Corticostatin-4 precursor

Recreational gamma-hydroxybutyrate (GHB) use, although less common than other substance use, is increasingly recognised and is over-represented in emergency toxicology presentations. This narrative review summarizes GHB pharmacology, current patterns of use, potential harms and management of GHB toxicity and withdrawal. There is a complex interplay between GHB and GABA as GHB is both a prodrug and metabolite of GABA and GHB activates both GHB and GABA receptors. GHB is rapidly absorbed, with effects seen within minutes of ingestion. Metabolism is non-linear at higher doses. While GHB is listed as a controlled substance, its precursor's gamma-butyrolactone (GBL) and 1,4-butanediol (1,4-BD) are easily available as both have industrial applications. National surveys indicate low rates of GHB use, with identification of high-risk populations in men who have sex with men and polysubstance users. GHB is one of the three drugs most commonly used in chemsex. GHB is often co-ingested with other interacting psychoactive substances. Acute toxicity is dose-dependent, and management is supportive care. Withdrawal management is generally with benzodiazepines with addition of baclofen for more severe withdrawal. Barbiturates may have a role. Titration and tapering of pharmaceutical GHB is commonly used in the Netherlands. Complicated withdrawal with delirium may require intensive care and treatment with intravenous sedation. There are high rates of relapse after withdrawal and medications for longer-term management are currently being investigated. Chronic use is associated with poorer mental, physical and sexual health, social dysfunction and poor work performance. Laboratory detection is complicated as GHB is an endogenous substance with a short half-life, and therefore not often routinely assayed in the clinical setting. Future research should focus on improving GHB detection and management of GHB withdrawal and dependence. Interventions specific for high-risk groups should be developed and assessed.

Hyperhomocysteinemia is an independent cardiovascular risk factor that possibly accounts for about one of 5 cardiovascular deaths. It is conceivable that the importance of hyperhomocysteinemia will increase when other risk factors, such as hypertension or hypercholesterolemia, will become less prevalent in the general population. In chronic renal failure (CRF), high plasma homocysteine levels are a common finding and in uremia almost the rule. However, a small subset of patients remains normohomocysteinemic. The cause of hyperhomocysteinemia in CRF, whether it lies in an impaired renal or extrarenal metabolism or through uremic retention toxins, is still under intensive scrutiny. As for the consequences of high homocysteine levels in the general population and in patients with CRF, these are many-fold and linked to the mechanism of homocysteine toxic action. In fact, homocysteine can be harmful to cells because (1) it evokes oxidative stress (through the production of reactive oxygen species), (2) binds to nitric oxide, (3) produces homocysteinylated proteins, or (4) leads to the accumulation of its precursor, S-adenosylhomocysteine, a potent inhibitor of biological transmethylations. Macromolecule hypomethylation is a common feature in CRF and uremia with possible functional consequences. Nutritional or pharmacologic interventions have been proposed in the treatment of hyperhomocysteinemia, while the results of large clinical trials designed to assess if lowering homocysteine levels is effective in reducing cardiovascular risk, are pending.

Hematogones were initially described as mysterious cells in bone marrow smears more than 70 years ago. These cells are normal bone marrow B-lymphocyte precursors with properties that overlap those of lymphoblasts. Their morphological and immunological features are described here with an update on the knowledge of hematogones in hematological and non-hematological disorders.