The Utility of Noninvasive Urinary Biomarkers for the Evaluation of Vesicoureteral Reflux in Children.

Vesicoureteral reflux (VUR) is one of the most important disorders encountered in pediatric nephrology due to its frequency and potential evolution to chronic kidney disease (CKD). The aim of our study was to identify noninvasive and easy-to-determine urinary markers to facilitate the diagnosis and staging of VUR. We performed a cross-section study including 39 patients with VUR followed over three years (August 2021-September 2023) and 39 children without urinary disorder (the control group). We measured the urinary concentration of interleukin-6 (IL-6), cathelicidin (LL-37), and neutrophil gelatinase-associated lipocalin (NGAL) in VUR and healthy controls. Moreover, we analyzed the correlation between these biomarkers and the presence of renal scars (RS), reflux nephropathy (RN), and CKD. The NGAL concentrations were significantly higher in patients with VUR than in the controls (p = 0.02). Regarding the severity of the reflux, NGAL/creatinine and LL-37/creatinine were positively correlated with severe reflux (p = 0.04, respectively, p = 0.02). In patients with VUR and RS, LL-37/creatinine was significantly lower (p = 0.01). LL-37/creatinine with an AUC of 0.71 and NGAL/creatinine with an AUC of 0.72 could be acceptable diagnostic tests for severe VUR. In conclusion, urinary IL-6, NGAL, and LL-37 could serve as valuable markers for diagnosing and predicting outcomes in patients with VUR and RN.

The Perspectives of Biomarkers in Predicting the Survival of the Renal Graft.

Kidney transplantation (KT) is currently the elective approach for patients with end-stage renal disease. Although it is a safe choice for these patients, the early complications can lead to graft dysfunction. One of the most redoubtable complications is delayed graft function (DGF), having no specific treatment. The effects of DGF on the graft survival are large enough to justify the formulation of specific biological protocols. Therefore, discovering biomarkers of acute impairment in renal transplanted patients is required. Creatinine is a poor marker to establish the kidney injury. Estimated glomerular filtration rate together with creatinine is ready to approximately measure the kidney function. Different serum and urine proteins are being studied as possible predictive biomarkers for delayed graft function. This review will concentrate on recent and existing research which provide insight concerning the contribution of some molecules for the estimation and evaluation of graft function after kidney transplantation. Further studies examining various aspects of DGF after KT are urgently needed to address a hitherto less-known clinical question.

Curcumin and Vitamin C Attenuate Gentamicin-Induced Nephrotoxicity by Modulating Distinctive Reactive Species.

Gentamicin remains widely used in all age groups despite its well-documented nephrotoxicity; however, no adjuvant therapies have been established to counteract this side effect. Our study aimed to experimentally determine whether curcumin and vitamin C have nephroprotective effects and whether certain reactive species could be used as markers of early gentamicin nephrotoxicity. Wistar adult male rats were evenly distributed into four groups: control, gentamicin, curcumin and gentamicin, vitamin C and gentamicin (gentamicin: 60 mg/kg/day, intraperitoneally, 7 days). We determined renal function (urea, creatinine), oxidative stress (malondialdehyde, nitric oxide, 3-nitrotyrosine, total oxidative stress), and antioxidant and anti-inflammatory status (thiols, total antioxidant capacity, interleukin-10). Nephrotoxicity was successfully induced, as shown by the elevated creatinine levels in the gentamicin group. In contrast, supplementation with curcumin and vitamin C prevented an increase in urea levels while decreasing total oxidative stress levels compared to the gentamicin group. Moreover, vitamin C and curcumin distinctively modulate the levels of nitric oxide and malondialdehyde. Histological analysis showed more discrete lesions in rats that received vitamin C compared to the curcumin group.

Accelerated lipid peroxidation in a rat model of gentamicin nephrotoxicity.

Kidney disease represents a burden for the health care system worldwide. As the prevalence continues to rise, discovering new biomarkers of early kidney damage has become crucial. Oxidative stress (OS) represents one of the main factors involved in the early stages of many syndromes leading to kidney damage. Therefore, it must be studied in detail. To date, many studies have focused on OS in advanced stages of acute kidney injury (AKI), with great success. The aim of the present study was to ascertain whether even mild renal function impairment can be linked to specific systemic markers of OS and systemic antioxidants in order to pinpoint certain biomarkers for early kidney damage. We used male rats (Rattus norvegicus) in which we induced kidney damage by injecting gentamicin for 7 days. Blood was collected 24 h after the last dose of gentamicin. Urea, creatinine, 3-nitrotyrosine (3-NT), nitric oxide (NO), malondialdehyde (MDA), thiols (TS), total oxidative stress (TOS), and interferon-γ (IFN-γ) were determined. In addition, for the antioxidant status we measured total antioxidant capacity (TAC) and interleukin-10 (IL-10). Our results demonstrated that the rats had mild renal impairment consistent with a pre-AKI stage due to the nephrotoxic effect of gentamicin. However, TOS, MDA and NO were significantly higher in the gentamicin group compared to the control group. In addition, TAC was higher in the control group. Hence, OS markers reach higher levels and may potentially be used as markers of kidney damage even in cases of mild renal function impairment.

Perspectives of gold nanoparticles and their applications in pancreatic cancer (Review).

Nanoparticles (NPs) represent a major point of interest in the scientific field, with an increasing number of studies revealing promising results. Nano-oncology is a relatively new area of research that continues to expand, revealing new perspectives in both diagnosing and treating cancer. Treating pancreatic cancer (PC) remains a major challenge, with modest positive results, thus an increasing number of studies have focused on this disease. Out of all the NPs that have been used in experimental studies, gold NPs (GNPs) appear to be the most efficient, with little systemic toxicity. This review aims to summarize the latest studies that reveal the effects that GNPs have on PC cells, focusing on different ways in which they can be used to diagnose this disease, to induce apoptosis or cause cytotoxicity in cancer cells. Although literature has limited data concerning this specific topic, the results are promising. However more studies are required until GNPs can be used in clinical practice.

Mitochondrial nanotargeting in malignancies (Review).

Malignancies represent a burden for the health system worldwide. Treating them represents a challenge through the prism of the cancer cell behaviour and the serious systemic side effects that usually occur. Both traditional (chemotherapy, radiotherapy and surgery) and associated therapies (immunotherapy and hormone therapy) have reached a plateau. The new trend for the management of malignancies includes nanoparticles (NPs) which are studied for both their diagnostic and therapeutical use. NPs can be designed in various ways, many of them targeting mitochondria causing cellular apoptosis. This review summarizes the main characteristics of NPs that are studied in different cancers to highlight their mechanism of action. Since mitochondria play a key role in the cellular homeostasis, they represent the main target for the experimental current studies. While there are NPs approved by the FDA for clinical use, most of them are still under extended research and still need to prove their efficacy and biocompatibility, preferable with minimal systemic side effects.

Eplet incompatibility in pediatric renal transplantation.

Eplet incompatibility appears to be a better predictor of the de novo appearance of DSA post-Tx than HLA antigen matching in adults. We evaluated the HLA Matchmaker® software (version 2.1) in our pediatric cohort to predict the appearance of DSA post-Tx. We included 70 pediatric patients (26 girls, 10 living donors, mean age 11.2 ± 3.9 years) after a first R-Tx (January 2010-August 2016), without prior immunization, having complete HLA typing (A, B, C, DRB1 and DQB1) and DSA follow-up for at least one year. The mean of HLA and eplet incompatibilities was 4.7 ± 1.3 and 15.5 ± 6.1, respectively, with a correlation coefficient r2 between these two variables of 0.34 (P < .001). The eplet load was 12.8 ± 5.0 in living donors vs 15.9 ± 6.2 in deceased donors (P = NS), 12.6 ± 6.1 in preemptive R-Tx (n = 14) vs 16.3 ± 5.9 for non-preemptive R-Tx (P = .04). Seven patients (10%) developed DSA during the 3.5 ± 1.2 years post-Tx. The eplet load was 13.7 ± 5.5 for those who developed DSA vs 15.7 ± 6.1 for the others (P = NS). In our single-center series of pediatric R-Tx with good HLA matching and lower eplet load than previously published series, eplet incompatibilities do not predict the development of DSA. The question of the HLA matching requirement and the daily interest of the HLA Matchmaker® software to help select the grafts remain open.

Oxidative stress as a potential target in acute kidney injury.

BACKGROUND: Acute kidney injury (AKI) is a major problem for health systems being directly related to short and long-term morbidity and mortality. In the last years, the incidence of AKI has been increasing. AKI and chronic kidney disease (CKD) are closely interconnected, with a growing rate of CKD linked to repeated and severe episodes of AKI. AKI and CKD can occur also secondary to imbalanced oxidative stress (OS) reactions, inflammation, and apoptosis. The kidney is particularly sensitive to OS. OS is known as a crucial pathogenetic factor in cellular damage, with a direct role in initiation, development, and progression of AKI. The aim of this review is to focus on the pathogenetic role of OS in AKI in order to gain a better understanding. We exposed the potential relationships between OS and the perturbation of renal function and we also presented the redox-dependent factors that can contribute to early kidney injury. In the last decades, promising advances have been made in understanding the pathophysiology of AKI and its consequences, but more studies are needed in order to develop new therapies that can address OS and oxidative damage in early stages of AKI. METHODS: We searched PubMed for relevant articles published up to May 2019. In this review we incorporated data from different types of studies, including observational and experimental, both in vivo and in vitro, studies that provided information about OS in the pathophysiology of AKI. RESULTS: The results show that OS plays a major key role in the initiation and development of AKI, providing the chance to find new targets that can be therapeutically addressed. DISCUSSION: Acute kidney injury represents a major health issue that is still not fully understood. Research in this area still provides new useful data that can help obtain a better management of the patient. OS represents a major focus point in many studies, and a better understanding of its implications in AKI might offer the chance to fight new therapeutic strategies.

Association of fragile X syndrome, Robertsonian translocation (13, 22) and autism in a child.

We describe the case of a 6-year-old boy with both fragile X syndrome and Robertsonian Translocation (45, XY, der (13; 22) (q10; q10)). This is the first reported case of a patient with fragile X syndrome with this Robertsonian translocation. Facial features and macroorchidism were consistent with fragile X syndrome. Cognitive impairment is more significant than in his sibling with fragile X syndrome, and the patient also has a prior diagnosis of autism spectrum disorder. We emphasize the challenges in his behavioral management and outline future directions for his management.

Can Apparent Diffusion Coefficient Predict the Clinical Outcome in Drowned Children?

INTRODUCTION: Pediatric cerebral hypoxic-ischemic injury frequently results in severe neurological outcome. Imaging with diffusion-weighted magnetic resonance imaging (DWi) demonstrates that the acute cerebral injury and apparent diffusion coefficient (ADC) allow the assessment of the severity of brain damage. The main objective was to examine if spatial distribution of reductions in ADC values is associated with clinical outcome in drowned children. METHODS: This is a retrospective study of 7 children (7 examinations) suffering from a hypoxic-ischemic event who underwent DWi. Seven subjects with normal DWi served as controls. The mean patient age was 4.88 ± 2.93 years and the male-to-female ratio was 5:2. The neurological outcome was divided into 2 categories: 4 children with Apallic syndrome and 3 deaths. We analysed the differences between the drowned children and the control group regarding clinical data, DWi abnormalities, and ADC values. RESULTS: The ADC values in the occipital and parietal grey matter were significantly different between the drowned children (765.14 ± 65.47 vs 920.95 ± 69.62; P = .003) and the control group (670.82 ± 233.99 vs 900.66 ± 92.72; P = .005). The ADC showed low values in the precentral area also (P = .044). CONCLUSION: The ADC reduction may be useful to predict the poor outcome in drowned children and can be a valuable tool for clinical assessment.

Ivemark syndrome-a rare entity with specific anatomical features.

Ivemark syndrome (IS) is a rare embryological disorder which results from failure of development of the left-right asymmetry of organs. It is often associated with cardiac and other organ abnormalities, which are the usual causes of death in early neonatal life. We report a 3 months old girl with IS with dextrocardia, transposition of the great vessels, atrio-ventricular connection, total anomalous pulmonary venous drainage, a right atrial and right pulmonary isomerism, a midline liver, a midline gallbladder, asplenia, intestinal malrotation and vena cava anomalies. To our knowledge, complete right heterotaxia syndrome has been rarely described in literature. Lateralization defects such as situs inversus, asplenia or polysplenia due to defective left-right axis development are considered as defects of the primary developmental field. Therefore, additional malformations in IS can be synchronic defects in the primary developmental field rather than causally independent malformations.

Ivemark syndrome-a rare entity with specific anatomical features / Síndrome de Ivermark. Informe de un caso

Ivemark syndrome (IS) is a rare embryological disorder which results from failure of development of the left-right asymmetry of organs. It is often associated with cardiac and other organ abnormalities, which are the usual causes of death in early neonatal life. We report a 3 months old girl with IS with dextrocardia, transposition of the great vessels, atrio-ventricular connection, total anomalous pulmonary venous drainage, a right atrial and right pulmonary isomerism, a midline liver, a midline gallbladder, asplenia, intestinal malrotation and vena cava anomalies. To our knowledge, complete right heterotaxia syndrome has been rarely described in literature. Lateralization defects such as situs inversus, asplenia or polysplenia due to defective left-right axis development are considered as defects of the primary developmental field. Therefore, additional malformations in IS can be synchronic defects in the primary developmental field rather than causally independent malformations.

El síndrome de Ivermark es un desorden embriológico raro resultante de una falla en el desarrollo de la asimetría izquierda y derecha de los órganos. Usualmente se asocia con anomalías cardíacas y de otros órganos, que son la causa usual de muerte en la vida neonatal. Presentamos una niña de 3 meses con dextrocardia, trasposición de los grandes vasos, comunicación aurículo-ventricular, drenaje anómalo total de la vena pulmonar, isomerismo de la aurícula y pulmón derecho, hígado y vesícula en la línea media, asplenia, malrotación intestinal y anomalías de la vena cava. Una heterotaxia derecha completa ha sido raramente descrita en la literatura. Los defectos de lateralización como situs inverso, asplenia o poli esplenia causados por defectos en el desarrollo izquierda derecha son considerados como defectos del campo de desarrollo primario. Por lo tanto, las manifestaciones adicionales del síndrome de Ivemark pueden ser defectos sincrónicos del campo de desarrollo primario más que malformaciones causalmente independientes.

The activity of 8-iso-prostaglandin F2alpha as an oxidative stress marker in vivo in paediatric patients with type 1 diabetes mellitus and associated autoimmunities.

BACKGROUND: Oxidative stress and inflammatory reactions are known to hold an important role in the etiopathogeny and persistence of acute or chronic clinical entities. Isoprostanes--a group of prostaglandin-like compounds, active products of arachidonic acid--have proved to be representative biomarkers of lipid peroxidation. The aim of this study was to determine the activity of serum 8-iso-prostaglandin F2alpha, (8iPGF2alpha), as an in vivo oxidative stress marker, in paediatric patients with diabetes mellitus type 1 (DM1) and in a control group. The main goals of this study were the following: establishing a possible correlation between the activity of 8iPGF2alpha and the presence of an autoimmune disease associated with DM1 and identifying a possible correlation between 8iPGF2alpha, the value of glycosylated hemoglobin (HbA1c) and the pancreatic autoimmune markers GAD65, IA2, IA in the group of patients with DM1 and other associated autoimmune diseases. METHODS: Fifty-one children and adolescents (31 males) aged 11.65 +/- 4.1 years with DM1 were enrolled in the study. Twenty-seven healthy children, age- and gender-matched, were enrolled as controls. Patients and controls underwent the 8iPGFzalpha assessment through an ELISA serum method. RESULTS: The mean 8iPGF2alpha value was 2090.6 +/- 3536.5 in the DM1 patient group and 509.9 +/- 493.5 in controls (p = 0.03). The mean 8iPGF2alpha value was 2178.19 +/- 4017.05 in patients with DM1 who did not suffer from other associated autoimmune diseases (n = 38) vs. 1834.95 +/- 1504.73 in patients with DM1 and other associated autoimmune diseases (n = 13) (p = 0.76). The correlation between the 8iPGF2alpha and the HbA1c values was determined by obtaining a correlation coefficient r = 0.38 and p = 0.0057. No correlation was observed between GAD65 and 8iPGF2alpha (r = 0.3; p = 0.29), IA2 and 8iPGF2alpha (r = -0.02; p = 0.92), IAA and 8iPGF2alpha (r = 0.4; p = 0.12). CONCLUSIONS: Oxidative stress reactions are more intense in patients with diabetes mellitus type 1 than in healthy patients. Similar results were obtained in patients associating other autoimmune diseases. 8iPGF2alpha can be an ideal marker for determining oxidative reactions in vivo.

Immunological manifestations in type I diabetic children.

In the past decade a number of studies suggested that type 1 diabetes mellitus is an oxidative stress influenced disease. Paraoxonase 1 enzyme plays a crucial role in antiatherogenic-antioxidant circle. The aim of our study was to examine the possible differences in paraoxonase 1 enzymatic activities in diabetic children associated other autoimmune diseases versus a control group. Another objective of the study was to determine if there is any difference according to the gender in paraoxonase 1 activities (arylesterase and paraoxonase activities). Paraoxonase 1 activities were determined in 51 diabetic children and 36 healthy controls. In diabetic children we determined also the C-peptide level. The paraoxonase 1 arylesterase activity was lower in diabetic females compared with diabetic males. The level of C-peptide is in an inverse correlation with the years of the disease. The paraoxonase activities have a correlation with the level of insulin antibodies in type I diabetic children. Our data suggest that paraoxonase enzymatic pattern may be different in these two activities. PON1 arylesterase activity may exhibit a tendency to low levels in women in comparison to men. The C-peptide level is a valuable tool in assessing the restant beta cell function.

Granulomatous cheilitis of Miescher: the diagnostic proof for a Melkersson-Rosenthal syndrome.

BACKGROUND: The Melkersson-Rosenthal syndrome (MRS) is a very rare clinical entity and its classical form is being characterized by the following triad: facial nerve palsy, swelling of the lips and fissured tongue. However, the monosymptomatic form is more common and the typical manifestation is facial edema and/or enlargement of the lips. CASE REPORT: We report a case of monosymptomatic MRS with a positive biopsy of granulomatous cheilitis. CONCLUSIONS: In the daily practice as a pediatrician, it is not usual to diagnose a patient as having MRS. We consider that this is partly because of misdiagnosis. We therefore believe that this case report will supply additional information, in the scope of recurrent facial paralysis and orofacial edema in both children and adults.

Ectodermal Dysplasia Showing the Clinical Overlap between Hay Wells Syndrome and Bowen Armstrong Syndrome.

BACKGROUND: Several clinical entities combine ectodermal dysplasia (ED) and cleft lip and/or palate (CL/P). These disorders have been recognized with a narrow phenotypic spectrum and very similar clinical features. CASE PRESENTATION: We report a case with a clinical diagnosis of Hay Wells syndrome (ankyloblepharon, ED and CL/P), who is a descendent of a mother with Bowen Armstrong syndrome (ED, CL/P, mental retardation). CONCLUSION: Due to the clinical similarities, we suggest that Hay Wells syndrome and Bowen Armstrong syndrome may be the same clinical entity with variable manifestations. This case highlights the difficulties in trying to classify the ED syndromes on clinical features.