Sensory modulation and trauma-related symptoms during rocket attacks.

BACKGROUND: War is a highly traumatogenic experience that may result in trauma-related symptoms during exposure. Although most individuals exhibit recovery after the trauma ends, symptomatology during exposure may serve as an initial indicator underlying symptomatology at the posttraumatic phase, hence the imperative to identify risk factors for trauma-related symptoms during the peritraumatic phase. While research has uncovered several factors associated with peritraumatic distress, such as age, gender, history of mental disorder, perceived threat, and perceived social support, the role of sensory modulation has not been explored. METHOD: To address this gap, 488 Israeli citizens were assessed using an online survey for sensory modulation and trauma-related symptoms during rocket attacks. RESULTS: Analyses revealed that while the association between high sensory responsiveness and elevated levels of specific trauma-related symptoms is somewhat weak (0.19

High sensory responsiveness was related to trauma-related symptoms.Low sensory responsiveness was unrelated to trauma-related symptoms.The risk for elevated trauma-related symptoms during exposure was doubled for each increase in high sensory-responsiveness score.

Bretschneider Solution and Two Antianginal Drugs Protect Peripheral Tissue in an Animal Model of Hemorrhagic Shock.

ABSTRACT: Shock and subsequent resuscitation provoke ischemia-reperfusion injury. Trimetazidine (TMZ), allopurinol (ALO), and histidine-tryptophan-ketoglutarate (HTK) solution, can protect from ischemia-reperfusion injury in chronic coronary syndromes and in transplantation. The objective of the current study is to compare, in a hemorrhagic shock and standard resuscitation animal model, organ damage parameters between placebo and treatment with TMZ, ALO, or HTK. Shock was induced in Wistar rats by controlled arterial bleeding, maintaining mean arterial pressure between 38 and 42 mm Hg for 60 minutes; then, drawn blood was reinfused. Animals were divided into: Sham (n = 4), Control (n = 6), TMZ (n = 7), ALO (n = 9), and HTK (n = 7). At the end of the experiment, animals were sacrificed and tissue harvested. TMZ, ALO and HTK decreased histopathologic damage in heart [Control: 1.72 (1.7-1.77); TMZ: 1.75 (1.72-1.79); ALO: 1.75 (1.74-1.8); HTK: 1.82 (1.78-1.85); all P < 0.05], kidney [Control: 3 (2-3); TMZ: 1 (1-2); ALO: 1 (1-1); HTK: 1(1-1); all P < 0.05] and intestine [Control: 3 (2-3); TMZ: 1 (1-2); ALO: 1 (1-1); HTK: 1 (0-2); all P < 0.05]. Also, treatment with TMZ, ALO, and HTK increased immunohistochemical expression of thioredoxin-1 in heart [Control: 6.6 (5.6-7.4); TMZ: 9.5 (8.1-9.7); ALO: 9.1 (8.4-10.2); HTK: 14.2 (12.6-15); all P < 0.05]; and kidney [Control: 4.6 (4-5.1); TMZ: 9.7 (9.3-9.9); ALO: 9.6 (9-9.9); HTK: 16.7 (16.1-17); all P < 0.05]. In an experimental model of hemorrhagic shock, TMZ, ALO, and HTK solution attenuated cell damage in multiple parenchyma and increased antioxidant defenses.

Uncommon Presentation of Atypical Hemolytic Uremic Syndrome: A Case Report.

Atypical hemolytic uremic syndrome (aHUS) is an ultra-rare disease characterized by microangiopathic hemolytic anemia, thrombocytopenia and renal damage. Its presentation as nephrotic syndrome (NS) during first year of life is uncommon; we describe a child with clinical and laboratory findings of NS whose renal biopsy revealed thrombotic microangiopathy (TMA). A previously healthy 4-month-old male was admitted with severe dehydration, diarrhea and anuria. Laboratory results showed electrolyte disturbances, increased serum creatinine, anemia without schistocytes, thrombocytosis, normal lactic dehydrogenase (LDH) levels, hypoalbuminemia hypercholesterolemia and decreased C3 levels. After rehydration hematuria and massive proteinuria were also documented and an initial diagnosis of NS of the first year was established. Studies seeking for infectious agents were negative. During hospitalization he continued to be oligo-anuric needing dialysis and a renal biopsy was performed, which showed TMA findings. We here considered the diagnosis of aHUS and started plasma infusions as a bridge until starting eculizumab. After two infusions urine output improved leading to discontinuation dialysis. The diagnoses of STEC infection and thrombocytopenic thrombotic purpura were ruled out. Factor B, H, I and properdin levels were normal. Antibodies against CFH negative were negative. Screening for genes causative of aHUS detected a heterozygous variant in CFHR3 of uncertain significance. On day 20, treatment was switched to eculizumab, which induced a progressive remission of the NS. This case outlines the need for a heightened diagnosis suspicion of this already rare disease since early initiation of eculizumab therapy improves its prognosis.

Chronic exposure to low concentrations of chlorpyrifos affects normal cyclicity and histology of the uterus in female rats.

Chlorpyrifos (CPF), the most used insecticide in Argentina, can act as an endocrine disruptor at low doses. We previously demonstrated that chronic exposure to CPF induces hormonal imbalance in vivo. The aim of this work was to study the effects of low concentrations of CPF (0.01 and 1 mg/kg/day) on the reproductive system of virgin adult rats. In the ovary, we studied the effects of CPF on steroidogenesis by determining steroid hormone content by RIA and CYP11 and CYP19 enzyme expression by qRT-PCR. The estrous cycle was evaluated by microscopic observation of vaginal smear, as well as by changes in uterine histology. In endometrium, we determined the fractal dimension and expression of PCNA, ERα and PR by IHC. Our results showed that chronic exposure to CPF affects ovarian steroid synthesis, causing alterations in the normal cyclicity of animals. In addition, CPF induced proliferative changes in the uterus, suggesting that it could affect reproduction or act as a risk factor in the development of uterine proliferative pathologies.

Nefropatía por inmunoglobulina M: características histopatológicas y clínicas. Serie de casos / Immunoglobulin M nephropathy: histopathological and clinical characteristics. Case series

La nefropatía por inmunoglobulina M (NIgM) es una glomerulopatía idiopática caracterizada por depósitos mesangiales globales y difusos de IgM. Se realizó un estudio retrospectivo de las características clínicas e histopatológicas de los pacientes con NIgM atendidos en nuestro servicio. De 241 biopsias renales, 21 correspondieron a NIgM (8,7 %). Se incluyeron 18 pacientes (14 de sexo femenino, mediana de edad: 3,08 años). Se excluyó a 1 paciente por enfermedad sistémica asociada y a 2 por seguimiento menor a 1 año. Catorce pacientes se manifestaron con síndrome nefrótico (SN) y 4 con proteinuria aislada o asociada a hematuria. En la microscopia óptica, 13 presentaron hiperplasia mesangial, y 5 esclerosis focal y segmentaria. De los pacientes con SN, 7 fueron corticorresistentes, 4 corticodependientes y 3 presentaban recaídas frecuentes. Todos los pacientes con SN y 1 con proteinuria-hematuria recibieron inmunosupresores; los 18 pacientes recibieron, además, antiproteinúricos. Luego de 5,2 años (2-17,5) de seguimiento, 6 pacientes evolucionaron a enfermedad renal crónica

Immunoglobulin M nephropathy (IgMN) is an idiopathic glomerulopathy characterized by diffuse global mesangial deposits of IgM. We retrospectively studied the clinical and histopathological characteristics of the patients with IgMN seen in our service. Of 241 renal biopsies, 21 corresponded to IgMN (8.7 %). One patient was excluded due to associated systemic disease and 2 due to follow-up less than 1 year, 18 were included (14 girls, median age 3.08 years). Fourteen manifested with nephrotic syndrome (NS) and the remaining with proteinuria (isolated or associated with hematuria). On light microscopy, 13 had hyperplasia with mesangial expansion and 5 had focal and segmental sclerosis. Of the patients with NS, 7 were steroid-resistant, 4 steroid-dependent, and 3 frequent relapsers. All patients with NS and 1 with proteinuria-hematuria received immunosuppressants; the 18 patients also received antiproteinuric drugs. After 5.2 years (2-17.5) of follow-up, 6 patients developed chronic kidney disease.

[Immunoglobulin M nephropathy: histopathological and clinical characteristics. Case series]. / Nefropatía por inmunoglobulina M: características histopatológicas y clínicas. Serie de casos.

Immunoglobulin M nephropathy (IgMN) is an idiopathic glomerulopathy characterized by diffuse global mesangial deposits of IgM. We retrospectively studied the clinical and histopathological characteristics of the patients with IgMN seen in our service. Of 241 renal biopsies, 21 corresponded to IgMN (8.7 %). One patient was excluded due to associated systemic disease and 2 due to follow-up less than 1 year, 18 were included (14 girls, median age 3.08 years). Fourteen manifested with nephrotic syndrome (NS) and the remaining with proteinuria (isolated or associated with hematuria). On Nefropatía por inmunoglobulina M: características histopatológicas y clínicas. Serie de casos Immunoglobulin M nephropathy: histopathological and clinical characteristics. Case series light microscopy, 13 had hyperplasia with mesangial expansion and 5 had focal and segmental sclerosis. Of the patients with NS, 7 were steroid-resistant, 4 steroid-dependent, and 3 frequent relapsers. All patients with NS and 1 with proteinuria-hematuria received immunosuppressants; the 18 patients also received antiproteinuric drugs. After 5.2 years (2-17.5) of follow-up, 6 patients developed chronic kidney disease.

La nefropatía por inmunoglobulina M (NIgM) es una glomerulopatía idiopática caracterizada por depósitos mesangiales globales y difusos de IgM. Se realizó un estudio retrospectivo de las características clínicas e histopatológicas de los pacientes con NIgM atendidos en nuestro servicio. De 241 biopsias renales, 21 correspondieron a NIgM (8,7 %). Se incluyeron 18 pacientes (14 de sexo femenino, mediana de edad: 3,08 años). Se excluyó a 1 paciente por enfermedad sistémica asociada y a 2 por seguimiento menor a 1 año. Catorce pacientes se manifestaron con síndrome nefrótico (SN) y 4 con proteinuria aislada o asociada a hematuria. En la microscopia óptica, 13 presentaron hiperplasia mesangial, y 5 esclerosis focal y segmentaria. De los pacientes con SN, 7 fueron corticorresistentes, 4 corticodependientes y 3 presentaban recaídas frecuentes. Todos los pacientes con SN y 1 con proteinuria-hematuria recibieron inmunosupresores; los 18 pacientes recibieron, además, antiproteinúricos. Luego de 5,2 años (2-17,5) de seguimiento, 6 pacientes evolucionaron a enfermedad renal crónica.

Structural changes in endocrine pancreas of male Wistar rats due to chronic cola drink consumption. Role of PDX-1.

AIM: The objective of this work was to analyze the structural changes of the pancreatic islets in rats, after 6 month consuming regular and light cola for 6 months. Also, we have analyzed the possible role of PDX-1 in that process. Finally, with the available knowledge, we propose a general working hypothesis that explains the succession of phenomena observed. Previously, we reported evidence showing that chronic cola consumption in rats impairs pancreatic metabolism of insulin and glucagon and produces some alterations typically observed in the metabolic syndrome, with an increase in oxidative stress. Of note It is worth mentioning that no apoptosis nor proliferation of islet cells could be demonstrated. In the present study, 36 male Wistar rats were divided into three groups to and given free access to freely drink regular cola (C), light cola (L), or water (W, control). We assessed the impact of the three different beverages in on glucose tolerance, lipid levels, creatinine levels and immunohistochemical changes addressed for the expression of insulin, glucagon, PDX-1 and NGN3 in islet cells, to evaluate the possible participation of PDX-1 in the changes observed in α and ß cells after 6 months of treatment. Moreover, we assessed by stereological methods, the mean volume of islets (Vi) and three important variables: the fractional ß -cell area, the cross-sectional area of alpha (A α-cell) and beta cells (A ß-cell), and the number of ß and α cell per body weight. Data were analyzed by two-way ANOVA followed by Bonferroni's multiple t-test or by Kruskal-Wallis test, then followed by Dunn's test (depending on distribution). Statistical significance was set at p<0.05. Cola drinking caused impaired glucose tolerance as well as fasting hyperglycemia (mean:148; CI:137-153; p<0.05 vs W) and an increase of in insulin immunolabeling (27.3±19.7; p<0.05 vs W and L). Immunohistochemical expression for PDX-1 was significantly high in C group compared to W (0.79±0.71; p<0.05). In this case, we observed cytoplasmatic and nuclear localization. Likewise, a mild but significant decrease of in Vi was detected after 6 months in C compared to W group (8.2±2.5; p<0.05). Also, we observed a significant decrease of in the fractional ß cell area (78.2±30.9; p<0.05) compared to W. Accordingly, a reduced mean value of islet α and ß cell number per body weight (0.05±0.02 and 0.08±0.04 respectively; both p<0.05) compared to W was detected. Interestingly, consumption of light cola increased the Vi (10.7±3.6; p<0.05) compared to W. In line with this, a decreased cross-sectional area of ß-cells was observed after chronic consumption of both, regular (78.2±30.9; p<0.05) and light cola (110.5±24.3; p<0.05), compared to W. As for, NGN3, it was negative in all three groups. Our results support the idea that PDX-1 plays a key role in the dynamics of the pancreatic islets after chronic consumption of sweetened beverages. In this experimental model, the loss of islets cells might be attributed to autophagy, favored by the local metabolic conditions and oxidative stress.

Coronary Intimal Thickening Begins in Fetuses and Progresses in Pediatric Population and Adolescents to Atherosclerosis.

The prevalence of coronary intimal thickening (IT) was assessed in fetuses and pediatric population. We studied the coronary arteries of 63 hearts obtained from fetuses, infants, children, and adolescents, deceased from noncardiac disease or trauma. Histomorphometric analysis, planimetry, and immunohistochemical studies were conducted. Intimal thickening consisted of proliferation of smooth muscle cells and scarce monocytes embedded in amorphous deposits within the internal elastic membrane (IEM). Intermingled lesions of intimal hyperplasia and parietal nonstenotic plaques were also observed. Intimal thickening was found in 10% of 20 fetuses, in 33.3% of 18 infants, 73.3% of 15 children, and 100% of 10 adolescents. A significant correlation (r = 0.671, P < 0.001) was found between the extent of IT and age. The IEM was duplicated or interrupted in 43% of patients, showing a positive correlation with the degree of IT (P = 0.01). Intimal thickening was predominantly found near bifurcation sites in the left anterior descending coronary artery (55.6%) and in zones free of bifurcation in the right coronary artery (75%). In conclusion, the prevalence and extension of IT lesions are higher at older ages within a young population. Intimal thickening may be regarded as the first event occurring in coronary preatherosclerosis, preceding lipid deposition.

Pancreatoblastoma in a paediatric patient: anatomo-pathological aspects of a case with multiple hepatic metastases.

Pancreatoblastoma is a rare paediatric malignant neoplasm. The treatment of choice is complete surgical resection. However, it is often unresectable due to its large size, local infiltration or distant metastasis. Since the condition is rare, there is currently no standard treatment regimen. We outline the case of a 4-year-old child who presented with abdominal pain and distention, together with an enlarged liver and elevated serum α-fetoprotein levels. Imaging studies showed the presence of an abnormal pancreatic tumour and multiple nodular lesions in the liver, the biopsies from which led to a diagnosis of pancreatoblastoma. In this case, the patient received cycles of neoadjuvant chemotherapy, combining cisplatin and doxorubicin. The patient subsequently underwent scheduled surgery in which the primary pancreatic lesion was resected, obtaining a circumscribed and nodular specimen measuring 7 × 6 cm and weighing 150 g. Given the extent of the metastasis, the child is currently awaiting a liver transplant.

Environmental pollutant hexachlorobenzene induces hypertension in a rat model.

Hexachlorobenzene (HCB) is a dioxin-like environmental pollutant, widely distributed in the environment. New research links exposure to high levels of persistent organic environmental toxicants to cardiovascular disease, however little is known about the effect of HCB on vascular function and on blood pressure. The purpose of the present study was to evaluate biochemical and cardiovascular changes resulting from subchronic HCB exposure. Adult female Sprague-Dawley rats were treated with vehicle or HCB (5 or 500 mg/kg b.w) for 45 days. Systolic blood pressure (BP), recorded by tail cuff plethysmography, was significantly increased at 35, 40 and 45 days of 500 mg/kg HCB-treatment. HCB (500 mg/kg) increased arterial thickness, while both 5 and 500 mg/kg HCB decreased proliferating cell nuclear antigen (PCNA) protein levels and cellular nuclei in abdominal aortas indicating a hypertrophic process. Also, aortas from both groups of HCB-treated rats presented higher sensitivity to noradrenalin (NA) and a significant decrease in maximum contractile response. Arteries from 500 mg/kg HCB-treated rats showed a significant increase in the levels of transforming growth factor-ß1 (TGF-ß1) mRNA and angiotensin II type1 receptor (AT1), and a significant decrease in estrogen receptor alpha (ERα), endothelial nitric oxidide synthase (eNOS) protein expression and deiodinase II (DII) mRNA levels. In conclusion, we have demonstrated for the first time that subchronic HCB administration significantly increases BP and alters associated cardiovascular parameters in rats. In addition, HCB alters the expression of key vascular tissue molecules involved in BP regulation, such as TGF-ß1, AT1, ERα, eNOS and DII.

Effects of chronic fructose overload on renal dopaminergic system: alteration of urinary L-dopa/dopamine index correlates to hypertension and precedes kidney structural damage.

Insulin resistance induced by a high-fructose diet has been associated to hypertension and renal damage. The aim of this work was to assess alterations in the urinary L-dopa/dopamine ratio over three time periods in rats with insulin resistance induced by fructose overload and its correlation with blood pressure levels and the presence of microalbuminuria and reduced nephrin expression as markers of renal structural damage. Male Sprague-Dawley rats were randomly divided into six groups: control (C) (C4, C8 and C12) with tap water to drink and fructose-overloaded (FO) rats (FO4, FO8 and FO12) with a fructose solution (10% w/v) to drink for 4, 8 and 12 weeks. A significant increase of the urinary L-dopa/dopamine ratio was found in FO rats since week 4, which positively correlated to the development of hypertension and preceded in time the onset of microalbuminuria and reduced nephrin expression observed on week 12 of treatment. The alteration of this ratio was associated to an impairment of the renal dopaminergic system, evidenced by a reduction in renal dopamine transporters and dopamine D1 receptor expression, leading to an overexpression and overactivation of the enzyme Na+, K+-ATPase with sodium retention. In conclusion, urinary L-dopa/dopamine ratio alteration in rats with fructose overload positively correlated to the development of hypertension and preceded in time the onset of renal structural damage. This is the first study to propose the use of the urinary L-dopa/dopamine index as marker of renal dysfunction that temporarily precedes kidney structural damage induced by fructose overload.

Cardiovascular, liver, and renal toxicity associated with an intravenous ferric carboxymaltose similar versus the originator compound.

BACKGROUND: Ferric carboxymaltose (FCM) is a stable, non-dextran-based intravenous iron complex used to treat iron deficiency of various etiologies. As FCM is a nonbiological complex drug and cannot be fully characterized by physicochemical analyses, it is important to demonstrate in nonclinical models that FCM similars (FCMS) have similar biodistribution. MATERIALS AND METHODS: A total of 30 nonanemic rats were treated weekly with 40 mg iron/kg body weight intravenous FCM, FCMS, or isotonic saline (controls) for 4 weeks. Blood pressure, liver enzymes, and renal function were evaluated. In liver, heart, and kidney tissue, markers for oxidative stress (malondialdehyde to assess lipid peroxidation and antioxidant enzymes) and inflammation (TNFα and IL6) were measured. Iron deposits were localized. RESULTS: The FCMS-treated group had significantly lower blood pressure, higher liver enzymes, increased proteinuria, and reduced creatinine clearance versus the FCM and control groups by day 29. Serum iron and transferrin saturation were significantly higher with FCMS versus FCM or controls. Iron deposition was altered in FCMS-treated animals, with decreased ferritin deposits and iron deposition outside the physiological storage compartments. Markers for lipid peroxidation and antioxidant-enzyme activity were significantly increased after FCMS administration versus FCM and controls, as were inflammatory markers. CONCLUSION: Results from this blinded nonclinical study demonstrated significant differences between the originator FCM and this FCMS.

Síndrome urémico hemolítico asociado a diarrea sin trombocitopenia / Postdiarrhoeal haemolytic uraemic syndrome without thrombocytopenia

Antecedentes: La presencia de trombocitopenia es una marca distintiva del síndrome urémico hemolítico asociado a diarrea (SUH D+); sin embargo, puede ser transitoria y, por lo tanto, no ser detectada. Existe limitada información sobre la prevalencia y el curso de la enfermedad en niños con SUH D+ sin trombocitopenia. Objetivo: Determinar la prevalencia de SUH D+ sin trombocitopenia y describir las características clínicas de una serie de niños con esta particularidad. Pacientes y métodos: Fueron revisadas las historias clínicas de los pacientes con SUH D+ internados entre 2000 y 2016 para identificar a aquellos sin trombocitopenia (>150.000mm3). De los casos seleccionados se recolectaron las variables demográficas, clínicas y de laboratorio, las cuales fueron analizadas descriptivamente. Resultados: De 161 pacientes internados durante el periodo de estudio se identificaron 9 sin trombocitopenia (5,6%). La mediana de la edad al diagnóstico fue de 17 meses (7-32) y la de la duración del periodo prodrómico, de 15 días (7-21). Ocho pacientes mantuvieron diuresis normal y uno requirió diálisis. Ningún paciente presentó compromiso extrarrenal severo y/o hipertensión arterial. Conclusiones: La prevalencia de SUH D+ sin trombocitopenia fue del 5,6% y la mayoría de los casos fueron leves; sin embargo, el requerimiento de diálisis en uno de ellos señala que la normalización del recuento de plaquetas no siempre es un marcador preciso de resolución de la enfermedad. Nuestros resultados también confirman que el momento de presentación de los pacientes con SUH D+ sin trombocitopenia está usualmente alejado de los primeros síntomas intestinales, por lo que es necesario un alto índice de sospecha diagnóstica (AU)

Background: Thrombocytopenia is a hallmark of postdiarrhoeal haemolytic uraemic syndrome (D+ HUS), although it can be transient and therefore undetected. There is scarce information regarding the prevalence and the course of the disease in children with D+ HUS without thrombocytopenia. Objective: To determine the prevalence of D+ HUS without thrombocytopenia and to describe the clinical characteristics of a series of children with this condition. Patients and methods: The medical records of patients with D+ HUS hospitalised between 2000 and 2016 were reviewed to identify those without thrombocytopenia (>150,000mm3). Demographic, clinical and laboratory parameters of the selected cases were collected and descriptively analysed. Results: Nine cases (5.6%) without thrombocytopenia were identified among 161 patients hospitalised during the study period. Median age at diagnosis was 17 months (7-32) and median prodromal symptom duration was 15 days (7-21). Eight patients maintained normal urine output while the remaining one required dialysis. No patient presented with severe extrarenal compromise and/or hypertension. Conclusions: The prevalence of non-thrombocytopenic D+ HUS was 5.6% and most cases occurred with mild forms of the disease; however, the need for dialysis in one of them indicated that normalisation of platelet count is not always an accurate marker for disease remittance. Our results also confirm that the time of onset of D+ HUS in patients without thrombocytopenia is usually delayed with respect to the initial intestinal symptoms; thus, heightened diagnostic suspicion is necessary (AU)

Postdiarrhoeal haemolytic uraemic syndrome without thrombocytopenia. / Síndrome urémico hemolítico asociado a diarrea sin trombocitopenia.

BACKGROUND: Thrombocytopenia is a hallmark of postdiarrhoeal haemolytic uraemic syndrome (D+ HUS), although it can be transient and therefore undetected. There is scarce information regarding the prevalence and the course of the disease in children with D+ HUS without thrombocytopenia. OBJECTIVE: To determine the prevalence of D+ HUS without thrombocytopenia and to describe the clinical characteristics of a series of children with this condition. PATIENTS AND METHODS: The medical records of patients with D+ HUS hospitalised between 2000 and 2016 were reviewed to identify those without thrombocytopenia (>150,000mm3). Demographic, clinical and laboratory parameters of the selected cases were collected and descriptively analysed. RESULTS: Nine cases (5.6%) without thrombocytopenia were identified among 161 patients hospitalised during the study period. Median age at diagnosis was 17 months (7-32) and median prodromal symptom duration was 15 days (7-21). Eight patients maintained normal urine output while the remaining one required dialysis. No patient presented with severe extrarenal compromise and/or hypertension. CONCLUSIONS: The prevalence of non-thrombocytopenic D+ HUS was 5.6% and most cases occurred with mild forms of the disease; however, the need for dialysis in one of them indicated that normalisation of platelet count is not always an accurate marker for disease remittance. Our results also confirm that the time of onset of D+ HUS in patients without thrombocytopenia is usually delayed with respect to the initial intestinal symptoms; thus, heightened diagnostic suspicion is necessary.

Malignant extra-adrenal pelvic paraganglioma in a paediatric patient.

The extra-adrenal paraganglioma is a neoplasm originating in regional structures, uncommon in paediatrics. We report on a case of a 13-year-old patient who began with severe arterial hypertension, tachycardia, dilated cardiomyopathy and elevated levels of catecholamines in the blood and urine. The presence of a retrovesical pelvic mass in contact with the right vaginal dome was determined by imaging studies. A diagnosis of malignant extra-adrenal pelvic paraganglioma with lymph node metastases was reached through biopsy and the surgical resection of subsequent local recurrences. Paragangliomas are usually located in the paravertebral zones from the base of the skull to the retroperitoneum and are benign in 90% of cases. This kind of neoplasia is uncommon in paediatrics, especially those located in the pelvis. In cases of masses of a gynaecological origin, a differential diagnosis should be considered, and a histological and immunohistochemical study is essential in certifying the diagnosis.

Markers of oxidative/nitrosative stress and inflammation in lung tissue of rats exposed to different intravenous iron compounds.

Iron deficiency anemia is a frequent complication in clinical conditions such as chronic kidney disease, chronic heart failure, inflammatory bowel disease, cancer, and excessive blood loss. Given the ability of iron to catalyze redox reactions, iron therapy can be associated with oxidative stress. The lung is uniquely susceptible to oxidative stress, and little is known about the effects of intravenous iron treatment in this organ. This study characterized changes in markers of oxidative/nitrosative stress and inflammation in the lung of non-iron deficient, non-anemic rats treated with five weekly doses (40 mg iron per kg body weight) of low molecular weight iron dextran (LMWID), iron sucrose (IS), ferric carboxymaltose (FCM), ferumoxytol (FMX), iron isomaltoside 1000 (IIM), or saline (control). Rats treated with LMWID, FMX, or IIM showed significant changes in most measures of oxidative/nitrosative stress, inflammation, and iron deposition compared to the saline-treated controls, with greatest changes in the LMWID treatment group. Increases in products of lipid peroxidation (thiobarbituric acid reactive substances) and protein nitrosation (nitrotyrosine) were consistent with increases in the activity of antioxidant enzymes (catalase, Cu,Zn-SOD, GPx), decreases in antioxidative capacity (reduced:oxidized GSH ratio), increased levels of transcription factors involved in the inflammatory pathway (NF-κB, HIF-1α), inflammatory cytokines (TNF-α, IL-6), adhesion molecules (VCAM-1), markers of macrophage infiltration (ED-1), and iron deposition (Prussian blue, ferritin). Since changes in measured parameters in FCM- or IS-treated rats were generally modest, the results suggest that FCM and IS have a low propensity to induce lung inflammation. The relevance of these findings to clinical safety profiles of the tested intravenous iron products requires further investigation.

Immunohistochemical expression of intrarenal renin angiotensin system components in response to tempol in rats fed a high salt diet.

AIM: To determine the effect of tempol in normal rats fed high salt on arterial pressure and the balance between antagonist components of the renal renin-angiotensin system. METHODS: Sprague-Dawley rats were fed with 8% NaCl high-salt (HS) or 0.4% NaCl (normal-salt, NS) diet for 3 wk, with or without tempol (T) (1 mmol/L, administered in drinking water). Mean arterial pressure (MAP), glomerular filtration rate (GFR), and urinary sodium excretion (UVNa) were measured. We evaluated angiotensin II (Ang II), angiotensin 1-7 (Ang 1-7), angiotensin converting enzyme 2 (ACE2), mas receptor (MasR), angiotensin type 1 receptor (AT1R) and angiotensin type 2 receptor (AT2R) in renal tissues by immunohistochemistry. RESULTS: The intake of high sodium produced a slight but significant increase in MAP and differentially regulated components of the renal renin-angiotensin system (RAS). This included an increase in Ang II and AT1R, and decrease in ACE-2 staining intensity using immunohistochemistry. Antioxidant supplementation with tempol increased natriuresis and GFR, prevented changes in blood pressure and reversed the imbalance of renal RAS components. This includes a decrease in Ang II and AT1R, as increase in AT2, ACE2, Ang (1-7) and MasR staining intensity using immunohistochemistry. In addition, the natriuretic effects of tempol were observed in NS-T group, which showed an increased staining intensity of AT2, ACE2, Ang (1-7) and MasR. CONCLUSION: These findings suggest that a high salt diet leads to changes in the homeostasis and balance between opposing components of the renal RAS in hypertension to favour an increase in Ang II. Chronic antioxidant supplementation can modulate the balance between the natriuretic and antinatriuretic components of the renal RAS.

Long-term outcomes for transobturator tension-free vaginal tapes in women with urodynamic mixed urinary incontinence.

AIMS: To assess the long-term patient reported outcomes following transobturator tension-free vaginal tapes (TO-TVT) in women with urodynamic mixed urinary incontinence (MUI). METHODS: A secondary analysis of the 9-year follow-up of the E-TOT study: 341 women with predominant stress urinary incontinence symptoms were randomized to undergo either inside-out or outside-in TO-TVT between April 2005 and April 2007. Forty-eight women had preoperative urodynamic MUI and were available for 9-year follow-up. Primary outcome was the patient-reported success rate defined as very/much improved on Patient's Global Impression of Improvement PGI-I. Secondary outcomes included impact on women's quality of life, sexual function, overactive bladder symptoms,and late adverse events. Statistical analysis was performed using SPSS v.23. RESULTS: Forty-eight women completed the 9-year follow-up, with adjusted response rate of 63%. The success based on the PGI-I was 64.6% (n = 31), with a further 14.6% (n = 7) who reported "improved." There was no significant difference between groups (OR 1.11; 95%CI 0.33, 3.70; P > 0.999). Clinically significant improvement in quality of life was found in 85.3%. Cure of urgency and UUI was reported by 35% and 41%, whereas worsening was reported in 6.5% and 2.3%, respectively. One patient reported chronic groin/leg pain. The small sample size and the sizeable loss to follow-up are limitations in this study. CONCLUSIONS: This is the first study to report the long-term outcomes of TO-TVT in women with urodynamic MUI; TO-TVT is associated with a good and sustained patient-reported success rate in women with MUI up to 9-years follow-up.

Long-term outcomes of transobturator tension-free vaginal tapes as secondary continence procedures.

PURPOSE: To assess the long-term patient-reported outcomes following TO-TVT as a secondary continence procedure in women with recurrent stress urinary incontinence (R-SUI). METHODS: A secondary analysis of the 9-year follow-up of the E-TOT study was performed: 341 women with predominant SUI symptoms were randomised to undergo either Inside-out or Outside-in TO-TVT between April 2005 and April 2007. Forty-six women had R-SUI following previously failed continence surgery at time of randomisation and are the basis of this analysis as a one single cohort. Primary outcome was the patient-reported success rate defined as very/much improved on Patient's Global Impression of Improvement (PGI-I). Secondary outcomes included late adverse events and impact on women's quality of life and sexual function. Statistical analysis was performed using SPSS version 23. RESULTS: Sixty-three per cent completed the 9-year follow-up. The success based on the PGI-I was 62.1% with no significant difference between groups (OR 5.33; 95% CI 1.03, 27.76; p = 0.094). Clinically significant improvement in QoL was found in 84.2%. Adverse events included vaginal erosions (n = 3) and groin pain (n = 2). The small sample size is a limitation in this study; nevertheless, this is one of the largest cohorts reported for women with R-SUI and the first to report the long-term outcomes of TO-TVT as a secondary continence procedure. CONCLUSIONS: TO-TVT operations are associated with good patient-reported success rates (62%) in women with previous failed continence surgery with up to 9-years follow-up. There is a non-significant trend towards better outcomes with the inside-out TO-TVT.