Neurotoxicity and metabolism of the catecholamine-derived 3,4-dihydroxyphenylacetaldehyde and 3,4-dihydroxyphenylglycolaldehyde: the role of aldehyde dehydrogenase

Aldehydes are highly reactive molecules formed during the biotransformation of numerous endogenous and exogenous compounds, including biogenic amines. 3,4-Dihydroxyphenylacetaldehyde is the aldehyde metabolite of dopamine, and 3,4-dihydroxyphenylglycolaldehyde is the aldehyde metabolite of both norepinephrine and epinephrine. There is an increasing body of evidence suggesting that these compounds are neurotoxic, and it has been recently hypothesized that neurodegenerative disorders may be associated with increased levels of these biogenic aldehydes. Aldehyde dehydrogenases are a group of NAD(P)+ -dependent enzymes that catalyze the oxidation of aldehydes, such as those derived from catecholamines, to their corresponding carboxylic acids. To date, 19 aldehyde dehydrogenase genes have been identified in the human genome. Mutations in these genes and subsequent inborn errors in aldehyde metabolism are the molecular basis of several diseases, including Sj?gren-Larsson syndrome, type II hyperprolinemia, gamma-hydroxybutyric aciduria, and pyridoxine-dependent seizures, most of which are characterized by neurological abnormalities. Several pharmaceutical agents and environmental toxins are also known to disrupt or inhibit aldehyde dehydrogenase function. It is, therefore, possible to speculate that reduced detoxification of 3,4-dihydroxyphenylacetaldehyde and 3,4-dihydroxyphenylglycolaldehyde from impaired or deficient aldehyde dehydrogenase function may be a contributing factor in the suggested neurotoxicity of these compounds. This article presents a comprehensive review of what is currently known of both the neurotoxicity and respective metabolism pathways of 3,4-dihydroxyphenylacetaldehyde and 3,4-dihydroxyphenylglycolaldehyde with an emphasis on the role that aldehyde dehydrogenase enzymes play in the detoxification of these two aldehydes.     

Mapping frailty in people living with HIV: A nationwide study in Greece

Objectives

Frailty is known to affect people living with HIV prematurely, compared to the ageing seronegative population. In this cross-sectional study, we aimed to assess frailty prevalence in people living with HIV in Greece and find associations of frailty criteria with clinical data.

Methods

Demographic and clinical data were collected from 477 participants in six HIV clinics. Fried's frailty phenotype was used to assess frailty prevalence, and participants were classified as frail, pre-frail or robust. Associations of several factors with overall frailty phenotype, as well as with frailty criteria, were explored.

Results

The median age was 43 years old (IQR = 51.5) and 444/477 (93%) were men. Most of the participants (429/477, 93.5%) had an undetectable HIV viral load, and a CD4 cell count over 500 cells/μl (366/477, 76.7%). Frailty assessment classified 285/477 (62.1%) as robust, 155/477 (33.8%) as pre-frail and 19/477 (4.1%) as frail. Weakness in grip strength was the most prevalent criterion (128/477, 26.8%), followed by exhaustion (46/477, 9.6%). Lower CD4 cell count, history of AIDS diagnosis, CNS disorders, psychiatric diagnoses, and polypharmacy were strongly associated with frailty.

Conclusions

Although the prevalence of frailty in people living with HIV in Greece is uncommon, when combined with pre-frailty over a third of people are affected, which requires attention in clinical practice. The physical and psychological aspects of frailty highlight the need for a holistic approach to prevent or counteract it. The diverse associations of frailty criteria with HIV-related and non-HIV-related factors suggest a possible variation in people's different healthcare needs.     

Metastatic renal cell carcinoma presenting as a duodenal mass

We report a case of renal cell carcinoma metastasis to the duodenum.