Accumulation In Urine Research Articles

Changes in blood biochemical parameters in highly productive cows with ketosis.

Biochemical blood testing is the main diagnostic indicator of the clinical condition of highly productive animals and a method of determining changes in metabolic disorders. This study focuses on metabolic changes (ketosis), which are of the utmost importance in the assessment of the health status of animals, as well as differences in intergroup characteristics. The main focus of this study is to demonstrate the influence of subclinical ketosis in highly productive cows on changes in biochemical blood parameters during different physiological periods to further prevent this disease, adjust feeding rations, and prevent premature culling of animals. This study aimed to evaluate and establish changes in the biochemical status dynamics of highly productive cows with metabolic disorders in an industrial livestock complex. Blood samples were systematically collected from highly productive cows of the Simmental breed (n = 60) and served as the primary material for subsequent analyses. Each methodological step was designed to ensure evaluation of the metabolic changes associated with post-calving adjustments in highly productive dairy cows. This study employed a comprehensive approach integrating clinical assessments, laboratory analyses, biochemical evaluations, instrumental measurements, and statistical analyses. A biochemical blood test showed that the number of ketone bodies in the experimental group exceeded the norm, varied depending on the physiological state of the animals, and ranged from 0.89 to 1.45 mmol/L. At 10 days after calving, the highest indicator was 1.45 ± 0.05 mmol/L. This indicator was 1.05 mmol/L higher than that in the control group and exceeded the norm by 0.95. Excess ketone bodies in the blood of animals led to accumulation in urine and milk, indicating a disturbance in metabolic processes in the body and a decrease in the quality of animal husbandry products. The sample size and the focus on a single breed from one geographical location may limit the generalizability of the findings. Further research should explore the mechanistic bases of ketosis development, potentially integrating genomic and proteomic approaches to understand the genetic predispositions and molecular pathways involved.

Urinary markers of pain in children in neonatal intensive care units: a cross-section study

Introduction: Repetitive exposition to pain negatively affects newborns development. Procedural pain in newborn in Neonatal Intensive Care Unit (NICU) triggers a series of physiological, behavioral and hormonal disorders that may set off the impairment of the neurological development in preterm infants, who undergo long periods of hospitalization at a moment of physiological immaturity and fast brain development. Objective: This study aimed not only to observe the pain score in newborns and infants when undergoing painful procedures in neonatal intensive care units but also to analyse urinary IL-8 and cortisol levels at such stressful moments. Methods: Patients were submitted to venipuncture and to other methods of blood collection. Cortisol and IL-8 levels were measured by immunometric assay and chemiluminescence detection. For the collection of data regarding observation of neonatal pain, the Neonatal Infant Pain Scale was used with immediate results. To describe the qualitative variables, absolute and relative frequencies were used. For the quantitative variables with normal distribution, mean, standard deviation, minimum and maximum were used. Results: A total of 81 patients were included: 47 were submitted to venipuncture and 36 to other methods of blood collection. Significance for cortisol can be seen (p=0.04); however, IL-8 levels, when associated with the pain scale, were not sensitive enough (p=0.11). Conclusion: The results showed that cortisol is a better marker for pain than IL-8, and its accumulation in urine may help the detection and interpretation of pain. Conclusion: Based on this information, nurses can step in to reduce the discomfort brought by painful procedures, and thus highlight humanistic practices in nursing assistance.

Nickel Accumulation in Saliva and Urine Post Orthodontic Fixed Appliance Treatment in Malay Population

Objective: Prolonged nickel exposure, even in low amounts, is cytotoxic, genotoxic and carcinogenic. The study aims to evaluate the salivary and urinary nickel levels post-orthodontic fixed appliance treatment. Materials and Methods: Saliva and urine samples of fourteen orthodontic patients were taken at debonding (T0), after one month (T1), and three months post-debonding (T2), and compared with the control group. Samples were analysed using Inductively Coupled Plasma Optical Mass Spectrometry (ICP-MS) and IBM SPSS Version 27 was used for statistical analyses. Results: The mean (SD) of orthodontic treatment duration was 33.6 (9.6) months. In comparison to the control group, the mean (SD) nickel levels in saliva and urine were highest at debonding (T0) with 12.71 ppb (9.64) and 9.71 ppb (8.27), respectively. In the test group, there was a significant difference in nickel level in saliva between T0 and T1 (MD = 9.75, 95% CI: 3.71, 15.71; p < 0.05) and in urine between T0 and T1 (MD = 6.46, 95% CI: 1.38, 11.55; p = 0.012). Conclusion: Our results clearly demonstrated that the nickel level in saliva and urine remained higher at the end of orthodontic treatment compared to the control group. Further studies with a longer duration of observation and larger samples are suggested. Furthermore, our study indicates it is essential to confirm the effects of long-duration of orthodontic treatment and its post-treatment nickel level. This study raised attention about the biocompatibility of mechanical orthodontic treatment vs sustainable general health.

The role of thioredoxin and glutathione systems in arsenic-induced liver injury in rats under glutathione depletion

ABSTRACT Antioxidant systems like thioredoxin (Trx) and glutaredoxin (Grx) maintain oxidative stress balance. These systems have cross-talk supported by some in vitro studies. We investigated the underlying mechanisms of arsenic-induced liver injury in glutathione-deficient rats and whether there was any cross-talk between the Trx and Grx systems. The rats in arsenic-treated groups were administered with sodium arsenite (10, 20 mg/kg b w/d) for four weeks. In buthionine sulfoximine (BSO, an inhibitor of GSH) and 20 mg/kg arsenic combined groups, rats were injected with 2 mmol/kg BSO intraperitoneally twice per week. BSO exacerbated arsenic-induced liver injury by increasing arsenic accumulation in urine, serum, and liver while decreasing glutathione activity and resulting in upregulated mRNA expression of the Trx system and downregulation of Grx mRNA expression. The impact of Trx lasted longer than that of the Grx. The Trx system remained highly expressed, while GSH, Grx1, and Grx2 levels were decreased. The inhibitory effect of only BSO treatment on Grx1 and Grx2 was not pronounced. However, the combined impact of arsenic and BSO upregulated Trx expression, primarily related to further reduction of GSH. As a result, the suppressed Grxs were protected by the upregulated Trxs, which serve as a backup antioxidant defense system in the liver.

Changes in arsenic accumulation and metabolic capacity after environmental management measures in mining area

Due to the public health concern of arsenic, environmental management measures in mining areas had been implemented. To assess the effect of environmental management measures in the mining area comprehensively, arsenic accumulation in the urine, hair, nails, and urinary metabolites of residents in a realgar mining area in Hunan province, China were investigated in 2019, and the changes in arsenic levels in the biomarkers during 2012–2019 were tracked. The importance of confounding factors (age, sex, occupation, residence, clinical history, vegetable source, cooking fuel, smoking, alcohol consumption, BMI) was analyzed using the Boruta algorithm. After the implementation of environmental management measures (including ceasing mining and smelting activities, building landfills, adjusting the planting structure, and soil restoration), urine, hair, and nail arsenic concentration decreased drastically but were still excessive. Arsenic accumulation was highest in older male miners who were long settled in the mining area and consumed homegrown vegetables. The only factor for changes in urinary arsenic levels was the cooking fuel type; residents using wood as cooking fuel experienced sustained arsenic exposure. Occupation and sex were important for determining arsenic changes in the hair and nails. Short-term arsenic accumulation in urine was affected by arsenic exposure, while long-term accumulation in hair and nails by arsenic metabolic capacity. The percentage of urinary arsenic metabolism and arsenic methylation indices of the participants in the mining area were within the normal range (%iAs: 10–30 %, %MMA: 10–20 %, % DMA: 60–80 %); samples indicated worse metabolic capacity than the reference population. The arsenic metabolic capacity of male miners was relatively weak, probably aggravated by alcohol drinking and smoking. Without soil remediation, arsenic exposure will continue. Homegrown vegetables and biomass fuels should be abandoned; reduced cigarette and alcohol consumption is recommended. Urinary arsenic would be more proper for assessing environmental remediation in mining areas.

Quinolones as a Potential Drug in Genitourinary Cancer Treatment-A Literature Review.

Quinolones, broad-spectrum antibiotics, are frequently prescribed by urologists for many urological disorders. The mechanism of their bactericidal activity is based on the inhibition of topoisomerase II or IV complex with DNA, which consequently leads to cell death. It has been observed that these antibiotics also act against the analogous enzymes present in eukaryotic cells. Due to their higher accumulation in urine and prostate tissue than in serum, these drugs seem to be ideal candidates for application in genitourinary cancer treatment. In this study, an extensive literature review has been performed to collect information about concentrations achievable in urine and prostate tissue together with information about anticancer properties of 15 quinolones. Special attention was paid to the application of cytotoxic properties of quinolones for bladder and prostate cancer cell lines. Data available in the literature showed promising properties of quinolones, especially in the case of urinary bladder cancer treatment. In the case of prostate cancer, due to low concentrations of quinolones achievable in prostate tissue, combination therapy with other chemotherapeutics or another method of drug administration is necessary.

Organic Acidemias.

Organic Acidemias.

Bioenergetic maladaptation and release of HMGB1 in calcineurin inhibitor-mediated nephrotoxicity

Calcineurin inhibitors (CNIs) are potent immunosuppressive agents, universally used following solid organ transplantation to prevent rejection. Although effective, the long-term use of CNIs is associated with nephrotoxicity. The etiology of this adverse effect is complex, and effective therapeutic interventions remain to be determined. Using a combination of in vitro techniques and a mouse model of CNI-mediated nephrotoxicity, we found that the CNIs, cyclosporine A (CsA), and tacrolimus (TAC) share a similar mechanism of tubular epithelial kidney cell injury, including mitochondrial dysfunction and release of High-Mobility Group Box I (HMGB1). CNIs promote bioenergetic reprogramming due to mitochondrial dysfunction and a shift toward glycolytic metabolism. These events were accompanied by diminished cell-to-cell adhesion, loss of the epithelial cell phenotype, and release of HMGB1. Notably, Erk1/2 inhibitors effectively diminished HMGB1 release, and similar inhibitor was observed on inclusion of pan-caspase inhibitor zVAD-FMK. In vivo, while CNIs activate tissue proremodeling signaling pathways, MAPK/Erk1/2 inhibitor prevented nephrotoxicity, including diminished HMGB1 release from kidney epithelial cells and accumulation in urine. In summary, HMGB1 is an early indicator and marker of progressive nephrotoxicity induced by CNIs. We suggest that proremodeling signaling pathway and loss of mitochondrial redox/bioenergetics homeostasis are crucial therapeutic targets to ameliorate CNI-mediated nephrotoxicity.

An investigation of calcium carbonate core-shell particles for incorporation of 225Ac and sequester of daughter radionuclides: in vitro and in vivo studies

Alpha therapy provides an outstanding prospect in the treatment of recalcitrant and micrometastatic cancers. However, side effects on the normal tissues and organs (especially, kidneys) due to the release of daughter isotopes from α-emitters remain a bottleneck. In this work, calcium carbonate core-shell particles of different sizes were considered as isotope carriers for encapsulation of 225Ac (highly powerful alpha-emitter that generates 4 net alpha particle isotopes in a short decay chain) in order to achieve in vitro and in vivo retention of 225Ac and its daughter isotopes. According to the in vitro studies, the developed calcium carbonate core-shell particles were able to retain 225Ac and its daughter isotopes (221Fr and 213Bi) exhibited good stability in biological media and dose-dependent biocompatibility (over 30 d). The SPECT imaging demonstrated the size-dependent distribution of 225Ac-doped core-shell particles. Further, in vivo studies confirmed the high retention efficiency of calcium carbonate core-shell particles, which was demonstrated in normal Wistar rats (up to 10 d). Interestingly, the radioactivity accumulation in kidney and urine was significantly less for encapsulated 225Ac than in case of non-encapsulated form of 225Ac (225Ac conjugated with albumin), indicating the absence of radioisotope leakage from the developed particles. Thus, our study validates the application of 225Ac-doped core-shell particles to sequester α-emitter (225Ac) and its decay products in order to reduce their systemic toxicity during alpha therapy.

Capillary electrophoresis with capacitively coupled contactless conductivity detection for the determination of urinary ethylmalonic acid for the diagnosis of ethylmalonic aciduria.

Ethylmalonic acid is a metabolic organic acid, and its accumulation in urine is diagnostic of ethylmalonic aciduria. In this study, a simple and fast method employing capillary electrophoresis equipped with capacitively coupled contactless conductivity detection was developed for the detection of ethylmalonic acid in urine samples. The optimized electrophoretic separation was performed in 50mmol/L 2-(N-morpholino)ethanesulfonic acid solution, buffered at a pH of 6.5, and contained 0.13mmol/L cetyltrimethylammonium bromide as an electroosmotic modifier. Electrophoresis was run at 28kV in reversed polarity. The linear range of ethylmalonic acid concentration was between 1 and 100mg/L with a regression coefficient of 0.9998. This method had good intra- and interday precision with<5% relative standard deviations. The detection limit (signal-to-noise ratio=3) and the quantification limit (signal-to-noise ratio=10) values were 0.139 and 0.466mg/L, respectively. Using our optimized conditions, the method was successfully employed for the detection of ethylmalonic acid in urine sample of ethylmalonic aciduria patient.

Urinary mitochondrial DNA associates with delayed graft function following renal transplantation.

Ischaemia-reperfusion (IR) injury is an important determinant of delayed graft function (DGF) affecting allograft function. Mitochondrial DNA (mtDNA) is released upon cell death and platelet activation into the extracellular environment and has been suggested to be a biomarker in several diseases. Whether extracellular mtDNA accumulates in plasma and/or urine upon renal IR and predisposes DGF is unknown. C57BL/6J wild-type mice were subjected to renal IR. In addition, an observational case-control study was set up enrolling 43 patients who underwent kidney transplantation. One day post-IR in mice and a few days following renal transplantation in human, blood and urine were collected. Patients were stratified into DGF and non-DGF groups. mtDNA-encoded genes accumulate in urine and plasma in both mice subjected to renal IR injury and in humans following renal transplantation. In human renal transplant recipients, cold ischaemia time and renal function correlate with urinary mtDNA levels. Urinary mtDNA levels but not urinary nuclear DNA levels were significantly higher in the DGF group compared with the non-DGF group. Multiple receiver operating characteristic curves revealed significant diagnostic performance for mtDNA-encoded genes cytochrome c oxidase III (COXIII); nicotinamide adenine dinucleotide hydrogen subunit 1 (NADH-deh); mitochondrially encoded, mitochondrially encoded nicotinamide adenine dinucleotide dehydrogenase 2 (MT-ND2) with an area under the curve of, respectively, 0.71 [P = 0.03; 95% confidence interval (CI) 0.54-0.89], 0.75 (P = 0.01; 95% CI 0.58-0.91) and 0.74 (P = 0.02; 95% CI 0.58-0.89). These data suggest that renal ischaemia time determines the level of mtDNA accumulation in urine, which associates with renal allograft function and the diagnosis of DGF following renal transplantation.

The significance of NGAL and KIM-1 proteins for diagnosis of acute kidney injury (AKI) in clinical practice

Introduction. Despite advances in medical care AKI (acute kidney injury) is associated with high morbidity and mortality. The lack of adequate early renal injury biomarkers is often a problem for an early AKI diagnosis. In recent years, numerous scientific studies have been carried out which reveal new urine and serum markers to assess the period of the kidney injury before revealing its late clinical effects. In most clinical settings, AKI is due to acute renal tubular necrosis which results in protein accumulation in urine. Determination of the concentrations of proteins such as NGAL (neutrophil gelatinase-associated lipocalin) and KIM-1 (kidney injury molecule-1) are of great significance in the diagnosis of AKI. Aim. The purpose of the study was to review the literature about significance of NGAL and KIM-1 proteins for diagnosis of acute kidney injury (AKI) in clinical practice. Materials and method. Analysis of Polish and foreign literature.

Identification of Metabolites of Maresin 1 in Human Neutrophils

The resolution of inflammation, once considered to be rather passive, is now understood to be a complex, regulated process. One of the components in this process is the action of pro‐resolving lipid mediators, including lipoxins, resolvins, protectins and maresins. Maresin 1 (MaR1), derived from the oxidation of docosahexaenoic acid (22:6, n‐3), exhibits biological activities relevant to the resolution of inflammation, such as inhibiting accumulation of neutrophils and enhancing efferocytosis by macrophages.Measurements of lipid mediators derived from arachidonic acid (20:4, n‐6) or docosahexaenoic acid have been quite successful in tissue exudates or cell culture‐based systems. However, efforts to measure these lipids in blood as a correlate to their production in vivo during an inflammatory episode have not been as straightforward and are somewhat controversial. In fact, much of our understanding of the role of prostaglandins and leukotrienes produced in vivo has come from measurement of urinary metabolites rather than plasma measurements.This work is aimed at identifying metabolites of MaR1 and their accumulation in urine, which will then allow us to develop sensitive and specific mass spectrometry‐based assays for their quantitation. As a first approach, we have investigated the metabolism of MaR1 by human neutrophils, which are key cells recruited to inflammatory sites where MaR1 is known to be produced in the first place. Using a combination of liquid chromatography, gas chromatography, UV spectrometry and mass spectrometry, we have identified five novel metabolites of maresin 1, which are produced in a time‐ and dose‐dependent manner by human neutrophils We present here the chromatographic and spectral properties of these metabolites, as well as their proposed chemical structures. Four of these metabolites are oxidized forms of MaR1, and contain one or two hydroxyl groups. Preliminary evidence suggests that at least one of these metabolites may also be present in the urine of mice injected with MaR1.These results open the possibility of investigating the role of MaR1 in experimental animal models and in human disease by analyzing its urinary metabolites. This will provide insight into the progression and possible treatment of several human diseases that include inflammation as a component in their progression.Support or Funding InformationThis work is supported in part by a grant from the Cayman Biomedical Research Institute.

The effect of endurance exercise on intestinal integrity in well-trained healthy men.

Exercise is one of the external factors associated with impairment of intestinal integrity, possibly leading to increased permeability and altered absorption. Here, we aimed to examine to what extent endurance exercise in the glycogen‐depleted state can affect intestinal permeability toward small molecules and protein‐derived peptides in relation to markers of intestinal function. Eleven well‐trained male volunteers (27 ± 4 years) ingested 40 g of casein protein and a lactulose/rhamnose (L/R) solution after an overnight fast in resting conditions (control) and after completing a dual – glycogen depletion and endurance – exercise protocol (first protocol execution). The entire procedure was repeated 1 week later (second protocol execution). Intestinal permeability was measured as L/R ratio in 5 h urine and 1 h plasma. Five‐hour urine excretion of betacasomorphin‐7 (BCM7), postprandial plasma amino acid levels, plasma fatty acid binding protein 2 (FABP‐2), serum pre‐haptoglobin 2 (preHP2), plasma glucagon‐like peptide 2 (GLP2), serum calprotectin, and dipeptidylpeptidase‐4 (DPP4) activity were studied as markers for excretion, intestinal functioning and recovery, inflammation, and BCM7 breakdown activity, respectively. BCM7 levels in urine were increased following the dual exercise protocol, in the first as well as the second protocol execution, whereas 1 h‐plasma L/R ratio was increased only following the first exercise protocol execution. FABP2, preHP2, and GLP2 were not changed after exercise, whereas calprotectin increased. Plasma citrulline levels following casein ingestion (iAUC) did not increase after exercise, as opposed to resting conditions. Endurance exercise in the glycogen depleted state resulted in a clear increase of BCM7 accumulation in urine, independent of DPP4 activity and intestinal permeability. Therefore, strenuous exercise could have an effect on the amount of food‐derived bioactive peptides crossing the epithelial barrier. The health consequence of increased passage needs more in depth studies.

Late-onset cutaneous porphyria in a patient heterozygous for a uroporphyrinogen III synthase gene mutation

Deficiency of uroporphyrinogen III synthase (UROS) causes congenital erythropoietic porphyria (CEP). The disease, originating from the inheritance of mutations within the UROS gene, presents a recessive form of transmission. In a few patients, a late-onset CEP-like phenotype without UROS mutations appears to be associated with a myelodysplastic syndrome. We report a 60-year-old man with late-onset signs of cutaneous porphyria and accumulation in urine, plasma and faeces of type I porphyrin isomers characteristic of CEP. Analysis of DNA from peripheral leucocytes, skin and bone marrow aspirate showed that he was a heterozygous carrier of a Cys73Arg (c.217 T>C) mutation within UROS. Sequencing of cDNA from peripheral blood confirmed heterozygosity and expression of the normal allele. Measurement of UROS enzymatic activity in erythrocytes showed values ~70% of normal, indirectly indicating expression of the normal allele. Differently from other cases of late-onset uroporphyria, the patient did not present thrombocytopenia or any evidence of a myelodysplastic syndrome. Five years of clinical follow-up showed persistence of skin signs and increased excretion of porphyrins, independently of lifestyle factors or changes in medication regimes. We hypothesize acquired mosaicism (in the bone marrow) affecting the UROS gene. Thus, unstable cellular clones initiated overproduction of isomer I porphyrins leading to a CEP phenotype. This could be explained either by a clonal expansion of the porphyric (Cys73Arg) allele or by loss of function of the normal allele. Cellular turnover would facilitate release of uroporphyrins into circulation and subsequent skin lesions. This is the first case of a CEP heterozygous carrier presenting clinical manifestations.

Association of Inorganics Accumulation with the Activation of NF-κB Signaling Pathway and the iNOS Expression of Lung Tissue in Xuanwei Lung Cancer Patients

背景与目的室内空气污染不仅会诱发哮喘，也会导致慢性阻塞性肺疾病(chronic obstructive pulmonary disease, COPD)，甚至促进肺癌发生。随着宣威肺癌的病因学研究，发现室内空气污染最终造成肺部无机颗粒物的沉积，这些物质可以造成肺泡细胞损伤、信号通路激活，最终促进肿瘤的发生。本研究旨在探讨宣威肺癌患者肺部中无机杂质的赋存以及核转录因子(nuclear factor κB, NF-κB) -诱导型一氧化氮合成酶(inducible nitric oxide synthase, iNOS)信号通路的激活情况。方法选取48例2013年12月-2014年11月在昆明医科大学第三附属医院行手术治疗的宣威肺癌患者与其他地区的肺癌患者作为研究对象，用透射电镜(transmission electron microscope, TME)对患者术后标本进行超微结构的观察，探究无机颗粒物的赋存情况；对患者的血清行细胞因子检测；对术后的标本行免疫组化以及蛋白质印迹(Western blot)，了解NF-κB-p65蛋白以及iNOS蛋白的表达；对肺癌组织中和尿液中的8-OHdG赋存进行检测。结果在宣威肺癌患者癌旁组织的肺泡Ⅱ型细胞、巨噬细胞中可见到大量纳米级无机物赋存；对无机物进行元素分析，含有硅(Silicon, Si)成分；宣威地区患者血清中白介素(interleukin, IL) -1β(31.50±19.16) pg/mL较其他地区肺癌患者(11.33±6.94) pg/mL高，差异有统计学意义(P < 0.01)；宣威肺癌与其他地区肺癌患者的术后病理组织中癌组织有NF-κB-p65和iNOS表达，较非宣威地区明显升高；癌旁和正常组织之间未见明显差异；宣威肺癌组织和尿液8-OHdG较非宣威地区肺癌患者高，肺癌患者尿液中的8-OhdG(40.124±8.597) ng/mgCr与其他地区患者(25.673±7.986) ng/mgCr相比，差异有统计学意义(P < 0.05)。结论肺部无机物的赋存以及NF-κB-iNOS信号通路的激活可能促进了宣威肺癌的发生。

Conflicts between Communities and Industry and Conflict Management from Evidence-Based Solutions: A Case Study of Zinc Mine Project, Mae Sod District, Tak Province, Thailand

This study was conducted to 1) study and analyze causes and results of conflict solving between zinc mine project and the community in the case of cadmium-contamination in Mae Tao watershed, Mae Sod District, Tak Province over the past 10 years, 2) prove the results of conflict resolution between both parties (Project and the community) by using new evidence based concepts to minimize conflicts between zinc mine project and the local community with respect to cadmium contamination in Mae Tao watershed in the past 10 years (2004-2014); as the problems involved many aspects in terms of such as economy, society, watershed structure, distribution of mineral deposit and mining, cadmium contamination in paddy soil, cadmium contamination in rice and cadmium contamination in human health status. This upon the least case of evidence-based information study found that case 1: problem concerning cadmium contamination in paddy soil in Mae Tao watershed has not yet been dealt with and conflicts are likely to arise again in case there appears stimulus, case 2: upon the use of evidence-based information to moderate extent, problem about cadmium contamination in rice grown in Mae Tao watershed was partially resolved and case 3: by criteria of using evidence-based information to the greatest event and the past that come related issues have been solved, cadmium accumulation in urine of people residing nearby and around Mae Tao watershed was believed not to get worse to cause Itai-Itai disease. Evidence base concept apparently gives a new neutral power in analysis of conflict resolutions in three case studies. However, the degree of success in conflict management by this approach depends on the complexity of the problems in individual case. The present study provides a convincing conclusion that the more the evidence-based knowledge the greater the success in conflict resolution.

Liver Damage Induced by Succinylacetone: A Shared Redox Imbalance Mechanism between Tyrosinemia and Hepatic Porphyrias

To show liver failure mediated by 5-aminolevulinic acid (ALA), a heme precursor accumulated in inborn and acquired porphyrias, rats were treated with succinylacetone methyl ester (SAME). Treated rats underwent the expected ALA accumulation in plasma, liver and urine as a result from inhibition of ALA dehydratase (ALAD) activity. The enzyme activity decreased concomitantly with diminished urinary coproporphyrin levels. Additionally, liver protein carbonyls, iron and ferritin were higher in groups treated with a lower concentration of SAME whereas malondialdehyde was higher in the group treated with a higher ester dose. Consistent with these biochemical data, chronic treatment SAME was associated with induced oxidative subcellular and tissue damage revealed by cytosolic and mitochondrial changes within the liver cells. Altogether, these data expand the understanding of the direct biochemical mechanism for liver cell death in hepatic inborn disorders by generating excess ALA and may foster future therapeutic-driven strategies to preserve liver function.

Bioavailability of selenium in ‘Jose’ tall wheatgrass (Thinopyrum ponticum var ‘Jose’) hay as a substitute for sodium selenite in the diets of dairy cattle

Due to its potential toxicity to wildlife, selenium (Se) is a highly regulated trace element in the San Joaquin Valley (SJV) of California. Tall wheatgrass (TWG) is a Se-accumulating, salt tolerant forage suitable for cropping systems which re-use agricultural drainage waters. Utilization of TWG hay as an alternative Se supplement for dairy cattle could reduce the importation of ‘new’ Se into the SJV in the form of sodium selenite (SS) diet supplements. Our study used Se-enriched (4.65mg/kg DM) TWG hay as a Se source for lactating dairy cows and measured Se accumulation in milk, blood, urine and feces to assess its bioavailability using several indices. Using a 3×3 Latin Square design, three pens of ~310 cows each were fed a similar total mixed ration over 4week periods, except for Se which was higher in TWG and SS diets (0.53 and 0.65mg/kg DM) vs. Control diet (0.35mg/kg DM). Feeding Se-enriched TWG increased blood Se by 6.4% over Control; whereas SS increased it by 4.8%, suggesting higher Se bioavailability for TWG vs. SS. Marginal Se outputs in milk, feces and urine were judged to be better indicators of bioavailability as they estimate Se specifically from supplemental SS or TWG hay. In milk, TWG cows expressed 3.0% of supplemented Se vs. 0.6% for SS cows, supporting higher Se bioavailability for TWG. In contrast, more supplemental Se was retained and not expressed in feces by the SS cows (72.5%) vs. TWG cows (55.1%) which suggested higher Se bioavailability for SS. Based on published guidelines, Se intakes were ‘adequate’ for cows in all treatment groups, but milk and fat production increased with Se supplementation suggesting that Control cows were Se-deficient to some extent. Collectively, results suggest that the Se in TWG hay had comparable bioavailability to Se in the base diet.

Rapid screening of classic galactosemia patients: a proof-of-concept study using high-throughput FTIR analysis of plasma.

Classic galactosemia is an autosomal recessive metabolic disease involving the galactose pathway, caused by the deficiency of galactose-1-phosphate uridyltransferase. Galactose accumulation induces in newborns many symptoms, such as liver disease, cataracts, and sepsis leading to death if untreated. Neonatal screening is developed and applied in many countries using several methods to detect galactose or its derived product accumulation in blood or urine. High-throughput FTIR spectroscopy was investigated as a potential tool in the current screening methods. IR spectra were obtained from blood plasma of healthy, diabetic, and galactosemic patients. The major spectral differences were in the carbohydrate region, which was first analysed in an exploratory manner using principal component analysis (PCA). PCA score plots showed a clear discrimination between diabetic and galactosemic patients and this was more marked as a function of the glucose and galactose increased concentration in these patients' plasma respectively. Then, a support vector machine leave-one-out cross-validation (SVM-LOOCV) classifier was built with the PCA scores as the input and the model was tested on median, mean and all spectra from the three population groups. This classifier was able to discriminate healthy/diabetic, healthy/galactosemic, and diabetic/galactosemic patients with sensitivity and specificity rates ranging from 80% to 94%. The total accuracy rate ranged from 87% to 96%. High-throughput FTIR spectroscopy combined with the SVM-LOOCV classification procedure appears to be a promising tool in the screening of galactosemia patients, with good sensitivity and specificity. Furthermore, this approach presents the advantages of being cost-effective, fast, and straightforward in the screening of galactosemic patients.