Post COVID-19 Reflections and Questions: How Prepared Are We for the Next Pandemic?

While the end of the COVID-19 pandemic was announced earlier in 2023 by WHO, the currently dominating COVID-19 virus variants, such as the omicron sub-lineages XBB [...

Benefits and Risks in Polypathology and Polypharmacotherapy Challenges in the Era of the Transition of Thalassaemia from a Fatal to a Chronic or Curable Disease.

Beta thalassaemia major (TM), a potentially fatal haemoglobinopathy, has transformed from a fatal to a chronic disease in the last 30 years following the introduction of effective, personalised iron chelation protocols, in particular the use of oral deferiprone, which is most effective in the removal of excess iron from the heart. This transition in TM has been achieved by the accessibility to combination therapy with the other chelating drugs deferoxamine and deferasirox but also therapeutic advances in the treatment of related co-morbidities. The transition and design of effective personalised chelation protocols was facilitated by the development of new non-invasive diagnostic techniques for monitoring iron removal such as MRI T2*.

Conventional and Unconventional Approaches for Innovative Drug Treatments in COVID-19: Looking Outside of Plato's Cave.

Thousands of drugs and nutraceuticals along with their combinations can be used to select candidate therapeutics for targeting the transmission, proliferation and the fatal or severe symptoms of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in order to reduce the unacceptably high mortality rate observed in the coronavirus disease 2019 (COVID-19) pandemic and its associated negative effects on daily life worldwide [...

New Era in the Treatment of Iron Deficiency Anaemia Using Trimaltol Iron and Other Lipophilic Iron Chelator Complexes: Historical Perspectives of Discovery and Future Applications.

The trimaltol iron complex (International Non-proprietary Name: ferric maltol) was originally designed, synthesised, and screened in vitro and in vivo in 1980-1981 by Kontoghiorghes G.J. following his discovery of the novel alpha-ketohydroxyheteroaromatic (KHP) class of iron chelators (1978-1981), which were intended for clinical use, including the treatment of iron deficiency anaemia (IDA).

Trying to Solve the Puzzle of the Interaction of Ascorbic Acid and Iron: Redox, Chelation and Therapeutic Implications.

Iron and ascorbic acid (vitamin C) are essential nutrients for the normal growth and development of humans, and their deficiency can result in serious diseases. Their interaction is of nutritional, physiological, pharmacological and toxicological interest, with major implications in health and disease. Millions of people are using pharmaceutical and nutraceutical preparations of these two nutrients, including ferrous ascorbate for the treatment of iron deficiency anaemia and ascorbate combination with deferoxamine for increasing iron excretion in iron overload.

Effect of HBB genotype on survival in a cohort of transfusion-dependent thalassemia patients in Cyprus.

Initiation of regular transfusion in transfusion-dependent thalassemia (TDT) is based on the assessment of clinical phenotype. Pathogenic HBB variants causing β-thalassemia are important determinants of phenotype and could be used to aid decision making. We investigated the association of HBB genotype with survival in a cohort study in the four thalassemia centres in Cyprus.

The Scope for Thalassemia Gene Therapy by Disruption of Aberrant Regulatory Elements.

The common IVSI-110 (G>A) β-thalassemia mutation is a paradigm for intronic disease-causing mutations and their functional repair by non-homologous end joining-mediated disruption. Such mutation-specific repair by disruption of aberrant regulatory elements (DARE) is highly efficient, but to date, no systematic analysis has been performed to evaluate disease-causing mutations as therapeutic targets. Here, DARE was performed in highly characterized erythroid IVSI-110(G>A) transgenic cells and the disruption events were compared with published observations in primary CD34 cells.

Transfusion-Related Acute Lung Injury (TRALI) in two Thalassaemia Patients Caused by the Same Multiparous Blood Donor.

We report two separate episodes of transfusion-related acute lung injury (TRALI) in two thalassaemia patients who received red blood cell transfusions from the same multiparous donor. Both cases had the same symptomatology and occurred within 60 minutes of transfusion. The patients presented dyspnoea, sweating, fatigue, dizziness, fever, and sense of losing consciousness.

Chelation protocols for the elimination and prevention of iron overload in thalassaemia.

Iron overload toxicity is the main cause of mortality and morbidity in thalassaemia patients. The complete elimination and prevention of iron overload is the main aim of chelation therapy, which can be achieved by chelation protocols that can effectively remove excess iron load and maintain body iron at normal levels. Deferiprone and selected combinations with deferoxamine can be designed, adjusted and used effectively for removing all excess stored iron and for maintaining normal iron stores (NIS) in different categories of thalassaemia patients.

New targeted therapies and diagnostic methods for iron overload diseases.

Millions of people worldwide suffer from iron overload toxicity diseases such as transfusional iron overload in thalassaemia and hereditary haemochromatosis. The accumulation and presence of toxic focal iron deposits causing tissue damage can also be identified in Friedreich's ataxia, Alzheimer's, Parkinson's, renal and other diseases. Different diagnostic criteria of toxicity and therapeutic interventions apply to each disease of excess or misplaced iron.

Prevention of Iron Overload and Long Term Maintenance of Normal Iron Stores in Thalassaemia Major Patients using Deferiprone or Deferiprone Deferoxamine Combination.

Decrease in mortality and morbidity is observed in thalassaemia major patients with reduced iron load in comparison to heavy iron loaded patients. Effective and complete treatment of transfusional iron overload can be achieved by chelation protocols that can eliminate excess iron and maintain normal iron stores (NIS). The maintenance of NIS, i.

Hb A Episkopi - a novel δ-globin chain variant [HBD:c.428C>T] in a family of mixed Cypriot-Lebanese descent.

Objectives: Thalassaemia is a potentially lethal inherited anaemia, caused by reduced or absent synthesis of globin chains. Measurement of the minor adult haemoglobin Hb A, combining α- with δ-globin, is critical for the routine diagnosis of carrier status for α- or β-thalassaemia. Here, we aim to characterize a novel δ-globin variant, Hb A Episkopi, in a single family of mixed Lebanese and Cypriot ancestry with mild hypochromic anaemia and otherwise normal globin genotype, which also presents with a coincidental 0.

The molecular spectrum and distribution of haemoglobinopathies in Cyprus: a 20-year retrospective study.

Haemoglobinopathies are the most common monogenic diseases, posing a major public health challenge worldwide. Cyprus has one the highest prevalences of thalassaemia in the world and has been the first country to introduce a successful population-wide prevention programme, based on premarital screening. In this study, we report the most significant and comprehensive update on the status of haemoglobinopathies in Cyprus for at least two decades.

Phytochelators Intended for Clinical Use in Iron Overload, Other Diseases of Iron Imbalance and Free Radical Pathology.

Iron chelating drugs are primarily and widely used in the treatment of transfusional iron overload in thalassaemia and similar conditions. Recent in vivo and clinical studies have also shown that chelators, and in particular deferiprone, can be used effectively in many conditions involving free radical damage and pathology including neurodegenerative, renal, hepatic, cardiac conditions and cancer. Many classes of phytochelators (Greek: phyto (φυτό)-plant, chele (χηλή)-claw of the crab) with differing chelating properties, including plant polyphenols resembling chelating drugs, can be developed for clinical use.

Transition of Thalassaemia and Friedreich ataxia from fatal to chronic diseases.

Thalassaemia major (TM) and Friedreich's ataxia (FA) are autosomal recessive inherited diseases related to the proteins haemoglobin and frataxin respectively. In both diseases abnormalities in iron metabolism is the main cause of iron toxicity leading to increased morbidity and mortality. Major efforts are directed towards the prevention of these diseases and also in their treatment using iron chelation therapy.

Antioxidant targeting by deferiprone in diseases related to oxidative damage.

The design of antioxidant pharmaceuticals is a major challenge for the treatment of many clinical conditions and in aging. Free radical damage (FRD) is primarily catalysed by iron catalytic centers. Most of the natural and synthetic antioxidants are ineffective in inhibiting FRD because of the achievement of low concentrations at the affected tissues.

Potential clinical applications of chelating drugs in diseases targeting transferrin-bound iron and other metals.

Introduction: Iron is essential for normal, neoplasmic and microbial cells. Transferrin (Tf) is responsible for iron transport and its interactions with chelators are of physiological and toxicological importance and could lead to new therapeutic applications.

Areas Covered: Differential interactions of Tf with chelators such as deferiprone (L1) could be used to modify toxicity and disease pathways in relation to iron and other metal metabolism.

The importance of spleen, spleen iron, and splenectomy for determining total body iron load, ferrikinetics, and iron toxicity in thalassemia major patients.

The importance of spleen, spleen iron and splenectomy has been investigated in 28 male and 19 female β-thalassemia major (β-ΤΜ), adult patients. In one study, an increase from about five (615 g; 19.5 × 11.

EDTA chelation reappraisal following new clinical trials and regular use in millions of patients: review of preliminary findings and risk/benefit assessment.

EDTA chelation therapy is regularly used in thousands of patients worldwide. An FDA approval of more than 50 years ago for heavy metal detoxification prompted many physicians to use EDTA as an alternative medicine for many categories of patients. Recently, NIH initiated the so-called Trial to Assess Chelation Therapy (TACT), which has been designed to evaluate whether EDTA and high dose oral vitamins and mineral therapy could offer clinical, quality of life, and economic benefits for patients with a previous myocardial infraction.

Liver iron and serum ferritin levels are misleading for estimating cardiac, pancreatic, splenic and total body iron load in thalassemia patients: factors influencing the heterogenic distribution of excess storage iron in organs as identified by MRI T2*.

A comparative assessment of excess storage iron distribution in the liver, heart, spleen and pancreas of β-thalassemia major (β-ΤΜ) patients has been carried out using magnetic resonance imaging (MRI) relaxation times T2*. The β-ΤΜ patients (8-40 years, 11 males, 9 females) had variable serum ferritin levels (394-5603 μg/L) and were treated with deferoxamine (n = 10), deferiprone (n = 5) and deferoxamine/deferiprone combination (n = 5). MRI T2* assessment revealed that excess iron is not proportionally distributed among the organs but is stored at different concentrations in each organ and the distribution is different for each β-ΤΜ patient.

Interactions of hydroxycarbamide (hydroxyurea) with iron and copper: implications on toxicity and therapeutic strategies.

Presented at the 19th International Conference on Chelation, London, UK, 13-16 November 2009 Preliminary spectrophotometric and potentiometric studies have shown that hydroxycarbamide or hydroxyurea (HU) can interact with copper(II) [Cu(II)], iron(II) [Fe(II)] and Fe(III) ions and form complexes, for example, a ratio of 1 HU:1 metal at pH 5. The affinity for Cu (log β1 = 3.1) and Fe (log β1 = 5) by HU is much lower than that of the Fe and Cu chelating drug deferiprone (L1), which is used for the treatment of iron overload.

Efficacy, compliance and toxicity factors are affecting the rate of normalization of body iron stores in thalassemia patients using the deferiprone and deferoxamine combination therapy.

The international committee on chelation (ICOC) of deferiprone (L1) and deferoxamine (DFO) combination therapy was the first protocol reported to have achieved normal range body iron store levels (NRBISL) in β-thalassemia major (β-TM) patients. A follow-up study in eight β-TM patients has been designed to investigate the factors affecting the rate of iron removal leading to NRBISL. The patients had variable serum ferritin [mean ± SE (standard error) =1692 ± 366, range 539-3845 μg/L)] and magnetic resonance imaging (MRI) T2* relaxation times cardiac (mean ± SE =11.