scholarly journals Chelators for Treatment of Iron and Copper Overload: Shift from Low-Molecular-Weight Compounds to Polymers

Polymers ◽  
2021 ◽  
Vol 13 (22) ◽  
pp. 3969
Author(s):  
Martin Hruby ◽  
Irma Ivette Santana Martínez ◽  
Holger Stephan ◽  
Pavla Pouckova ◽  
Jiri Benes ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Side Effects ◽  
Critical Evaluation ◽  
Hereditary Diseases ◽  
Proper Function ◽  
Infusion Therapy ◽  
Low Molecular Weight ◽  
Golden Standard ◽  
New Perspective ◽  
Copper Overload

Iron and copper are essential micronutrients needed for the proper function of every cell. However, in excessive amounts, these elements are toxic, as they may cause oxidative stress, resulting in damage to the liver and other organs. This may happen due to poisoning, as a side effect of thalassemia infusion therapy or due to hereditary diseases hemochromatosis or Wilson’s disease. The current golden standard of therapy of iron and copper overload is the use of low-molecular-weight chelators of these elements. However, these agents suffer from severe side effects, are often expensive and possess unfavorable pharmacokinetics, thus limiting the usability of such therapy. The emerging concepts are polymer-supported iron- and copper-chelating therapeutics, either for parenteral or oral use, which shows vivid potential to keep the therapeutic efficacy of low-molecular-weight agents, while avoiding their drawbacks, especially their side effects. Critical evaluation of this new perspective polymer approach is the purpose of this review article.

scholarly journals PCSK9 as a Target for Development of a New Generation of Hypolipidemic Drugs

Molecules ◽  
2022 ◽  
Vol 27 (2) ◽  
pp. 434
Author(s):  
Nikolay Kuzmich ◽  
Elena Andresyuk ◽  
Yuri Porozov ◽  
Vadim Tarasov ◽  
Mikhail Samsonov ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Side Effects ◽  
Mechanisms Of Action ◽  
Lipid Lowering ◽  
Low Molecular Weight ◽  
Pcsk9 Inhibitors ◽  
Ldl Receptors ◽  
Orally Bioavailable ◽  
New Generation ◽  
Membrane Cell

PCSK9 has now become an important target to create new classes of lipid-lowering drugs. The prevention of its interaction with LDL receptors allows an increase in the number of these receptors on the surface of the cell membrane of hepatocytes, which leads to an increase in the uptake of cholesterol-rich atherogenic LDL from the bloodstream. The PCSK9 antagonists described in this review belong to different classes of compounds, may have a low molecular weight or belong to macromolecular structures, and also demonstrate different mechanisms of action. The mechanisms of action include preventing the effective binding of PCSK9 to LDLR, stimulating the degradation of PCSK9, and even blocking its transcription or transport to the plasma membrane/cell surface. Although several types of antihyperlipidemic drugs have been introduced on the market and are actively used in clinical practice, they are not without disadvantages, such as well-known side effects (statins) or high costs (monoclonal antibodies). Thus, there is still a need for effective cholesterol-lowering drugs with minimal side effects, preferably orally bioavailable. Low-molecular-weight PCSK9 inhibitors could be a worthy alternative for this purpose.

scholarly journals Higher Adherence to Treatment With Low-Molecular-Weight-Heparin Nadroparin Than Enoxaparin Because of Side Effects in Cancer-Associated Venous Thromboembolism

HemaSphere ◽  
2018 ◽  
Vol 2 (1) ◽  
pp. e19 ◽  
Author(s):  
Sake J. van der Wall ◽  
Frederikus A. Klok ◽  
Paul L. den Exter ◽  
Deisy Barrios ◽  
Raquel Morillo ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Venous Thromboembolism ◽  
Side Effects ◽  
Low Molecular Weight Heparin ◽  
Low Molecular Weight ◽  
Adherence To Treatment

CEREBRAL THROMBOLYSIS WITH INTRAVENOUSLY ADMINISTERED RECOMBINANT LOW- MOLECULAR-WEIGHT-UROKINASE AND RECOMBINANT PRO-UROKINASE IN A DOG MODEL

1987 ◽  
Author(s):  
M Hirschberg ◽  
A Manoutchei ◽  
B Klemens ◽  
B Hofferberth
Keyword(s):  
Molecular Weight ◽  
Side Effects ◽  
Acute Stroke ◽  
Cerebral Arteries ◽  
Bleeding Complications ◽  
Low Molecular Weight ◽  
Post Mortem ◽  
Surgical Wounds ◽  
Systemic Side Effects

There is increasing evidence that recombinant prourokinase (rec-pro-UK) is a proenzyme which in vivo systems may induce activation of the fibrinolytic system with a better thrombus selectivity than that obtained with active urokinase.In order to study the effects of rec-pro-UK and low-molecular-weight-urokinase (LMW-UK) on acute stroke, a thrombus was induced in the middle cerebral artery (MCA) of anesthetized mongrel dogs (n=12). Occlusion of the vessel was confirmed by angiography. Following a 1 hour period of MCA occlusion, in six animals LMW-UK was administered intravenously at a dose of 4000 lU/kg/min. Angiographically confirmed thrombolysis occurred after 30 minutes. Thrombolysis by LMW-UK was accompanied by bleeding from all surgical wounds and consumption of plasminogen, alpha-2-antiplasmin and fibrinogen. Rec-pro-UK was administered to six other dogs in a LMW-UK-equivalent dosis. Thrombolysis was achieved after 30 minutes in all six cases without inducing a systemic lytic state. Neither in the LMW-UK-group nor in the group treated with rec-pro-UK intracerebral bleeding complications were observed on post mortem examination.Our findings indicate that intravenous administration of rec-pro-UK - because of the lack of systemic side-effects - may be a safe way of rapid thrombolysis of occluded cerebral arteries in acute stroke.

scholarly journals Retroperitoneal Haematoma Associated with Low Molecular Weight Heparin

2002 ◽  
Vol 30 (5) ◽  
pp. 665-667 ◽  
Author(s):  
G. E. Power ◽  
P. Rogers
Keyword(s):  
Molecular Weight ◽  
Renal Failure ◽  
Acute Renal Failure ◽  
Side Effects ◽  
Blood Transfusion ◽  
Low Molecular Weight Heparin ◽  
Inotropic Support ◽  
Low Molecular Weight ◽  
Retroperitoneal Haematoma

Enoxaparin (a low molecular weight heparin) has been used extensively for its antithrombotic properties. Complications of its haemorrhagic side-effects have previously been described. We report two cases of extensive retroperitoneal haematoma requiring blood transfusion and inotropic support. One patient developed acute renal failure and did not respond to intensive resuscitative efforts.

Protein corona-guided tumor targeting therapy via the surface modulation of low molecular weight PEG

Nanoscale ◽  
2021 ◽  
Author(s):  
Teng Cui ◽  
Yu Ma ◽  
Jian-Yong Yang ◽  
Shang Liu ◽  
Zhenzhen Wang ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Polyethylene Glycol ◽  
Targeted Therapy ◽  
Tumor Targeting ◽  
Protein Corona ◽  
Low Molecular Weight ◽  
Targeting Therapy ◽  
Surface Modulation ◽  
New Perspective

Modulating the nature of protein corona on the surface of a nanomedicine via low molecular weight polyethylene glycol provides a new perspective for the regulation of nanomedicine functions such as the protein corona-guided tumor targeted therapy.

Prevention of Venous Thromboembolism and Pregnancy Complications using Low-Molecular-Weight Heparin during Pregnancy: A Systematic Review of Safety and Thromboprophylactic Efficacy.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1781-1781
Author(s):  
Ian A. Greer ◽  
Catherine Nelson-Piercy
Keyword(s):  
Systematic Review ◽  
Molecular Weight ◽  
Venous Thromboembolism ◽  
Side Effects ◽  
Pregnancy Complications ◽  
Low Molecular Weight Heparin ◽  
Low Molecular Weight ◽  
Skin Reactions ◽  
Safety And Efficacy ◽  
Vte Prophylaxis

Abstract Introduction Low-molecular-weight heparin (LMWH) is used in pregnancy for venous thromboembolism (VTE) prophylaxis and for prevention of pregnancy complications, because of efficacy greater than or equal to unfractionated heparin, and a lower rate of side effects observed in non-pregnant patients. Due to the lack of data from large randomized controlled trials to guide physician’s practices, there is a need for increased data on safety and efficacy of LMWH for these indications. Our aim was to evaluate the safety and efficacy of using LMWH during pregnancy for preventing VTE and pregnancy complications by performing a systematic review of data from published literature. Methods Data from published studies on the use of LMWH during pregnancy as VTE prophylaxis or LMWH for prevention of pregnancy complications were identified by searching MEDLINE and EMBASE databases up to the end of 2003. The reference lists from identified articles were also hand searched. Data on the LMWH regime, incidence of VTE, pregnancy complications, clinical outcomes and side effects were extracted and entered into pre-piloted forms. Results Fifty studies reporting 2,322 pregnancies were included in this analysis. LMWH was received antenatally in 1883 (81%) of cases, and only peri or postpartum in 389 (17%) of cases. Dalteparin and enoxaparin were the most commonly used LMWH, but certoparin, nadroparin, rivaparin, and tinzaparin were also used. There were no maternal deaths. VTE was reported in 26 (1.1%) pregnancies. Severe maternal bleeding occurred in 46 (2%) pregnancies and was generally associated with obstetric causes. Thrombocytopenia occurred in 10 (0.4%) pregnancies and was not associated with thrombosis. Minor allergic skin reactions occurred in 23 (1%) pregnancies, and osteoporosis in two (0.09%) pregnancies. Conclusion Data from this systematic review of the literature suggest that LMWH is both safe and effective for use as VTE prophylaxis during pregnancy.

scholarly journals Cysteine-rich granulin-3 rapidly promotes amyloid-β fibrils in both redox states

2019 ◽  
Vol 476 (5) ◽  
pp. 859-873 ◽  
Author(s):  
Anukool A. Bhopatkar ◽  
Gaurav Ghag ◽  
Lauren M. Wolf ◽  
Dexter N. Dean ◽  
Melissa A. Moss ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Amyloid Β ◽  
Low Molecular Weight ◽  
Redox Control ◽  
Redox States ◽  
Aβ Aggregation ◽  
Cellular Apoptosis ◽  
New Perspective ◽  
The Relationship ◽  
Insight Into

Abstract Granulins (GRNs 1–7) are cysteine-rich proteolytic products of progranulin (PGRN) that have recently been implicated in neurodegenerative diseases including frontotemporal dementia (FTD) and Alzheimer's disease (AD). Their precise mechanism in these pathologies remains uncertain, but both inflammatory and lysosomal roles have been observed for GRNs. Among the seven GRNs, GRN-3 is well characterized and is implicated within the context of FTD. However, the relationship between GRN-3 and amyloid-β (Aβ), a protein relevant in AD pathology, has not yet been explored. To gain insight into this mechanism, we investigated the effect of both oxidized and reduced GRN-3 on Aβ aggregation and found that both GRN-3 (oxidized) and rGRN-3 (reduced) bind to monomeric and oligomeric Aβ42 to promote rapid fibril formation with subtle rate differences. As low molecular weight oligomers of Aβ are well-established neurotoxins, rapid promotion of fibrils by GRN-3 mitigates Aβ42-induced cellular apoptosis. These data provide valuable insights in understanding GRN-3's ability to modulate Aβ-induced toxicity under redox control and presents a new perspective toward AD pathology. These results also prompt further investigation into the role(s) of other GRNs in AD pathogenesis.

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