Objectives: The aim of this study was to explore the trend of ischemic heart disease (IHD) admission and the prescriptions of IHD medications in England and Wales. Methods: A secular trends study was conducted during the period of 1999 to 2019. We extracted hospital admission data for patients from all age groups from the Hospital Episode Statistics database in England and the Patient Episode Database for Wales. Prescriptions of IHD medications were extracted from the Prescription Cost Analysis database from 2004 to 2019. The chi-squared test was used to assess the difference between the admission rates and the difference between IHD medication prescription rates. The trends in IHD-related hospital admission and IHD-related medication prescription were assessed using a Poisson model. The correlation between hospital admissions for IHD and its IHD medication-related prescriptions was assessed using the Pearson correlation coefficient. Results: Our study detected a significant increase in the rate of cardiovascular disease (CVD) medication prescriptions in England and Wales, representing a rise in the CVD medications prescription rate of 41.8% (from 539,334.95 (95% CI = 539,286.30–539,383.59) in 2004 to 764,584.55 (95% CI = 764,545.55–764,623.56) in 2019 prescriptions per 100,000 persons), with a mean increase of 2.8% per year during the past 15 years. This increase was connected with a reduction in the IHD hospital admission rate by 15.4% (from 838.50 (95% CI = 836.05–840.94) in 2004 to 709.78 (95% CI = 707.65–711.92) in 2019 per 100,000 persons, trend test, p < 0.01), with a mean decrease of 1.02% per year during the past 15 years and by 5% (from 747.43 (95% CI = 745.09–749.77) in 1999 to 709.78 (95% CI = 707.65–711.92) in 2019 per 100,000 persons, trend test, p < 0.01) with a mean decrease of 0.25% per year during the past two decades in England and Wales. Conclusion: The rate of hospitalisation due to IHD has decreased in England and Wales during the past two decades. Hospitalisation due to IHD was strongly and negatively correlated with the increase in the rates of dispensing of IHD-related medications. Other factors contributing to this decline could be the increase in controlling IHD risk factors during the past few years. Future studies exploring other risk factors that are associated with IHD hospitalisation are warranted.

The data reported here are a comparison among four different methods for the detection of carbonylated proteins, a validated biomarker of oxidative stress. The reference samples were heart and kidney extracts of Guinea pigs transfused with hemoglobin-based oxygen carriers (Alomari et al. FRBM, [11]). We measured the carbonyl content of organ extracts by using i) the Levine spectrophotometric method, which takes advantage of the chromogenic reaction of carbonyl groups with 2,4-dinitrophenylhydrazine (DNPH), ii) a commercially available ELISA assay based on an anti-DNPH antibodies, iii) a commercially available Western blot method based on anti-DNPH antibodies and iv) an in-gel detection approach with the fluorophoric reagent fluorescein-5-thiosemicarbazide. The former two methods measure total protein carbonylation of a sample, whereas the latter two require an electrophoretic separation and therefore potentially allow for the identification of specific carbonylated proteins.

Hemoglobin-based oxygen carriers (HBOCs) are an investigational replacement for blood transfusions and are known to cause oxidative damage to tissues. To investigate the correlation between their oxygen binding properties and these detrimental effects, we investigated two PEGylated HBOCs endowed with different oxygen binding properties - but otherwise chemically identical - in a Guinea pig transfusion model. Plasma samples were analyzed for biochemical markers of inflammation, tissue damage and organ dysfunction; proteins and lipids of heart and kidney extracts were analyzed for markers of oxidative damage. Overall, both HBOCs produced higher oxidative stress in comparison to an auto-transfusion control group. Particularly, tissue 4-hydroxynonenal adducts, tissue malondialdehyde adducts and plasma 8-oxo-2'-deoxyguanosine exhibited significantly higher levels in comparison with the control group. For malondialdehyde adducts, a higher level in the renal tissue was observed for animals treated with the high-affinity HBOC, hinting at a correlation between the HBOCs oxygen binding properties and the oxidative stress they produce. Moreover, we found that the high-affinity HBOC produced greater tissue oxygenation in comparison with the low affinity one, possibly correlating with the higher oxidative stress it induced.

Alpha 1-antitrypsin is one of the first protein therapeutics introduced on the market – more than 30 years ago – and, to date, it is indicated only for the treatment of the severe forms of a genetic condition known as alpha-1 antitrypsin deficiency. The only approved preparations are derived from plasma, posing potential problems associated with its limited supply and high processing costs. Moreover, augmentation therapy with alpha 1-antitrypsin is still limited to intravenous infusions, a cumbersome regimen for patients. Here, we review the recent literature on its possible future developments, focusing on i) the recombinant alternatives to the plasma-derived protein, ii) novel formulations, and iii) novel administration routes. Regulatory issues and the still unclear noncanonical functions of alpha 1-antitrypsin – possibly associated with the glycosylation pattern found only in the plasma-derived protein – have hindered the introduction of new products. However, potentially new therapeutic indications other than the treatment of alpha-1 antitrypsin deficiency might open the way to new sources and new formulations.