DSpace Collection: 63 - 136

Irreversible neurological effects of late diagnosis phenylketonuria: A case presentation

2024-11-20T02:47:24Z

Title: Irreversible neurological effects of late diagnosis phenylketonuria: A case presentation Authors: Gupta, Khyati; Jain, Aviral; Sawant, Vishal Dnyaneshwar; Save, Sushma Abstract: Phenylketonuria (PKU) is an autosomal recessive hereditary disorder due to deficiency of enzyme phenylalanine hydroxylase or the cofactor tetrahydrobiopterin. Its late manifestation leads to irreversible neurological changes. The aim of our work is to emphasize the difference in presentation in late diagnosis of the disease verses classical presentation making it difficult to correctly diagnose and also point out the reasons for late diagnosis and missed cases in India. A 9-year-old patient presented with global developmental delay and severe behavioral problems. Hypertonia and spasticity with low intelligence quotient (IQ) were seen. Baseline investigations such as renal function, thyroid function, electrolytes, uric acid, folate, and blood adrenocorticotropic hormone level were within range; hence, magnetic resonance imaging (MRI) was advised which revealed areas of bilateral demyelination suggesting metabolic leukodystrophy. PKU was thereafter confirmed with metabolic profile and clinical exome study. Early routine screening of all newborns for common inherited and metabolic disorders should be mandatory to later prevent irreversible damage. Cases of delayed diagnosis deviate considerably from classical clinical and radiological findings of the disease making correct and prompt diagnosis difficult. Education of parents and prenatal counseling should be encouraged.

Adapter protein – FADD bridges the apoptosis

2024-11-20T02:44:57Z

Title: Adapter protein – FADD bridges the apoptosis Authors: Marikar, Faiz; Zi-Chun, Hua Abstract: More than a century ago, the very first adverse human health effects of Fas-associated death domain (FADD) were reported with cell death. It is most well-known role in apoptosis, FADD has also been seen to play a role in other processes including proliferation, cell cycle regulation, and development. It contains two main domains: A C terminal death domain (DD) and an N terminal death effector domain. On stimulation by the Fas ligand, the Fas receptor trimerises. Many receptors, including Fas, contain a cytoplasmic DD and are therefore named death receptors. FADD binds to the DD of this trimeric structure through its DD leads to apoptosis. FADD also plays a role in regulating necroptosis, a process requiring the serine/threonine kinases. Activated caspase 8 cleaves these kinases, inhibiting necroptosis. Application of Taxol is a drug used in anticancer therapies due to its ability to interfere with microtubule assembly, which leads to cell cycle arrest. It has been suggested that inhibition of FADD might work as a potential targeted therapy for drug-resistant ovarian cancer.

Soluble FMS-like tyrosine kinase-1: An overview

2024-11-20T02:42:52Z

Title: Soluble FMS-like tyrosine kinase-1: An overview Authors: Selvarajan, Sathya; Ramalingam, Jothimalar; Venugopal, Veena Abstract: The soluble FMS-like tyrosine kinase-1 (sFLT-1) or soluble vascular endothelial growth factor receptor 1 (VEGF-R1) is a receptor tyrosine kinase which inhibits the mitogenic activity of VEGF by decreasing its availability for binding with transmembrane receptors. VEGFRs exist in various isoforms due to alternative splicing from the same gene. sFLT-1 along with another of its isoform sFLT1-14 is found in abundance in the cytotrophoblast of placenta, and also in the cornea, liver, brain, and kidney. Hypoxia is the key trigger in inducing production of sFLT-1. In normal pregnancy, the soluble receptor regulates the process of vascular transformation by modulating the balance between VEGF-R1 and sFLT-1 activity. Proteinuria and hypertension in pre-eclamptic women have been found to be associated with an elevated level of sFLT-1. sFLT-1 blocks the podocyte-derived VEGF and induces damage of the glomerular endothelium leading to proteinuria and blockage of endothelial nitric oxide signaling pathways resulting in hypertension. In ectopic pregnancy, the abnormal implantation of the embryo simulates a hypoxic environment inducing excess production of VEGF and its consequent binding to sFLT-1. The usage of sFLT-1 as an early biomarker of preeclampsia, ectopic pregnancy, and other failing pregnancies is being studied. Variation in sFLT-1 levels has also been identified in cardiovascular diseases, chronic kidney disease, non-healing ulcers, and liver cirrhosis to name a few. Therapeutic use of sFLT-1 to reduce angiogenesis in various conditions like cancer is currently being pursued.

Effect of underfilling of tubes with EDTA on PTH assay measured by cobas analyzer

2024-11-20T02:39:31Z

Title: Effect of underfilling of tubes with EDTA on PTH assay measured by cobas analyzer Authors: Guven, Berrak; Benice, Ismail Abstract: Objectives: The purpose of this study is to evaluate cobas parathyroid hormone (PTH) measurement effect of plasma samples obtained from underfilled tubes with ethylenediaminotetraacetic acid (EDTA). Methods: Two blood collection tubes with K3-EDTA from 67 patients at the same time were taken. One of them was for routine PTH measurement, which was filled to its capacity, while another tube was underfilled. All EDTA tubes were immediately centrifuged at 4°C. Plasma PTH concentrations were measured by electrochemiluminescence immunoassay method on the cobas e 601 (Roche Diagnostics GmbH, Mannheim, Germany) analyzer. Results: The underfilled sample tubes were grouped according to their being up to 25% (n=9), 25–50% (n=35), and 50–100% (n=23) of the appropriate amount. In all groups of underfilled tubes, the PTH values were found to decrease concerning those fulfilled (p<0.001). The agreement among underfilled and fulfilled for measuring PTH demonstrated a bias of −3.2 pg/mL (−5.9%) for the underfilled tubes. Conclusion: Insufficiently filled blood in tubes with EDTA has a significant effect on PTH levels. However, further studies are needed to show whether this effect is clinically significant.