scholarly journals Non-suicidal intentional ingestion of iron tablets and severe intoxication: the result of adolescent boy’s impulsive risky behaviour in the school

2021 ◽  
Vol 8 (12) ◽  
pp. 1987
Author(s):  
Krutika Rahul Tandon ◽  
Rahul Tandon ◽  
Amola Khandwala ◽  
Tanvi Mehta
Keyword(s):  
Therapeutic Drug ◽  
Iron Level ◽  
Risky Behaviour ◽  
Elemental Iron ◽  
Cellular Processes ◽  
Intentional Ingestion ◽  
Lactating Mothers ◽  
Severe Intoxication ◽  
Iron Poisoning ◽  
Supportive Management

Acute iron poisoning is a potentially fatal intoxication in children. As the Iron preparations are commonly administered to pregnant women, lactating mothers, toddlers, it is easily available at home. So younger children are prone to consume it accidently. Although iron is a therapeutic drug in recommended dosages, excessive iron in the free state can produce toxicity by affecting multiple cellular processes by catalysing redox reactions with lipid peroxidation and free radical formation. The severity of intoxication depends on the amount of elemental iron ingested. Serious toxicity is usually associated with a dose of >40 mg/kg of elemental iron. Levels more than 100 mg/kg are almost always fatal. We report a case where a 12-year male child intentionally taken 60 tablets of iron (ferrous fumarate) at his school as a part of competition or bet to other schoolmate and presented with acute iron poisoning with hepatic encephalopathy to us. Important initial laboratory parameters were AST-4,879 U/L, Prothrombin time-60 sec and Iron level-213 microgram/dl. With timely specific management i.e., deferoxamine infusion along with all required intensive care supportive management in PICU the patient was discharged successfully. We chose to report this case to highlight the risky behaviour of adolescence who usually grows physically and emotionally earlier but their prefrontal lobes are yet immature to take proper and correct decision. Thus, impulse activity may prove fatal for them.

scholarly journals The syndrome of hepatic veno-occlusive disease after marrow transplantation

Blood ◽  
1995 ◽  
Vol 85 (11) ◽  
pp. 3005-3020 ◽  
Author(s):  
SI Bearman
Keyword(s):  
Serum Bilirubin ◽  
Recombinant Tissue Plasminogen Activator ◽  
Clinical Syndrome ◽  
Therapeutic Drug ◽  
High Dose ◽  
Cellular Mechanisms ◽  
Tissue Plasminogen ◽  
Pharmacologic Prophylaxis ◽  
Supportive Management ◽  
To Receive

The clinical syndrome of VOD is a frequent cause of nonrelapse mortality among patients receiving high-dose cytoreductive regimens. Patients likely to develop VOD have existing liver dysfunction, evidence of infection before conditioning, tend to receive more intensive preparative regimens, and often receive marrow from alternative donors. Therapeutic drug monitoring of busulfan and pharmacokinetic dose adjustments appear to be useful in reducing the incidence of VOD in patients receiving this agent. Data are contradictory as regards whether pharmacologic prophylaxis is effective. Patients who will develop severe VOD are characterized by a rapid increase in serum bilirubin as well as weight. Supportive management of these patients should attempt to preserve respiratory as well as renal function, sometimes a very difficult task. Treatment with recombinant tissue plasminogen activator has promise. However, given its potential for toxicity, a prospective randomized trial should be performed. Hopefully, as more data regarding the molecular and cellular mechanisms of this illness are elucidated, more thoughtful prevention strategies will be developed. This will be necessary, particularly as newer, more intensive preparative regimens are being developed, as access to alternative donors increases, and as more diseases will be treated with this approach.

scholarly journals Robust high-throughput assays to assess discrete steps in ubiquitination and related cascades

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Gabriel Fenteany ◽  
Paras Gaur ◽  
Gaurav Sharma ◽  
Lajos Pintér ◽  
Ernő Kiss ◽  
...  
Keyword(s):  
High Throughput ◽  
Basic Research ◽  
Nuclear Antigen ◽  
Therapeutic Drug ◽  
Post Translational Modification ◽  
Good Correspondence ◽  
Cellular Processes ◽  
Protein Ubiquitination ◽  
Ubiquitin Conjugating Enzyme ◽  
Covalent Adducts

Abstract Background Ubiquitination and ubiquitin-like protein post-translational modifications play an enormous number of roles in cellular processes. These modifications are constituted of multistep reaction cascades. Readily implementable and robust methods to evaluate each step of the overall process, while presently limited, are critical to the understanding and modulation of the reaction sequence at any desired level, both in terms of basic research and potential therapeutic drug discovery and development. Results We developed multiple robust and reliable high-throughput assays to interrogate each of the sequential discrete steps in the reaction cascade leading to protein ubiquitination. As models for the E1 ubiquitin-activating enzyme, the E2 ubiquitin-conjugating enzyme, the E3 ubiquitin ligase, and their ultimate substrate of ubiquitination in a cascade, we examined Uba1, Rad6, Rad18, and proliferating cell nuclear antigen (PCNA), respectively, in reconstituted systems. Identification of inhibitors of this pathway holds promise in cancer therapy since PCNA ubiquitination plays a central role in DNA damage tolerance and resulting mutagenesis. The luminescence-based assays we developed allow for the quantitative determination of the degree of formation of ubiquitin thioester conjugate intermediates with both E1 and E2 proteins, autoubiquitination of the E3 protein involved, and ubiquitination of the final substrate. Thus, all covalent adducts along the cascade can be individually probed. We tested previously identified inhibitors of this ubiquitination cascade, finding generally good correspondence between compound potency trends determined by more traditional low-throughput methods and the present high-throughput ones. Conclusions These approaches are readily adaptable to other E1, E2, and E3 systems, and their substrates in both ubiquitination and ubiquitin-like post-translational modification cascades.

Accidental Childhood Iron Poisoning: A Problem of Marketing and Labeling

PEDIATRICS ◽  
1979 ◽  
Vol 63 (4) ◽  
pp. 591-596
Author(s):  
Edward P. Krenzelok ◽  
Julie V. Hoff
Keyword(s):  
Dosage Forms ◽  
High Availability ◽  
Iron Compound ◽  
Product Labeling ◽  
Compound A ◽  
Elemental Iron ◽  
Iron Poisoning

Accidental iron poisoning still represents a significant hazard in children less than 5 years of age. The problem is compounded by the attractiveness of dosage forms, their high availability, and ambiguities in product labeling. Manufacturers accentuate label ambiguity by not specifically designating the iron as being total elemental iron or iron compound. A list of products that contain iron has been prepared to help clarify this issue.

scholarly journals Investigation of Anaemia in Geriatric patients Admitted to Norfolk & Norwich University teaching Hospital Old People’s Medicine/Geriatric Department

2021 ◽  
Vol 2 (5) ◽  
pp. 01-05
Author(s):  
Emmanuel Tigalya ◽  
Lamabadusuriya Lamabadusuriya ◽  
Yasmine Karachiwala
Keyword(s):  
Vitamin B12 ◽  
Teaching Hospital ◽  
Laboratory Tests ◽  
Geriatric Patients ◽  
Target Population ◽  
University Teaching ◽  
Iron Level ◽  
Medicine Department ◽  
Elemental Iron ◽  
High Prevalence

Aims To assess if anaemia detected in geriatric patients admitted to the Old Peoples Medicine Department at Norfolk and Norwich University Teaching Hospital was investigated with appropriate laboratory tests- haematinics and iron level tests. Also increase awareness among doctors of the high prevalence of anaemia in geriatric patients and the need to investigate to start treat if indicated. Target population or scope All patients aged 80 and above admitted under the care of NNUH OPM department on a given day incidentally found to have anaemia. Criteria All over 80 year olds admitted to hospital found incidentally to have low HB (anaemia) should be investigated by having elemental iron level and haematinic checks; Iron level check Vitamin B12 and folate check Ferritin Target population or scope All patients aged 80 and above admitted under the care of NNUH OPM department on a given day incidentally found to have anaemia.

Development of Novel Therapeutics Targeting Isocitrate Dehydrogenase Mutations in Cancer

2018 ◽  
Vol 18 (6) ◽  
pp. 505-524 ◽  
Author(s):  
Horrick Sharma
Keyword(s):  
Isocitrate Dehydrogenase ◽  
Glutamine Metabolism ◽  
Therapeutic Drug ◽  
Cellular Processes ◽  
Cellular Defense ◽  
Altered Gene Expression ◽  
Idh1 And Idh2 Mutations ◽  
Altered Gene ◽  
Mutant Idh1 ◽  
Oxidative Respiration

Isocitrate dehydrogenases 1 and 2 (IDH1 and IDH2) are key metabolic enzymes that catalyze the conversion of isocitrate to α-ketoglutarate (αKG). IDH1 and IDH2 regulate several cellular processes, including oxidative respiration, glutamine metabolism, lipogenesis, and cellular defense against oxidative damage. Mutations in IDH1 and IDH2 have recently been observed in multiple tumors, including gliomas, acute myeloid leukemia, myelodysplastic syndromes, and chondrosarcoma. IDH1 and IDH2 mutations involve a gain in neomorphic activity that catalyzes αKG conversion to (R)-2- hydroxyglutarate ((R)-2HG). IDH mutation-mediated accumulation of (R)-2HG results in epigenetic dysregulation, altered gene expression, and a block in cellular differentiation. Targeting mutant IDH by development of small molecule inhibitors is a rapidly emerging therapeutic approach as evidenced by the recent approval of the first selective mutant IDH2 inhibitor AG-221 (enasidenib) for the treatment of IDH2-mutated AML. This review will focus on mutant isocitrate dehydrogenase as a therapeutic drug target and provides an update on selective and pan-mutant IDH1/2 inhibitors in clinical trials and other mutant IDH inhibitors that are under development.

Tubulin structure at intermediate resolution

1995 ◽  
Vol 53 ◽  
pp. 852-853
Author(s):  
K. H. Downing ◽  
S. G. Wolf ◽  
E. Nogales
Keyword(s):  
High Resolution ◽  
Structural Data ◽  
Therapeutic Drug ◽  
Zinc Ions ◽  
Two Dimensional ◽  
X Ray Diffraction ◽  
X Ray ◽  
Negative Stain ◽  
Functional Mechanisms ◽  
Tubulin Structure

Microtubules are involved in a host of critical cell activities, many of which involve transport of organelles through the cell. Different sets of microtubules appear to form during the cell cycle for different functions. Knowledge of the structure of tubulin will be necessary in order to understand the various functional mechanisms of microtubule assemble, disassembly, and interaction with other molecules, but tubulin has so far resisted crystallization for x-ray diffraction studies. Fortuitously, in the presence of zinc ions, tubulin also forms two-dimensional, crystalline sheets that are ideally suited for study by electron microscopy. We have refined procedures for forming the sheets and preparing them for EM, and have been able to obtain high-resolution structural data that sheds light on the formation and stabilization of microtubules, and even the interaction with a therapeutic drug.Tubulin sheets had been extensively studied in negative stain, demonstrating that the same protofilament structure was formed in the sheets and microtubules. For high resolution studies, we have found that the sheets embedded in either glucose or tannin diffract to around 3 Å.

vitreal cells and specialized phagocytes in the chick embryo retina: A TEM and SEM study

1990 ◽  
Vol 48 (3) ◽  
pp. 330-331
Author(s):  
M.A. Cuadros ◽  
M.J. Martinez-Guerrero ◽  
A. Rios
Keyword(s):  
Cell Death ◽  
Plasma Membrane ◽  
Acid Phosphatase ◽  
Chick Embryo ◽  
Basement Membrane ◽  
Sem Images ◽  
Intimate Contact ◽  
Cellular Processes ◽  
Sem Study ◽  
Free Cells

In the chick embryo retina (days 3-4 of incubation), coinciding with an increase in cell death, specialized phagocytes characterized by intense acid phosphatase activity have been described. In these preparations, all free cells in the vitreal humor (vitreal cells) were strongly labeled. Conventional TEM and SEM techniques were used to characterize them and attempt to determine their relationship with retinal phagocytes.Two types of vitreal cells were distinguished. The first are located at some distance from the basement membrane of the neuroepithelium, and are rounded, with numerous vacuoles and thin cytoplasmic prolongations. Images of exo- and or endocytosis were frequent; the cells showed a well-developed Golgi apparatus (Fig. 1) In SEM images, the cells was covered with short cellular processes (Fig. 3). Cells lying parallel to or alongside the basement membrane are elongated. The plasma membrane is frequently in intimate contact with the basement membrane. These cells have generally a large cytoplasmic expansion (Fig. 5).

E3 ubiquitin ligases

2005 ◽  
Vol 41 ◽  
pp. 15-30 ◽  
Author(s):  
Helen C. Ardley ◽  
Philip A. Robinson
Keyword(s):  
Protein Complexes ◽  
Loss Of Function ◽  
Direct Role ◽  
Cellular Processes ◽  
Substrate Protein ◽  
Protein Ubiquitination ◽  
C Terminus ◽  
Full Complement ◽  
Spatio Temporal ◽  
Eukaryotic Organisms

The selectivity of the ubiquitin–26 S proteasome system (UPS) for a particular substrate protein relies on the interaction between a ubiquitin-conjugating enzyme (E2, of which a cell contains relatively few) and a ubiquitin–protein ligase (E3, of which there are possibly hundreds). Post-translational modifications of the protein substrate, such as phosphorylation or hydroxylation, are often required prior to its selection. In this way, the precise spatio-temporal targeting and degradation of a given substrate can be achieved. The E3s are a large, diverse group of proteins, characterized by one of several defining motifs. These include a HECT (homologous to E6-associated protein C-terminus), RING (really interesting new gene) or U-box (a modified RING motif without the full complement of Zn2+-binding ligands) domain. Whereas HECT E3s have a direct role in catalysis during ubiquitination, RING and U-box E3s facilitate protein ubiquitination. These latter two E3 types act as adaptor-like molecules. They bring an E2 and a substrate into sufficiently close proximity to promote the substrate's ubiquitination. Although many RING-type E3s, such as MDM2 (murine double minute clone 2 oncoprotein) and c-Cbl, can apparently act alone, others are found as components of much larger multi-protein complexes, such as the anaphase-promoting complex. Taken together, these multifaceted properties and interactions enable E3s to provide a powerful, and specific, mechanism for protein clearance within all cells of eukaryotic organisms. The importance of E3s is highlighted by the number of normal cellular processes they regulate, and the number of diseases associated with their loss of function or inappropriate targeting.

Module 7: Cellular Processes

2014 ◽  
Vol 6 ◽  
pp. csb0001007 ◽  
Author(s):  
Michael J. Berridge
Keyword(s):  
Cellular Processes
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