69 research outputs found

    Systematic Review of Potential Health Risks Posed by Pharmaceutical, Occupational and Consumer Exposures to Metallic and Nanoscale Aluminum, Aluminum Oxides, Aluminum Hydroxide and Its Soluble Salts

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    Aluminum (Al) is a ubiquitous substance encountered both naturally (as the third most abundant element) and intentionally (used in water, foods, pharmaceuticals, and vaccines); it is also present in ambient and occupational airborne particulates. Existing data underscore the importance of Al physical and chemical forms in relation to its uptake, accumulation, and systemic bioavailability. The present review represents a systematic examination of the peer-reviewed literature on the adverse health effects of Al materials published since a previous critical evaluation compiled by Krewski et al. (2007). Challenges encountered in carrying out the present review reflected the experimental use of different physical and chemical Al forms, different routes of administration, and different target organs in relation to the magnitude, frequency, and duration of exposure. Wide variations in diet can result in Al intakes that are often higher than the World Health Organization provisional tolerable weekly intake (PTWI), which is based on studies with Al citrate. Comparing daily dietary Al exposures on the basis of “total Al”assumes that gastrointestinal bioavailability for all dietary Al forms is equivalent to that for Al citrate, an approach that requires validation. Current occupational exposure limits (OELs) for identical Al substances vary as much as 15-fold. The toxicity of different Al forms depends in large measure on their physical behavior and relative solubility in water. The toxicity of soluble Al forms depends upon the delivered dose of Al+ 3 to target tissues. Trivalent Al reacts with water to produce bidentate superoxide coordination spheres [Al(O2)(H2O4)+ 2 and Al(H2O)6 + 3] that after complexation with O2•−, generate Al superoxides [Al(O2•)](H2O5)]+ 2. Semireduced AlO2• radicals deplete mitochondrial Fe and promote generation of H2O2, O2 • − and OH•. Thus, it is the Al+ 3-induced formation of oxygen radicals that accounts for the oxidative damage that leads to intrinsic apoptosis. In contrast, the toxicity of the insoluble Al oxides depends primarily on their behavior as particulates. Aluminum has been held responsible for human morbidity and mortality, but there is no consistent and convincing evidence to associate the Al found in food and drinking water at the doses and chemical forms presently consumed by people living in North America and Western Europe with increased risk for Alzheimer\u27s disease (AD). Neither is there clear evidence to show use of Al-containing underarm antiperspirants or cosmetics increases the risk of AD or breast cancer. Metallic Al, its oxides, and common Al salts have not been shown to be either genotoxic or carcinogenic. Aluminum exposures during neonatal and pediatric parenteral nutrition (PN) can impair bone mineralization and delay neurological development. Adverse effects to vaccines with Al adjuvants have occurred; however, recent controlled trials found that the immunologic response to certain vaccines with Al adjuvants was no greater, and in some cases less than, that after identical vaccination without Al adjuvants. The scientific literature on the adverse health effects of Al is extensive. Health risk assessments for Al must take into account individual co-factors (e.g., age, renal function, diet, gastric pH). Conclusions from the current review point to the need for refinement of the PTWI, reduction of Al contamination in PN solutions, justification for routine addition of Al to vaccines, and harmonization of OELs for Al substances

    Prognostic model to predict postoperative acute kidney injury in patients undergoing major gastrointestinal surgery based on a national prospective observational cohort study.

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    Background: Acute illness, existing co-morbidities and surgical stress response can all contribute to postoperative acute kidney injury (AKI) in patients undergoing major gastrointestinal surgery. The aim of this study was prospectively to develop a pragmatic prognostic model to stratify patients according to risk of developing AKI after major gastrointestinal surgery. Methods: This prospective multicentre cohort study included consecutive adults undergoing elective or emergency gastrointestinal resection, liver resection or stoma reversal in 2-week blocks over a continuous 3-month period. The primary outcome was the rate of AKI within 7 days of surgery. Bootstrap stability was used to select clinically plausible risk factors into the model. Internal model validation was carried out by bootstrap validation. Results: A total of 4544 patients were included across 173 centres in the UK and Ireland. The overall rate of AKI was 14·2 per cent (646 of 4544) and the 30-day mortality rate was 1·8 per cent (84 of 4544). Stage 1 AKI was significantly associated with 30-day mortality (unadjusted odds ratio 7·61, 95 per cent c.i. 4·49 to 12·90; P < 0·001), with increasing odds of death with each AKI stage. Six variables were selected for inclusion in the prognostic model: age, sex, ASA grade, preoperative estimated glomerular filtration rate, planned open surgery and preoperative use of either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Internal validation demonstrated good model discrimination (c-statistic 0·65). Discussion: Following major gastrointestinal surgery, AKI occurred in one in seven patients. This preoperative prognostic model identified patients at high risk of postoperative AKI. Validation in an independent data set is required to ensure generalizability

    Broadcasting Transitions in the United Arab Emirates

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    Immunoregulatory effect of Lactobacillus paracasei VL8 exopolysaccharide on RAW264.7 cells by NF-κB and MAPK pathways

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    This study explored the immunoregulatory mechanism of VL8-EPS, obtained from Viili. An RAW264.7 macrophage cell-line was used along with real-time quantitative PCR to evaluate the impact of VL8-EPS on mRNA expression of IL-1β, TNF-α, IL-6, IL-10, and TLR4. Moreover, western blot assay was conducted to study the signal pathway of NF-κB and MAPK. The VL8-EPS was found to upregulate the mRNA expression of these cytokines and TLR4, while it promoted protein phosphorylation of p65, IκBα, ERK1/2, and JNK. The immunofluorescence staining and inhibitor blocking experiments proved that TLR4, NF-κB, and MAPK signal pathway were involved to secrete immune-enhancing substances. In conclusion, VL8-EPS was involved to activate downstream signal pathways of NF-κB and MAPK through TLR4 identification, which caused an increase in mRNA expression and cytokines release, ultimately exerting immune regulation

    Novel antioxidant peptides from protein hydrolysates of scallop (Argopecten irradians) mantle using enzymatic and microbial methods: Preparation, purification, identification and characterization

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    The aim of this study was to isolate, purify, identify, and characterize novel antioxidant peptides from protein hydrolysates of scallop (Argopecten irradians) mantle. Antioxidant peptides were obtained following protein hydrolysis, using a neutral protease, and microbial fermentation which was carried out by Bacillus licheniformis CICC 20033 under optimized conditions. Antioxidant peptides from the scallop mantle hydrolysates were then purified through fractionation using ultrafiltration membranes, and the fraction (<3 kDa) showed the highest oxygen radical absorbance capacity (ORAC) with the value of 0.362 μM trolox equivalent (TE)/mg. Subsequently, this fraction furtherly purified by Sephadex G-15 chromatography and reversed-phase high performance liquid chromatography (RP-HPLC) showed that the ORAC value was 2.96 ± 0.10 μM TE/mg. The ORAC value of fermented hydrolysates increased from 0.359 μM TE/mg to 0.425 μM TE/mg through 3 kDa ultrafiltration membrane. Five peptides from hydrolysates by enzyme treatment and twelve peptides from fermented scallop mantle hydrolysates were identified using LC-MS/MS. All selected sequences except Lys-Asp-Ala-Ala-Lys-Thr-Lys showed clear differences in scavenging activity for various radicals, which were dependent on the content and position of charged polar amino acids, aromatic amino acids and sulfur-containing amino acid in sequences
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