODS: Data were obtained for 90 patients from 12 Spanish renal units who were receiving MF as induction therapy for LN. Patients were classified into 2 groups: group 1 (estimated glomerular filtration rate [eGFR] ≥60 ml/min/1.73 m(2)) and group 2 (eGFR <60 ml/min/ 1.73 m(2)). The primary outcome measure was the percentage of patients who achieved any response and its relationship with initial eGFR. The secondary outcome measures were the percentage of patients who achieved a complete response (CR) or partial response (PR) and the appearance of relapses during treatment and side effects. RESULTS: At initiation of MF treatment, there were no differences in the main parameters between group 1 (n = 63; eGFR 87 ± 23 ml/min/ 1.73 m(2)) and group 2 (n = 27; eGFR 44 ± 12 ml/min/1.73 m(2)). Exposure to prednisone and MF was similar. The percentages of patients who achieved a response in groups 1 and 2 were, respectively, 69.2 and 43.8% at 6 months and 81.3 and 73.7% at 12 months. CR was more frequent in group 1, whereas PR was similar in both groups. Four patients relapsed and side effects were unremarkable. CONCLUSIONS: MF is effective and safe as induction therapy for LN, and response is even achieved in patients with baseline renal impairment.

Angiotensinase and vasopressinase activities in hypothalamus, plasma, and kidney after inhibition of angiotensin-converting enzyme: basis for a new working hypothesis.

Reducing angiotensin II (Ang II) production via angiotensin-converting enzyme (ACE) inhibitors is a key approach for the treatment of hypertension. However, these inhibitors may also affect other enzymes, such as angiotensinases and vasopressinase, responsible for the metabolism of other peptides also involved in blood pressure control, such as Ang 2-10, Ang III, Ang IV, and vasopressin. We analyzed the activity of these enzymes in the hypothalamus, plasma, and kidney of normotensive adult male rats after inhibition of ACE with captopril. Aspartyl- (AspAP), glutamyl- (GluAP), alanyl- (AlaAP) and cystinyl-aminopeptidase (CysAP) activities were measured fluorimetrically using arylamides as substrates. Systolic blood pressure (SBP), water intake, and urine flow were also measured. Captopril reduced SBP and increased urine flow. In the hypothalamus, GluAP and AspAP increased, without significant changes in either AlaAP or CysAP. In contrast with effects in plasma, GluAP was unaffected, AspAP decreased, while AlaAP and CysAP increased. In the kidney, enzymatic activities did not change in the cortex, but decreased in the medulla. These data suggest that after ACE inhibition, the metabolism of Ang I in hypothalamus may lead mainly to Ang 2-10 formation. In plasma, the results suggest an increased formation of Ang IV together with increased vasopressinase activity. In the kidney, there is a reduction of vasopressinase activity in the medulla, suggesting a functional reduction of vasopressin in this location. The present data suggest the existence of alternative pathways in addition to ACE inhibition that might be involved in reducing BP after captopril treatment.

Understanding risks and consequences of pathogen infections on the physiological performance of outmigrating Chinook salmon.

The greatest concentration of at-risk anadromous salmonids is found in California (USA)-the populations that have been negatively impacted by the degradation of freshwater ecosystems. While climate-driven environmental changes threaten salmonids directly, they also change the life cycle dynamics and geographic distribution of pathogens, their resulting host-pathogen interactions and potential for disease progression. Recent studies have established the correlation between pathogen detection and salmonid smolt mortality during their migration to the ocean. The objective of the present study was to screen for up to 47 pathogens in juvenile Chinook salmon (Oncorhynchus tshawytscha) that were held in cages at two key sites of the Sacramento River (CA, USA) and measure potential consequences on fish health. To do so, we used a combination of transcriptomic analysis, enzymatic assays for energy metabolism and hypoxia and thermal tolerance measures. Results revealed that fish were infected by two myxozoan parasites: Ceratonova shasta and Parvicapsula minibicornis within a 2-week deployment. Compared to the control fish maintained in our rearing facility, infected fish displayed reduced body mass, depleted hepatic glycogen stores and differential regulation of genes involved in the immune and general stress responses. This suggests that infected fish would have lower chances of migration success. In contrast, hypoxia and upper thermal tolerances were not affected by infection, suggesting that infection did not impair their capacity to cope with acute abiotic stressors tested in this study. An evaluation of long-term consequences of the observed reduced body mass and hepatic glycogen depletion is needed to establish a causal relationship between salmon parasitic infection and their migration success. This study highlights that to assess the potential sublethal effects of a stressor, or to determine a suitable management action for fish, studies need to consider a combination of endpoints from the molecular to the organismal level.

The profile of fatty acids in frontal cortex of rats depends on the type of fat used in the diet and correlates with neuropeptidase activities.

The kind of fat in the diet modifies the profile of fatty acids in brain and also affects aminopeptidase activities in tissues. Although modifications in brain fatty acids, neurotransmitters, or enzymes due to dietary fat composition have been reported, no direct relationship has yet been described between specific brain fatty acid changes and neuropeptide metabolism following the fat composition of the diet. We investigated the lipid profile and some neuropeptidase activities in the frontal cortex of adult male rats after a period in which diets were supplemented with fatty acids differing in their degrees of saturation such as fish oil (rich in polyunsaturated fatty acids, PUFAs), olive oil (rich in monounsaturated fatty acids, MUFAs), and coconut oil (rich in saturated fatty acids, SAFAs). It is observed that the diet composition affects fatty acid distribution in the brain. Although there is no change of global aminopeptidase/neuropeptidase, their activities in the brain correlate positively or negatively with the dietary fat composition. It is hypothesized that fatty acid in the diet modifies membrane fluidity, peptidases tertiary structure, and therefore, the availability and function of neuropeptides. The present results support the notion that cognitive functions may be modulated depending on the type of fat used in the diet.

No-touch hepatic hilum technique to treat early portal vein thrombosis after pediatric liver transplantation.

A 'no-touch' hilum technique used to treat early portal vein complications post-liver transplantation in five children with body weight <10 kg is described. Four patients developed thrombosis and one portal flow absence secondary to collateral steal flow. A vascular sheath was placed through the previous laparotomy in the ileocolic vein (n = 2), inferior mesenteric vein (n = 1) or graft umbilical vein (n = 1). Portal clots were mechanically fragmented with balloon angioplasty. In addition, coil embolization of competitive collaterals (n = 3) and stent placement (n = 1) were performed. The catheter was left in place and exteriorized through the wound (n = 2) or a different transabdominal wall puncture (n = 3). A continuous transcatheter perfusion of heparin was subsequently administered. One patient developed recurrent thrombosis 24 h later which was resolved with the same technique. Catheters were removed surgically after a mean of 10.6 days. All patients presented portal vein patency at the end of follow-up. Three patients are alive after 5 months, 1.5 and 3.5 years, respectively; one patient required retransplantation 18 days postprocedure and the remaining patient died of adenovirus infection 2 months postprocedure. In conclusion, treatment of early portal vein complications following pediatric liver transplantation with this novel technique is feasible and effective.

Hypothalamic and plasmatic angiotensin metabolism in L-NAME treated rats.

In order to study the interaction between the renin-angiotensin system (RAS) and nitric oxide (NO), we analyzed the activity of aspartyl- (AspAP), glutamyl- (GluAP), alanyl- (AlaAP), and cystinylaminopeptidase (CysAP) enzymes involved in the RAS cascade, in the hypothalamus, and plasma of normotensive adult male rats after the inhibition of NO production with the NO synthase inhibitor L-NAME (L-N (G)-nitroarginine methyl ester). L-NAME treatment produced a significant increase of systolic blood pressure (SBP). In plasma, while GluAP activity decreased significantly, suggesting a lower Ang III formation, the other aminopeptidases did not change after L-NAME treatment. In hypothalamus, the activities of AspAP and CysAP were not affected after L-NAME treatment. In contrast, GluAP and AlaAP increased significantly. These results suggested mainly a higher formation of Ang III, but also higher levels of Ang IV in the hypothalamus of L-NAME treated rats. Both peptides have hypertensive properties at central level. On the contrary, Ang III may counteract the hypertensive action of Ang II at the periphery. Therefore, the increased SBP in L-NAME treated rats may be due in part to the increased activity of GluAP and AlaAP in hypothalamus and to a decreased activity of GluAP in plasma.

[Progress in understanding the pathogenesis of IgA nephropathy: new perspectives for the near future?]. / Avances en el conocimiento de la patogenia de la nefropatía IgA: ¿nuevas perspectivas para un futuro inmediato?

Progress in understanding the pathogenesis of IgA nephropathy has shown that probably there is no a single IgA nephropathy with the same pathogenic mechanism, clinical course and response to therapy. The evidence currently available suggests the existence of at least two possible mechanisms of IgA deposition in the renal mesangium. In a small percentage of patients, mesangial deposition of IgA1 colocalizes with secretory component, indicating that the deposited IgA1 in glomeruli originates completely or partly in the mucose-associated lymphoid tissue. This deposition pattern has been associated with activation of complement by the lectin pathway and has been associated with a worse prognosis, although this last statement needs to be confirmed in long-term studies. The mechanisms responsible for secretory IgA deposition are not known. In the majority of patients with IgA nephropathy secretory component is not detectable in the mesangium. In these cases, the presence of elevated circulating levels of galactose-deficient IgA, produced by bone marrow plasma cells would be a predisposing factor but not sufficient to induce nephropathy. To produce kidney disease, galactose-deficient IgA1 must be deposited in the renal mesangium, and once there, either by interaction with specific receptors (CD71?), by direct activation of complement or by being the target of an IgG autoimmune response anti-IgA, induce activation, proliferation and increased mesangial matrix synthesis and eventually cell injury. In parallel, galactose-deficient IgA, through interaction with the RR Fc alpha/gamma, may activate circulating lymphocytes and monocytes and enhance their response to chemoattractants produced by the mesangial cell, causing, thus, the inflammatory infiltrate to initiate and maintain the interstitial injury. In the next few years, advances recently added to the knowledge of the pathogenesis of nephropathy IgA1 could provide new variables that allow walking in the direction of having a classification of patients based not only in clinical and morphological criteria but also having a greater pathogenic basis.

[Long term follow-up of bile duct stenosis treated with interventional radiology in pediatric liver transplantation]. / Seguimiento a largo plazo de las estenosis de la vía biliar tratadas con radiología intervencionista en el trasplante hepático pediátrico.

The reported incidence of biliary strictures following pediatric liver transplantation has ranged between 5-34%, with a higher incidence in segmental grafts. Currently, percutaneous transhepatic balloon dilatation of biliary strictures is considered as the first line treatment owing to its minimal invasiveness. Between 1995-2006, 20 children who underwent liver transplantation developed biliary complications treated with interventional radiology. 16/20 developed biliary stricture, of whom 10 were treated with percutaneous transhepatic balloon dilatation. The mean age at the procedure was 6.6 years (range 8 m--14 years). The allograft types included whole (n=4), split (n=3), and reduced (n=3) livers. The procedure was performed at a mean time post-transplantation of 2.6 years. All patients are alive with a mean follow-up post-procedure of 24 months (range: 4 months-11 years). Currently, only 4 have a normal appearing biliary tree by imaging techniques and 6 developed stricture recurrence; of whom 3 developed biliary cirrhosis (2 splits, 1 reduced), one patient underwent successful rescue surgery, one was treated again percutaneously, and the remaining was lost to followup. In conclusion, treatment of percutaneous transhepatic balloon dilatation of biliary strictures is effective avoiding surgical correction. However, stricture recurrence in the medium- long term follow-up is frequent, particularly in segmental grafts. [corrected]

Is there a link between depression, neurochemical asymmetry and cardiovascular function?

Although at present depression is one of the most disabling disorders in our social environment, the understanding of its pathogenesis and the resources for its treatment are still unsatisfactory. The importance of brain asymmetry in the pathogenesis of disorders in brain function, including mood disorders such as depression, is a highly unexplored, sometimes underrated, and even ignored topic. It is important to note that the basal and pathological functional lateralization must have an underlying neurochemical substrate. It is also necessary to indicate that the brain asymmetry extends to a neurovisceral integration whose behavior may also be lateralized. One of the most studied axis from the functional point of view is the brain-heart connection, in whose operation there are observations that suggest an asymmetric behavior in basal conditions that is modified by central and peripheral changes, as well as by pharmacological treatments. There are evidences that connect cardiovascular function, neurochemical asymmetries, and depression. A deep understanding of the bilateral behavior of the brain following pathophysiological changes in blood pressure as well as pharmacologically induced, can provide us with therapeutic suggestions for the treatment of depression. In this article, we analyze remarkable results of some representative selected contributions, with which we discuss our proposal on the relationship between hypertension, depression and neurochemical asymmetry.

Angiotensin II, dopamine and nitric oxide. An asymmetrical neurovisceral interaction between brain and plasma to regulate blood pressure.

Vital functions, such as blood pressure, are regulated within a framework of neurovisceral integration in which various factors are involved under normal conditions maintaining a delicate balance. Imbalance of any of these factors can lead to various pathologies. Blood pressure control is the result of the balanced action of central and peripheral factors that increase or decrease. Special attention for blood pressure control was put on the neurovisceral interaction between Angiotensin II and the enzymes that regulate its activity as well as on nitric oxide and dopamine. Several studies have shown that such interaction is asymmetrically organized. These studies suggest that the neuronal activity related to the production of nitric oxide in plasma is also lateralized and, consequently, changes in plasma nitric oxide influence neuronal function. This observation provides a new aspect revealing the complexity of the blood pressure regulation and, undoubtedly, makes such study more motivating as it may affect the approach for treatment.