A Mini Review: Mucormycosis in Coronavirus Disease-19, Host-Iron Assimilation, and Probiotics as Novel Therapy

Mucormycosis is an acute fungal infection with 90% of cases in the form of rhino-orbito-cerebellar. It is an aggressive and life-threatening fungal infection causing 50% mortality in people with coronavirus disease 2019 (COVID-19). In COVID-infected patients due to, diabetic ketoacidosis, epithelial damage, ciliary dysfunction, dysfunctional phagocytic mechanism, and immunosuppression, there is impaired chemotaxis and defective intracellular killing leads to fungal spores to invade, germinate and penetrate in surrounding tissues. The use of broad-spectrum antibiotics disrupts the normal microbiomes and increases the probability of growth of Rhizopus spp. Commercially available probiotics such as Lactobacillus, Bifidobacterium, Enterococcus, Streptococcus, and Saccharomyces when administered in adequate quantities form siderophores which induces iron stress in fungus and inhibits spore germination.

Hepatic and Cardiac Iron-load in Children on Long-term Chelation with Deferiprone for Thalassemia Major

Objective: To evaluate the efficacy of prolonged deferiprone monotherapy in patients with ?-thalassemia major. Methods: This cross-sectional study included 40 patients (age range 9 to38 years) with thalassemia major receiving deferiprone for ?5 years. Serum ferritin, andmyocardial iron concentration (MIC) and liver iron concentration (LIC) assessed by T2*MRIwere recorded. Results: The patients were receiving deferiprone for a mean (SD) duration of12.1 (4.7) years. The median (IQR) dose of deferiprone was 85 (74.3, 95) mg/kg/day. TheMIC was normal or had a mild, moderate or severe elevation in 29 (72.5%), 3 (7.5%), 3(7.5%), and 5 (12.5%) patients. The LIC was normal or had a mild, moderate or severeelevation in 2 (5%), 4 (10%), 11 (27.5%) and 23 (57.5%) patients. Conclusions: The majorityof patients receiving deferiprone had a moderate/severe hepatic but normal cardiac iron load.Prolonged deferiprone monotherapy was suboptimal for hepatic iron load in the majority.

A concurrent parallel study to compare the efficacy and safety of oral iron chelators, defrasirox and defriprone in patients of beta thalassaemia major

Background: This study was planned to evaluate all the cases of ? thalassaemia major, already receiving one of the oral iron chelators for a comparison among the efficacy, safety and economy of deferasirox and deferiprone to establish the better option in an Indian scenario.Methods: We identified two groups of patients: 38 treated with deferasirox and 35 treated with deferiprone. Laboratory parameters such as serum ferritin, creatinine, SGPT, Hb, CBC and urine were recorded at the time of inclusion and at 1, 3 and 6 months after the inclusion. The primary outcome variable was serum Ferritin level at the start and at the end of study. Serum ferritin level was carried out by microparticle enzyme linked immunoassay.Results: Before the study, the mean hemoglobin level was 7.32±1.50mg/dL ranged from 4 to 10.8 in deferasirox group and 7.54±1.15mg/dL ranged from 5.5 to 8.8 in deferiprone group. At the time of inclusion, study population was characterized by a mean serum ferritin value of 4735.11±450.01 SE in deferasirox and 4315.97±340.75 SE in deferiprone group. After one month the mean serum ferritin increases to 4578.66±371.96 in deferasirox and 4388.82±316.16 in deferiprone group. After three month the mean serum ferritin reduces to 4295.60±377.37 in deferasirox and 3988.88±349.84 in Deferiprone group.Conclusions: Thus, we conclude that deferasirox and deferiprone are well tolerated, have few adverse effects and almost have a comparable effect in lowering of the patient's serum ferritin level. Deferiprone is more cost effective but needs a strict control on compliance owing to requirement in three divided doses per day.

Modulatory effect of iron chelators on adenosine deaminase activity and gene expression in Trichomonas vaginalis

Trichomonas vaginalis is a flagellate protozoan that parasitises the urogenital human tract and causes trichomoniasis. During the infection, the acquisition of nutrients, such as iron and purine and pyrimidine nucleosides, is essential for the survival of the parasite. The enzymes for purinergic signalling, including adenosine deaminase (ADA), which degrades adenosine to inosine, have been characterised in T. vaginalis. In the evaluation of the ADA profile in different T. vaginalisisolates treated with different iron sources or with limited iron availability, a decrease in activity and an increase in ADA gene expression after iron limitation by 2,2-bipyridyl and ferrozine chelators were observed. This supported the hypothesis that iron can modulate the activity of the enzymes involved in purinergic signalling. Under bovine serum limitation conditions, no significant differences were observed. The results obtained in this study allow for the assessment of important aspects of ADA and contribute to a better understanding of the purinergic system in T. vaginalis and the role of iron in establishing infection and parasite survival.

Protective action of deferiprone and deferoxamine in erythrocytes isolated from patients with B-thalassemias / Ação protetora de deferiprona e desferoxamina nos eritrócitos isolados de pacientes com B-talassemias

One of the most deleterious consequences of iron overload in thalassemia is the presence of non-transferrin bound iron (NTBI), a free radical that acts as a catalyst for free oxygen radicals, in particular for hydroxyl free radicals (OH.). These radicals oxidize both membrane lipids and proteins causing irreversible damage to biologically important molecules and cellular structures. Treatment with iron chelators has been important to improve survival of these individuals. The aim of this work was the study on the effects of deferoxamine (DFO) and deferiprone (DFP) on erythrocytes under the pro-oxidative action of TBHP isolated from normal individuals and patients with β-thalassemia. The in vitro action of deferoxamine and deferiprone on the oxidative metabolism of erythrocytes from β-thalassemic patients treated at the Centro de Hematologia e Hemoterapia do Paraná (HEMEPAR), Brazil, under the pro-oxidative action of TBHP was studied. Methemoglobin concentrations, reduced glutathione (GSH), hemolysis indexes and the enzyme activities of G6-PD and GR were determined. The oxidation indexes were higher in erythrocytes of β-thalassemic individuals than those from normal individuals. Treatment of the normal and β-thalassemic erythrocytes with DFO and/or DFP protected against the formation of GSH promoted by TBHP.

Uma das maiores consequências da sobrecarga do ferro na β-talassemia é a presença de ferro não ligado à transferrina (NTBI), um radical livre que age como um catalisador do radical livre do oxigênio, particularmente radical hidroxil (OH.). Estes radicais oxidam os lipídeos e as proteínas da membrana causando danos irreversíveis às moléculas biologicamente importantes e às estruturas celulares. O tratamento com quelantes do ferro é importante para a melhoria da sobrevivência destes indivíduos. O objetivo deste trabalho foi o estudo sobre o efeito da desferoxamina (DFO) e da deferiprona (DFP) em eritrócitos isolados de indivíduos normais e de pacientes com β-talassemias, sob a ação pró-oxidativa de TBHP. Neste trabalho foi estudada a ação in vitro da desferoxamina e o deferiprona no metabolismo oxidativo dos eritrócitos de pacientes β-talassêmicos atendidos no Centro de Hematologia e Hemoterapia do Paraná (Hemepar), Brasil, sob a ação pró-oxidativa de TBHP. Concentrações de metahemoglobina glutationa reduzida, índices de hemólises, atividades das enzimas G6PD e GR foram determinadas. Os índices de oxidação analisados foram maiores nos eritrócitos de indivíduos β-talassêmicos do que nos normais. Tratamentos dos eritrócitos normais e β-talassêmicos com DFO e/ou DFP protegem contra a oxidação de GSH promovida por TBHP.