Dyslipidemia in children with chronic kidney disease-findings from the Cardiovascular Comorbidity in Children with Chronic Kidney Disease (4C) study.

BACKGROUND: Dyslipidemia is an important and modifiable risk factor for CVD in children with CKD. METHODS: In a cross-sectional study of baseline serum lipid levels in a large prospective cohort study of children with stage 3-5 (predialysis) CKD, frequencies of abnormal lipid levels and types of dyslipidemia were analyzed in the entire cohort and in subpopulations defined by fasting status or by the presence of nephrotic range proteinuria. Associated clinical and laboratory characteristics were determined by multivariable linear regression analysis. RESULTS: A total of 681 patients aged 12.2 ± 3.3 years with a mean eGFR of 26.9 ± 11.6 ml/min/1.73 m2 were included. Kidney diagnosis was classified as CAKUT in 69%, glomerulopathy in 8.4%, and other disorders in 22.6% of patients. Nephrotic range proteinuria (defined by a urinary albumin/creatinine ratio > 1.1 g/g) was present in 26.9%. Dyslipidemia was found in 71.8%, and high triglyceride (TG) levels were the most common abnormality (54.7%). Fasting status (38.9%) had no effect on dyslipidemia status. Except for a significant increase in TG in more advanced CKD, lipid levels and frequencies of dyslipidemia were not significantly different between CKD stages. Hypertriglyceridemia was associated with younger age, lower eGFR, shorter duration of CKD, higher body mass index (BMI-SDS), lower serum albumin, and higher diastolic blood pressure. CONCLUSIONS: Dyslipidemia involving all lipid fractions, but mainly TG, is present in the majority of patients with CKD irrespective of CKD stage or fasting status and is significantly associated with other cardiovascular risk factors.

ON/OFF based synergetic plasmonic photothermal drug release approach through core-satellite like mussel-inspired polydopamine nanoparticles.

One of the studies on new drug delivery and release systems that has increased in recent years is the study using plasmonic nanoparticles. In this study, polydopamine nanoparticles (PDOP NPs), which contribute to photothermal drug release by near infrared radiation (NIR), were decorated with gold nanoparticles (AuNPs) to utilize their plasmonic properties, and a core-satellite-like system was formed. With this approach, epirubicin (EPI)-loaded PDOP NPs were prepared by utilizing the plasmonic properties of AuNPs. Scanning Electron Microscope (SEM), Fourier Transform Infrared Spectroscopy (FTIR), and X-ray Diffraction (XRD) methods were used to evaluate the structural properties of these particles. The release behavior of the prepared structures in acidic (pH 5.0) and neutral (pH 7.4) environments based on the ON/OFF approach was also examined. The biocompatibility properties of the particles were evaluated on mouse fibroblast (L929) and anticancer activities on neuroblastoma (SH-SY5Y) cells. The effects of prepared EPI-loaded particles and laser-controlled drug release on ROS production, genotoxicity, and apoptosis were also investigated in SH-SY5Y cells. With the calculated combination index (CI) value, it was shown that the activity of EPI-loaded AuNP@PDOP NPs increased synergistically with the ON/OFF-based approach. The developed combination approach is considered to be remarkable and promising for further evaluation before clinical use.

Is a non-cytotoxic and non-genotoxic novel bioinspired dipeptide structure synthesis possible for theragnostic applications?

The diagnosis and treatment of the diseases in a certain coordination is a subject that has been emphasized in recent years. Theragnostics approaches allow simultaneous diagnosis and treatment of chronic diseases such as cancer. An ideal theragnostic should be biocompatible and can be used safely in humans. Although several types of theragnostics have been developed, none of yet satisfied these criteria. Bioinspired materials with noble metal centers encapsulating therapeutic and imaging agents were shown to possess theragnostic activities. In this study, it was aimed to synthesize, characterize, and evaluate the cytotoxic and genotoxic effects of self-assembly of diphenylalanine (Phe-Phe) dipeptides presence of mercury (Hg2+) ions to be used for theragnostic. Cytotoxicity and genotoxicity studies were done in mouse fibroblast (NIH/3T3) cells by 3-(4,5-Dimethylthiazol-2-yl)- 2,5-diphenyltetrazolium bromide (MTT) and single cell gel electrophoresis (Comet) assays, respectively. It was found that cell viability decreased in a dose-dependent manner in 24-, 48-, and 72-h treatment. Also, Phe-Phe dipeptides did not cause any significant changes in DNA damage at the concentrations of 1, 2, and 5 mg/mL in 4- and 24-h exposures. In the 48-h exposure, Phe-Phe peptide exposure at concentrations of 2 and 5 mg/mL caused a significant increase in DNA damage and in the 72-h of exposure, a significant increase in DNA damage was observed at all studied concentrations. According to the results of the study, it can be said that Phe-Phe dipeptides presence of Hg2+ ions are biocompatible and can be used safely for theragnostic purposes.

Evaluation of cytotoxic and genotoxic effects of paclitaxel-loaded PLGA nanoparticles in neuroblastoma cells.

Neuroblastoma, a neoplasm of the sympathetic nervous system, is the second most common extracranial malignant tumor of childhood and the most common solid tumor of infancy. Paclitaxel (taxol), a diterpenoid pseudoalkaloid isolated from the shells of Taxus brevifolia, is the first taxane derivative used in the clinic for cancer treatment. Poly (lactic-co-glycolic acid) (PLGA) is one of the most successfully used biodegradable polymers for drug delivery which has a minimum systemic toxicity. This study aimed to evaluate the cytotoxicity and genotoxicity of paclitaxel nanoencapsulated with PLGA. Cytotoxic effects were determined by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method and genotoxic effects were determined by single cell gel electrophoresis (Comet) method in human neuroblastoma cells (SH-SY5Y). According to our results, the viability of cells treated with concentrations higher than 10 nM of free paclitaxel and paclitaxel loaded PLGA nanoparticles for 48 and 72 h was found lower than 50%. Additionally, DNA damage increased with the increase of nanoparticle dose when the cells exposed to paclitaxel loaded PLGA nanoparticles for 24, 48 and 72 h. It can be concluded that PLGA nanoparticles can be considered as a biocompatible carrier system for drug delivery and might be promising agent against neuroblastoma.

Microalbuminuria and Serum Cystatin C in Prediction of Early-Renal Insufficiency in Children with Obesity.

OBJECTIVE: Serum cystatin-C (SCysC) and microalbuminuria are well-recognized early markers of renal damage. This study aims to assess whether these early markers are elevated in children with obesity and normal serum creatinine (SCr). METHODS: Pediatric patients diagnosed with obesity were included (n = 105, ages 4-18 y) in this study. The patients were divided into three groups as follows: solely obese, metabolic syndrome and type 2 diabetes. Serum cystatin-C, 24-h microalbuminuria, SCr and glomerular filtration rate (GFR) were evaluated in all patients. All patients were examined with history, physical examination, laboratory analysis and ultrasonography evaluation. RESULTS: The findings showed that renal function, GFR and SCr levels were normal in all patients. There was microalbuminuria in six patients and SCysC was elevated in eight patients. There were also both elevated SCysC and microalbuminuria in eight patients. Significant elevations of both microalbuminuria and SCysC were detected in cases with type 2 diabetes (p < 0.05). CONCLUSIONS: The findings suggest that SCysC may have a diagnostic value in early-renal insufficiency. Although there was not any statistically significant difference between groups in GFR, significant elevations for both microalbuminuria and SCysC in patients with type 2 diabetes were detected. This suggests that the risk factors of diabetes may have a direct relation with renal damage. Regarding renal function in type 2 diabetic and obese pediatric patients, microalbuminuria and SCysC may be screened to observe early-renal damage, even in cases with normal GFR and SCr levels.

Metabolic acidosis is common and associates with disease progression in children with chronic kidney disease.

Recent studies in adult chronic kidney disease (CKD) suggest that metabolic acidosis is associated with faster decline in estimated glomerular filtration rate (eGFR). Alkali therapies improve the course of kidney disease. Here we investigated the prevalence and determinants of abnormal serum bicarbonate values and whether metabolic acidosis may be deleterious to children with CKD. Associations between follow-up serum bicarbonate levels categorized as under 18, 18 to under 22, and 22 or more mmol/l and CKD outcomes in 704 children in the Cardiovascular Comorbidity in Children with CKD Study, a prospective cohort of pediatric patients with CKD stages 3-5, were studied. The eGFR and serum bicarbonate were measured every six months. At baseline, the median eGFR was 27 ml/min/1.73m2 and median serum bicarbonate level 21 mmol/l. During a median follow-up of 3.3 years, the prevalence of metabolic acidosis (serum bicarbonate under 22 mmol/l) was 43%, 60%, and 45% in CKD stages 3, 4, and 5, respectively. In multivariable analysis, the presence of metabolic acidosis as a time-varying covariate was significantly associated with log serum parathyroid hormone through the entire follow-up, but no association with longitudinal growth was found. A total of 211 patients reached the composite endpoint (ESRD or 50% decline in eGFR). In a multivariable Cox model, children with time-varying serum bicarbonate under 18 mmol/l had a significantly higher risk of CKD progression compared to those with a serum bicarbonate of 22 or more mmol/l (adjusted hazard ratio 2.44; 95% confidence interval 1.43-4.15). Thus, metabolic acidosis is a common complication in pediatric patients with CKD and may be a risk factor for secondary hyperparathyroidism and kidney disease progression.

Hemostasis vs. epidural fibrosis?: A comparative study on an experimental rat model of laminectomy.

AIM: The aim of this study was to evaluate the histopathological and biochemical impact and effectiveness of two hemostatic agents, Ankaferd blood stopper (ABS) and Microporous Polysaccharide Hemospheres (MPH), on epidural fibrosis in an experimental rat laminectomy model. MATERIAL AND METHODS: Twenty adult Wistar albino rats were divided into MPH-treated (n=6), ABS-treated (n=6) and control (n=8) groups. Laminectomy of the lumbar spine was performed in all animals and treatment groups were exposed to MPH and ABS while closure was applied in control group as per usual. Epidural fibrosis was evaluated in all groups macroscopically, histopathologically, biochemically and with electron microscopy four weeks later. RESULTS: Statistically, it was found that MPH-treated group had significantly less epidural fibrosis compared to ABS-treated and control groups. CONCLUSION: We compared two hemostatic agents for their propensity to cause adhesions in the present study. Our results show that MPH significantly reduces epidural scar formation and dural adhesion in a rat model of laminectomy while ABS increases postoperative fibrosis.

Fabrication of Plasmonic Nanorod-Embedded Dipeptide Microspheres via the Freeze-Quenching Method for Near-Infrared Laser-Triggered Drug-Delivery Applications.

Control of drug release by an external stimulus may provide remote controllability, low toxicity, and reduced side effects. In this context, varying physical external stimuli, including magnetic and electric fields, ultrasound, light, and pharmacological stimuli, have been employed to control the release rate of drug molecules in a diseased region. However, the design and development of alternative on-demand drug-delivery systems that permit control of the dosage of drug released via an external stimulus are still required. Here, we developed near-infrared laser-activatable microspheres based on Fmoc-diphenylalanine (Phe-Phe) dipeptides and plasmonic gold nanorods (AuNRs) via a simple freeze-quenching approach. These plasmonic nanoparticle-embedded microspheres were then employed as a smart drug-delivery platform for native, continuous, and pulsatile doxorubicin (DOX) release. Remarkable sustained, burst, and on-demand DOX release from the fabricated microspheres were achieved by manipulating the laser exposure time. Our results demonstrate that AuNR-embedded dipeptide microspheres have great potential for controlled drug-delivery systems.

Tumor-to-tumor metastasis of the central nervous system.

Tumor-to-tumor metastasis is a well recognized phenomenon. Although any tumor may be potential recipient of metastasis, renal cell carcinoma and meningioma are the most common malignant and benign recipients, respectively, whereas the lung and breast are the most common metastatic donors respectively, in both settings. Patients with hereditary cancer syndromes may be at higher risk for the development of tumor-to-tumor metastases. The most common pattern of tumor-to-tumor metastasis for intracranial neoplasms is the type in which an aggressive high-grade malignancy serves as the source of tumor and a more indolent neoplasm serves as the recipient tumor. The development of tumor metastasis from a second primary malignancy is uncommon and remains biologically puzzling. Its low incidence has made its full biological characterization evasive. Although rare, neurosurgeons should be aware of the entity of tumor-to-tumor metastasis.

A single-center experience on percutaneously performed partial omentectomy in pediatric peritoneal dialysis patients.

OBJECTIVE: This study describes a single-center experience on percutaneously performed partial omentectomy procedure in pediatric peritoneal dialysis (PD) patients who showed early catheter dysfunction and required catheter replacement due to catheter flow obstruction. MATERIALS AND METHODS: We performed a retrospective review of clinical outcomes from pediatric PD patients who underwent percutaneous catheter replacement by pediatric nephrologists between November 1995 and December 2012. Partial omentectomy was performed in those patients in whom omental or adhesion trapping to the catheter tip was seen. RESULTS: During the study period, catheter dysfunction that eventually required percutaneous catheter replacement occurred in 32 (23.7%) children. Of these, 9 patients were performed partial omentectomy. Mean age at initiation of PD and time of omentectomy was 97.48 ± 46.06 and 98.53 ± 45.55 months, respectively. Catheter dysfunction appeared after a mean 1.20 ± 1.0 months. The causes of catheter dysfunction were omental wrapping and malposition. No peritonitis occurred before omentectomy. Mean total operation time was 60 ± 8.83 min. No complications were encountered during the procedure. After omentectomy, mean catheter survival period was 5.92 ± 6.88 months. A total of five peritonitis episodes occurred. Three patients were transferred to hemodialysis. Six patients were on PD treatment without any problem at the end of the first year of their follow-up. Two patients underwent kidney transplantation. Four patients were still on chronic PD treatment at the end of the study period. CONCLUSION: When performed by an experienced nephrologist, the performance of partial omentectomy by percutaneous route, when required, is an easy, safe and efficient therapeutic procedure in children on chronic PD treatment.

Laser-triggered degelation control of gold nanoparticle embedded peptide organogels.

Further understanding of the interactions between nanoparticles (NPs) and biological molecules offers new possibilities in the applications of nanomedicine and nanodiagnostics. The properties of NPs, including size, shape, and surface functionality, play a decisive role in these interactions. Herein, we evaluated the influences of gold NPs (AuNPs) with different sizes (5-60 nm) and shapes (i.e., spherical, rod, and cage) on the self-assembly of diphenylalanine (Phe-Phe) dipeptides. We found that the size of AuNPs smaller than 10 nm did not affect the self-assembly process of Phe-Phe, while bigger AuNPs (>10 nm) caused the formation of starlike peptide morphologies connected to one center. In the case of shape differences, nanorod and nanocage morphologies acted differently than spherical ones and caused the formation of densely packed, networklike dipeptide morphologies. In addition to these experiments, by combining photothermal properties of AuNPs with a Phe-Phe-based organogel having a thermo-responsive property, we demonstrated that the degelation process of AuNPs embedded organogels may be controlled by laser illumination. Complete degelation was achieved in about 10 min. We believe that such control may open the door to new opportunities for a number of applications, such as controlled release of drugs and tissue engineering.

May we use communication as an instrument? A simple neuromonitoring method peripheral nerve tumour resection.

We performed a procedure called awake simple peripheral nerve monitoring of the distal lower extremity. In this procedure we aimed to protect the patient's peroneal nerve during the successful removal of a tumour arising from this nerve. This is the first report that explores the use of communication with the patient during peripheral nerve tumour resection.

Alpha-lipoic acid reduces peridural fibrosis after laminectomy of lumbar vertebrae in rabbits.

BACKGROUND: Peridural fibrosis is an inevitable healing process causing failed back surgery syndrome after lumbar spinal operations. In this study, alpha-lipoic acid (ALA), reported to reduce fibrosis in liver, oral mucosa, and peritoneum, investigated as a potential candidate for prevention of peridural fibrosis. METHOD: Twelve adult New Zealand white male rabbits were divided into control (n = 5) and ALA groups (n = 7). Laminectomy of lumbar spine was performed and ALA was applied on the exposed dura mater topically in ALA group. RESULTS: According to histological peridural grading, the ALA group (median grade 1) showed significantly less peridural fibrosis than the control group (median grade 3, p = 0.005). CONCLUSIONS: ALA is a promising substance in the prevention of peridural fibrosis, especially in early preoperative and postoperative period.

A rare emergency condition in neurosurgery: foot drop due to Paget's disease.

Paget's disease is a chronic, focal skeletal disorder that usually affects the pelvis and spine. Spinal cases are generally asymptomatic; in the symptomatic cases, the neurological dysfunctions are related to non-compressive vascular defects, hemorrhage, sarcomatoid degeneration, spinal stenosis, or pathological fractures, primarily in the lumbar region. The Neurosurgeon should have a fundamental understanding of the complications of Paget's disease and should be familiar with the indications for treatment, as well as available medical and surgical therapies. In the present paper, we report a case of Paget's disease that presented with an isolated foot drop due to a pathological fracture of L5 vertebra, and then discuss the therapeutic strategies presented in the literature.

Postnatal management of infants with antenatally detected hydronephrosis.

With the increasing use of antenatal sonography, fetal hydronephrosis has been reported more frequently. Because of the lack of consensus regarding treatment of these infants, the postnatal approach toward fetal renal pelvis enlargement remains controversial. The aim of this prospective study is to demonstrate the postnatal investigation, treatment, and outcome of infants with prenatally diagnosed hydronephrosis. Infants whose antenatal ultrasound scan showed a fetal renal pelvis of 5 mm or greater were investigated postnatally using ultrasound (US) and voiding cystourethrography. When indicated, isotope studies and intravenous urograms were also performed. We followed prospectively neonates with antenatally diagnosed hydronephrosis and recommended management guidelines on the basis of our findings. In 156 neonates (193 kidney units) that were found to have hydronephrosis, the average gestational age at which the diagnosis was made was 32.94+/-5.10 weeks. The mean duration of postnatal follow-up was 26.3+/-13.56 months (range 3-60 months). The mean APPD of the fetal renal pelvis was 10.35+/-3.24 mm (5-9 mm in 84 kidneys, 10-14 mm in 96 kidneys and > or =15 mm in 13 kidneys). Of the 193 kidney units, 145 units were found to be pathological. The most common detected underlying abnormalities were ureteropelvic junction obstruction (in 91 kidneys; 62.7%) and vesicoureteral reflux (in 24 kidneys; 16.6%). Postnatally, 23 (45%) of 51 patients whose first US was normal were diagnosed postnatally as having urinary tract abnormality. There was a negative correlation between APPD and the rate of spontaneous resolution and positive correlation between APPD and the rate of surgery (P<0.01). In conclusion, because it is not possible to determine an upper limit of normal for the antenatal renal pelvis, any baby with AH should not be considered clinically insignificant. Infants with antenatal renal pelvis measurements > or =5 mm should be investigated postnatally. A normal postnatal ultrasound scan does not preclude the presence of urinary tract abnormality.

Percutaneous nephrostomy in children: diagnostic and therapeutic importance.

The aim of this study was to evaluate the effectiveness and safety of percutaneous nephrostomy (PN) in terms of diagnostic and therapeutic approach in children with urological problems. PN was performed on 39 kidneys in 28 patients (12 girls, 16 boys) aged 4.5 months to 13 years (average 5.38+/-3.41 years) during the period from January 1996 to December 2003. Underlying abnormalities were ureteropelvic junction obstruction (UPJO) in 14 patients (17 kidneys), ureterovesical junction obstruction (UVJO) in six patients (eight kidneys), supravesical obstruction due to tumour or hydatid cyst or ureteral stone in three patients (five kidneys), and severe vesicoureteral reflux (VUR) with/without neurogenic bladder associated with pyonephrotic kidneys in five patients (nine kidneys). The duration of catheter insertion was between 2 and 160 days (average 80+/-65.01 days). The complications were haematuria (six cases), infection (five cases) and displacement of catheter (four cases). Radical surgical management was performed in 25 patients (33 kidneys): pyeloplasty in eight cases (ten kidneys), UVJO correction in six cases (eight kidneys), nephrectomy in five cases (five kidneys), ureteroneocystostomy in four cases (seven kidneys), hydatid cyst operation in one case (two kidneys) and stone extraction in one case (one kidney). PN is an easy, safe and efficient diagnostic and therapeutic procedure with few complications in childhood.