Porphyrias are a group of diseases that are clinically and genetically heterogeneous and originate mostly from inherited dysfunctions of specific enzymes involved in heme biosynthesis. Such dysfunctions result in the excessive production and excretion of the intermediates of the heme biosynthesis pathway in the blood, urine, or feces, and these intermediates are responsible for specific clinical presentations. Porphyrias continue to be underdiagnosed, although laboratory diagnosis based on the measurement of metabolites could be utilized to support clinical suspicion in all symptomatic patients. Moreover, the measurement of enzymatic activities along with a molecular analysis may confirm the diagnosis and are, therefore, crucial for identifying pre-symptomatic carriers. The present review provides an overview of the laboratory assays used most commonly for establishing the diagnosis of porphyria. This would assist the clinicians in prescribing appropriate diagnostic testing and interpreting the testing results.

The WHO reported that high blood pressure (BP) is one of the primary causes of death worldwide. Hypertension (HPT) is a major risk factor for CVD and related diseases as well as for diseases, leading to a considerable increase in cardiovascular risk. Since BP response could also be influenced by caffeine, which is widely consumed with coffee and other items, it is important to define the possible effects associated with caffeine intake. The most recent findings aimed at clarifying the role of caffeine consumption on BP and HPT risk/incidence are conflicting and difficult to interpret. Therefore, in the present narrative review, we aimed to examine various methodological inaccuracies/aspects and factors that make studies difficult to be compared, in order to obtain a single consensus on the effects of caffeine intake on the risk of BP and HPT. We observed that this heterogeneity in results could be due to the presence of: (i) several variables affecting BP (such as age, sex, genetic and lifestyle aspects); (ii) different caffeine content of food and beverages; and (iii) caffeine metabolism. Moreover, different methodological aspects in the evaluation of daily dietary caffeine intake and in the BP measurement could add some other bias in the interpretation of results. Therefore, it is mandatory to consider all methodological aspects and confounding factors to generate a standardised methodology in order to increase cross-study consistency and minimise confounding effects of different variables on the relationship between BP response and HPT risk/incidence after caffeine intake.

Metabolic requirements vary during development, and our understanding of how metabolic activity influences cell specialization is incomplete. Here, we describe a switch from glutamine catabolism to synthesis required for erythroid cell maturation. Glutamine synthetase (GS), one of the oldest functioning genes in evolution, is activated during erythroid maturation to detoxify ammonium generated from heme biosynthesis, which is up-regulated to support hemoglobin production. Loss of GS in mouse erythroid precursors caused ammonium accumulation and oxidative stress, impairing erythroid maturation and recovery from anemia. In β-thalassemia, GS activity is inhibited by protein oxidation, leading to glutamate and ammonium accumulation, whereas enhancing GS activity alleviates the metabolic and pathological defects. Our findings identify an evolutionarily conserved metabolic adaptation that could potentially be leveraged to treat common red blood cell disorders.