Urinary Proteomics in Nephrotic Syndrome

Nephrotic syndrome is the commonest glomerular disease. Typical symptoms could be proteinuria, low serum albumin and oedema. The mechanism of proteinuria in nephrotic syndrome is a defective glomerular filtration barrier. Renal biopsy is the gold standard for diagnosis of nephrotic syndrome currently which is invasive and based on histopathological features, therefore it seems to be necessary to search for noninvasive biomarkers to be used as the complementary tests in the diagnostics and prognostics of glomerular diseases, particularly when renal biopsy is limited or contraindicated. While a big proportion of urinary proteins originate from kidney tissue and these tissue specific proteins excrete more in kidney injury, therefore the identification of urinary proteins can further our understanding of renal dysfunction and renal disease including nephrotic syndrome. The interest of scientist to  urinary proteomics is also growing for biomarker discovery. This review focuses on some types of nephrotic syndrome and proteomic studies applying urine specimen which have been reported

Dietary habits and nutrient intake in adolescent girls living in Northern Iran

Rapid changes in lifestyle and industrialization of communities have an important effect on food intake pattern of society. Regarding the lack of enough data about dietary habits and nutrient intake of adolescents in our society, this study was performed in a group of adolescent girls in Lahijan, North of Iran. In this cross-sectional study, 400 high school girls aged 14-17 years selected by random stratified sampling. Nutritional data were collected by 24-hour dietary recall, food habits and food frequency questionnaires for all samples. The mean energy intake was 2338±611 kcal/d. The contributions of carbohydrate, protein and fat to the total energy intake were 59.3, 11.9 and 28.8%, respectively. The daily intake of energy obtained from breakfast, lunch, dinner and snacks were 16.3, 23.5, 25.9 and 34.3%, respectively. The mean intakes of vitamin A, vitamin D, calcium, phosphorous and zinc were below the Recommended Daily Allowances. The consumption of fresh vegetables and fruit was generally low. Twelve percent in total did not drink milk at all. Almost all the subjects had a prepared meal, most often in the evening, at least four times a week. Regarding the undesirable food pattern and proportions of nutrient intakes, it is necessary to development means of motivating adolescents to eat nutritionally rich foods, good for health and well-being

A study on the activity and thermal stability of adenosine deaminase in the presence of spermine

Adenosine Deaminase is an aminohydrolase (EC 3.5.4.4) which participates in the purine metabolism where it degrades either adenosine or 2'-deoxyadenosine producing inosine or 2'-deoxyinosine, respectively. The enzyme contains a parallel alpha/beta -barrel motif with eight central beta strands and eight peripheral alpha helices. ADA is located both in the cytosol and on the cell membrane. Since spermine, a natural metabolite, exists in all cells and tissues and its effect on the cell proliferation and enzyme regulation have been reported,  thermal inactivation of the ADA and spermine regulatory effect on the ADA activity have been investigated in this study. Percentage of ADA activity in the presence and absence of spermine (1000 µM) in Tris buffer 50 mM, pH 7.5 at physiologic and pathologic temperatures have been reported in the present study. Thermal inactivation curves for ADA in the absence and presence of spermine (1000 µM) in different temperatures ranging from 55 oC to 70 oC have been drawn. Our data showed that spermine activates the enzyme in the low concentrations of adenosine at 37 oC. However, it inhibits ADA activity at 42 oC in the same concentrations of substrate. It is concluded that spermine regulatory effect depends on combined influence of temperature and adenosine concentration. Furthermore, thermal stability of the enzyme also depends on temperature in presence of spermine. Binding site of spermine on the enzyme has been identified by docking analysis

A study on the activity and thermal stability of adenosine deaminase in the presence of spermine

ABSTRACT Adenosine Deaminase is an aminohydrolase (EC 3.5.4.4) which participates in the purine metabolism where it degrades either adenosine or 2'-deoxyadenosine producing inosine or 2'-deoxyinosine, respectively. The enzyme contains a parallel alpha/beta -barrel motif with eight central beta strands and eight peripheral alpha helices. ADA is located both in the cytosol and on the cell membrane. Since spermine, a natural metabolite, exists in all cells and tissues and its effect on the cell proliferation and enzyme regulation have been reported, thermal inactivation of the ADA and spermine regulatory effect on the ADA activity have been investigated in this study. Percentage of ADA activity in the presence and absence of spermine (1000 µM) in Tris buffer 50 mM, pH 7.5 at physiologic and pathologic temperatures have been reported in the present study. Thermal inactivation curves for ADA in the absence and presence of spermin

Effects of different therapeutical doses of ibuprofen on the adenosine deaminase activity at physiologic and pathologic temperatures

Introduction: Adenosine deaminase (ADA) is a purine catabolic enzyme that removes amino group of adenosine or 2' deoxyadenosine irreversibly. ADA enhances immune system and also intervenes the inflammation process. In this study, the effect of ibuprofen as an anti- inflammatory drug has been studied on the ADA activity in the physiologic and pathologic temperatures. Materials and Methods: ADA was assessed in the presence of 3 different doses of ibuprofen at 37oC and 42oC via spectrometry in 265 nm. Results: Ibuprofen at high and low doses had an activation effect on the ADA activity at 37oC and moderated the sensitivity of enzyme activity to its substrate. It also decreased the anti-inflammatory effect of adenosine via decrease of its concentration and had a positive effect on immune system as well. The activation of the enzyme by Ibuprofen was decreased at 42oC and also Ibuprofen moderated the effect of temperature on dependency of enzyme activity to its substrate. Ibuprofen effects on immune system and anti-inflammatory effects of adenosine decreased at 42oC. Conclusion: Ibuprofen is a putative activator for adenosine deaminase and administration of this drug could be useful for immune deficiency. Since there is no activator for ADA so far, this drug is important. Ibuprofen decreases anti-inflammatory effect of adenosine. In-vivo studies would be needed

Classification of Chronic Kidney Disease Patients via k-important Neighbors in High Dimensional Metabolomics Dataset

Background: Chronic kidney disease (CKD), characterized by progressive loss of renal function, is becoming a growing problem in the general population. New analytical technologies such as “omics”-based approaches, including metabolomics, provide a useful platform for biomarker discovery and improvement of CKD management. In metabolomics studies, not only prediction accuracy is attractive, but also variable importance is critical because the identified biomarkers reveal pathogenic metabolic processes underlying the progression of chronic kidney disease. We aimed to use k-important neighbors (KIN), for the analysis of a high dimensional metabolomics dataset to classify patients into mild or advanced progression of CKD. Methods: Urine samples were collected from CKD patients (n=73). The patients were classified based on metabolite biomarkers into the two groups: mild CKD (glomerular filtration rate (GFR)> 60 mL/min per 1·73 m2) and advanced CKD (GFR<60 mL/min per 1·73 m2). Accordingly, 48 and 25 patients were in mild (class 1) and advanced (class 2) groups respectively. Recently, KIN was proposed as a novel approach to high dimensional binary classification settings. Through employing a hybrid dissimilarity measure in KIN, it is possible to incorporate information of variables and distances simultaneously. Results: The proposed KIN not only selected a few number of biomarkers, it also reached a higher accuracy compared to traditional k-nearest neighbors (61.2% versus 60.4%) and random forest (61.2% versus 58.5%) which are currently known as the best classifieres. Conclusion: Real metabolomics dataset demonstrate the superiority of proposed KIN versus KNN in terms of both classification accuracy and variable importance. Keywords Chronic kidney disease Classification High dimensional data KNN SCA

A Rare Case Report of Adenoid Cystic Carcinoma of the Anterior Maxilla in a Young Patient

Background and Objective: Adenoid cystic carcinoma (ACC) of the maxilla is a rare malignancy arising from minor salivary glands. The clinical and radiological appearance may be similar to any odontogenic/nonodontogenic pathology. This study aims to report a rare case of primary central ACC of the anterior maxilla. Case Report: A 31-year-old man was referred to the Department of Oral and Maxillofacial Surgery complaining of swelling and pain in the right anterior maxilla for 3 months. The patient has noticed swelling and pain in this side since about five months before and instead of diagnosing this tumoral lesion, false diagnosis and unsuccessful root canal therapy were considered. A biopsy was performed in the central region and microscopically, the lesion showed tumor cells arranged in sheets in fibrous stroma islands of epithelial cells showing a classical “Swiss cheese” pattern. Based on clinical, radiographic, and CBCT evaluation and positive immunohistochemistry of CD63, and C-Kit confirmed ACC diagnosis. After the diagnosis, the lesion was completely removed by enucleation and curettage performed by the surgeon. Postoperative radiotherapy was performed. Follow-up within 3 years since the initial diagnosis showed no sign of recurrence. Conclusion: Based on the results of this study, early diagnosis and treatment of ACC can lead to successful treatment and patient survival

Urinary Prognostic Biomarkers and Classification of IgA Nephropathy by High Resolution Mass Spectrometry Coupled with Liquid Chromatography

<div><p>IgA nephropathy is the most common cause of primary glomerulonephritis. There are different pathologic biopsy-based scoring systems in use, but there is no consensus among nephrologists yet regarding the best classification method. Our aim was to test urine proteomics as a non-invasive method for classification of IgA nephropathy. This aim was pursued by discovering novel prognostic protein biomarkers in urine, and linking them to pathogenesis of the disease through known signaling and metabolic pathways. 13 urine samples of the patients with biopsy-proven IgA nephropathy were analyzed via two proteomics approaches: nanoflow LC-MS/MS and GeLC-MS/MS. The results of label-free quantification were subjected to multivariate statistical analysis, which could classify patients into two groups, broadly corresponding to the primary and advance stages. The proteome classification correlated well with biopsy-based scoring systems, especially endocapillary hypercellularity score of the Oxford’s classification. Differentially excreted candidate proteins were found as potential prognostic biomarkers: afamin, leucine-rich alpha-2-glycoprotein, ceruloplasmin, alpha-1-microgolbulin, hemopexin, apolipoprotein A-I, complement C3, vitamin D-binding protein, beta-2-microglobulin, and retinol-binding protein 4. Pathway analysis suggested impairment of Extra Cellular Matrix (ECM)-Receptor Interaction pathways as well as activation of complement and coagulation pathway in progression of IgA nephropathy.</p> </div

A Novel Homozygous MYO7A Mutation: Case Report

MYO7A is an unconventional myosin that is essential for ordinary hearing and vision; mutations in the MYO7A gene result in Usher syndrome type 1B and other disorders. In this manuscript, we reported a mutation (c.4705delA) in exon 35, causing the alteration of a Ser amino acid to Ala at codon 1569 (p.H2027del) located within the first FERMdomain of the human protein myosin VIIA. This mutation involved in the pathogenesis of hearing loss, congenital night blindness, muscular weakness, skin problem, and difficulty in keeping balance in the 13-year-old female. After checkup the patient’s DNA was extracted from peripheral blood and amplification was performed by PCR. Sequencing method was performed for identification of the mutation. The c.4705delA mutation in exon 35 was found in the patient in heterozygosis form; this means that her mother and father were carriers. This mutation is located on the tail of the myosinVIIA protein and is associated with several disorders