Introduction: Lipohypertrophies (LHs) due to incorrect insulin injection techniques have been described in the literature for decades. Their rate averages 38%, but this is still controversial because of the vast range reported by different publications, most of which fail to describe the selected detection protocol and therefore are not entirely reliable. We still need to identify the real LH rate, and only consistently using a standardized method in a large cohort of insulin-treated (IT) patients make this possible.
Hyperhomocysteinemia is a risk factor for cardiovascular disease in the general population. In chronic renal failure (CRF), plasma homocysteine levels rise when the glomerular filtration rate (GFR) is reduced 50%, and in uremia the majority of patients are hyperhomocysteinemic. The purpose of this study was to review possible mechanisms of homocysteine toxicity. Homocysteine, a sulfur amino acid found in blood in micromolar concentrations, can have toxic effects through a handful of general possible mechanisms. These mechanisms include oxidative stress (through the production of reactive oxygen species), binding to nitric oxide, production of homocysteinylated/acylated proteins, and accumulation of its precursor, S-adenosyl-homocysteine, a potent inhibitor of transmethylation reactions. Methyltransferase inhibition actually occurs in CRF and in uremia, and can have several functional consequences.
Pain is a major health problem in end-stage renal disease (ESRD) affecting half of the dialysis patients; most of them experience a moderate to severe degree of pain. Nevertheless, the impact of chronic pain and its consequences are often underestimated. Sources of pain related to the uremic environment are renal bone disease (osteitis fibrosa cystica, amyloidosis, osteomalacia), osteoarthritis, calcific uremic arteriolopathy and peripheral neuropathy. Moreover, comorbid conditions such as ischemic peripheral artery disease, diabetic neuropathy, osteopenia/osteoporosis (due to long-standing hypertension, diabetes, or old age) result in various kinds of pain. Also the primary kidney disease (e.g. autosomal dominant polycystic kidney disease (ADPKD)) as well as performance of hemodialysis or peritoneal dialysis are important causes of pain. Potential consequences of persistent pain are disturbed sleep, weakened memory/attention, altered mood (anxiety and depressive disorder), impotence, poorer physical state, less social activities and consideration of withdrawal from dialysis. Consequently the health-related-quality of life (HRQOL) is diminished, associated with a higher morbidity and mortality. In the therapy of pain the WHO three-step analgesic ladder adapted for ESRD, was shown to be effective in dialysis patients. Of fundamental importance are various forms of non-pharmacological strategies including electrotherapy. Recently the so-called high tone external muscle stimulation (HTEMS) was very effective in the management of neuropathic pain in ESRD patients.
Hyperhomocysteinemia, an independent cardiovascular risk factor, is present in the majority of hemodialysis patients. Among the postulated mechanisms of toxicity, protein homocysteinylation is potentially able to cause significant alterations in protein function. Protein homocysteinylation occurs through various mechanisms, among which is the post-translational acylation of free amino groups (protein-N-homocysteinylation, mediated by homocysteine (Hcy) thiolactone). Another type of protein homocysteinylation occurs through the formation of a covalent -S-S- bond, found primarily with cysteine residues (protein-S-homocysteinylation). Scant data are available in the literature regarding the extent to which alterations in protein homocysteinylation are present in uremic patients on hemodialysis, and the effects of folate treatment are not known. Protein homocysteinylation was measured in a group of hemodialysis patients (n=28) compared to controls (n=14), with a new method combining protein reduction, gel filtration and Hcy derivatization. Chemical hydrolysis was performed, followed by high-pressure liquid chromatography separation. The effects of folate treatment on protein homocysteinylation, as well as in vitro binding characteristics were evaluated. Plasma Hcy, protein-N-homocysteinylation and protein-S-homocysteinylation were significantly higher in patients vs controls. Plasma Hcy and protein-S-homocysteinylation were significantly correlated. After 2 months of oral folate treatment, protein-N-homocysteinylation was normalized, and protein-S-homocysteinylation was significantly reduced. Studies on albumin-binding capacity after in vitro homocysteinylation show that homocysteinylated albumin is significantly altered at the diazepam-binding site. In conclusion, increased protein homocysteinylation is present in hemodialysis patients, with possible consequences in terms of protein function. This alteration can be partially reversed after folate treatment.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with đź’™ for researchers
Part of the Research Solutions Family.