Soil-plant-gall relationships: from gall development to ecological patterns.

The adaptive nature of the galler habit has been tentatively explained by the nutrition, microenvironment, and enemy hypotheses. Soil attributes have direct relationships with these three hypotheses at the cellular and macroecological scales, but their influence has been restricted previously to effects on the nutritional status of the host plant on gall richness and abundance. Herein, we discuss the ionome patterns within gall tissues and their significance for gall development, physiology, structure, and for the nutrition of the gallers. Previous ecological and chemical quantification focused extensively on nitrogen and carbon contents, evoking the carbon-nutrient defence hypothesis as an explanation for establishing the plant-gall interaction. Different elements are involved in cell wall composition dynamics, antioxidant activity, and regulation of plant-gall water dynamics. An overview of the different soil-plant-gall relationships highlights the complexity of the nutritional requirements of gallers, which are strongly influenced by environmental soil traits. Soil and plant chemical profiles interact to determine the outcome of plant-herbivore interactions and need to be addressed by considering not only the soil features and galler nutrition but also the host plant's physiological traits. The quantitative and qualitative results for iron metabolism in gall tissues, as well as the roles of iron as an essential element in the physiology and reproduction of gallers suggest that it may represent a key nutritional resource, aligning with the nutrition hypothesis, and providing an integrative explanation for higher gall diversity in iron-rich soils.

The role of iron metabolism in the pathogenesis and treatment of multiple sclerosis.

Multiple sclerosis is a severe demyelinating disease mediated by cells of the innate and adaptive immune system, especially pathogenic T lymphocytes that produce the pro-inflammatory cytokine granulocyte-macrophage colony stimulating factor (GM-CSF). Although the factors and molecules that drive the genesis of these cells are not completely known, some were discovered and shown to promote the development of such cells, such as dietary factors. In this regard, iron, the most abundant chemical element on Earth, has been implicated in the development of pathogenic T lymphocytes and in MS development via its effects on neurons and glia. Therefore, the aim of this paper is to revise the state-of-art regarding the role of iron metabolism in cells of key importance to MS pathophysiology, such as pathogenic CD4+ T cells and CNS resident cells. Harnessing the knowledge of iron metabolism may aid in the discovery of new molecular targets and in the development of new drugs that tackle MS and other diseases that share similar pathophysiology.

MliR, a novel MerR-like regulator of iron homeostasis, impacts metabolism, membrane remodeling, and cell adhesion in the marine Bacteroidetes Bizionia argentinensis.

The MerR family is a group of transcriptional activators with conserved N-terminal helix-turn-helix DNA binding domains and variable C-terminal effector binding regions. In most MerR proteins the effector binding domain (EBD) contains a cysteine center suited for metal binding and mediates the response to environmental stimuli, such as oxidative stress, heavy metals or antibiotics. We here present a novel transcriptional regulator classified in the MerR superfamily that lacks an EBD domain and has neither conserved metal binding sites nor cysteine residues. This regulator from the psychrotolerant bacteria Bizionia argentinensis JUB59 is involved in iron homeostasis and was named MliR (MerR-like iron responsive Regulator). In silico analysis revealed that homologs of the MliR protein are widely distributed among different bacterial species. Deletion of the mliR gene led to decreased cell growth, increased cell adhesion and filamentation. Genome-wide transcriptomic analysis showed that genes associated with iron homeostasis were downregulated in mliR-deletion mutant. Through nuclear magnetic resonance-based metabolomics, ICP-MS, fluorescence microscopy and biochemical analysis we evaluated metabolic and phenotypic changes associated with mliR deletion. This work provides the first evidence of a MerR-family regulator involved in iron homeostasis and contributes to expanding our current knowledge on relevant metabolic pathways and cell remodeling mechanisms underlying in the adaptive response to iron availability in bacteria.

Stress response and virulence factors in bacterial pathogens relevant for Chilean aquaculture: current status and outlook of our knowledge.

The study of the stress responses in bacteria has given us a wealth of information regarding the mechanisms employed by these bacteria in aggressive or even non-optimal living conditions. This information has been applied by several researchers to identify molecular targets related to pathogeny, virulence, and survival, among others, and to design new prophylactic or therapeutic strategies against them. In this study, our knowledge of these mechanisms has been summarized with emphasis on some aquatic pathogenic bacteria of relevance to the health and productive aspects of Chilean salmon farming (Piscirickettsia salmonis, Tenacibaculum spp., Renibacterium salmoninarum, and Yersinia ruckeri). This study will aid further investigations aimed at shedding more light on possible lines of action for these pathogens in the coming years.

Serum ferritin and incident cardiometabolic diseases in Scottish adults.

BACKGROUND: Iron stores, estimated as ferritin levels, and type 2 diabetes (T2D) have been associated previously, while findings regarding coronary heart disease (CHD) and cerebrovascular disease (CEVD) are still inconclusive. No study has focused on simultaneous evaluation of associations between iron stores and the above cardiometabolic diseases (CMD) in the same population. We aim to evaluate the association between serum ferritin and risk of T2D, CHD and CEVD in Scottish population over a wide range of ferritin levels. METHODS: Longitudinal study in 6,497 participants of the 1995 and 1998 Scottish health surveys, who were followed-up until 2011. Cox regression models were conducted adjusting for age, sex/menopausal status, fibrinogen, GGT levels, smoking, alcohol consumption, total cholesterol, HDL-cholesterol, blood pressure, and BMI. Ferritin was used as continuous (sex/menopausal status-specific Z score) and categorical variable (sex/menopausal status-specific quartiles, quintiles and sextiles). RESULTS: During follow-up, 4.9% of the participants developed T2D, 5.3% CHD, and 2.3% CEVD. By using ferritin quartiles, serum ferritin was positively associated with T2D, CHD and CEVD but only the association with T2D remained after adjustment for covariates [Quartile 4 v. 1: adjusted HR 95% CI 1.59 (1.10-2.34); P = 0.006]. When ferritin sextiles were used (6 v. 1), the ferritin-CEVD association became slightly stronger and significant [adjusted HR 95% CI 2.08 (1.09-3.94); P = 0.024]. CONCLUSIONS: Iron stores relate differently to each CMD. Serum ferritin levels were positively and independently associated with incident T2D, and with incident CEVD if higher cut-off points for high ferritin levels were considered.

HFE hemochromatosis: an overview about therapeutic recommendations

Abstract Hemochromatosis is currently characterized by the iron overload caused by hepcidin deficiency. Large advances in the knowledge on the hemochromatosis pathophysiology have occurred due to a better understanding of the protein of the iron metabolism, the genetic basis of hemochromatosis and of other iron overload diseases or conditions which can lead to this phenotype. In the present review, the main aims are to show updates on hemochromatosis and to report a practical set of therapeutic recommendations for the human factors engineering protein (HFE) hemochromatosis for the p.Cys282Tyr (C282Y/C282Y) homozygous genotype, elaborated by the Haemochromatosis International Taskforce.

HFE hemochromatosis: an overview about therapeutic recommendations.

Hemochromatosis is currently characterized by the iron overload caused by hepcidin deficiency. Large advances in the knowledge on the hemochromatosis pathophysiology have occurred due to a better understanding of the protein of the iron metabolism, the genetic basis of hemochromatosis and of other iron overload diseases or conditions which can lead to this phenotype. In the present review, the main aims are to show updates on hemochromatosis and to report a practical set of therapeutic recommendations for the human factors engineering protein (HFE) hemochromatosis for the p.Cys282Tyr (C282Y/C282Y) homozygous genotype, elaborated by the Haemochromatosis International Taskforce.

Stress response and virulence factors in bacterial pathogens relevant for Chilean aquaculture: current status and outlook of our knowledge

The study of the stress responses in bacteria has given us a wealth of information regarding the mechanisms employed by these bacteria in aggressive or even non-optimal living conditions. This information has been applied by several researchers to identify molecular targets related to pathogeny, virulence, and survival, among others, and to design new prophylactic or therapeutic strategies against them. In this study, our knowledge of these mechanisms has been summarized with emphasis on some aquatic pathogenic bacteria of relevance to the health and productive aspects of Chilean salmon farming (Piscirickettsia salmonis, Tenacibaculum spp., Renibacterium salmoninarum, and Yersinia ruckeri). This study will aid further investigations aimed at shedding more light on possible lines of action for these pathogens in the coming years.

Brazilian family with hyperferritinemia-cataract syndrome: case report

ABSTRACT Hereditary hyperferritinemia-cataract syndrome is a rare autosomal dominant disease caused by a genetic mutation in the iron responsive element in the 5' untranslated region of the ferritin light chain gene. Hereditary hyperferritinemia-cataract syndrome is characterized by elevated serum ferritin levels and bilateral cataract development early in life and may be misdiagnosed as hemochromatosis. This case report describes a Brazilian family with a clinical diagnosis of hereditary hyperferritinemia-cataract syndrome, which was submitted to ferritin light chain gene sequencing. The genetic mutation c.-164C>G was identified in the 5' untranslated region. In conclusion, genetic testing can be used for accurate diagnosis of hereditary hyperferritinemia-cataract syndrome to avoid misdiagnosis of hemochromatosis, other diseases associated with iron overload or ophthalmic diseases.

Laboratory profile of malnutrition in hospitalized dogs / Perfil laboratorial da desnutrição em cães hospitalizados

Malnutrition occurs when the supply of available nutrients is less than organic demand. It is an underdiagnosed problem in veterinary medicine and can result in several negative metabolic consequences, with greater morbidity and mortality. Currently, the classification of nutritional status (NS) is performed subjectively in veterinary medicine, so studies and discoveries about laboratory markers (objectives) of malnutrition are desirable. This study evaluated the correlations between several laboratory variables (practical and low cost measurements) and the nutritional status (NS) of 246 dogs from a veterinary school hospital in southern Brazil. In this way, the laboratory profile of malnutrition in this population is evident. NS was classified by body condition score (BCS) and muscle mass score (MMS). A patient was considered to be malnourished if the BCS was less than 3 (values from 1 to 9). The laboratory variables analyzed were hemogram, cholesterol, total protein (TP), albumin, C-reactive protein (CRP), CRP/albumin ratio, total iron-binding capacity (TIBC), transferrin (TF), transferrin saturation index (TSI), and transthyretin. The means and standard deviations of the variables, correlation analyses, and comparative analyses (Kruskal-Wallis in α = 5%) were calculated. This research aimed to identify objective and practical malnutrition markers that help in the elaboration of a protocol for nutritional evaluation in diseased dogs. Low values of TF, TIBC, TP, hemogram, and TSI elevation were indicative of malnutrition. Additionally, cholesterol and albuminemia are not good markers of malnutrition in dogs with systemic diseases. For the graduation of the inflammatory state (important to differentiate inflammatory hypoproteinemia from protein malnutrition), it is more reliable to measure the [...].

A desnutrição ocorre quando a oferta de nutrientes disponíveis é inferior à demanda orgânica. É um problema subdiagnosticado em medicina veterinária e pode resultar em diversas consequências metabólicas negativas, com maior morbidade e mortalidade. Atualmente, a classificação do estado nutricional (EN) é feita subjetivamente na medicina veterinária, de maneira que estudos e descobertas sobre marcadores laboratoriais objetivos de desnutrição são desejáveis. O propósito da pesquisa foi encontrar marcadores de desnutrição objetivos e práticos que ajudem na elaboração de protocolos de avaliação nutricional em cães doentes. Este estudo avaliou as correlações entre diversas variáveis laboratoriais (de mensurações práticas e de baixo custo) com o estado nutricional (EN) de 246 cães deum hospital veterinário escola do sul do Brasil, evidenciando o perfil laboratorial da desnutrição desta população. O EN foi classificado por meio do escore de condição corporal (ECC) e escore de massa muscular (EMM). Foram considerados desnutridos os animais com ECC ≤ 3 (Laflamme, 1997) ou EMM ≤2 (World Small Animal Veterinary Association [WSAVA], 2013). As variáveis laboratoriais analisadas foram: hemograma, colesterol, proteína total (PT), albumina, proteína C reativa (PCR), relação PCR/albumina, capacidade total de ligação com ferro (CTLF), transferrina (TF), índice de saturação da transferrina (IST)e transtirretina. Foram calculadas as médias e desvios-padrões das variáveis, análises de correlação e análises comparativas (Kruskal-Wallis em α = 5%). Foram indicativos de desnutrição: baixos valores de TF, CTLF e PT, anemia e elevações da IST. Ademais, o colesterol e a albumina não são bons marcadores de desnutrição em cães com doenças sistêmicas. Para a graduação do estado inflamatório (importante para diferenciar hipoproteinemia inflamatória da desnutrição proteica), é mais confiável a mensuração da relação PCR/albumina. A transtirretina canina não pode ser mensurada com [...].

Laboratory profile of malnutrition in hospitalized dogs / Perfil laboratorial da desnutrição em cães hospitalizados

Malnutrition occurs when the supply of available nutrients is less than organic demand. It is an underdiagnosed problem in veterinary medicine and can result in several negative metabolic consequences, with greater morbidity and mortality. Currently, the classification of nutritional status (NS) is performed subjectively in veterinary medicine, so studies and discoveries about laboratory markers (objectives) of malnutrition are desirable. This study evaluated the correlations between several laboratory variables (practical and low cost measurements) and the nutritional status (NS) of 246 dogs from a veterinary school hospital in southern Brazil. In this way, the laboratory profile of malnutrition in this population is evident. NS was classified by body condition score (BCS) and muscle mass score (MMS). A patient was considered to be malnourished if the BCS was less than 3 (values from 1 to 9). The laboratory variables analyzed were hemogram, cholesterol, total protein (TP), albumin, C-reactive protein (CRP), CRP/albumin ratio, total iron-binding capacity (TIBC), transferrin (TF), transferrin saturation index (TSI), and transthyretin. The means and standard deviations of the variables, correlation analyses, and comparative analyses (Kruskal-Wallis in α = 5%) were calculated. This research aimed to identify objective and practical malnutrition markers that help in the elaboration of a protocol for nutritional evaluation in diseased dogs. Low values of TF, TIBC, TP, hemogram, and TSI elevation were indicative of malnutrition. Additionally, cholesterol and albuminemia are not good markers of malnutrition in dogs with systemic diseases. For the graduation of the inflammatory state (important to differentiate inflammatory hypoproteinemia from protein malnutrition), it is more reliable to measure the [...].(AU)

A desnutrição ocorre quando a oferta de nutrientes disponíveis é inferior à demanda orgânica. É um problema subdiagnosticado em medicina veterinária e pode resultar em diversas consequências metabólicas negativas, com maior morbidade e mortalidade. Atualmente, a classificação do estado nutricional (EN) é feita subjetivamente na medicina veterinária, de maneira que estudos e descobertas sobre marcadores laboratoriais objetivos de desnutrição são desejáveis. O propósito da pesquisa foi encontrar marcadores de desnutrição objetivos e práticos que ajudem na elaboração de protocolos de avaliação nutricional em cães doentes. Este estudo avaliou as correlações entre diversas variáveis laboratoriais (de mensurações práticas e de baixo custo) com o estado nutricional (EN) de 246 cães deum hospital veterinário escola do sul do Brasil, evidenciando o perfil laboratorial da desnutrição desta população. O EN foi classificado por meio do escore de condição corporal (ECC) e escore de massa muscular (EMM). Foram considerados desnutridos os animais com ECC ≤ 3 (Laflamme, 1997) ou EMM ≤2 (World Small Animal Veterinary Association [WSAVA], 2013). As variáveis laboratoriais analisadas foram: hemograma, colesterol, proteína total (PT), albumina, proteína C reativa (PCR), relação PCR/albumina, capacidade total de ligação com ferro (CTLF), transferrina (TF), índice de saturação da transferrina (IST)e transtirretina. Foram calculadas as médias e desvios-padrões das variáveis, análises de correlação e análises comparativas (Kruskal-Wallis em α = 5%). Foram indicativos de desnutrição: baixos valores de TF, CTLF e PT, anemia e elevações da IST. Ademais, o colesterol e a albumina não são bons marcadores de desnutrição em cães com doenças sistêmicas. Para a graduação do estado inflamatório (importante para diferenciar hipoproteinemia inflamatória da desnutrição proteica), é mais confiável a mensuração da relação PCR/albumina. A transtirretina canina não pode ser mensurada com [...].(AU)

Does the Combined Effect of Resistance Training with EPO and Iron Sulfate Improve Iron Metabolism in Older Individuals with End-Stage Renal Disease?

We sought to investigate the effects of resistance training (RT) combined with erythropoietin (EPO) and iron sulfate on the hemoglobin, hepcidin, ferritin, iron status, and inflammatory profile in older individuals with end-stage renal disease (ESRD). ESRD patients (n: 157; age: 66.8 ± 3.6; body mass: 73 ± 15; body mass index: 27 ± 3), were assigned to control (CTL; n: 76) and exercise groups (RT; n: 81). The CTL group was divided according to the iron treatment received: without iron treatment (CTL-none; n = 19), treated only with iron sulfate or EPO (CTL-EPO or IRON; n = 19), and treated with both iron sulfate and EPO (CTL-EPO + IRON; n = 76). The RT group followed the same pattern: (RT-none; n = 20), (RT-EPO or IRON; n = 18), and (RT-EPO + IRON; n = 86). RT consisted of 24 weeks/3 days per week at moderate intensity of full-body resistance exercises prior to the hemodialysis section. The RT group, regardless of the iron treatment, improved iron metabolism in older individuals with ESRD. These results provide some clues on the effects of RT and its combination with EPO and iron sulfate in this population, highlighting RT as an important coadjutant in ESRD-iron deficiency.

Potential application of a knowledgebase of iron metabolism of Acidithiobacillus ferrooxidans as an alternative platform

BACKGROUND: Acidithiobacillus ferrooxidans is a facultative anaerobe that depends on ferrous ion oxidation as well as reduced sulfur oxidation to obtain energy and is widely applied in metallurgy, environmental protection, and soil remediation. With the accumulation of experimental data, metabolic mechanisms, kinetic models, and several databases have been established. However, scattered data are not conducive to understanding A. ferrooxidans that necessitates updated information informed by systems biology. RESULTS: Here, we constructed a knowledgebase of iron metabolism of A. ferrooxidans (KIMAf) system by integrating public databases and reviewing the literature, including the database of bioleaching substrates (DBS), the database of bioleaching metallic ion-related proteins (MIRP), the A. ferrooxidans bioinformation database (Af-info), and the database for dynamics model of bioleaching (DDMB). The DBS and MIRP incorporate common bioleaching substrates and metal ion-related proteins. Af-info and DDMB integrate nucleotide, gene, protein, and kinetic model information. Statistical analysis was performed to elucidate the distribution of isolated A. ferrooxidans strains, evolutionary and metabolic advances, and the development of bioleaching models. CONCLUSIONS: This comprehensive system provides researchers with a platform of available iron metabolism-related resources of A. ferrooxidans and facilitates its application.

PAP/SAL1 retrograde signaling pathway modulates iron deficiency response in alkaline soils.

Iron (Fe) is an essential micronutrient for plants and is present abundantly in the Earth's crust. However, Fe bioavailability in alkaline soils is low due to the decreased solubility of the ferric ions. Previously, we have demonstrated the relationship between the PAP/SAL1 retrograde signaling pathway, the activity of Strategy I Fe uptake genes (FIT, FRO2, IRT1), and ethylene signaling. In this work, we have characterized mutant lines that are deficient in this retrograde signaling pathway and their ability to grow in alkaline soils. This adverse growth condition caused less impact on mutant plants, which showed less reduced rosette area, and higher carotenoid, chlorophyll and Fe content than wild-type plants. Several genes involved in the biosynthesis and excretion of secondary metabolites derived from the phenylpropanoid pathway, which improve Fe uptake, were elevated in mutant plants. Finally, we observed an increase in excreted fluorescent phenolic compounds in mutant lines compared to wild-type plants. In this way, PAP/SAL1 mutants showed alterations in the biosynthesis of metabolites that mobilize Fe, which ultimately improved these plants ability to grow in alkaline soils. Results agree with the existence of a link between the PAP/SAL1 retrograde signaling pathway and the regulation of Fe deficiency responses in Arabidopsis.

Hereditary hemochromatosis associated with the development of liver cirrhosis / Hemocromatose hereditária associada ao desenvolvimento da cirrose hepática

ABSTRACT Hereditary hemochromatosis (HH) is an autosomal recessive disease, most often associated with mutations in the HFE gene, which result in continuous absorption of iron, causing its overload. Liver tissue is the main site of iron deposition; thus, high levels of iron, when interacting with oxygen, induce the formation of free radicals that will act on proteins, lipids, and deoxyribonucleic acid (DNA), which may trigger deleterious effects at cellular and tissue levels. In order to elucidate the development and progression of liver cirrhosis due to iron overload, the purpose of this study is to describe the pathophysiology of the hepatic system in patients diagnosed with HH. For this purpose, searches for scientific articles were carried out in the main academic databases. We found that patients diagnosed with HH are more likely to develop liver cirrhosis, since chronic iron deposition in liver tissue induces injury and consequent tissue regeneration, progressing to collagen fibers synthesis surrounding the hepatocytes, leading to loss of liver function and development of cirrhosis. Therefore, it is necessary to carry out tests such as iron, ferritin and transferrin measurements, to evaluate body's iron stores, aiming at an early diagnosis of iron overload, thus avoiding deleterious damage at cellular and tissue levels.

RESUMEN La hemocromatosis hereditária (HH) es uma enfermedad autosómica recesiva, asociada, la mayoría de las veces, a mutaciones del gen HFE, que producen absorción continua de hierro, con sobrecarga de esa sustancia. El tejido hepático es el principal sitio de almacenamiento de hierro; así, niveles elevados de hierro, al interactuar con oxígeno, inducen la formación de radicales libres que actuarán sobre proteínas, lípidos y ácido desoxirribonucléico (ADN), pudiendo acarrear efectos dañosos a nível celular y tisular. Para aclarar el mecanismo de desarrollo de la cirrosis hepática debido a sobrecarga de hierro, el objetivo de este estudio es describir la fisiopatologia del sistema hepático en pacientes diagnosticados con HH. Para eso, se efectuaron búsquedas por artículos científicos en los principales bancos de datos acadêmicos. Verificamos que pacientes diagnosticados con HH presentan mayor predisposición a desarrollar cirrosis hepática, porque el depósito crônico de hierro en el tejido hepático causa lesión y consecuente regeneración de tejido, progresando a la formación de fibras de colágeno que rodean los hepatocitos, llevando la pérdida de la función hepática y al desarrollo de la cirrosis. Ante esto, es necesario medir hierro, ferritina y transferrina para evaluación de las provisiones de hierro del cuerpo, buscando un diagnóstico temprano de la sobrecarga de hierro, para evitar efectos deletereos a nível celular y tisular.

RESUMO A hemocromatose hereditária (HH) é uma doença autossômica recessiva, associada, na maioria das vezes, a mutações do gene HFE, que resultam em absorção contínua de ferro, ocasionando a sobrecarga dessa substância. O tecido hepático é o principal sítio de depósito do ferro; dessa forma, níveis elevados de ferro, ao interagir com o oxigênio, induzem a formação de radicais livres que irão agir sobre proteínas, lipídios e ácido desoxirribonucleico (DNA), podendo desencadear efeitos deletérios a níveis celulares e teciduais. Visando elucidar o mecanismo de desenvolvimento da cirrose hepática decorrente da sobrecarga de ferro, o objetivo deste estudo é descrever a fisiopatologia do sistema hepático em pacientes diagnosticados com HH. Para isso, foram realizadas buscas por artigos científicos nos principais bancos de dados acadêmicos. Verificamos que pacientes diagnosticados com HH apresentam maior predisposição de desenvolver cirrose hepática, pois o depósito crônico de ferro no tecido hepático provoca lesão e consequente regeneração tecidual, progredindo para formação de fibras de colágeno que circundam os hepatócitos, levando à perda da função hepática e ao desenvolvimento da cirrose. Diante disso, faz-se necessária a realização de exames como dosagem de ferro, ferritina e transferrina para avaliação dos estoques de ferro do organismo, objetivando um diagnóstico precoce da sobrecarga de ferro, a fim de evitar danos deletérios a níveis celulares e teciduais.

Laboratory profile of malnutrition in hospitalized dogs / Perfil laboratorial da desnutrição em cães hospitalizados

Malnutrition occurs when the supply of available nutrients is less than organic demand. It is an underdiagnosed problem in veterinary medicine and can result in several negative metabolic consequences, with greater morbidity and mortality. Currently, the classification of nutritional status (NS) is performed subjectively in veterinary medicine, so studies and discoveries about laboratory markers (objectives) of malnutrition are desirable. This study evaluated the correlations between several laboratory variables (practical and lowcost measurements) and the nutritional status (NS) of 246 dogs from a veterinary school hospital in southern Brazil. In this way, the laboratory profile of malnutrition in this population is evident. NS was classified by body condition score (BCS) and muscle mass score (MMS). A patient was considered to be malnourished if the BCS was less than 3 (values from 1 to 9). The laboratory variables analyzed were hemogram, cholesterol, total protein (TP), albumin, C-reactive protein (CRP), CRP/albumin ratio, total iron-binding capacity (TIBC), transferrin (TF), transferrin saturation index (TSI), and transthyretin. The means and standard deviations of the variables, correlation analyses, and comparative analyses (Kruskal-Wallis in α = 5%) were calculated. This research aimed to identify objective and practical malnutrition markers that help in the elaboration of a protocol for nutritional evaluation in diseased dogs. Low values of TF, TIBC, TP, hemogram, and TSI elevation were indicative of malnutrition. Additionally, cholesterol and albuminemia are not good markers of malnutrition in dogs with systemic diseases. For the graduation of the inflammatory state (important to differentiate inflammatory hypoproteinemia from protein malnutrition), it is more reliable to measure the CRP/albumin ratio. Canine transthyretin cannot be measured with reagents designed for humans, such as those used in this study. It was possible to conclude that laboratory indicators of malnutrition in sick dogs include low values of TF, TIBC, and TP, anemia, and elevations of TSI. The joint changes in these markers gradually reinforced the diagnosis.(AU)

A desnutrição ocorre quando a oferta de nutrientes disponíveis é inferior à demanda orgânica. É um problema subdiagnosticado em medicina veterinária e pode resultar em diversas consequências metabólicas negativas, com maior morbidade e mortalidade. Atualmente, a classificação do estado nutricional (EN) é feita subjetivamente na medicina veterinária, de maneira que estudos e descobertas sobre marcadores laboratoriais objetivos de desnutrição são desejáveis. O propósito da pesquisa foi encontrar marcadores de desnutrição objetivos e práticos que ajudem na elaboração de protocolos de avaliação nutricional em cães doentes. Este estudo avaliou as correlações entre diversas variáveis laboratoriais (de mensurações práticas e de baixo custo) com o estado nutricional (EN) de 246 cães de um hospital veterinário escola do sul do Brasil, evidenciando o perfil laboratorial da desnutrição desta população. O EN foi classificado por meio do escore de condição corporal (ECC) e escore de massa muscular (EMM). Foram considerados desnutridos os animais com ECC ≤ 3 (Laflamme, 1997) ou EMM ≤ 2 (World Small Animal Veterinary Association [WSAVA], 2013). As variáveis laboratoriais analisadas foram: hemograma, colesterol, proteína total (PT), albumina, proteína C reativa (PCR), relação PCR/albumina, capacidade total de ligação com ferro (CTLF), transferrina (TF), índice de saturação da transferrina (IST) e transtirretina. Foram calculadas as médias e desvios-padrões das variáveis, análises de correlação e análises comparativas (Kruskal-Wallis em α = 5%). Foram indicativos de desnutrição: baixos valores de TF, CTLF e PT, anemia e elevações da IST. Ademais, o colesterol e a albumina não são bons marcadores de desnutrição em cães com doenças sistêmicas. Para a graduação do estado inflamatório (importante para diferenciar hipoproteinemia inflamatória da desnutrição proteica), é mais confiável a mensuração da relação PCR/albumina. A transtirretina canina não pode ser mensurada com reagentes elaborados para humanos, como os utilizados nesta pesquisa. Foi possível concluir que são indicadores laboratoriais da desnutrição em cães doentes: baixos valores de TF, CTLF e PT, anemia e elevações da IST. As alterações conjuntas desses marcadores reforçam gradativamente o diagnóstico.(AU)

Ferroptosis Mechanisms Involved in Neurodegenerative Diseases.

Ferroptosis is a type of cell death that was described less than a decade ago. It is caused by the excess of free intracellular iron that leads to lipid (hydro) peroxidation. Iron is essential as a redox metal in several physiological functions. The brain is one of the organs known to be affected by iron homeostatic balance disruption. Since the 1960s, increased concentration of iron in the central nervous system has been associated with oxidative stress, oxidation of proteins and lipids, and cell death. Here, we review the main mechanisms involved in the process of ferroptosis such as lipid peroxidation, glutathione peroxidase 4 enzyme activity, and iron metabolism. Moreover, the association of ferroptosis with the pathophysiology of some neurodegenerative diseases, namely Alzheimer's, Parkinson's, and Huntington's diseases, has also been addressed.

Leukocyte telomere length is associated with iron overload in male adults with hereditary hemochromatosis.

BACKGROUND: Hereditary hemochromatosis (HH) is a primary iron overload (IO) condition. Absolute telomere length (ATL) is a marker of cellular aging and DNA damage associated with chronic diseases and mortality. AIM: To evaluate the relationship between ATL and IO in patients with HH. METHODS: Cross-sectional study including 25 patients with HH: 8 with IO and 17 without IO (ferritin < 300 ng/ml) and 25 healthy controls. Inclusion criteria were: age > 18 years, male sex and HH diagnosis. Patients with diabetes or other endocrine and autoimmune diseases were excluded. ATL was measured by real-time PCR. RESULTS: HH patients with IO were older (P<0.001) and showed higher ferritin concentration (P<0.001). Patients with HH, disregarding the iron status, showed higher glucose and body mass index (BMI) than controls (both P<0.01). ATL was shorter in patients with IO than controls [with IO: 8 (6-14), without IO: 13 (9-20), and controls: 19 (15-25) kilobase pairs, P<0.01]; with a linear trend within groups (P for trend <0.01). Differences in ATL remained statistically significant after adjusting by age, BMI and glucose (P<0.05). DISCUSSION: Patients with IO featured shorter ATL while patients without IO showed only mild alterations vs. controls. Screening for IO is encouraged to prevent iron-associated cellular damage and early telomere attrition.

Prevalence and Factors Associated with Hepatic Iron Overload in Obese Individuals Undergoing Bariatric Surgery: a Cross-Sectional Study.

BACKGROUND: Slight to moderate hepatic iron overload (HIO) can be found in cases of liver disease, including non-alcoholic fatty liver disease (NAFLD), but the mechanism is not completely understood, as well as its relationship with obesity. OBJECTIVE: To determine the prevalence of HIO assessed through histopathological examination in obese individuals undergoing bariatric surgery and to identify correlations between this condition and demographic, anthropometric, clinical, laboratory, and NAFLD-related aspects. METHODS: This is a cross-sectional study which enrolled individuals undergoing bariatric surgery from January 2018 to February 2019 at a tertiary university hospital. NAFLD and HIO were assessed through histological examination. RESULTS: Of 125 individuals, 87.2% were female and the average age was 38.8 ± 9.2 years. The average BMI was 37.2 ± 3.1 kg/m2. NAFLD was present in 66.4% and HIO in 17.6%, with 63.6% of patients with overload classified as mild (grade I) and 22.7% moderate (grade II). HIO was significantly more frequent in males (p = 0.003) and was significantly associated with higher levels of glucose (92.1 ± 28.4 vs. 80.7 ± 39.6; p = 0.02), ferritin (385.5 ± 290.9 vs. 131.6 ± 99.7; p < 0.0001), serum iron (82.4 ± 35.7 vs. 66.6 ± 25.1; p = 0.03), glutamic-oxaloacetic transaminase (27.3 ± 19.5 vs. 20.6 ± 8.8; p = 0.02), and glutamic-pyruvic transaminase (37.6 ± 36.4 vs. 24.6 ± 16.3; p = 0.01). Multivariate analysis showed that HIO intensity was significant and independently associated with ferritin levels (R = 0.19; p = 0.01), serum iron (R = 0.25; p < 0.0001), blood glucose (R = 0.16; p = 0.001), and total cholesterol (R = - 0.17; p < 0.0001). CONCLUSION: In obese individuals, HIO presented a high prevalence and was associated with higher levels of ferritin, serum iron, glucose, and transaminases; lower levels of total cholesterol; and male gender.

Comparison of automated and manual protocols for magnetic resonance imaging assessment of liver iron concentration.

OBJECTIVE: To compare automated and manual magnetic resonance imaging protocols for estimating liver iron concentrations at 1.5 T. MATERIALS AND METHODS: Magnetic resonance imaging examination of the liver was performed in 53 patients with clinically suspected hepatic iron overload and in 21 control subjects. Liver iron concentrations were then estimated by two examiners who were blinded to the groups. The examiners employed automated T2* and T1 mapping, as well as manual T2* and signal-intensity-ratio method. We analyzed accuracy by using ROC curves. Interobserver and intraobserver agreement were analyzed by calculating two-way intraclass correlation coefficients. RESULTS: The area under the ROC curve (to discriminate between patients and controls) was 0.912 for automated T2* mapping, 0.934 for the signal-intensity-ratio method, 0.908 for manual T2*, and 0.80 for T1 mapping, the last method differing significantly from the other three. The level of interobserver and intraobserver agreement was good (intraclass correlation coefficient, 0.938-0.998; p < 0.05). Correlations involving T1 mapping, although still significant, were lower. CONCLUSION: At 1.5 T, T2* mapping is a rapid tool that shows promise for the diagnosis of liver iron overload, whereas T1 mapping shows less accuracy. The performance of T1 mapping is poorer than is that of T2* methods.

OBJETIVO: Comparar protocolos automatizados e manuais de ressonância magnética para estimar a concentração hepática de ferro em 1,5 T. MATERIAIS E MÉTODOS: Foi realizada ressonância magnética hepática em 53 pacientes com suspeita de sobrecarga de ferro hepática e 21 controles, seguida da estimativa cega da concentração hepática de ferro por dois examinadores usando mapas automáticos T2* e T1, assim como o manual T2* e o método signal-intensity-ratio. O desempenho foi medido usando curvas ROC e a correlação interobservador e intraobservador usando o coeficiente de correlação intraclasse bidirecional. RESULTADOS: O desempenho da curva ROC separando pacientes e controles mostrou áreas sob a curva de 0,912 para o mapa automático T2*, 0,934 para o método signal-intensity-ratio, 0,908 para manual T2* e 0,80 para mapa T1 (este difere significativamente dos outros três métodos). Houve boa correlação interobservador e intraobservador (coeficiente de correlação intraclasse entre 0,938 e 0,998; p < 0,05). Correlações envolvendo o mapa T1, embora ainda significativas, foram menores. CONCLUSÃO: Em 1,5 T, o mapa T2* representa uma nova ferramenta rápida e promissora para avaliar o diagnóstico de sobrecarga de ferro hepática, enquanto o mapa T1 mostrou menor precisão. O desempenho do mapa T1 foi menor que o dos métodos T2*.