Since the discovery of vitamin C, the number of its known biological functions is continually expanding. Both the names ascorbic acid and vitamin C reflect its antiscorbutic properties due to its role in the synthesis of collagen in connective tissues. Ascorbate acts as an electron-donor keeping iron in the ferrous state thereby maintaining the full activity of collagen hydroxylases; parallel reactions with a variety of dioxygenases affect the expression of a wide array of genes, for example via the HIF system, as well as via the epigenetic landscape of cells and tissues. In fact, all known physiological and biochemical functions of ascorbate are due to its action as an electron donor. The ability to donate one or two electrons makes AscH(-) an excellent reducing agent and antioxidant. Ascorbate readily undergoes pH-dependent autoxidation producing hydrogen peroxide (H(2)O(2)). In the presence of catalytic metals this oxidation is accelerated. In this review, we show that the chemical and biochemical nature of ascorbate contribute to its antioxidant as well as its prooxidant properties. Recent pharmacokinetic data indicate that intravenous (i.v.) administration of ascorbate bypasses the tight control of the gut producing highly elevated plasma levels; ascorbate at very high levels can act as prodrug to deliver a significant flux of H(2)O(2) to tumors. This new knowledge has rekindled interest and spurred new research into the clinical potential of pharmacological ascorbate. Knowledge and understanding of the mechanisms of action of pharmacological ascorbate bring a rationale to its use to treat disease especially the use of i.v. delivery of pharmacological ascorbate as an adjuvant in the treatment of cancer.
Malnutrition (over and under-nutrition) is highly prevalent in patients admitted to hospital and it is a well-known risk factor for increased morbidity and mortality. Nutritional problems are often misdiagnosed, and especially the coexistence of over and undernutrition is not usually recognized. We aimed to develop and validate a screening tool for the easy detection and reporting of both undernutrition and overnutrition, specifically identifying the clinical conditions where the two types of malnutrition coexist.
Studies of contemporary populations have demonstrated an association between decreased dietary diversity due to resource scarcity or underutilization and an increase in diseases related to poor micronutrient intake. With a reduction of dietary diversity, it is often the women and children in a population who are the first to suffer the effects of poor micronutrient status. Scurvy, a disease of prolonged vitamin C deficiency, is a micronutrient malnutrition disorder associated with resource scarcity, low dietary diversity, and/or dependence on high carbohydrate staple-foods. The aim of this paper is to assess the potential impact of nutritional transition on the prevalence of diseases of nutritional insufficiency in an archaeological sample. Here, we report palaeopathological findings from an Early Formative Period transitional site located in coastal Northern Chile (Quiani-7). The subadult cohort from this site is composed of four perinates who exhibit a number of non-specific skeletal changes suggestive of a systemic pathological condition. One of these is associated with an adult female exhibiting diagnostic skeletal lesions of scurvy. We argue that the lesions exhibited by these perinates may represent maternal transmission of vitamin C deficiency but acknowledge that there are difficulties in applying current diagnostic criteria for scurvy to individuals this young.
The vitamin C deficiency disease scurvy is characterised by musculoskeletal pain and recent epidemiological evidence has indicated an association between suboptimal vitamin C status and spinal pain. Furthermore, accumulating evidence indicates that vitamin C administration can exhibit analgesic properties in some clinical conditions. The prevalence of hypovitaminosis C and vitamin C deficiency is high in various patient groups, such as surgical/trauma, infectious diseases and cancer patients. A number of recent clinical studies have shown that vitamin C administration to patients with chronic regional pain syndrome decreases their symptoms. Acute herpetic and post-herpetic neuralgia is also diminished with high dose vitamin C administration. Furthermore, cancer-related pain is decreased with high dose vitamin C, contributing to enhanced patient quality of life. A number of mechanisms have been proposed for vitamin C’s analgesic properties. Herein we propose a novel analgesic mechanism for vitamin C; as a cofactor for the biosynthesis of amidated opioid peptides. It is well established that vitamin C participates in the amidation of peptides, through acting as a cofactor for peptidyl-glycine α-amidating monooxygenase, the only enzyme known to amidate the carboxy terminal residue of neuropeptides and peptide hormones. Support for our proposed mechanism comes from studies which show a decreased requirement for opioid analgesics in surgical and cancer patients administered high dose vitamin C. Overall, vitamin C appears to be a safe and effective adjunctive therapy for acute and chronic pain relief in specific patient groups.
Streptococcus equi subsp. zooepidemicus is a known zoonotic pathogen. In this public health investigation conducted in Virginia, USA, in 2013, we identified a probable family cluster of S. zooepidemicus cases linked epidemiologically and genetically to infected guinea pigs. S. zooepidemicus infections should be considered in patients who have severe clinical illness and report guinea pig exposure.
Ascorbate (vitamin C) is best known for its role in scurvy, in which the hydroxylation of collagen catalyzed by dioxygenases is incomplete due to ascorbate deficiency. Here, we report a novel function of ascorbate in the hydroxylation of 5-methylcytosine (5-mC) to 5-hydroxymethylcytosine (5-hmC) in DNA catalyzed by Tet (ten-eleven translocation) methylcytosine dioxygenase. The content of 5-hmC is extremely low in mouse embryonic fibroblasts (MEFs) cultured in ascorbate-free medium. Additions of ascorbate dose- and time-dependently enhance the generation of 5-hmC, without any effects on the expression of Tet genes. Treatment with another reducer glutathione (GSH) does not change the level of 5-hmC. Further, blocking ascorbate entry into cells by phloretin and knocking down Tet1-3 expression by short interference RNAs (siRNA) significantly inhibit the effect of ascorbate on 5-hmC. These results suggest that ascorbate enhances 5-hmC generation, most likely by acting as a cofactor for Tet methylcytosine dioxygenase to hydroxylate 5-mC. Thus, we have uncovered a novel role for ascorbate in modulating the epigenetic control of genome activity.
- International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases
- Published about 3 years ago
We describe a case of scurvy in a 10-year-old boy with autism spectrum disorder. His clinical presentation was initially thought to be due to osteomyelitis, for which empirical antimicrobial therapy was initiated. Further invasive and ultimately unnecessary investigations were avoided when scurvy was considered in the context of a restricted diet and classic signs of vitamin C deficiency. Infectious Diseases specialists should be aware of scurvy as an important mimicker of osteoarticular infections when involved in the care of patients at risk for nutritional deficiencies.
Protected Mealtimes is an intervention developed to address the problem of malnutrition in hospitalised patients through increasing positive interruptions (such as feeding assistance) whilst minimising unnecessary interruptions (including ward rounds and diagnostic procedures) during mealtimes. This clinical trial aimed to measure the effect of implementing Protected Mealtimes on the energy and protein intake of patients admitted to the subacute setting.
Rabbits and guinea pigs are increasingly popular pets in the UK, yet little is known about their common ailments, or how these relate to what appears in the published literature. The aim of this study was to characterise the common conditions of rabbits and guinea pigs, and to compare these with the topics found in the published literature. Information about the common conditions seen in rabbits and guinea pigs in clinical practice was obtained from a survey of UK veterinarians. The common conditions seen were compared with results from a structured literature search. Conditions relating to the dental (29.9%), and skin (37.6%) body systems were commonly nominated by veterinarians for rabbits and guinea pigs, respectively. A total of 655 rabbit and 1086 guinea pig citations were examined and there appeared to be a mismatch between the conditions nominated in the veterinary questionnaire, and those found in the literature. This is the first time that the published literature has been compared to the nominated caseload of veterinarians in practice, and there is concern that the literature about rabbits and guinea pigs may not be representative of, or relevant to the caseload seen in clinical practice. This is of importance for clinicians being able to apply an objective, evidence-based approach. The publishing of clinically-relevant, research-based evidence should be prioritised.
Impacts of High-Protein Oral Nutritional Supplements Among Malnourished Men and Women with Sarcopenia: A Multicenter, Randomized, Double-Blinded, Controlled Trial
- Journal of the American Medical Directors Association
- Published over 4 years ago
Recent evidence suggests that nutritional interventions may improve muscle outcomes in malnutrition and sarcopenia.