A Novel Mutation in the OXCT1 Gene Causing Succinyl-CoA:3-Ketoacid CoA Transferase (SCOT) Deficiency Starting with Neurologic Manifestations

  Succinyl-CoA:3-oxoacid CoA-transferase (SCOT) deficiency is an inborn error of ketone body utilization characterized by intermittent ketoacidosis crises. This study reports the first Iranian patient with SCOT deficiency who presented with seizure and hypotonia at birth.Accordingly, she was consequently re-hospitalized due to hypotonia and respiratory distress. Laboratory tests revealed hyperammonemia, ketonuria, and metabolic acidosis. Besides, the plasma glucose level was normal without any other abnormality. Despite treatment with high-dose bicarbonate, severe acidosis persisted. Poor response to treatment raised a significant diagnostic challenge among specialists until genetic investigation identified a homozygous nonsense mutation (c.79G>T; p.Gly27*) in the OXCT1 gene (NM_000436), causing SCOT deficiency. Genetic studies help clinicians achieve a definite diagnosis of such metabolic disorders. In this case, the accurate and early diagnosis of SCOT deficiency opened new therapeutic possibilities, including frequent carbohydrate-rich meals and low fat and protein diet. Moreover, our findings expand the mutational and clinical spectrum of SCOT deficiency

The Role of Ischemia Reperfusion Damage on Renal Transplant, what are the new treatments?

How to Cite This Article: Otukesh H, Hoseini R, Rahimzadeh N, Hosseini S, Ahmadpoor P, Javadi Larijani F. The role of Ischemia reperfusion damage on renal transplant, what are the new treatments? J Ped. Nephrology 2013 July;1(1):1-7.Ischemia reperfusion damage usually occurs after renal transplantation. These injuries can stimulate the innate immune system, trigger an inflammatory response and ultimately activate the adaptive immune system. These events may result in rejection, graft fibrosis and chronic allograft nephropathy. Different mechanisms contribute to innate immune system activation following ischemia reperfusion injury in renal transplants. Some of these mechanisms are known and described by investigators while the remaining are still unknown. To clarify the precise mechanisms underlying the innate immune system activation and rejection progression helps us to plan therapeutic protocols to reduce immunologic responses to ischemic events and to improve the graft function and outcome. In this review, we will discuss how innate and adaptive immune systems are activated during an ischemic insult and thereafter discuss related therapeutic interventions to block the activating pathways. Keywords: Ischemia; Renal transplantation; Reperfusion

The innate immune response during acute urinary tract infections; an overview

The components of immune system are specific (adaptive immunity) and non-specific (innate immunity). Regardless of antigenic properties, the non-specific components function either as eliminators or barriers of wide range of pathogens. A person is born with innate immunity as the natural resistances, which has three kinds; anatomic mechanical and biochemical factors. The resistances are provided by innate immunity via various chemical, cellular and physical approaches. The colonization, entry and spread of microorganisms can be prevented by innate immunity. Two main sub-divided types of adaptive immunity are humeral and cellular. Active immunity resulting from the development of antibodies in response to the presence of an antigen is a long-term and acquired immunity. This review article summarizes some important potential mechanisms in innate immune system. The host renal tract which has been investigated from many aspects of the pathogenesis of urinary tract infection (UTI) are still poorly defined and require a better understanding of the pathophysiology immune system

Tumour suppressive effects of WEE1 gene silencing in breast cancer cells.

Background: WEE1 is a G2/M checkpoint regulator protein. Various studies have indicated that WEE1 could be a good target for cancer therapy. The main aim of this study was to asssess the tumor suppressive potential of WEE1 silencing in two different breast cancer cell lines, MCF7 which carries the wild-type p53 and MDA-MB468 which contains a mutant type. Materials and Methods: After WEE1 knockdown with specific shRNAs downstream effects on cell viability and cell cycle progression were determined using MTT and flow cytometry analyses, respectively. Real-time PCR and Western blotting were conducted to assess the effect of WEE1 inhibition on the expression of apoptotic (p53) and anti-apoptotic (Bcl2) factors and also a growth marker (VEGF). Results: The results showed that WEE1 inhibition could cause a significant decrease in the viability of both MCF7 and MDA-MB-468 breast cancer cell lines by more than 50%. Interestingly, DNA content assays showed a significant increase in apoptotic cells following WEE1 silencing. WEE1 inhibition also induced upregulation of the apoptotic marker, p53, in breast cancer cells. A significant decrease in the expression of VEGF and Bcl-2 was observed following WEE1 inhibition in both cell lines. Conclusions: In concordance with previous studies, our data showed that WEE1 inhibition could induce G2 arrest abrogation and consequent cell death in breast cancer cells. Moreover, in this study, the observed interactions between the pro- and anti-apoptotic proteins and decrease in the angiogenesis marker expression confirm the susceptibility to apoptosis and validate the tumor suppressive effect of WEE1 inhibition in breast cancer cells. Interestingly, the levels of the sensitivity to WEE1 silencing in breast cancer cells, MCF7 and MDA-MB468, seem to be in concordance with the level of p53 expression

Primjena D-optimalnog dizajna za poboljšanje fizikalnih i senzorskih svojstava pljeskavica sa smanjenim udjelom masnoća, izrađenih od goveđeg mesa uz dodatak inulina, β-glukana i biljnih ulja

In this study, the D-optimal mixture design methodology was applied to determine the optimised proportions of inulin, β-glucan and breadcrumbs in formulation of low-fat beef burgers containing pre-emulsified canola and olive oil blend. Also, the effect of each of the ingredients individually as well as their interactions on cooking characteristics, texture, colour and sensory properties of low-fat beef burgers were investigated. The results of this study revealed that the increase of inulin content in the formulations of burgers led to lower cooking yield, moisture retention and increased lightness, overall acceptability, mouldability and desired textural parameters. In contrast, incorporation of β-glucan increased the cooking yield, moisture retention and decreased lightness, overall acceptability, mouldability and desired textural parameters of burger patt ies. The interaction between inulin and β-glucan improved the cooking characteristics of the burgers without significantly negative effect on the colour or sensory properties. The results of the study clearly stated that the optimum mixture for the burger formulation consisted of (in g per 100 g): inulin 3.1, β-glucan 2.2 and breadcrumbs 2.7. The texture parameters and cooking characteristics were improved by using the mixture of inulin, β-glucan and breadcrumbs, without any negative effects on the sensory properties of the burgers.U ovom je radu pomoću D-optimalnog dizajna određen optimalan omjer inulina, β-glukana i krušnih mrvica u smjesi za pljeskavice kojoj je prethodno dodana mješavina repičinog i maslinovog ulja. Osim toga, ispitan je pojedinačan i zbirni učinak sastojaka na kalo kuhanja, teksturu, boju i senzorska svojstva pljeskavica sa smanjenim udjelom masnoća. Rezultati pokazuju da se povećanjem udjela inulina povećao kalo kuhanja, smanjilo zadržavanje vlage, a dobivene su pljeskavice dobre teksture, svjetlije boje, koje se lako oblikuju te nakon pečenja postižu bolje senzorske ocjene. Interakcijom inulina i β-glukana poboljšana su svojstva pljeskavica tijekom pečenja, bez negativnog učinka na boju i senzorske osobine. Optimalna smjesa za izradu pljeskavica dobivena je dodatkom 3,1 g inulina, 2,2 g β-glukana i 2,7 g krušnih mrvica. Tekstura pljeskavica te njihova svojstva tijekom pečenja bitno su poboljšana dodatkom inulina, β-glukana i krušnih mrvica, pri čemu se senzorske ocjene nisu smanjile

Effect of Resistant Starch and β-Glucan Combination on Oxidative Stability, Frying Performance, Microbial Count and Shelf Life of Prebiotic Sausage During Refrigerated Storage

Svrha je ovog istraživanja bila procijeniti svojstva dvaju tipova prebiotičkih kobasica, pripremljenih s rezistentnim škrobom i ekstraktom β-glukana (u omjerima 2,216:1,328 i 2,75:1,875), tijekom prženja i skladištenja pri niskim temperaturama. Određeni su indeksi oksidacijske stabilnosti i broj mikroorganizama. Dodatak dvaju prebiotičkih dijetalnih vlakana povećao je gubitke pri prženju i adsorpciju ulja. Međutim, količina vlage u prebiotičkim kobasicama nakon proizvodnje bila je veća u usporedbi sa standardnim (neprebiotičkim) kobasicama, te se postepeno smanjivala tijekom skladištenja. Rezultati pokazuju da dodatak preporučenog omjera rezistentnog škroba i β-glukana (2,216:1,328) može dovesti do smanjenja oksidacije masti u kobasicama tijekom skladištenja zbog antioksidacijskih svojstava ekstrakta β-glukana, no dodatak većih količina rezistentnog škroba i β-glukana nije moguć zbog daljnjeg porasta oksidacije masti. Konačan broj živih stanica rastao je do četrdeset i petog dana, nakon čega je došlo do njegovog postepenog pada. Dodatak ekstrakta β-glukana poboljšao je antioksidacijska svojstva proizvoda. Također, njegov antimikrobni učinak i smanjenje udjela vlage mogli bi inhibirati rast mikroorganizama. Nadalje, dodatak rezistentnog škroba doveo je do povećanja tiobarbiturnog i peroksidnog broja.This study aims to evaluate the performance of two types of prebiotic sausages formulated with resistant starch (RS) and β-glucan (BG) extract (in ratios of 2.22:1.33 and 2.75:1.88) during frying and chilled storage. The oxidative stability indices and microbial counts were determined. The incorporation of two types of prebiotic dietary fibre increased frying loss and oil absorption. However, the moisture content of prebiotic sausages after production was higher than of conventional sausages and it decreased significantly during storage. The use of sausage sample containing 2.22 % RS and 1.33 % BG as a recommended formulation can decrease fat oxidation of sausages during storage due to antioxidant properties of BG extract, but higher levels of RS and BG could not be used due to further increase in fat oxidation. Total viable count increased up to day 45 and decreased afterwards. The addition of BG extract improved the antioxidant properties of sausages. Additionally, the antimicrobial properties of BG and moisture reduction could inhibit microbial growth. Moreover, the addition of RS caused an increase in thiobarbituric acid and peroxide values

Pediatric Long-term follow up for renal disorders in ALL children by evaluating urine NGAL

Introduction: Recent Developments in cancer treatment could provide a better survival rate for Acute Lymphoblastic Leukemia (ALL) patients. Survivors faced different long term complication after treatment, for instance cardiac, neurologic and kidney complications. Assessment of the late complications could be useful in the optimization of treatment protocols. The objective of this study was to evaluate the late kidney complications, renal function in ALL patients after therapy.Material & Methods: In this study, we used 46 children. The treatment preformed based on ICBFM protocol. The mean age at the start of the treatment was 53±23 and the mean follow up time was 48±11 months. The tubular damage in these patients was evaluated by urinary NGAL level and the renal function was assessed by GFR.Results: in this study 56.7% of the patients were male. The NGAL level shows abnormally high in 8.9% of patients and the mean urine NGAL was 63±113ng/mL. Also, the mean GFR at the time of the diagnosis and at the time of the start of the follow up were 102.8 ±25.6 mL/min/1.73 m2 and 93.6 ±29.1 mL/min/1.73 m2, respectively. The study indicated GFR were less than 60 mL/min/1.73 m2 in 13.3% of patients. Conclusion: this study indicated the long term follow up of the ALL survivors for kidney disorders are an important manner. The urinary NGAL level shows that 8.9% of the patients are tubular damage by using this treatment protocol. The study concluded that ICBFM protocol is a safe protocol with little long term damage.

Improvement of product selectivity in bicarbonate reduction into formic acid on a tin-based catalyst by integrating nano-diamond particles

In this study, the efficiency of electrochemical reduction of bicarbonate into formic acid was improved by using a composite electrode made up of tin (Sn), nanodiamond (ND) and carbon nanotube (CNT). In the absence of ND, a compositional ratio of 10/90 (Sn/CNT) demonstrated the highest current density. However, by adding ND in a compositional ratio of 10/90/100 (Sn/CNT/ND) the highest efficiency towards formate/formic acid was achieved. It was observed that the presence of ND enhanced the selectivity of product for formic acid. The effects of bicarbonate concentration and scan rate have also been studied to understand the reduction mechanism. The peak potential shifted towards larger negative values of applied potential with an increase in the scan rate from 0.01 to 0.1 V/s, confirming the irreversible nature of the reduction process. The linear relationship between the current and the square root of the scan rate (with a slope value of 0.519) suggested that the reaction process is fully diffusion-controlled. Formic acid was produced using both electrodes; however, the electrode containing nano-diamond successfully improved the process yield for formic acid. Electrochemical impedance study revealed a significant difference between Warburg coefficient for oxidation and reduction processes with values of 29.63 × 1012 and 67.4 Ω. S−0.5 for the applied potentials of 0.5 V and −0.4 V, respectively. This difference confirmed a low resistance at the electrode/electrolyte interface for the reduction potentials

Standard Multiple and Single Daily Dosing of Amikacin in Premature Infants

Background: Bacterial sepsis is highly prevalent among premature infants. Amikacin is an antibiotic widely recommended for the treatment of neonatal sepsis, one of the consequences of which might be nephrotoxicity. The present study aimed to compare the efficacy and nephrotoxicity of multiple daily dosing (MDD) and once-daily dosing (ODD) of amikacin in preterm infants suspected of sepsis. Methods: This triple-blind, randomized, controlled clinical trial was conducted on 40 premature infants suspected of sepsis, who were randomly divided into two groups. In addition to ampicillin, one group was administered with the standard daily dose, and the other group received an ODD of intravenous amikacin. Maximum and minimum serum levels of amikacin and urine neutrophil gelatinase-associated lipocalin (NGAL) were measured in both groups. Data were extracted and analyzed based on the research hypothesis and literature review. Results: No significant differences were observed between the study groups in terms of gender, gestational age, mode of delivery, birth weight, and Apgar score. After the intervention, mean plasma creatinine reduced in both groups, while the mean reduction was significantly higher in the group administered with the ODD of amikacin (P=0.0001). However, mean changes in the urine NGAL had no significant difference between the groups (P=0.635). Minimum and maximum serum levels of amikacin in the study groups indicated a more significant reduction in mean level of the infants administered with the ODD of amikacin compared to the MDD group (P=0.0001). Conclusion: Considering the higher maximum and lower minimum levels of amikacin in the neonates receiving the daily dosage regimen, it seems that this regimen is more effective in the treatment of sepsis in preterm infants. Moreover, no significant difference was observed in the efficacy and nephrotoxicity of the daily amikacin dosing in the premature infants suspected of sepsis compared to those treated by multiple doses of amikacin