The Relationship between Osteogenesis Imperfecta and Spinal Muscular Atrophy

ObjectiveA 4-month-old female with osteogenesis imperfecta (OI) type II was admitted in PICU of our center due to severe respiratory distress and fever with a diagnosis of severe pneumonia, and mechanical ventilation was initiated. Due to severe hypotonia, NCV and EMG were performed, and spinal muscular atrophy (SMA) type I was diagnosed.Keywords: Osteogenesis imperfecta; spinal muscular atrophy; hypotoni

Neural Differentiation of Human Umbilical Cord Mesenchymal Stem Cells by Cerebrospinal Fluid

How to Cite This Article: : Farivar S, Mohamadzade Z, Shiari R, Fahimzad AR. Neural Differentiation of Human Umbilical CordMesenchymal Stem Cells by Cerebrospinal Fluid. . Iran J Child Neurol. 2015 Winter; 9(1):87-93.  Abstract Objective Wharton’s jelly (WJ) is the gelatinous connective tissue from the umbilical cord. It is composed of mesenchymal stem cells, collagen fibers, and proteoglycans. The stem cells in WJ have properties that are interesting for research. For example, they are simple to harvest by noninvasive methods, provide large numbers of cells without risk to the donor, the stem cell population may be expanded in vitro, cryogenically stored, thawed, genetically manipulated, and differentiated in vitro. In our study, we investigated the effect of human cerebrospinal fluid (CSF) on neural differentiation of human WJ stem cells.Material & Methods The cells in passage 2 were induced into neural differentiation with different concentrations of human cerebrospinal fluid. Differentiation along with neural lineage was documented by expression of three neural markers: Nestin, Microtubule-Associated Protein 2 (MAP2), and Glial Fibrillary Astrocytic Protein (GFAP) for 21 days. The expression of the identified genes was confirmed by Reverse Transcriptase PCR (RT-PCR).Results Treatment with 100 and 200μg/ml CSF resulted in the expression of GFAP and glial cells marker on days 14 and 21. The expression of neural-specific genes following CSF treatment was dose-dependent and time-dependent. Treatment of the cells with a twofold concentration of CSF, led to the expression of MAP2 on day 14 of induction. No expression of GFAP was detected before day 14 or MAP2 before day 21, which shows the importance of the treatment period. In the present study, expression analysis for the known neural markers: Nestin, GFAP, and MAP2 using RT-PCR were performed. The data demonstrated that CSF could play a role as a strong inducer.Conclusion RT-PCR showed that cerebrospinal fluid promotes the expression of Nestin, MAP2, and GFAP mRNA in a dose-dependent manner, especially at a concentration of 200 μl/ml. In summary, CSF induces neurogenesis of WJ stem cells that encourages tissue engineering applications with these cells for treatments of neurodegenerative defects and traumatic brain injury.References Gage, F. H. Mammalian neural stem cells. Science 2000 Feb 25;287(5457):1433-8.Da Silva Meirelles L, Chagastelles PC, Nardi NB. Mesenchymal stem cells reside in virtually all postnatal organs and tissues. J Cell Sci 2006 Jun 1;119(Pt 11):2204- 13. Epub 2006 May 9.Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, Moorman MA, Simonetti DW, Craig S, Marshak DR. Multilineage potential of adult human mesenchymal stem cells Science 1999 Apr 2;284(5411):143-7.Tse WT, Pendleton JD, Beyer WM, Egalka MC, Guinan EC. Suppression of allogeneic T-cell proliferation by human marrow stromal cells: implications in transplantation. Transplantation 2003 Feb 15;75(3):389- 97.Le Blanc K. Immuno-modulatory effects of fetal and adult mesenchymal stem cells. Cytotherapy 2003;5(6):485-9.Stenderup K, Justesen J, Clausen C, Kassem M. Aging is associated with decreased maximal life span and accelerated senescence of bone marrow stromal cells. Bone 2003 Dec;33(6):919-26.Bongso A, Fong CY, Gauthaman K. Taking stem cells to the clinic: major challenges. J Cell Biochem 2008 Dec 15;105(6):1352-60. doi: 10.1002/jcb.21957.Fong CY, Chak LL, Biswas A. Human Wharton’s jelly stem cells have unique transcriptome profiles compared to human embryonic stem cells and other mesenchymal stem cells. Stem Cell Rev 2011 Mar;7(1):1-16. doi: 10.1007/s12015-010-9166-x.Troyer DL, Weiss ML. Wharton’s jelly-derived cells are a primitive stromal cell population. Stem Cells 2008 Mar; 26(3):591-9. Epub 2007 Dec 6.Yuan X, Desiderio DM. Proteomics analysis of human cerebrospinal fluid. J Chromatogr B Analyt Technol Biomed Life Sci 2005 Feb 5;815(1-2):179-89.Thompson, EJ. Cerebrospinal fluid. J Neurol Neurosurg Psychiatry 1995 Oct;59(4):349-57.Alcazar A, Regidor I, Masjuan J, Salinas M, Alvarez- Cermeno JC. Induction of apoptosis by cerebrospinal fluid from patients with primary-progressive multiple sclerosis in cultured neurons. Neurosci Lett 1998 Oct 16;255(2):75-8.Colombo JA, Napp MI. Cerebrospinal fluid from L-dopa-treated Parkinson’s disease patients is dystrophic for various neural cell types exvivo: effects of astroglia. Exp Neurol 1998 Dec;154(2):452-63.Redzic ZB, Preston JE, Duncan JA, Chodobski A, Szmydynger-Chodobska J. The choroid plexus-cerebrospinal fluid system: from development to aging. Current topics in developmental biology 2005; (71): 1-52.Bachy I, Kozyraki R, Wassef M. The particles of the embryonic cerebrospinal fluid: how could they influence brain development? Brain Res Bull 2008 Mar 18;75(2- 4):289-94. doi: 10.1016/j.brainresbull.2007.10.010.Parada C, Gato A, Bueno D. Mammalian embryonic cerebrospinal fluid proteome has greater apo-lipoprotein and enzyme pattern complexity than the avian proteome. Journal of proteome research 2005; 4(6): 2420- 2428.Martin C, Bueno D, Alonso MI, Moro JA, Callejo S, Parada C, Martin P, Carnicero E, Gato A. FGF2 plays a key role in embryonic cerebrospinal fluid trophic properties over chick embryo neuro epithelial stem cells. Dev Biol 2006 Sep 15;297(2):402-16. Epub 2006 May 19.Huttner HB, Janich P, Kohrmann M, Jaszai J, Siebzehnrubl F, Blumcke I, Suttorp M, Gahr M, Kuhnt D, Nimsky C. The stem cell markerprominin-1/CD133 on membrane particles in human cerebrospinal fluid offers novel approaches for studying central nervous system disease. Stem Cells 2008 Mar;26(3):698-705.Nordin C, Gupta RC, Sjodin I. Cerebrospinal fluid amino acids in pathological gamblers and healthy controls. Neuropsychobiology 2007;56(2-3):152-8. doi: 10.1159/000115782. Epub 2008 Feb 7.Gato A, Martin P, Alonso MI, Martin C, Pulgar MA, Moro JA. Analysis of cerebro-spinal fluid protein composition in early developmental stages in chick embryos. J Exp Zool A Comp Exp Biol 2004 Apr 1;301(4):280-9.Mitchell KE, Weiss ML. Matrix cells from Wharton’s jelly form neurons and glia. Stem Cells 2003;21(1):50-60.Marcus AJ, Woodbury D. Fetal stem cells from extra-embryonic tissues: do not discard. J Cell Mol Med 2008 Jun;12(3):730-42. doi: 10.1111/j.1582- 4934.2008.00221.x. Epub 2008 Jan 11.Miao Z, Jin J, Chen L, Zhu J, Huang W, Zhao J, Quian H, Zhang X. Isolation of mesenchymal stem cells from human placenta: comparison with human bone marrow mesenchymal stem cells. Cell Biol Int 2006 Sep;30(9):681-7. Epub 2006 Apr 22.In ‘tAnker PS, Scherjon SA, Kleijburg-van der Keur C, Noort WA, Claas FHJ, Willemze R, Fibbe WE, Kanhai HHH. Amniotic fluid as a novel source of mesenchymal stem cells for therapeutic transplantation. Blood 2003;102(4):1548-49.Magatti M, De Munari S, Vertua E, Gibelli L, Wengler GS, Parolini O. Human amnion mesenchyme harbors cells with allogeneic T-cell suppression and stimulation capabilities. Stem Cells 2008 Jan;26(1):182-92. Epub 2007 Sep 27.Kang XQ, Zang WJ, Bao LJ, Li DL, Xu XL, Yu XJ. Differentiating characterization of human umbilical cord blood-derived mesenchymal stem cells in vitro. Cell Biol Int 2006 Jul;30(7):569-75. Epub 2006 Mar 6.Kern S, Eichler H, Stoeve J, Kluter H, Bieback K. Comparative analysis of mesenchymal stem cells from bone marrow, umbilical cord blood, or adipose tissue. Stem Cells 2006 May;24(5):1294-301. Epub 2006 Jan 12.Wagner W, Wein F, Seckinger A, Frankhauser M, Wirkner U, Krause U, et al. Comparative characteristics of mesenchymal stem cells from human bone marrow, adipose tissue, and umbilical cord blood. Exp Hematol 2005 Nov;33(11):1402-16.Jackson JS, Golding JP, Chapon C, Jones WA, Bhakoo KK: Homing of stem cells to sites of inflammatory brain injury after intracerebral and intravenous administration: a longitudinal imaging study. Stem Cell Res Ther 2010 Jun 15;1(2):17. doi: 10.1186/scrt17.Romanov YA, Svintsitskaya VA, Smirnov VN. Searching for alternative sources of postnatal human mesenchymal stem cells: candidate MSC-like cells from umbilical cord. Stem Cells 2003;21(1):105-10.Weiss ML, Medicetty S, Bledsoe AR. Human umbilical cord matrix stem cells: Preliminary characterization and effect of transplantation in a rodent model of Parkinson’s disease. Stem Cells 2006 Mar;24(3):781-92.Carlin R, Davis D, Weiss M. Expression of early transcription factors Oct4, Sox2 and Nanog by porcine umbilical cord (PUC) matrix cells. Reprod Biol Endocrinol. 2006 Feb;6(4):8.Usha Nekanti, Sumitava Dastidar, Parvathy Venugopal, Satish Totey and Malancha Ta. Increased Proliferation and Analysis of Differential Gene Expression in Human Wharton’s Jelly-derived Mesenchymal Stromal Cells under Hypoxia. Int J Biol Sci. 2010; 6(5): 499–512

Clinical Characteristics and Mortality of a Hospitalized 13 Years Old Patient with Covid-19: A Case Report

The corona virus is a global problem that threatens human life. According to the latest data from different countries the mortality of this virus in children is less than adult. A 13-year-old girl was hospitalized for 6 months following a gunshot trauma and its complications. When her general condition was finally improving, she was diagnosed with the corona virus and passed away. Children who are suffering from underlying diseases and need medical care are at a higher risk of death from the corona virus

Prevalence of resistance to colistin, tigecycline and minocycline in Acinetobacter baumannii isolated from clinical samples in 2014

Background: Colonization rate of Acinetobacter baumannii is increasing in hospitalized patients especially in long term hospitalized one and / or who were treat with extended spectrum antibiotics or anticancer. Antibiotic resistance in A. baumannii is considerable because more prevalence of them cause nosocomial infections and can impose high cost to health systems and patients. The aim of this study was determination of tigecycline, minocycline and colistin resistance A. baumannii in selected center in Tehran, Iran. Materials and Methods: This study was descriptive and functional foundation. In this study A. baumannii were collected from Milad, Mofid, Taleghani, Motahari and Loghman hospital, Tehran and transferred to laboratory of pediatric infections research center. Collected bacteria were identified by conventional microbiology tests. Antibiotic susceptibility testing was determined according to CLSI guide line. Tigecycline, minocycline and colistin resistance strains were isolated.  Results: In this study, 105 A. baumannii were collected from five selected hospitals: 48 (46%) from Milad, 33 (31%) from Motahari, 17 (16%) from Loghman, 4 (4%) from Mofid and 3 (3%) from Taleghani hospital. The highest resistance was observed against cefepime and high frequency of carbapenem and minocycline was observed. On the other hand, observed resistance to aminoglycosides was 93% at least. Tigecycline is the most effective antibiotic after colistin. Colistin resistant confirmed just in one isolate by E. test. Conclusion: The results of this study indicated that high rate of antibiotic resistance in A. baumannii even resistant to third and fourth generation of cephalosporin and carbapenem antibiotics. The treatment of MDR strains of A. baumannii become more complicated if the spread of them were not been controlled

A Comparative Analysis of Clinical Characteristics and Laboratory Findings of COVID-19 between Intensive Care Unit and Non-Intensive Care Unit Pediatric Patients: A Multicenter, Retrospective, Observational Study from Iranian Network for Research in Viral

Introduction: To date, little is known about the clinical features of pediatric COVID-19 patients admitted to intensive care units (ICUs). Objective: Herein, we aimed to describe the differences in demographic characteristics, laboratory findings, clinical presentations, and outcomes of Iranian pediatric COVID-19 patients admitted to ICU versus those in non-ICU settings. Methods: This multicenter investigation involved 15 general and pediatrics hospitals and included cases with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection based on positive real-time reverse transcription polymerase chain reaction (RT-PCR) admitted to these centers between March and May 2020, during the initial peak of the COVID-19 pandemic in Iran. Results: Overall, 166 patients were included, 61 (36.7%) of whom required ICU admission. The highest number of admitted cases to ICU were in the age group of 1–5 years old. Malignancy and heart diseases were the most frequent underlying conditions. Dyspnea was the major symptom for ICU-admitted patients. There were significant decreases in PH, HCO3 and base excess, as well as increases in creatinine, creatine phosphokinase (CPK), lactate dehydrogenase (LDH), and potassium levels between ICU-admitted and non-ICU patients. Acute respiratory distress syndrome (ARDS), shock, and acute cardiac injury were the most common features among ICU-admitted patients. The mortality rate in the ICU-admitted patients was substantially higher than non-ICU cases (45.9% vs. 1.9%, respectively; p<0.001). Conclusions: Underlying diseases were the major risk factors for the increased ICU admissions and mortality rates in pediatric COVID-19 patients. There were few paraclinical parameters that could differentiate between pediatrics in terms of prognosis and serious outcomes of COVID-19. Healthcare providers should consider children as a high-risk group, especially those with underlying medical conditions

Evaluation of Antibiotic Resistance in Pediatric Urinary Tract Infection in Shahid Beheshti University Hospitals During 2016-2017

Background and Aim: Urinary tract infection (UTI) is one of the most common and important childhood diseases that may lead to complications such as acute pyelonephritis, renal scaring, and renal failure if not diagnosed and treated properly. The antibiotic resistance rate has increased recently because of unnecessary antibiotic consumption. In order to prescribe an appropriate drug as empirical therapy, it is necessary to know the prevalence of pathogens causing UTI and their antibiotic resistance rate in the community. Therefore, this study was conducted to present an appropriate guideline for UTI empirical therapy through evaluating the rate of antibiotic resistance in a sample of hospitalized patients suffering from UTI.Methods: This retrospective descriptive analytical study was conducted in 130 children with UTI whose medical records included antibiogram results in hospitals affiliated with Shahid Beheshti University during 2016-2017.Results: Of 130 patients, 73.07% were girls and 26.92% were boys. About 50% of the patients were under one-year-old, 33.07% were 1-3 years old, and 16.15% were over 3 years old. The detected pathogens were E. coli in 63.07%, Enterococcus in 14.61%, Klebsiella in 13.07%, Pseudomonas aeruginosa in 5.38%, and Enterobacter in 3.84%.Conclusion: Based on the data of the present study, ampicillin, co-trimoxazole and first-generation cephalosporins are not appropriate for UTI empirical therapy. Keywords: Antibiogram; Antibiotic resistance; Urinary tract infection

Comparison of Tuberculin Skin Test result and interferon gamma response to human PPD in BCG scar positive and negative children

Background: The aim of this study is to compare Tuberculin Skin Test (TST) result and interferon gamma response to human PPD (purified protein derivative), in scar positive and scar negative BCG-vaccinated children. Methods: Between August 2007 and May 2008 a total of 236 children aged 1–168 months (mean 21 months) admitted to Mofid Children’s Hospital, Tehran, Iran, were enrolled in a cross-sectional study. Each patient was examined for BCG vaccine scar and tested with TST and human PPD-based Interferon Gamma Release Assay (IGRA). Results: Two hundred and twenty one cases out of 236 (44% female, 1–168 months, mean age 21 months) were scar positive of whom 95% TST result was negative. Human PPD-based IGRA was positive in 110 (49.8%), negative in 85 (38.4 %) and indeterminate in 26 (11.8%) of scar positive patients. Fifteen children (40% female, 1–156 months; mean age 42 months) were scar negative. All the scar negative cases were TST negative. Human PPD-based IGRA was positive in 10 (66.7%), negative in 4 (26.7%) and indeterminate in 1 (6.7%) of scar negative patients. Conclusions: Immune responsiveness to human PPD antigens in scar positive and negative children may not correspond with results of the Tuberculin Skin Test

Diaper Type as a Risk Factor in Urinary Tract Infection of Children

Objective: Urinary tract is one of the most common sources of infection in children under the age of two years. Many known and unknown risk factors predispose to this important disease in children. This study was conducted to determine whether using a specific type of diaper plays a role in urinary tract infection (UTI) in girls under the age of 2 years. Methods: This case control study was performed in hospitalized children; girls with their first urinary tract infection were selected as cases, and those admitted for other reasons comprised the control group. Two groups were matched for age (±1 month), and other known risk factors for UTI. Type of diapers (superabsorbent, standard disposable and washable cotton), used for these children during six months, from October 2007 to March 2008, were compared in both groups. Findings: Fifty-nine matched pair infant girls less than 2 years were selected. It was revealed that in cases with UTI superabsorbent diapers were used more frequently than in controls (Odds ratio =3.29, P-value=0.005) There were no significant differences in other factors like number of diapers used per day, the time between defecation and diaper change, mothers’ educational level, level of family income and mother’s occupation. Conclusion: The use of superabsorbent diapers could be a risk factor for urinary tract infection in infant girls

Concurrent Adrenal Neuroblastoma and Kawasaki Disease: A Report of a Rare Case

Kawasaki disease (KD) is a systemic vasculitis of unknown etiology and a leading cause of acquired heart disease. It is assumed that there is an activation of the immune system by an infectious trigger in a genetically susceptible host. Neuroblastoma is the most common extracranial solid tumor in young children. It mainly originates from primordial neural crest cells that generate the adrenal medulla and sympathetic ganglia. A diagnosis of concurrent KD and neuroblastoma in a living child has been made in only one previous report. We report the second case and review the literature

Frequency of MDR Acinetobacter baumannii and the Most Common OXA- type Genes in Multiple Drug-Resistant Strains Isolated from Patients in Tabriz Imam Reza Hospital

Background and purpose: Acinetobacter is a pathogen that could cause nosocomial infections. The present study aimed at determining Acinetobacter cases in clinical cultures of patients hospitalized in Tabriz Imam Reza Hospital to determine the frequency of the most common oxa genes causing drug resistance in these specimens. Materials and methods: In this descriptive cross-sectional study, clinical specimens including the blood, urine, tracheal secretions, ulcers, and throat specimens were collected from July to October 2017. The bacteria were isolated and identified using standard bacteriological methods. The Clinical and Laboratory Standards Institute (CLSI, 2016) guideline was used to determine bacterial susceptibility and resistance. Bacterial DNA extraction was done and the OXA genes (23, 24, 48, 58) were identified using specific primers and PCR method. Results: We identified 66 (72.52) multiple drug-resistant (MDR) Acinetobacter strains. These isolates showed 100% resistance to cefepime, cefotaxime, piperacillin-tazobactam, and meropenem. In 100% of the samples, sensitivity to colistin was observed. According to findings, there was a significant relationship between the presence of oxa24 gene and resistance to tobramycin and amikacin (P= 0.005). Conclusion: This study showed high rate of MDR Acinetobacter strains, so, nosocomial infection control is highly necessary. Strategies such as identifying infected patients, detecting bacterial colonization, sterilizing equipment and units, and controlling antibiotic use in the hospital are recommended to prevent the development of multidrug-resistant bacteria and to control nosocomial infections