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new developments and controversies in iron metabolism and iron chelation therapy

World Journal of Methodology 2016年第1期6卷 1-19页

作者： christina n kontoghiorghe George J kontoghiorghes Post-graduate Research Institute of Science TechnologyEnvironment and Medicine

Iron is essential for all organisms including microbial,cancer and human cells. More than a quarter of the human population is affected by abnormalities of iron metabolism, mainly from iron deficiency and iron overload. Iron also plays an important role in free radical pathology and oxidative damage which is observed in almost all major diseases, cancer and ageing. new developments include the complete treatment of iron overload and reduction of morbidity and mortality in thalassaemia using deferiprone and selected deferiprone/deferoxamine combinations and also the use of the maltol iron complex in the treatment of iron deficiency anaemia. There is also a prospect of using deferiprone as a universal antioxidant in non iron overloaded diseases such as neurodegenerative, cardiovascular, renal, infectious diseases and cancer. new regulatory molecules of iron metabolism such as endogenous and dietary chelating molecules, hepcidin, mitochondrial ferritin and their role in health and disease is under evaluation. Similarly, new mechanisms of iron deposition, removal, distribution and toxicity have been identified using new techniques such as magnetic resonance imaging increasing our understanding of iron metabolic processes and the targeted treatment of related diseases. The uniform distribution of iron in iron overload between organs and within each organ is no longer valid. Several other controversies such as the toxicity impact of non transferrin bound iron vs injected iron, the excess levels of iron in tissues causing toxicity and the role of chelation on iron absorption need further investigation. Commercial interests of pharmaceutical companies and connections to leading journals are playing a crucial role in shaping worldwide medical opinion on drug sales and use but also patients' therapeutic outcome and safety. Major controversies include the selection criteria and risk/benefit assessment in the use of deferasirox in thalassaemia and more so in idiopathic haemochr

关键词： Iron metabolism Iron chelation therapy Deferiprone Deferoxamine Deferasirox Iron diseases Medical journals Controversies

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Transition of Thalassaemia and Friedreich ataxia from fatal to chronic diseases

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World Journal of Methodology 2014年第4期4卷 197-218页

作者： Annita Kolnagou christina n kontoghiorghe George J kontoghiorghes Postgraduate Research Institute of Science Technology Environment and Medicine Limassol 3021 Cyprus

Thalassaemia major(TM) and Friedreich's ataxia(FA) are autosomal recessive inherited diseases related to the proteins haemoglobin and frataxin respectively. In both diseases abnormalities in iron metabolism is the main cause of iron toxicity leading to increased morbidity and mortality. Major efforts are directed towards the prevention of these diseases and also in their treatment using iron chelation therapy. Both TM and FA are endemic in Cyprus, where the frequency per total population of asymptomatic heterozygote carriers and patients is the highest worldwide. Cyprus has been a pioneering nation in preventing and nearly eliminating the birth of TM and FA patients by introducing an organized health structure, including prenatal and antenatal diagnosis. Effective iron chelation therapy, improved diagnostic methods and transfusion techniques as well as supportive therapy from other clinical specializations have improved the survival and quality of life of TM *** the tiresome clinical management regimes many TM patients are successful in their professional lives, have families with children and some are now living well into their fifties. The introduction of deferiprone led to the elimination of cardiac failure induced by iron overload toxicity, which was the major cause of mortality in TM. Effective combinations of deferiprone with deferoxamine in TM patients caused the fall of body iron to normal physiological ranges. In FA different mechanisms of iron metabolism and toxicity apply to that of TM, which can be targeted with specific iron chelation protocols. Preliminary findings from the introduction of deferiprone in FA patients have increased the hopes for improved and effective therapy in this untreatable condition. new and personalised treatments are proposed in TM and FA. Overall, advances in treatments and in particular of chelation therapy using deferiprone are transforming TM and FA from fatal to chronic conditions. The paradigm of Cyprus in the

关键词： Thalassaemia Friedreich ataxia Prenatal diagnosis Survival Chelation therapy Deferiprone Deferoxamine Cyprus

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Effects of early postnatal gastric and colonic microbiota transplantation on piglet gut health

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Journal of Animal Science and Biotechnology 2024年第2期15卷 645-658页

作者： christina Larsen Simone Margaard Offersen Anders Brunse Mattia Pirolo Soumya Kanti Kar Luca Guadabassi Thomas Thymann Department of Veterinary and Animal Science University of CopenhagenDyrlagevej 681870 Frederiksberg CDenmark Animal nutrition Wageningen Livestock ResearchWageningen University&Research1 De Elst6708 WageningenThe Netherlands

Background Diarrhea is a major cause of reduced growth and mortality in piglets during the suckling and weaning periods and poses a major threat to the global pig *** and gut dysbiosis may in part be prevented via improved early postnatal microbial colonization of the *** secure better postnatal gut colonization,we hypothesized that transplantation of colonic or gastric content from healthy donors to newborn recipients would prevent diarrhea in the recipients in the post-weaning *** objective was to examine the impact of transplanting colonic or gastric content on health and growth parameters and paraclinical parameters in recipient single-housed piglets exposed to a weaning transition and challenged with enterotoxigenic Escherichia coli(ETEC).Methods Seventy-two 1-day-old piglets were randomized to four groups:colonic microbiota transplantation(CMT,n=18),colonic content filtrate transplantation(CcFT,n=18),gastric microbiota transplantation(GMT,n=18),or saline(COn,n=18).Inoculations were given on d 2 and 3 of life,and all piglets were milk-fed until weaning(d 20)and shortly after challenged with ETEC(d 24).We assessed growth,diarrhea prevalence,ETEC concentration,organ weight,blood parameters,small intestinal morphology and histology,gut mucosal function,and microbiota composition and *** Episodes of diarrhea were seen in all groups during both the milk-and the solid-feeding phase,possibly due to stress associated with single ***,CcFT showed lower diarrhea prevalence on d 27,28,and 29 compared to COn(all Pnce on d 27(Pnd a difference in beta diversity compared to COn(Pnd other paraclinical endpoints were similar across *** In conclusion,only CcFT reduced ETEC-related post-weaning ***,the protective effect was marginal,suggesting that higher doses,more effective modalities of administration

关键词： Colonic content filtrate transplantation Colonic microbiota transplantation Gastric microbiota transplantation Gut microbiota Mucosa neonatal Post-weaning diarrhea

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Males armed with big weapons win fights at limited cost in ant-mimickingjumping spiders

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Current Zoology 2024年第1期70卷 98-108页

作者： Guocheng Yu Boon Hui Wong christina J.Painting Hongze Li Long Yu Zengtao Zhang Shichang Zhang Daiqin Li State Key Laboratory of Biocatalysis and Enzyme Engineering and Centre for Behavioral Ecology and Evolution School of Life SciencesHubei UniversityWuhan430062China Departmentof Biological Sciences National University of Singapore14 Science Drive 4Singapore 117543Singapore Te Aka Matuatua School of Science University of WaikatoPrivate Bag 3105Hamilton 3240New Zealand

A core assumption of sexual selection theory is that sexually selected weapons,specialized morphological structures used directly in male con-tests,can improve an individual's reproductive success but only if the bearer can overcome associated costs,the negative effects on the bear-er's fitness ***,recent studies have shown that producing and wielding exaggerated weapons may not necessarily be ***,some traits can be selected for supporting,or compensating for,the expense of producing and wielding such exaggerated weapons.n the ant-mimicking jumping spider Myrmarachne gisti,exaggerated chelicerae are borne only by adult males and not females,showing sexual dimorphism and steep positive allometry with body ***,we determine the potential benefits of bearing exaggerated chelicerae during male contests and explore the potential for costs in terms of prey-capture efficiency and compensation between chelicera size and neighboring trait *** males with longer chelicerae won most of their male-male contests,we found no significant differences in prey-capture effi-ciency between males and females regardless of whether prey was winged or ***'elongated chelicerae thus do not impede their efficiency at capturing ***,we found that the sizes of all neighboring traits are positively correlated with chelicera size,suggesting that these traits may be under correlational *** together,our findings suggest that *** males armed with the exaggerated chelicerae that function as weapons win more fights at limited cost for performance in prey capture and compensate for neighboring structures.

关键词： allometry ant-mimic costs elongated chelicerae threat devices trait compensations

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The effect of high-flow oxygen via tracheostomy on respiratory pattern and diaphragmatic function in patients with prolonged mechanical ventilation:A randomized,physiological,crossover study

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Journal of Intensive Medicine 2024年第2期4卷 202-208页

作者： Elena Lytra Stelios Kokkoris Ioannis Poularas Dimitrios Filippiadis Demosthenes Cokkinos Dimitrios Exarhos Spyros Zakynthinos christina Routsi 1st Department of Intensive Care Medical SchoolNational and Kapodistrian University of AthensEvangelismos HospitalAthensGreece Radiology Department Evangelismos HospitalAthensGreece 2nd Radiology Department Medical SchoolNational and Kapodistrian University of AthensAttikon HospitalAthensGreece

Background Compared to conventional oxygen devices,high-flow oxygen treatment(HFOT)through the nasal cannulae has demonstrated clinical *** data exist on whether such effects are also present in HFOT through ***,we aimed to examine the short-term effects of HFOT through tracheostomy on diaphragmatic function and respiratory parameters in tracheostomized patients on prolonged mechanical *** A randomized,crossover,physiological study was conducted in our ICU between December 2020 and April 2021,in patients with tracheostomy and prolonged mechanical *** patients underwent a 30-min spontaneous breathing trial(SBT)and received oxygen either via T-piece or by HFOT through tracheostomy,followed by a washout period of 15-min breathing through the T-piece and receipt of 30-min oxygen with the other modality in a randomized crossover *** the start and end of each session,blood gasses,breathing frequency(f),and tidal volume(VT)via a Wright's spirometer were measured,along with diaphragm ultrasonography including diaphragm excursion and diaphragmatic thickening fraction,which expressed the inspiratory muscle *** Eleven patients were enrolled in whom 19 sessions were uneventfully completed;eight patients were studied twice on two different days with alternate sessions;and three patients were studied *** were randomly assigned to start the SBT with a T-piece(n=10 sessions)or with HFOT(n=9 sessions).With HFOT,VT and minute ventilation(VE)significantly increased during SBT(from[465±119]mL to[549±134]mL,Pnd from[12.4±4.3]L/min to[13.1±4.2]L/min,Pnot change significantly during SBT with T-piece(from[495±132]mL to[461±123]mL and from[12.8±4.4]mL to[12.0±4.4]mL,respectively);f/VT decreased during HFOT(from[64±31]breaths/(min∙L)to[49±24]breaths/(min∙L),Pnot change significantly during SBT with T-piece(from[59±28]breaths/(min∙L)to[64±33]breaths/(m

关键词： Diaphragm Diaphragm ultrasonography High-flow oxygen Prolonged mechanical ventilation Tracheostomy

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World health dilemmas: Orphan and rare diseases, orphan drugs and orphan patients

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World Journal of Methodology 2014年第3期4卷 163-188页

作者： christina n kontoghiorghe nicholas Andreou Katerina Constantinou George J kontoghiorghes Postgraduate Research Institute of Science Technology Environment and Medicine

According to global annual estimates hunger/malnutrition is the major cause of death(36 of 62 million). Cardiovascular diseases and cancer(5.44 of 13.43 million) are the major causes of death in developed countries, while lower respiratory tract infections, human immunodeficiency virus infection/acquired immunodeficiency syndrome, diarrhoeal disease, malaria and tuberculosis(10.88 of 27.12 million) are the major causes of death in developing countries with more than 70% of deaths occurring in children. The majority of approximately 800 million people with other rare diseases, including 100000 children born with thalassaemia annually receive no treatment. There are major ethical dilemmas in dealing with global health issues such as poverty and the treatment of orphan and rare diseases. Of approximately 50000 drugs about 10% are orphan drugs, with annual sales of the latter approaching 100 billion USD. In comparison, the annual revenue in 2009 from the top 12 pharmaceutical companies in Western countrieswas 445 billion USD and the top drug, atorvastatin, reached 100 billion USD. In the same year, the total government expenditure for health in the developing countries was 410 billion USD with only 6%-7% having been received as aid from developed countries. Drugs cost the national Health Service in the United Kingdom more than 20 billion USD or 10% of the annual health budget. Uncontrollable drug prices and marketing policies affect global health budgets, clinical practice, patient safety and survival. Fines of 5.3 billion USD were imposed on two pharmaceutical companies in the United States, the regulatory authority in France was replaced and clinicians were charged with bribery in order to overcome recent illegal practises affecting patient care. High expenditure for drug development is mainly related to marketing costs. However, only 2 million USD was spent developing the drug deferiprone(L1) for thalassaemia up to the stage of multicentre clinical trials. The criter

关键词： World health issues Global diseases Orphandrugs Orphan diseases Rare diseases Orphan patients Thalassaemia Deferiprone Deferasirox Deferoxamine Iron overload

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Retrospective study of the incidence, risk factors, treatment outcomes of bacterial infections at uncommon sites in cirrhotic patients

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World Journal of Hepatology 2024年第3期16卷 418-427页

作者： Sophie Schneitler christina Schneider Markus Casper Frank Lammert Marcin Krawczyk Sören L Becker Matthias Christian Reichert Institute of Medical Microbiology and Hygiene Saarland UniversityHomburg 66421Germany Department of Medicine II Saarland University Medical CenterHomburg 66421Germany Health Sciences Hannover Medical SchoolHannover 30625Germany Laboratory of Metabolic Liver Diseases Department of GeneralTransplant and Liver SurgeryCentre for Preclinical ResearchMedical University of WarsawWarsaw 02-097Poland

BACKGROUnD Bacterial infections(BI)negatively affect the natural course of *** most frequent BI are urinary tract infections(UTI),pneumonia,and spontaneousbacterial peritonitis(SBP).AIM To assess the relevance of bacterial infections beyond the commonly recognized types in patients with cirrhosis and to investigate their relationship with other clinical *** We retrospectively analyzed patients with cirrhosis and BI treated between 2015 and 2018 at our tertiary care *** were classified as typical and atypical,and clinical as well as laboratory parameters were compared between the two *** In a cohort of 488 patients with cirrhosis,we identified 225 typical BI(95 UTI,73 SBP,72 pulmonary infections)and 74 atypical BIs,predominantly cholangitis and soft tissue infections(21 each),followed by intra-abdominal BIs(n=9),cholecystitis(n=6),head/throat BIs(n=6),osteoarticular BIs(n=5),and endocarditis(n=3).We did not observe differences concerning age,sex,or etiology of cirrhosis in patients with typical vs atypical *** BIs were more common in patients with more advanced cirrhosis,as evidenced by Model of End Stage Liver Disease(15.1±7.4 vs 12.9±5.1;P=0.005)and Child-Pugh scores(8.6±2.5 vs 8.0±2;P=0.05).COnCLUSIOn Atypical BIs in cirrhosis patients exhibit a distinct spectrum and are associated with more advanced stages of the ***,the work-up of cirrhosis patients with suspected BI requires detailed work-up to elucidate whether typical BI can be identified.

关键词： Bacterial infection Empirical antibiotic therapy End-stage liver disease Escherichia coli Multi-resistant pathogens

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Friend or foe? Using eye-tracking technology to investigate the visual discrimination ability of giant pandas

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Current Zoology 2024年第4期70卷 430-439页

作者： Xinrui Huang Guo Li Guiquan Zhang Zixiang Li Lin Zhao Mengdie Zhu Qinghua Xiang Xuefeng Liu Mei Tian Hemin Zhang christina D.Buesching Dingzhen Liu Ministry of Education Key Laboratory of Biodiversity Science and Ecological EngineeringDepartment of EcologyCollege of Life SciencesBeijing Normal UniversityBeijing 100875China Key Laboratory of State Forestry and Grassland Administration on Conservation Biology of Rare Animals in the Giant Panda national Park China Conservation and Research Center for the Giant PandaSichuan 623004China School of Computer and Information Technology Beijing Jiaotong UniversityBeijing 100044China Beijing Key Laboratoryof CaptiveWildlife Technology Beijing ZooBeijing100044China Department of Biology Irving K.Barber Faculty of ScienceThe University of British ColumbiaOkanagan CampusKelownaBCCanada

The role that visual discriminative ability plays among giant pandas in social communication and individual discrimination has received less attention than olfactory and auditory ***,we used an eye-tracker technology to investigate pupil fixation patterns for 8 captive male giant pandas Ailuropoda *** paired images(n=26)of conspecifics against:1)sympatric predators(gray wolves and tigers),and non-threatening sympatric species(golden pheasant,golden snub-nosed monkey,takin,and red panda),2)conspecifics with atypical fur colora-tion(albino and brown),and 3)zookeepers/non-zookeepers wearing either work uniform or plain *** each session,we tracked the pan-da's pupil movements and measured pupil first fixation point(FFP),fixation latency,total fixation count(TFC),and duration(TFD)of attention to each ***,pandas exhibited similar attention(FFPs and TFCs)to images of predators and non-threatening sympatric *** of golden pheasant,snub-nosed monkey,and tiger received less attention(TFD)than images of conspecifics,whereas images of takin and red panda received more attention,suggesting a greater alertness to habitat or food competitors than to potential ***'TFCs were greater for images of black-white conspecifics than for albino or brown phenotypes,implying that familiar color elicited more *** reacted differently to images of men versus *** images of women only,pandas gave more attention(TFC)to familiar combinations(uniformed zookeepers and plain-clothed non-zookeepers),consistent with the familiarity *** pandas can use visual perception to discriminate intra-specifically and inter-specifically,including details of human appearance,has applications for panda conservation and captive husbandry.

关键词： eye movement tracker giant panda images total fixation duration total pupil fixation count visual discrimination.

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Highly n-doped carbon with low graphitic-n content as anode material for enhanced initial Coulombic efficiency of lithium-ion batteries

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Carbon Energy 2023年第2期5卷 236-249页

作者： Yihua Tang Jingjing Chen Zhiyong Mao christina Roth Dajian Wang Department of Electrochemical Process Engineering Universitat BayreuthBayreuthGermany Chair of Electrochemical Process Engineering Bavarian Center for Battery Technology(BayBatt)BayreuthGermany Tianjin Key Laboratory for Photoelectric Materials and Devices School of Materials Science and EngineeringTianjin University of TechnologyTianjinPR China

n-doped carbons as one of the most prominent anode materials to replace standard graphite exhibit outstanding Li+storage ***,n-doped carbon anodes still suffer from low n-doping levels and low initial Coulombic efficiency(ICE).In this study,high n-doped and low graphitic-n carbons(LGnCs)with enhanced ICE were synthesized by taking advantage of a denitrification strategy for graphitic carbon nitride(g-C_(3)n_(4)).In brief,more than 14.5 at%of n from g-C_(3)n_(4)(55.1 at%n)was retained by reacting graphitic-n with lithium,which was subsequently *** graphitic-n is largely responsible for the irreversible capacity,the anode's performance was significantly *** to general n-doped carbons with high graphitic-n proportion(>50%)and low n content(nCs delivered a low proportion of 10.8%-17.2% within the high n-doping content of 14.5-42.7 at%,leading to an enhanced specific capacity of 1499.9mAh g^(-1) at an ICE of 93.7% for the optimal sample of LGnC(4:1).This study provides a facile strategy to control the n content and speciation,achieving both high Li+storage capacity and high ICE,and thus promoting research and application of n-doped carbon materials.

关键词： denitrification graphitic carbon nitride graphitic-n lithium-ion batteries n-doped carbon

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Seasonal variations in nutritive and botanical composition properties of multispecies grazing swards over an entire dairy grazing season

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Grassland Research 2022年第4期1卷 221-233页

作者： Ciarán Hearn Michael Egan Mary Bridget Lynch christina Fleming Michael O'Donovan Teagasc Animal and Grassland Research and Innovation Centre MooreparkCorkIreland School of Agriculture and Food Science University College DublinDublinIreland Contribution:Formal analysis InvestigationMethodologyVisualizationWriting-original draftWriting-review&editing

Background Recently,there has been increasing interest in the use of multispecies(MS)swards in dairy grazing *** A plot grazing study was established to investigate the potential contribution of different sward species(perennial ryegrass,legumes and herbs)sown in grazing *** sward mixtures were sown,ranging in complexity from a perennial ryegrass(PRG)monoculture to binary mixtures including either forage legumes or herbs to a five-species mixture;four different nitrogen(n)application rates of 0,100,150 and 200 kg n ha−1 were applied to each *** Species abundance for all sward species components was associated with the interaction of time point and sward mixture;species abundance for all sward components,except PRG,was associated with the interaction of n application and sward *** interactions of time point and sward mixture,and time point and n application rate,were associated with all analysed sward chemical components,except for sward *** Increased n application rates reduced the level of clover in all sward *** levels of white clover led to increased sward crude protein levels;the inclusion of ribwort plantain led to some seasonal variation in the nutritive value of swards.

关键词： botanical composition chemical composition dairy production grazing multispecies swards

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