A new association of Oculoauriculovertebral spectrum and persistent fifth aortic arch -double lumen aorta: a case report.

BACKGROUND: Oculo-auriculo-vertebral spectrum is a heterogeneous group of genetic disorder, also known as Goldenhar Syndrome, which has several phenotypic features including craniofacial anomalies, cardiac, vertebral and central nervous system defects. Cardiovascular anomalies include ventricular septal defects, atrial septal defects, patent ductus arteriosus, Tetralogy of Fallot, double outlet right ventricle, aberrant right subclavian artery, coarctation of aorta, transposition of the great arteries, double inlet left ventricle, cor triatriatum, pulmonary artery stenosis, aortic stenosis, persistent left superior vena cava, partially or totally abnormal pulmonary venous return and bicuspid aortic valve. Persistent fifth aortic arch, also named as double lumen aortic arch, is a very rare cardivascular anomaly and usually associate other cardiac defects. CASE PRESENTATION: We present a 7 month old patient with oculo-auriculo-vertebral spectrum signs as facial asymmetry, short neck, choanal atresia, cleft palate, bilateral preauricular skin tags, bilateral hypoplastic ear lobes, epibulbar dermoid cyst, rib, vertebrae and cardiovascular anomalies. Cardiovascular anomalies detected with echocardiography and computed tomography were malalignment ventricular septal defect and double lumen aorta, known as persistent fifth aortic arch. CONCLUSION: Various cardiovascular anomalies may accompany Goldenhar Syndrome. We present a case with persistent fifth aortic arch and Oculo-auriculo-vertebral spectrum and this is a new association that was not reported before in the literature.

MRI diagnosed cardiac lipoma in tuberous sclerosis: a case report with a very rare association.

Tuberous sclerosis is a genetic multisystem disorder characterised by hamartomas in several organs. Cardiac rhabdomyomas are the main features of the disease but lipomas can very rarely be associated. Herein, we present a very rare association of tuberous sclerosis and cardiac lipoma detected by echocardiography and diagnosed as a lipoma via MRI and fat suppression technic, aim to report this very rare association, and emphasise usefulness of MRI in cardiac mass lesions.

The effects of pre-pregnancy obesity and gestational weight gain on maternal lipid profiles, fatty acids and insulin resistance.

OBJECTIVES: Pregnancy is associated with physiological alterations in insulin sensitivity and lipid metabolism. This study investigates the associations between pregestational body mass index (pBMI) and the rate of gestational weight gain (rGWG) in the second trimester with the biomarkers of lipid, fatty acids metabolism and insulin resistance. METHODS: Sixty nine pregnant women followed. The body weights of the pregnant women were measured and blood samples were obtained at 11-14th and 24-28th weeks of pregnancy. Glucose, total cholesterol, triglyceride, HDL cholesterol, LDL cholesterol, insulin levels and fatty acids were measured. Rate of GWG (kg/week) and The Homeostasis Model Assessment for Insulin Resistance (HOMA-IR) were calculated. The pregnant women were stratified according to their pBMI and the 2nd trimester rGWG. RESULTS: The rate of GWG was significantly higher for the group with pBMI<25, compared to the group with pBMI≥25 (p=0.024). Triglyceride, total cholesterol, LDL and HDL cholesterol were significantly increased in the second trimester compared with the first trimester. Palmitic acid, oleic acid, linoleic acid, myristic acid, docosahexaenoic acid (DHA), arachidonic acid (AA), total omega-6 (n - 6) and omega-3 (n - 3) fatty acid levels and n - 6/n - 3 ratio were significantly higher in the second trimester. Glucose was significantly decreased and insulin was increased in the second trimester. In the overweight/obese group; HOMA-IR, insulin, AA, palmitoleic acid and stearic acid were found to be high in comparison to the group with low/normal pBMI. No parameters were associated with rGWG. CONCLUSIONS: The changes in lipid parameters, free fatty acids, insulin and HOMA-IR in the second trimester were compatible with the changes in lipid metabolism and the development of insulin resistance. Pregestational BMI was shown to have a stronger influence on lipid profile, insulin resistance, and fatty acids than rGWG.

Cardiac functions in children with steroid-sensitive nephrotic syndrome.

BACKGROUND: The aim of the present study was to evaluate the presence of cardiac systolic and diastolic dysfunction in pediatric patients with steroid-sensitive nephrotic syndrome (NS). METHODS: The study population consisted of 19 patients with debut-relapse of NS aged 1-18 years and 30 sex and age-matched healthy controls. Blood and urine samples, two M-mode conventional echocardiograms and tissue Doppler velocity imaging were evaluated in both attack and remission periods. RESULTS: With regard to conventional pulse wave Doppler (cPWD), steroid-sensitive NS patients (both in debut / relapse and in remission periods) had a higher peak of late diastolic flow velocities (A peak), and patients in debut / relapse had a lower E/A ratio than the control group, indicating diastolic dysfunction (overall P = 0.003 and P = 0.006, respectively). Based on tissue Doppler velocity imaging echocardiography results, patients in debut/relapse had a higher A' and a lower E'/A' ratio (overall P < 0.001 and P = 0.001, respectively). There was also a significant difference in the cPWD E/TDI E' ratio between the patients showing an increased cPWD E/TDI E' ratio in remission periods compared to in debut/relapse periods (P = 0.09). The albumin levels were positively correlated with E'/A' and E/ E' ratio (r = 0.609; P = 0.007, r = 0.472; P = 0.041 respectively). CONCLUSIONS: Systolic cardiac functions are preserved but diastolic functions are affected in steroid-sensitive NS patients both in debut/relapse and in remission periods in a relatively short time. The persistence of left ventricular (LV) dysfunction during the remission period requires special attention during the follow up for early detection of cardiac abnormalities.

Corneal recovery in a rabbit limbal stem cell deficiency model by autologous grafts of tertiary outgrowths from cultivated limbal biopsy explants.

PURPOSE: To determine the corneal regenerative capacity of sequentially generated primary, secondary, and tertiary limbal explant outgrowths in a limbal stem cell deficiency (LSCD) surgical model. METHODS: Two-millimeter-long limbal shallow biopsies were surgically excised from the upper quadrant of the right eye of rabbits and set on preserved amniotic membrane for explant culture. After the generation of primary outgrowth, the biopsies were sequentially transferred to new amniotic membrane to generate secondary and then tertiary outgrowths. Eighteen rabbits were subjected to a 360° limbal peritomy extending into the scleral zone and combined with superficial keratectomy of the corneal periphery and thorough mechanical debridement of the central cornea in their left eye. Right eye outgrowths, six of each generation, were engrafted on the ocular surface. Clinical outcomes (neovascularization, corneal clarity, and corneal fluorescein staining) were graded after 6 months. Post-mortem corneas were compared with histology, immunochemistry for p63 and Krt3, ABCG2-dependent dye exclusion, and capacity for outgrowths in explant culture. RESULTS: Immunohistology and western blot of the outgrowths for p63 and Krt3 indicated no differences in expression between the primary and tertiary outgrowths for these two markers of growth and differentiation. Clinically, all rabbits treated with amniotic membrane alone developed severe LSCD. Most rabbits grafted with cell outgrowths from all three outgrowth generations achieved stable (>6 months) recovery of the ocular surface. There were partial failures of grafts performed with two secondary and tertiary outgrowths. However, Kruskal-Wallis statistical analysis of the clinical scores yielded no significant difference between the three groups (p=0.524). Histology showed full anatomic recovery of grafts made with primary and tertiary outgrowths. Krt3 and p63 expression throughout the whole limbal corneal epithelium with primary or tertiary outgrowths was not distinguishable from each other. The percentage of dye-excluding cells present within this zone and the capacity of the explant epithelial outgrowth of the regenerated peripheral corneal zone were also on par with those of the donor corneas. The Krt3-negative cells that characterize the basal epithelial layer of the normal limbus could not be found in any regenerated cornea from the primary to tertiary outgrowths. CONCLUSIONS: Our results demonstrate that in rabbits post-primary explant outgrowths retain the capacity for LSCD recovery found in primary explants.

Proteomic study of the microdissected aortic media in human thoracic aortic aneurysms.

Aortic aneurysm is a complex multifactorial disease, and its molecular mechanism is not understood. In thoracic aortic aneurysm (TAA), the expansion of the aortic wall is lead by extracellular matrix (ECM) degeneration in the medial layer, which leads to weakening of the aortic wall. This dilatation may end in rupture and-if untreated-death. The aortic media is composed of vascular smooth muscle cells (VSMCs) and proteins involved in aortic elasticity and distensibility. Delineating their functional and quantitative decrease is critical in elucidating the disease causing mechanisms as well as the development of new preventive therapies. Laser microdissection (LMD) is an advanced technology that enables the isolation of the desired portion of tissue or cells for proteomics analysis, while preserving their integrity. In our study, the aortic media layers of 36 TAA patients and 8 controls were dissected using LMD technology. The proteins isolated from these tissue samples were subjected to comparative proteomic analysis by nano-LC-MS/MS, which enabled the identification of 352 proteins in aortic media. Among these, 41 proteins were differentially expressed in the TAA group with respect to control group, and all were downregulated in the patients. Of these medial proteins, 25 are novel, and their association with TAA is reported for the first time in our study. Subsequent analysis of the data by ingenuity pathway analysis (IPA) shows that the majority of differentially expressed proteins were found to be cytoskeletal-associated proteins and components of the ECM which are critical in maintaining aortic integrity. Our results indicate that the protein expression profile in the aortic media from TAA patients differs significantly from controls. Further analysis of the mechanism points to markers of pathological ECM remodeling, which, in turn, affect VSMC cytosolic structure and architecture. In the future, the detailed investigation of the differentially expressed proteins may provide insight into the elucidation of the pathological processes underlying aneurysms.

Evaluation of apoptotic molecular pathways for smooth muscle cells isolated from thoracic aortic aneurysms in response to oxidized sterols.

Oxysterols, oxygenated derivatives of cholesterol, are found abundantly in the plasma and atherosclerotic plaques, a common risk factor for thoracic aortic aneurysms (TAAs). Among the oxysterols, namely 7-ketocholesterol (7-KC) and 25-hydroxycholesterol (25-OHC), lead both to induction of reactive oxygen species (ROS) in cells and to apoptosis in smooth muscle cells (SMCs) probably due to increased oxidative stress. Since loss of SMCs through apoptosis is a major event in TAA formation, it is important to understand the molecular pathways of apoptosis in response to ROS in TAAs. Very little is known about the effect of oxysterols on TAA SMCs. Therefore, we investigated molecular pathways participating in the oxysterol induced cell death of TAAs. Our results showed that TAA SMCs died mainly as a result of apoptosis as suggested by cellular shrinkage, blebbing, DNA condensation/fragmentation in response to oxysterol treatment. There was no significant difference in oxysterol induced cell death between TAA and control SMCs. Addition of antioxidant molecules prevented cell death, hence ROS appears to be involved in the apoptosis of these cells. While oxysterol treatment increased caspase 3 activity, cell death was not rescued in its absence. Efficient silencing of other targets including apoptotic proteins (p53, Bax), and survival proteins (Akt1, Akt2) showed that apoptosis can occur through p53, and Bax independent pathways. Silencing Akt1 or Akt2 did not lead to further cell death. These results indicate that oxysterols can induce several cell death pathways in TAA SMCs.

Exosomes encapsulated in hydrogels for effective central nervous system drug delivery.

The targeted delivery of pharmacologically active molecules, metabolites, and growth factors to the brain parenchyma has become one of the major challenges following the onset of neurodegeneration and pathological conditions. The therapeutic effect of active biomolecules is significantly impaired after systemic administration in the central nervous system (CNS) because of the blood-brain barrier (BBB). Therefore, the development of novel therapeutic approaches capable of overcoming these limitations is under discussion. Exosomes (Exo) are nano-sized vesicles of endosomal origin that have a high distribution rate in biofluids. Recent advances have introduced Exo as naturally suitable bio-shuttles for the delivery of neurotrophic factors to the brain parenchyma. In recent years, many researchers have attempted to regulate the delivery of Exo to target sites while reducing their removal from circulation. The encapsulation of Exo in natural and synthetic hydrogels offers a valuable strategy to address the limitations of Exo, maintaining their integrity and controlling their release at a desired site. Herein, we highlight the current and novel approaches related to the application of hydrogels for the encapsulation of Exo in the field of CNS tissue engineering.

Controlled release of imatinib mesylate from PLGA microspheres inhibit craniopharyngioma mediated angiogenesis.

Poly(lactic-co-glycolic acid) microspheres loaded with imatinib mesylate has been developed as a new therapeutic strategy to prevent craniopharyngioma recurrence. Microspheres composed of different lactic/glycolic acid ratios, molecular weights and drug compositions were synthesized and loaded with imatinib mesylate by modified double-emulsion/solvent evaporation technique and subsequently characterized by particle-size distribution, scanning electron microscopy, encapsulation efficiency and in vitro drug release. Inhibitory potential of imatinib containing microspheres on tumor neovascularization was investigated on craniopharyngioma tumor samples by rat cornea angiogenesis assay. Results showed that microspheres in different LA:GA ratios [LA:GA 50:50 (G50), 75:25 (G25), 85:15 (G15)] considerably reduced neovascularization induced by recurrent tumor samples in an in vivo angiogenesis assay (P < 0.01). Our data indicate that local delivery of imatinib mesylate to the post-surgical tumoral cavity using biodegradable microspheres may be a promising biologically selective approach to prevent the recurrence of craniopharyngiomas, via inhibition of neovascularization.

Foreign body aspiration in childhood: evaluation of diagnostic parameters.

BACKGROUND: Foreign body aspiration (FBA) is one of the most important preventable causes of childhood mortality and morbidity. OBJECTIVE: The aim of this study was to define the clinical and radiological features of FBA and investigate the diagnostic value of various parameters used to diagnose FBA. METHODS: The medical records of 147 children who were admitted to the hospital with a diagnosis of suspected FBA were examined. The sensitivity and specificity of the parameters used for the diagnosis of FBA and their predictive values were calculated. RESULTS: Of the patients, 75.5% were younger than 3 years, and 61.2% were male. Peak incidence was found in 18 months. A negative bronchoscopy rate of 19.7% was found, and 92.6% of these patients were younger than 3 years. The parameter with the highest diagnostic value was the presence of aspiration history (the sensitivity and positive and negative predictive values were 97%, 89%, and 80%, respectively). No significant difference was found in the classic triad of FBA (sudden onset of cough, wheezing, and unilaterally decreased breath sounds) between patients with and without FBA. The specificity and positive predictive value of the classic triad were high, and the sensitivity and negative predictive value were low (85% and 78%, and 13% and 19%, respectively). CONCLUSIONS: Especially, male children younger than 3 years have an increased risk of FBA. Neither clinical symptoms nor the radiological findings alone are sufficiently specific and sensitive in diagnosing FBA. The most important factor for diagnosis is the presence of aspiration history.

An Easy-to-Fabricate Microfluidic Shallow Trench Induced Three-Dimensional Cell Culturing and Imaging (STICI3D) Platform.

Compared to the established monolayer approach of two-dimensional cell cultures, three-dimensional (3D) cultures more closely resemble in vivo models; that is, the cells interact and form clusters mimicking their organization in native tissue. Therefore, the cellular microenvironment of these 3D cultures proves to be more clinically relevant. In this study, we present a novel easy-to-fabricate microfluidic shallow trench induced 3D cell culturing and imaging (STICI3D) platform, suitable for rapid fabrication as well as mass manufacturing. Our design consists of a shallow trench, within which various hydrogels can be formed in situ via capillary action, between and fully in contact with two side channels that allow cell seeding and media replenishment, as well as forming concentration gradients of various molecules. Compared to a micropillar-based burst valve design, which requires sophisticated microfabrication facilities, our capillary-based STICI3D can be fabricated using molds prepared with simple adhesive tapes and razors alone. The simple design supports the easy applicability of mass-production methods such as hot embossing and injection molding as well. To optimize the STICI3D design, we investigated the effect of individual design parameters such as corner radii, trench height, and surface wettability under various inlet pressures on the confinement of a hydrogel solution within the shallow trench using Computational Fluid Dynamics simulations supported with experimental validation. We identified ideal design values that improved the robustness of hydrogel confinement and reduced the effect of end-user dependent factors such as hydrogel solution loading pressure. Finally, we demonstrated cultures of human mesenchymal stem cells and human umbilical cord endothelial cells in the STICI3D to show that it supports 3D cell cultures and enables precise control of cellular microenvironment and real-time microscopic imaging. The easy-to-fabricate and highly adaptable nature of the STICI3D platform makes it suitable for researchers interested in fabricating custom polydimethylsiloxane devices as well as those who are in need of ready-to-use plastic platforms. As such, STICI3Ds can be used in imaging cell-cell interactions, angiogenesis, semiquantitative analysis of drug response in cells, and measurement of transport through cell sheet barriers.

Identification of novel neutralizing single-chain antibodies against vascular endothelial growth factor receptor 2.

Human vascular endothelial growth factor (VEGF) and its receptor (VEGFR-2/kinase domain receptor [KDR]) play a crucial role in angiogenesis, which makes the VEGFR-2 signaling pathway a major target for therapeutic applications. In this study, a single-chain antibody phage display library was constructed from spleen cells of mice immunized with recombinant human soluble extracellular VEGFR-2/KDR consisting of all seven extracellular domains (sKDR D1-7) to obtain antibodies that block VEGF binding to VEGFR-2. Two specific single-chain antibodies (KDR1.3 and KDR2.6) that recognized human VEGFR-2 were selected; diversity analysis of the clones was performed by BstNI fingerprinting and nucleotide sequencing. The single-chain variable fragments (scFvs) were expressed in soluble form and specificity of interactions between affinity purified scFvs and VEGFR-2 was confirmed by ELISA. Binding of the recombinant antibodies for VEGFR-2 receptors was investigated by surface plasmon resonance spectroscopy. In vitro cell culture assays showed that KDR1.3 and KDR2.6 scFvs significantly suppressed the mitogenic response of human umbilical vein endothelial cells to recombinant human VEGF(165) in a dose-dependent manner, and reduced VEGF-dependent cell proliferation by 60% and 40%, respectively. In vivo analysis of these recombinant antibodies in a rat cornea angiogenesis model revealed that both antibodies suppressed the development of new corneal vessels (p < 0.05). Overall, in vitro and in vivo results disclose strong interactions of KDR1.3 and KDR2.6 scFvs with VEGFR-2. These findings indicate that KDR1.3 and KDR2.6 scFvs are promising antiangiogenic therapeutic agents.

Bilateral reexpansion pulmonary edema associated with pleural empyema: a case report.

Reexpansion pulmonary edema is an uncommon complication following rapid reexpansion of the lungs. The risk increases with a prolonged duration of pulmonary collapse, the amount of drained liquid or air, and with decreased time of draining. Treatment is supportive. In general, the prognosis is favorable. A nine-year-old boy was presented with fever, cough, and respiratory distress. Pneumonia and left-sided pleural empyema were determined and a chest tube was emplaced. Clinical deterioration occurred in just a few minutes following chest tube insertion. His chest radiography revealed a pulmonary edema in the left lung. Despite mechanical ventilation, antibiotics, and diuretic treatment, no significant improvement occurred. Acute respiratory distress syndrome and multiple organ dysfunctions developed in the follow-up. The patient died on day 5 of hospitalization. In this report, a complicated reexpansion pulmonary edema with a lathal outcome in a 9-year-old child is presented.

The relationship between migraine and right-to-left shunt in children.

UNLABELLED: Migraine is the most common headache in childhood, and there are some reports that suggest the relationship between migraine and right-to-left shunt. The aim of this study was to evaluate the frequency of right-to-left shunt in children with migraine with aura and compare it with children with migraine without aura, and in healthy children. In a cross-sectional case-control study, we assessed 20 children with migraine with aura, 20 migraine without aura and 20 healthy age, and gender-matched control group. We determined the frequency of right-to-left shunt by transcranial doppler with contrast and transthoracic echocardiography without contrast. The dopplers and echocardiograms were performed blindly by the same examiners during headache-free periods. The presence of right-to-left shunt was found in 13/20 patients with migraine with aura compared with five of 20 migraine without aura and four of 20 control subjects. The frequency of right-to-left shunt in migraine with aura was statistically different from the other two groups (P < 0.005). There was no association between right-to-left shunt and frequency of attacks, duration and intensity of attacks, uni/bilateral occurence, familial occurrence, gender and age of patients. CONCLUSION: our findings suggest possible association of migraine with aura and right-to-left shunt. It seems that right-to-left shunt does not influence the clinical features of migraine.

Effects of different doses of remifentanil infusion on hemodynamics and recovery in children undergoing pediatric diagnostic cardiac catheterization.

OBJECTIVE: The present study aimed to compare 2 different doses of remifentanil infusion on hemodynamics, recovery period, and complications in children undergoing diagnostic pediatric cardiac catheterization. DESIGN: A prospective study. SETTING: A university hospital. PARTICIPANTS: Children undergoing diagnostic cardiac catheterization (n = 60). INTERVENTIONS: Children (2-12 years of age) scheduled for elective diagnostic cardiac catheterization under sedation were included in this study. The patients were assigned randomly to 2 groups as follows: patients in group 1 (n = 30) received a remifentanil infusion of 0.1 µg/kg/min, and patients in group 2 (n = 30) received a remifentanil infusion of 0.2 µg/kg/min. Heart rate (HR), systolic and diastolic blood pressures (BPs), oxygen saturation (SpO(2)), respiratory rate (RR), sedation, and recovery scores were recorded. MEASUREMENTS AND MAIN RESULTS: There were no significant differences between the groups in terms of systolic and diastolic BPs, HR, SpO(2), and RR during the study period. Additional drugs were required for 15 children in group 1; however, 27 patients maintained a satisfactory level of sedation with the 0.2-µg/kg/min remifentanil infusion. The time to achieve a recovery score of ≥5 was significantly shorter in group 2 than in group 1 (4.1 ± 0.3 minutes v 6.8 ± 0.8 minutes). No postoperative complications were reported in either group. CONCLUSION: After oral midazolam premedication and local prilocaine infiltration, 0.2 µg/kg/min of remifentanil provided adequate sedation without any hemodynamic compromise during pediatric diagnostic cardiac catheterization.

Preparation and in vitro characterization of vascular endothelial growth factor (VEGF)-loaded poly(D,L-lactic-co-glycolic acid) microspheres using a double emulsion/solvent evaporation technique.

Biodegradable Poly(lactic-co-glycolic acid; PLGA), microspheres encapsulating the angiogenic protein recombinant human vascular endothelial growth factor (rhVEGF) were formed to achieve VEGF release in a sustained manner. These microspheres are a promising delivery system which can be used for therapeutic angiogenesis. The PLGA microspheres incorporating two different initial loading amounts of rhVEGF have been prepared by a modified water-in-oil-in-water (w/o/w) double emulsion/solvent evaporation technique. The microspheres have been characterized by particle size distribution, environmental scanning electron microscopy (ESEM), light microscopy, encapsulation efficiency and their degradation was studied in vitro. The rhVEGF released from microspheres was quantified by the competitive enzyme-linked immunosorbent assay (ELISA) and human umbilical vein endothelial cell (HUVEC) proliferation assay was used to assess biological activity of the released VEGF. The microspheres were spherical with diameters of 10-60 µm and the encapsulation efficiency was between 46% and 60%. The release kinetics of rhVEGF was studied for two different amounts: 5 µg VEGF (V5) and 50 µg VEGF (V50) per 500 mg starting polymer. The total protein (VEGF:BSA) release increased up to 4 weeks for two rhVEGF concentrations. The ELISA results showed that the burst release for V5 and V50 microspheres were 4 and 27 ng/mL, respectively. For V5, the microspheres showed an initial burst release, followed by a higher steady-state release until 14 days. VEGF release increased up to 2 weeks for V50 microsphere. HUVEC proliferation assay showed that endothelial cells responded to bioactive VEGF by proliferating and migrating.

An Update on the Role of PCSK9 in Atherosclerosis.

Atherosclerosis is initiated by functional changes in the endothelium accompanied by accumulation, oxidation, and glycation of LDL-cholesterol in the inner layer of the arterial wall and continues with the expression of adhesion molecules and release of chemoattractants. PCSK9 is a proprotein convertase that increases circulating LDL levels by directing hepatic LDL receptors into lysosomes for degradation. The effects of PCSK9 on hepatic LDL receptors and contribution to atherosclerosis via the induction of hyperlipidemia are well defined. Monoclonal PCSK9 antibodies that block the effects of PCSK9 on LDL receptors demonstrated beneficial results in cardiovascular outcome trials. In recent years, extrahepatic functions of PCSK9, particularly its direct effects on atherosclerotic plaques have received increasing attention. Experimental trials have revealed that PCSK9 plays a significant role in every step of atherosclerotic plaque formation. It contributes to foam cell formation by increasing the uptake of LDL by macrophages via scavenger receptors and inhibiting cholesterol efflux from macrophages. It induces the expression of inflammatory cytokines, adhesion molecules, and chemoattractants, thereby increasing monocyte recruitment, inflammatory cell adhesion, and inflammation at the atherosclerotic vascular wall. Moreover, low shear stress is associated with increased PCSK9 expression. PCSK9 may induce endothelial cell apoptosis and autophagy and stimulate the differentiation of smooth muscle cells from the contractile phenotype to synthetic phenotype. Increasing evidence indicates that PCSK9 is a molecular target in the development of novel approaches toward the prevention and treatment of atherosclerosis. This review focuses on the molecular roles of PCSK9 in atherosclerotic plaque formation.

Is N-terminal pro-brain natriuretic peptide a reliable marker for body fluid status in children with chronic kidney disease?

INTRODUCTION: Brain natriuretic peptides, released in response to left ventricular stress, have a strong prognostic value in dialysis patients. However, their role in detecting abnormalities of fluid status is under debate; the relationship between volume status and brain natriuretic peptides (BNPs) differs among various studies. The aim of our study was to evaluate the clinical utility of N-terminal proBNP in the assessment of fluid status and cardiovascular risk in this setting. MATERIAL AND METHODS: The study included 65 children: 10 pre-dialysis, 13 hemodialysis, 12 peritoneal dialysis patients and 30 healthy controls. Volume status was determined by multifrequency bioimpedance and NT-pro-BNP, as well as echocardiography to estimate the left ventricle structure and function. RESULTS: The median log NT-proBNP values of hemodialysis and peritoneal dialysis patients were 3.66 (2.05-4.90) and 3.57 (2.51-4.13) pg/ml, respectively, and significantly higher compared with the control group (p < 0.001, p < 0.001). On simple correlation, NT-proBNP was correlated with markers of volume overload and cardiac dysfunction. On multivariate regression analysis, only left ventricle mass index (ß = 0.402, p = 0.003) and left atrium diameter (ß = 0.263, p = 0.018) were independently associated with NT-proBNP (adjusted R 2 of the model: 0.707, p < 0.001). CONCLUSIONS: Our research suggested that NT-proBNP, which was correlated with LV systolic and diastolic dysfunction and fluid overload as assessed by bioimpedance, can be used to evaluate cardiovascular states in a chronic kidney disease (CKD) population. From the early stages of CKD, periodic monitoring of NT-proBNP levels may be essential for early detection of patients with high risk of cardiovascular events, and for taking preventive intervention as soon as possible.

Charcoal haemoperfusion in amitriptyline poisoning: experience in 20 children.

AIM: Tricyclic antidepressant (TCA) toxicity is common among children and adults due to widespread use. Amitriptyline (AT) is one of the most commonly prescribed TCAs. Current guidelines do not recommend charcoal haemoperfusion (HP) for AT overdose due to high protein binding and large volume of distribution. However evidence regarding the efficacy of charcoal HP in addition to supportive measures is accumulating in the published reports. METHODS: Here we report our experience in 20 children (15 girls, 5 boys) with acute AT overdose aged between 1.5 and 15 years, successfully managed with HP in our institution between January 2000 and February 2007. RESULTS: The HP indications were mainly severe initial cardiac and respiratory involvement. After HP, all patients recovered dramatically with a mean hospital stay of 4 days (range: 2-12). Only one patient developed neurological sequelae due to prolonged hypoxia secondary to respiratory arrest. CONCLUSION: To our knowledge this is the largest case series reporting the efficacy of charcoal HP in acute AT overdose in children. Based on our findings, charcoal HP seems to be an effective treatment modality, especially in prompt correction of severe life-threatening cardiac and respiratory findings in children with serious AT overdose and resulting in a reduction of morbidity and mortality.

Anomalous systemic arterial supply to normal Basal segments of the left lower lobe of the lung: therapeutic implication.

We describe a 5-month old infant who presented with a continuous murmur and enlargement of the left heart. The patient's diagnosis was an anomalous systemic arterial supply to basal segments of the left lower lobe characterized by a lack of a pulmonary arterial supply. This condition was treated without lobectomy. To our knowledge, this report is the first to describe an anomalous systemic arterial supply to basal segments of the lower lobe of the left lung with a single arterial supply that was treated in childhood without lung resection. Our case offers an alternative treatment to surgical lobectomy for this abnormality.