Effects of Chlorhexidine mouthwash on the oral microbiome.

Following a single blind, cross-over and non-randomized design we investigated the effect of 7-day use of chlorhexidine (CHX) mouthwash on the salivary microbiome as well as several saliva and plasma biomarkers in 36 healthy individuals. They rinsed their mouth (for 1 min) twice a day for seven days with a placebo mouthwash and then repeated this protocol with CHX mouthwash for a further seven days. Saliva and blood samples were taken at the end of each treatment to analyse the abundance and diversity of oral bacteria, and pH, lactate, glucose, nitrate and nitrite concentrations. CHX significantly increased the abundance of Firmicutes and Proteobacteria, and reduced the content of Bacteroidetes, TM7, SR1 and Fusobacteria. This shift was associated with a significant decrease in saliva pH and buffering capacity, accompanied by an increase in saliva lactate and glucose levels. Lower saliva and plasma nitrite concentrations were found after using CHX, followed by a trend of increased systolic blood pressure. Overall, this study demonstrates that mouthwash containing CHX is associated with a major shift in the salivary microbiome, leading to more acidic conditions and lower nitrite availability in healthy individuals.

Therapeutic recommendations in HFE hemochromatosis for p.Cys282Tyr (C282Y/C282Y) homozygous genotype.

Although guidelines are available for hereditary hemochromatosis, a high percentage of the recommendations within them are not shared between the different guidelines. Our main aim is to provide an objective, simple, brief, and practical set of recommendations about therapeutic aspects of HFE hemochromatosis for p.Cys282Tyr (C282Y/C282Y) homozygous genotype, based on the published scientific studies and guidelines, in a form that is reasonably comprehensible to patients and people without medical training. This final version was approved at the Hemochromatosis International meeting on 12th May 2017 in Los Angeles.

Non-transferrin-bound iron is associated with biomarkers of oxidative stress, inflammation and endothelial dysfunction in type 2 diabetes.

AIMS: To investigate the association between circulating non-transferrin-bound iron [NTBI], and markers of oxidative stress, endothelial function and inflammation in subjects with type 2 diabetes and non-diabetic subjects with varying degrees of obesity. METHODS: Plasma NTBI was measured by HPLC, together with total iron, iron-binding capacity, transferrin saturation and soluble transferrin receptor, together with total and reduced ascorbate, malondialdehyde [MDA], E-selectin and high-sensitivity c-reactive protein [hs-CRP] in groups of 28 subjects with type 2 diabetes, 28 non-obese controls and 17 obese non-diabetic subjects. RESULTS: Levels of NTBI were higher than controls in the diabetes group, but the total serum iron levels were lower. MDA levels were higher than controls in both the diabetes and obese groups, and this was associated with higher levels of oxidised ascorbate. hs-CRP levels were higher in both the diabetes and obese groups, and E-selectin was significantly higher in the diabetes group. There were strong positive correlations between HbA1c levels and NTBI [P<0.01], HbA1c and E-selectin [P<0.001] and NTBI and E-selectin [P<0.02] in the diabetes group. CONCLUSION: These results support the hypothesis that iron-mediated oxidative stress may be a mechanism linking poor glycaemic control with vascular dysfunction in type 2 diabetes.

On the source of the non-transferrin-bound iron which accumulates in packed red blood cell units during storage.

BACKGROUND: Recent studies have shown large increases in non-transferrin-bound iron (NTBI) and biomarkers of oxidative stress in the extracellular medium of packed red blood cell units during storage. It has been further suggested that transfusion-mediated iron and oxidative load may contribute to transfusion-related morbidity in premature babies. The origin and nature of the NTBI is currently unclear, but the release of iron from oxidatively modified haemoglobin and haem has been suggested. The purpose of this study was to investigate whether this may be the case. MATERIALS AND METHODS: The concentration of haem in the extracellular fluid of paediatric packed cell units stored from 3 to 35 days was measured using a commercial haem assay. In vitro studies were conducted using haem (haemin; ferriprotoporphyrin IX chloride) to determine whether the NTBI assay was able to react with and measure iron associated with haem in the presence and absence of oxidising agents. RESULTS: The level of haem in the extracellular fluid of paediatric packed cell units rose gradually from day 3 to day 21, then more rapidly to day 35. Very little NTBI was released from haem in the absence of oxidising agents, but the amount rose in a dose- and time-dependent manner in proportion to the oxidation of haem by incubation with H2O2. DISCUSSION: The results of the study imply that the NTBI measured in previous studies may derive from the oxidatively modified haem that builds up in the extracellular fluid of packed red blood cell units during storage. The potential influence of this on transfusion mediated morbidity is discussed.

The influence of storage age on iron status, oxidative stress and antioxidant protection in paediatric packed cell units.

BACKGROUND: Receipt of blood transfusions is associated with the major consequences of prematurity such as bronchopulmonary dysplasia. Transfusion-mediated (iron-induced) oxidative damage, coupled with the limited ability of the premature baby to deal with enhanced iron and oxidative load may contribute to this. Adverse effects of transfusion may be related to duration of storage. This study examined the influence of storage on iron and oxidative status in paediatric packed red blood cell units. MATERIALS AND METHODS: Paediatric packed red blood cell units were sampled 3 days post-donation, then at 7 days and weekly until day 35. The extracellular medium was separated and the following measured: total iron concentration, total iron binding capacity, non-transferrin-bound iron, haemoglobin, total and reduced ascorbate, glutathione and malondialdehyde. RESULTS: Measurable total and non-transferrin bound iron were present in the extracellular fluid of paediatric packs on day 3. Both parameters rose almost linearly to maximal values at 35 days. Haemoglobin and malondialdehyde levels rose gradually from day 3 to day 21, then more steeply to day 35. Ascorbate existed mainly in the oxidised form and fell rapidly towards the end of storage. Intracellular GSH fell throughout the period of storage. Strong correlations existed between biomarkers of oxidative damage and iron parameters. DISCUSSION: These data suggest that iron released following the initial preparation of packed red blood cell units may derive from free radical-mediated oxidative damage to the red blood cells and haemoglobin, rather than from extracellular haemoglobin. Iron continues to be released during storage as antioxidant protection declines. A cycle of free radical-mediated damage may initiate and then further exacerbate iron release during storage which, in turn, may mediate further free radical-mediated cellular damage. The potential consequences to recipients of older stored blood may be significant.

Red meat, dietary heme iron, and risk of type 2 diabetes: the involvement of advanced lipoxidation endproducts.

There is growing evidence of disordered iron homeostasis in the diabetic condition, with links proposed between dietary iron intakes and both the risk of disease and the risk of complications of advanced disease. In the United States, Britain, and Canada, the largest dietary contributors of iron are cereals and cereal products and meat and meat products. This review discusses the findings of cohort studies and meta-analyses of heme iron and red meat intakes and the risk of type 2 diabetes. These suggest that processed red meat is associated with increased risk, with high intakes of red meat possibly also associated with a small increased risk. Historically, humans have relied on large quantities of heme iron and red meat in their diets, and therefore it is paradoxical that iron from meat sources should be associated with the risk of type 2 diabetes. A reason for this association may be drawn from studies of dietary advanced glycation and lipoxidation endproducts present in processed food and the mechanisms by which insulin output by pancreatic islet cells might be influenced by the protein modifications present in processed red meat.

The effect of maximum storage on iron status, oxidative stress and antioxidant protection in paediatric packed cell units.

BACKGROUND: Premature babies may receive multiple transfusions during the first weeks of their life. Strong associations exist between the receipt of blood transfusions and the development of the major consequences of prematurity such as retinopathy and chronic lung disease. The possible physiological link between the receipt of blood and disease is unclear, but iron-induced oxidative damage and/or bacterial colonisation would promote these conditions. Premature babies are poorly equipped to deal with any increases in iron and oxidative load that they may acquire via blood transfusions. To determine whether there are any relationships between these factors, we studied iron and oxidative status of just expired (i.e. 36 days old) paediatric red blood cell (RBC) packs. MATERIALS AND METHODS: Just expired paediatric RBC packs were obtained from the local blood bank. The extracellular medium surrounding the RBC was separated by centrifugation and the following parameters measured: total iron concentration, total iron binding capacity, non-transferrin-bound iron [NTBI], haemoglobin, total and reduced ascorbate, and malondialdehyde concentration. RESULTS: The extracellular fluid of the paediatric packs (n =13) was rich in iron, a high percentage of which (36%) was present as potentially toxic NTBI. It was highly redox active with limited antioxidant protection and iron-binding capacity. DISCUSSION: The extracellular medium surrounding packed RBC could potentially be toxic if administered to patients with limited iron sequestering and antioxidant capacity, such as premature babies. Further studies are required to determine at what point during storage these changes become potentially harmful so that clinical studies can examine the optimal storage time for blood destined for premature babies.