Heavy metal contamination of cooked foods hawked at Chuka town in Tharaka Nithi County, Kenya

Background: Contamination of cooked foods with heavy metals is an emerging global concern, particularly due to the associated health outcomes and economic considerations. These chemicals are introduced into cooked foods mainly through poor food handling practices and sometimes from their natural milieu such as soil, water, or air. Methods: This was a descriptive cross-sectional study. The study analysed 151 food samples collected from 151 hawkers of cooked foods in Chuka town. The samples were analysed for lead, cadmium, and copper using an atomic absorption spectrophotometer (AAS) assisted by closed microwave digestion. Results: The concentration of lead in the food samples ranged from ?0.001 to 0.7 mg/kg with a mean of 0.207±0.16, cadmium ranged from ?0.001 to 0.933 with a mean of 0.105±0.195, while copper ranged from ?0.001 to 2 mg/kg with a mean of 0.461±0.456. The recorded levels of copper were below the maximum allowable limits in all the food samples. However, 57 (37.7%) and 44 (29.1%) food samples were contaminated with lead and cadmium, respectively. Overall, more than half 86 (57%) of the hawked-cooked foods were contaminated with either lead, cadmium, or both lead and cadmium. Conclusions: Cooked foods hawked at Chuka town are contaminated with either lead, cadmium, or both lead and cadmium. The County government of Tharaka Nithi to champion interventions on preventing the sale of contaminated cooked foods.

Relevance of copper/zinc ratio and its association with redox status in chronic obstructive pulmonary disease

Background: Chronic obstructive pulmonary disease is a progressive and persistent inflammatory condition associated with significant morbidity and mortality. Increased oxidative stress amongst others, plays an important role in the pathogenesis of this disease. The objective of the present study was to conduct a preliminary yet comprehensive examination of metal exposure specifically copper and zinc levels and their association with overall oxidative stress in COPD. Methods: A cross sectional study was carried out in a tertiary care hospital in South India. Two groups were included in the study. One group with 20 COPD patients and the other group of 20 healthy controls. Plasma samples were obtained from both the groups and serum levels of copper and zinc were studied by atomic absorption spectrometry. Cu/Zn ratio obtained from the results was further correlated with oxidative stress index calculated from total oxidant status and total antioxidant status in COPD with respect to controls. Results: The copper levels were significantly higher and the zinc levels lower in the COPD group as compared to the control group. The copper/zinc ratio was higher in COPD as compared to control population. The correlation between Cu/Zn ratio and oxidative stress index showed a positive correlation with a regression coefficient of 0.7. Conclusions: The study throws light on the trace element imbalance in COPD and how these could induce oxidative stress, contributing to persistent inflammation in COPD. In the clinical perspective, monitoring Cu/Zn ratio in COPD patients may lead to better risk mitigation and thereby better therapeutic management of the disease.

Something left behind: a rare complication of copper-T insertion

This case report presents a unique and intriguing clinical scenario involving an incorrect copper T insertion following a caesarean section. The case presented the importance of training in the right technique for intra-uterine contraceptive device (IUCD) insertions in peripheral health facilities and the potential risks associated with inappropriate procedures. Prompt identification and management of misplaced IUCDs are crucial in minimizing patient discomfort, preventing complications, and optimizing reproductive health outcomes.

A girl with synostotic plagiocephaly: unfolding as rare case

Dysmorphic head shape can be a presenting complaint of craniosynostosis which needs to be investigated in detail for any genetic or syndromic associations. Many genetic mutations have been associated with craniosynostosis but ERF gene mutation has been found to be very rare. Here, we have discussed about an 8 years old girl who presented with dysmorphic head shape. She had crouzoid features like exorbitism, malar hypoplasia with copper beaten skull appearance and pansynostosis on CT Head but genetic evaluation revealed ERF gene mutation suggestive of craniosynostosis 4. She had short stature which was the unique association with it. Thus, high index of suspicion should be kept for craniosynostosis 4 when phenotypic features are suggestive of crouzon syndrome as crouzon syndrome can phenotypically mimic craniosynostosis with ERF gene mutation and genetic analysis should be done to look for alternate cause of craniosynostosis; especially to look for ERF gene mutation.

HAEMATO-BIOCHEMCIAL STUDIES OF NANOPARTICLE-BASED VACCINE AGAINST R2B STRAIN OF NEW CASTLE DISEASE IN CHICKS

Objective: The goal of the current study is to create a Newcastle disease vaccine based on green synthesised metal oxide nanoparticles and to study the haematological and biochemical effects of this vaccine in chicks.Methods: Copper Oxide Nanoparticles (CuONPs) from Momordica charantia were synthesised biologically. These copper oxide nanoparticles were combined with a commercially available freeze-dried Newcastle Di0sease (ND) vaccination of the live R2B strain to use it as a vaccine delivery method in the current work. Haematological and biochemical parameters were investigated in pre-challenged and post-challenged chicks.Results: After the injection of copper nanoparticles-based vaccines, it was found that the pre-challenged animals and post challeneged animals showed highly significant difference (P<0.05) in their total White Blood Cells (WBC) counts, hemoglobin concentration, hematocrit value, and Erythrocyte Sedimentation Rate (ESR) in comparison to control and live vaccinated groups. It was also investigated that for biochemical parameters After the injection of copper nanoparticles-based vaccines, both pre-challenged animals and post challeneged animals showed highly significant difference (P<0.05) in their blood glucose level, serum total protein, creatinine, serum alkaline phosphatase, Aspartate Amino Transferase (ALT) and Alanine Amino Transferasse (AST) in comparison to control and live vaccinated groups.Conclusion: The vaccine not only makes chicks healthier, but also shields them from the virus that causes Newcastle disease

The copper conundrum: a case of toxicity and altered mental status in a young male with opioid dependency

Copper is a trace element with higher concentrations in the brain, liver, and kidneys. Its toxicity is rare in humans because of its homeostatic mechanisms. This case highlights a 30-year-old male with a history of opioid abuse and occupational exposure to metallurgy. Despite treatment, a gradual neurological worsening prompted us for heavy metal screening and nerve conduction velocity study (NCV) which revealed copper toxicity and demyelinating polyneuropathy. Following the initiation of D-penicillamine therapy, he showed gradual improvement. The coexistence of opioid abuse and dependency posed challenges in the clinical presentation, necessitating a comprehensive approach to effectively manage both opioid withdrawal and evaluation for other toxic substances.

Cu0 Modification and Cu2+ Self-intercalation of Ti3C2Tx Two-dimensional Material for Electrocatalytic Reduction of CO2 / 分析化学

The conversion of carbon dioxide into high value-added energy has become a research hotspot.In this study,by using Ti3AlC2 and CuCl2·2H2O as precursors,accordion-like two-dimensional Cu0/Cu2+-Ti3C2Tx catalysts modified with Cu0 nanoparticles and Cu2+ self-intercalation were successfully prepared for electrocatalytic reduction of CO2.The performance of the material was tested,and the results showed that in a CO2-saturated 0.5 mol/L KHCO3 electrolyte solution,compared with the original Ti3AlC2,the initial potential of the electrocatalytic conversion of CO2 to C2H4 over Cu0/Cu2+-Ti3C2Tx catalyst decreased from ?0.65 V(vs RHE)to?0.01 V(vs RHE).The maximum current density increased from 0.19 mA/cm2 to 2.5 mA/cm2,the double layer capacitance(Cdl)value increased from 2.61 mF/cm2 to 55.06 mF/cm2.The material showed higher catalytic activity and faster electron transfer rate(Charge transfer resistance(Rct)value was only 16.9 Ω).Moreover,the material showed high electrochemical active area and excellent stability.This research provided a promising method for designing and preparing elcetrocatalytic reduction(ECR)catalysts in the future.

Advances in the treatment of Wilson disease / 国际儿科学杂志

Wilson disease（WD）is an inherited disorder caused by mutations in the ATP7B gene.It is characterized by pathological accumulation of copper in the organs throughout the body，especially the liver and brain. This article reviews the latest progress of existing and emerging therapies. At present，the most commonly used treatment methods are oral chelators of copper and zinc agents. Liver transplantation can be used as a treatment for end-stage patients. However，these treatment methods have some shortcomings：many side effects of drugs，poor treatment effect，lifelong treatment，poor patient compliance and so on. At present，the choice of drugs is still in the exploratory stage，and there are no guidelines to specify which patients should receive which treatment. In addition，there are many emerging therapies in different experimental stages，such as new chelators of copper，targeted molecular therapy，gene therapy and cell transplantation. The old methods have many disadvantages and lack large controlled clinical trials，and emerging research is still in its infancy，which are urgent questions.

Research progress in ceruloplasmin regulation of lipid metabolism homeostasis / 上海交通大学学报（医学版）

Ceruloplasmin(Cp)is a crucial protein secreted by the liver and plays a vital role in regulating the distribution and transport of copper throughout the body,thereby maintaining copper homeostasis.Additionally,Cp functions as a significant enzyme known as ferroxidase,which is involved in iron metabolism within the body.Numerous studies have suggested a close relationship between Cp and metabolic disorders,such as diabetes and cardiovascular diseases.Recent research has also shed light on the involvement of Cp in the regulation of lipid metabolism.The various activities associated with lipid metabolism,including lipid synthesis,adipose hydrolysis,fatty acid oxidation,lipid transport,and absorption,collectively contribute to maintaining lipid homeostasis.Dysregulation of lipid metabolism can lead to metabolic disorders and cardiovascular complications.Cp regulates lipid metabolism through two main mechanisms.Firstly,Cp participates in the regulation of oxidative stress by modulating iron metabolism through its ferroxidase activity and involvement in redox reaction.Secondly,copper along with copper-dependent enzymes directly participates in the processes such as cholesterol metabolism,lipoprotein metabolism,and fatty acid synthesis.As a result,the role of Cp in maintaining the homeostasis of copper and iron allows it to regulate lipid metabolism by influencing copper or iron-dependent enzymes and related pathways.Although the correlation between Cp and lipid metabolism has been identified,an in-depth exploration of the precise mechanisms by which Cp governs lipid metabolism is warranted.This article provides an overview of the role of Cp in lipid metabolism and highlights the progress in related research,with the aim of providing new insights for the development and treatment of disorders related to lipid metabolism.

Angiogenesis mechanism of metal ions and their application in bone tissue engineering / 中国组织工程研究

BACKGROUND:Owing to excellent angiogenesis activity and their participation in the physiological processes such as angiogenesis in osteogenesis,the researches and applications of a variety of metal ions are getting deeper in the field of bone tissue engineering. OBJECTIVE:To systematically explain the mechanism of angiogenesis of different metal ions such as copper ion(Cu2+),magnesium ion(Mg2+),strontium ion(Sr2+),zinc ion(Zn2+),cobalt ion(Co2+)and their current research situation as well as application in the treatment of diseases in the field of bone tissue engineering. METHODS:The two authors used PubMed and CNKI to search the literature published between 2017 and 2022 with the search terms"copper ion,magnesium ion,strontium ion,zinc ion,cobalt ion,bone,angiogenesis"in Chinese and"copper,cuprum,Cu,magnesium,Mg,strontium,Sr,zinc,Zn,cobalt,Co,metal ion,angiogenesis,bone"in English.After reading titles and abstracts,the articles were initially screened,and irrelevant articles were excluded.Finally,114 articles were included for review. RESULTS AND CONCLUSION:(1)Metal ions can regulate angiogenesis by acting on vascular endothelial growth factors,hypoxia-inducible factors,angiogenesis-related genes,endothelial cells and conducting immune regulation of macrophages.(2)Metal ions such as copper,magnesium,strontium,zinc and cobalt are often used to improve the performance of tissue engineering scaffolds due to their significant angiogenic effect.Among them,hydrogels,bioceramics and synthetic polymer materials are widely used at present,and magnesium and its alloys also have advantages due to their excellent bearing capacity.However,these materials all have some defects.Currently,there is no ideal bone replacement material.(3)Various metal ions show different application potentials in bone replacement materials:Copper has antibacterial,angiogenic and osteogenic properties,and is mainly used for bone defects caused by infection and tumors.Magnesium and zinc have strong biodegradability,so the degradation rate should be controlled.Magnesium is corrosive and is mainly used as an alloy.The angiogenesis mechanism of zinc is less involved.Magnesium and strontium are effective in treating osteoporotic bone defects.(4)The above five metal ions(copper,magnesium,strontium,zinc and cobalt)have a significant role in promoting angiogenesis and then promote osteogenesis through angiogenesis.Some ions,such as copper ions,have a bactericidal effect.These ions can be used as a new strategy for the treatment of bone defects caused by tumors,osteoporosis,infection and trauma,but the current clinical trials and application studies of products are relatively insufficient.

Molecular mechanisms of anti-inflammatory effects of metal ions / 中国组织工程研究

BACKGROUND:Resistance to the inflammatory response is an important part of promoting the repair of damaged tissue and improving the local inflammatory response caused by medical bio-implant materials has been a key issue to be addressed in recent years. OBJECTIVE:To summarize the anti-inflammatory effects of common metal ions and related molecular mechanisms to provide some theoretical references for improving the early inflammatory response of hosts caused by bio-implant materials. METHODS:A computer search of the relevant literature in PubMed,Web of Science,CNKI and WanFang databases was conducted using"metal ions,magnesium ion,zinc ion,silver ion,copper ion,inflammation,anti-inflammatory effects,oxidative stress,immunoregulation,signaling pathways"as Chinese and English search terms.Preliminary screening was conducted by reading the titles and abstracts.Finally,80 papers were included for result analysis and summary. RESULTS AND CONCLUSION:(1)Metal ions such as magnesium,zinc,silver and copper have a good anti-inflammatory effect.The strength of this anti-inflammatory effect is strongly correlated with the dose and duration of action.In the future,consideration can be given to controlling the release rate of ions and adjusting the appropriate therapeutic concentration to achieve the best anti-inflammatory effect.(2)Magnesium ions and zinc ions exhibit excellent anti-inflammatory activity,with magnesium ions often being beneficial in anti-inflammatory therapy in the form of compounds such as magnesium sulfate and zinc ions regulating the body's inflammatory response with zinc feed as the main source of zinc supplementation.(3)Silver and copper ions have some anti-inflammatory effects,but are still predominant for their excellent antibacterial activity,mainly in the form of nanoparticles and bio-coatings.(4)Magnesium and zinc metal ions can be combined with natural extracts to form complexes to exert anti-inflammatory effects,and this method has the advantage of being inexpensive and widely available and is a sustainable and green approach,which is worthy of clinical promotion.(5)Metal ions such as magnesium,zinc,silver and copper exert anti-inflammatory effects by reducing host oxidative stress damage,modulating immune cells and inhibiting inflammatory signaling pathways such as nuclear factor-κB,Toll-like receptor,STAT3 and NOD.(6)The molecular mechanism related to the anti-inflammation of metal ions is a complex network,which is not the effect of a single pathway,but should be a combination of multiple signaling pathways.There are still many potential mechanisms that have not yet been explored,and more systematic elucidation of the interconnections between various signaling pathways is needed in the future.

Biological and physicochemical properties of bioactive ion modified brushite cements / 中国组织工程研究

BACKGROUND:As a bone replacement and filling material,calcium phosphate stone bone cement has good biocompatibility,bone conductivity,and other advantages,especially its better biodegradability compared to other calcium phosphate bone cements.It has important application value in bone repair.However,due to its limitations such as insufficient mechanical properties,fast solidification reaction,and poor injection performance,it is currently only suitable for the repair of non weight-bearing bone. OBJECTIVE:To explore the modification of brushite cements with bioactive ions(metal and non metal ions)to expand its application range. METHODS:The author used PubMed,ScienceDirect,CNKI,and WanFang to search the literature published between 2018 and 2023 with the search terms"metal ion,iron,copper,strontium,magnesium,zinc,non-metal ion,modification,bone,brushite cements"in Chinese and"metal ion,iron,Fe,copper,Cu,strontium,Sr,magnesium,Mg,zinc,Zn,non-metal ion,modification,bone,brushite cements"in English.After reading titles and abstracts,the articles were initially screened,and irrelevant and duplicate articles were excluded.Finally,64 articles were included for review. RESULTS AND CONCLUSION:(1)Bioactive ions affect the hydration process of calcium phosphate bone cement.Different ions are substituted by ions and incorporated into the crystal structure of calcium phosphate bone cement,changing the crystal morphology of the cement and causing changes in physical and chemical properties such as setting time,injectability,and compressive strength.(2)Ionic modified calcium phosphate bone cement produces different ion release effects due to different crystal structures.Different types of ions have properties such as promoting angiogenesis/osteogenesis,antibacterial,anti-tumor,etc.In addition,calcium phosphate bone cement has good biodegradability,which has great advantages for the performance of various ions.(3)The physicochemical properties of calcium phosphate bone cement modified with different ions are as follows:iron,copper,strontium,magnesium,zinc,silver,and cobalt can prolong the setting time.Strontium,and magnesium can improve injection performance.Copper,strontium,magnesium,silver and silicon can enhance compressive strength.The ions that can simultaneously improve the three physical and chemical properties of calcium phosphate bone cement include strontium and magnesium.Good physical and chemical properties are a prerequisite for clinical application,so improving the setting time,injectability,compressive strength,and other properties of calcium phosphate bone cement with ions is of great significance for the research and application of bone cement.(4)The biological properties of calcium phosphate bone cement modified with different ions are as follows:copper,strontium,magnesium,zinc,cobalt,lithium,selenium,and silicon have promoting angiogenesis/osteogenic effects.Iron,copper,magnesium,zinc,and silver have antibacterial properties.Magnesium ions have anti-inflammatory properties.Copper and selenium have anti-tumor properties.(5)In summary,magnesium ions can improve the setting time,injectability,and compressive strength of calcium phosphate bone cement,while also promoting neovascularization/osteogenesis,antibacterial properties,and have good application prospects for the treatment of bone defects with concurrent infections.In addition,copper also has anti-tumor properties,so copper ions have great potential in the treatment of bone defects caused by infections and tumors.However,relevant research is still in the basic research stage,and the effects of different ion doping concentrations and synthesis conditions on the physicochemical properties of calcium phosphate bone cement need to be further explored.At the same time,the impact of biological properties also needs to be studied and observed for a longer period of time.

Analysis of the association between copper death-related genes and prostate cancer / 现代泌尿外科杂志

【Objective】 To analyze the association between copper death-related genes and prognosis of prostate cancer and immune cell infiltration based on the cancer genome atlas (TCGA). 【Methods】 The mRNA transcriptome data of all prostate cancer patients were downloaded from TCGA, including 501 prostate cancer tissues and 52 normal tissues.The expression matrix of copper death-related genes was extracted with R software.Differential analysis and multivariate regression analysis were conducted to screen out the prognostic genes, which were then analyzed to explore the correlation between prognosis-related genes and immune cells. 【Results】 GCSH gene was significantly correlated with the prognosis of prostate cancer, and significantly correlated with dendritic cells, CD8+ T cells and plasma cells (P<0.05). 【Conclusion】 GCSH gene plays an important role in the occurrence and development of prostate cancer, and may become a prognostic marker of the disease.

Bioceramic scaffolds with two-step internal/external modification of copper-containing polydopamine enhance antibacterial and alveolar bone regeneration capability / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Magnesium-doped calcium silicate (CS) bioceramic scaffolds have unique advantages in mandibular defect repair; however, they lack antibacterial properties to cope with the complex oral microbiome. Herein, for the first time, the CS scaffold was functionally modified with a novel copper-containing polydopamine (PDA(Cu2+‍)) rapid deposition method, to construct internally modified (*P), externally modified (@PDA), and dually modified (*P@PDA) scaffolds. The morphology, degradation behavior, and mechanical properties of the obtained scaffolds were evaluated in vitro. The results showed that the CS*P@PDA had a unique micro-/nano-structural surface and appreciable mechanical resistance. During the prolonged immersion stage, the release of copper ions from the CS*P@PDA scaffolds was rapid in the early stage and exhibited long-term sustained release. The in vitro evaluation revealed that the release behavior of copper ions ascribed an excellent antibacterial effect to the CS*P@PDA, while the scaffolds retained good cytocompatibility with improved osteogenesis and angiogenesis effects. Finally, the PDA(Cu2+)-modified scaffolds showed effective early bone regeneration in a critical-size rabbit mandibular defect model. Overall, it was indicated that considerable antibacterial property along with the enhancement of alveolar bone regeneration can be imparted to the scaffold by the two-step PDA(Cu2+) modification, and the convenience and wide applicability of this technique make it a promising strategy to avoid bacterial infections on implants.

Identification of copper death related subtypes,construction of prognosis model and analysis of immune cell infiltration in osteosarcoma / 中国免疫学杂志

Objective:To analyze identification of copper death gene related subtypes,construction of prognosis model and influence of immune infiltration in osteosarcoma(OS)on basis of copper death gene.Methods:Survival and prognosis of OS associated copper death gene were analyzed combining by TARGET and GEO database.OS was divided into different subtypes of copper death by consistent clustering method.SSGSEA was used to analyze difference of immune cells in classification of copper death.Setting P value= 0.05 and q value=0.05,GO and KEGG enrichment analysis were performed on differential genes of copper death typing.Prognosis model was constructed according to results of Lasso regression analysis and cross validation,risk assessment analysis and ROC curve were used to evaluate accuracy of model prediction.Combined with clinical characteristics,nomograms were constructed to predict survival time of patients,and risk differences were analyzed.Immune cell infiltration and tumor microenvironment analysis were performed on OS samples."pRRophetic"package in R software was used to analyze drug sensitivity of OS samples.Results:FDX1,GLS,DLAT and PDHB as high-risk genes for OS prognosis were identified.According to copper death classification of OS samples,OS could be divided into two types:CRGclusterA and CRGclusterB.CRGclusterA was associated with Th2 cells,and CRGclusterB was associated with Th1 cells.Most OS copper death genes were highly expressed in CRGclusterA.Immune cell infiltration analysis results showed that γδ T cells,resting mast cells and resting dendritic cells were positively correlated with risk score,while CD8 T cells were negatively correlated with risk score.Drug sensitivity analysis showed that OS showed higher sensitivity to Elesclomol and GW.441756.Conclusion:Two subtypes of CRGclusterA and CRGclusterB are identified in this study.Four high-risk prognostic genes FDX1,GLS,DLAT and PDHB are identified,providing new insights into prognostic evaluation and immunotherapy target candidates for OS.

Element profiles of benzoapyrene malignantly transformed 16HBE cells and joint effects of copper with cisplatin or vinorelbine on cell proliferation / 中国药理学与毒理学杂志

OBJECTIVE To assess the profiles of elements in benzo[a]pyrene(BaP)induced carci-nogenesis,and explore the joint effects of copper with cisplatin or vinorelbine on cell proliferation.METHODS Forty-four elements were measured using an inductively coupled plasma mass spectrometer in 16HBE cells and BaP malignantly transformed 16HBE(T-16HBE-C1)cells.Partial least square was used to validate the robustness of cell classification of elements.Cell viability was measured by MTT assay for copper(0,237,340,487,1000 and 1432 μmol·L-1),cisplatin(0,4.4,6.1,8.6,12.0 and 16.8 μmol·L-1),and vinorelbine(0,3.8,9.8,25.0,40.0 and 64.0 μmol·L-1)to acquire their half maximal inhibitory concentra-tion(IC50).Mixtures of copper and chemotherapeutics were prepared according to the ratio of each IC50.Their joint effects on cell viability were assessed by MTT assay and isobolographic analysis.Inhibition effect of copper(0,50,100,200,400 and 800 μmol·L-1)with IC50 of cisplatin or vinorelbine on prolifera-tion of T-16HBE-C1 cells was also assessed.RESULTS A total of 29 elements were quantified in 16HBE and T-16HBE-C1 cells,among which concentrations of copper,zinc,silver,selenium and rubidium decreased(P<0.05,P<0.01),while those of molybdenum,arsenic,lithium,germanium,strontium,nickel,lanthanum,mercury,iron,and cesium increased(P<0.05,P<0.01)in T-16HBE-C1 cells.Element concen-tration could be used to distinguish T-16HBE-C1 cells from 16HBE cells.Copper concentration-dependently inhibited proliferation of both cells,with a statistically significant lower IC50 of(613±16)μmol·L-1 in 16HBE cells than(776±15)μmol·L-1 in T-16HBE-C1 cells(P<0.01).Mixtures of copper and cisplatin(1∶69.5)or vinorelbine(1∶33.4)could inhibit cell proliferation,and copper had additive effects with cisplatin or vinorelbine.When copper concentration was higher than 400 μmol·L-1,copper combined with IC50 of cisplatin or vinorelbine inhibited cell proliferation of T-16HBE-C1 cells compared with IC50 of cisplatin(11.2 μmol·L-1)or vinorelbine(23.2 μmol·L-1)alone.CONCLUSION Element profiles and correlations can change significantly after 16HBE cells are malignantly transformed by BaP.Copper could inhibit the proliferation of T-16HBE-C1 cells and have additive effects with cisplatin or vinorelbine in higher concentration.

Studies on bioaccumulation patterns, biochemical and genotoxic effects of copper on freshwater fish, Catla catla: an in vivo analysis

Abstract During present study, the copper (Cu) mediated oxidative stress was measured that induced DNA damage by concentrating in the tissues of fish, Catla catla (14.45±1.24g; 84.68±1.45mm) (Hamilton,1822). Fish fingerlings were retained in 5 groups for 14, 28, 42, 56, 70 and 84 days of the exposure period. They were treated with 2/3, 1/3, 1/4 and 1/5 (T1-T4) of 96h lethal concentration of copper. Controls were run along with all the treatments for the same durations. A significant (p 0.05) dose and time dependent concentration of Cu was observed in the gills, liver, kidney, muscles, and brain of C. catla. Among organs, the liver showed a significantly higher concentration of Cu followed by gills, kidney, brain, and muscles. Copper accumulation in these organs caused a significant variation in the activities of enzymes viz. superoxide dismutase (SOD), catalase (CAT) and peroxidase (POD). The SOD activity varied significantly in response to the exposure time of Cu as 56 > 70 > 42 > 84 > 28 > 14 days while CAT activity exhibited an inverse relationship with the increase in Cu concentration. POD activity showed a significant rise with an increase in Cu exposure duration. Comet assay exhibited significant DNA damage in the peripheral erythrocytes of Cu exposed C. catla. Among four exposure concentrations, 2/3rd of LC50 (T1) caused significantly higher damage to the nuclei compared to control. Increased POD and SOD activity, as well as a decrease in CAT activity in response to Cu, demonstrates the involvement of a protective mechanism against reactive oxygen species (ROS), whereas increased ROS resulted in higher DNA damage. These above-mentioned molecular markers can be efficiently used for the biomonitoring of aquatic environments and conservation of edible fish fauna.

Resumo Durante o presente estudo, o estresse oxidativo mediado pelo cobre (Cu) foi medido que induziu danos ao DNA por concentração nos tecidos de peixes, Catla catla (14,45 ± 1,24g; 84,68 ± 1,45mm) (Hamilton, 1822). Os alevinos foram retidos em 5 grupos por 14, 28, 42, 56, 70 e 84 dias do período de exposição. Eles foram tratados com 2/3, 1/3, 1/4 e 1/5 (T1-T4) de 96h de concentração letal de cobre. Os controles foram executados junto com todos os tratamentos para as mesmas durações. Uma significativa (p 0,05) concentração dependente do tempo e da dose de Cu foi observada nas brânquias, fígado, rim, músculos e cérebro de C. catla. Entre os órgãos, o fígado apresentou uma concentração significativamente maior de cobre, seguido por guelras, rins, cérebro e músculos. O acúmulo de cobre nesses órgãos causou uma variação significativa nas atividades das enzimas viz. superóxido dismutase (SOD), catalase (CAT) e peroxidase (POD). A atividade de SOD variou significativamente em resposta ao tempo de exposição de Cu como 56> 70> 42> 84> 28> 14 dias, enquanto a atividade de CAT exibiu uma relação inversa com o aumento na concentração de Cu. A atividade POD mostrou um aumento significativo com um aumento na duração da exposição ao Cu. O ensaio do cometa exibiu dano significativo ao DNA induzido por Cu nos eritrócitos periféricos de C. catla. Entre as quatro concentrações de exposição, 2/3 do LC50 (T1) causou danos significativamente maiores aos núcleos em comparação com o controle. O aumento da atividade de POD e SOD, bem como uma diminuição na atividade de CAT em resposta ao Cu, demonstra o envolvimento de um mecanismo protetor contra espécies reativas de oxigênio (ROS), enquanto o aumento de ROS resultou em maior dano ao DNA. Esses marcadores moleculares mencionados acima podem ser usados de forma eficiente para o biomonitoramento de ambientes aquáticos e conservação da ictiofauna comestível.

Wilson disease: the diagnostic challenge and treatment outcomes in a series of 262 cases / Doença de Wilson: o desafio diagnóstico e resultados do tratamento em uma série de 262 casos

Abstract Background Wilson disease (WD) is an autosomal recessive disorder that leads to organ toxicity due to copper overload. Early diagnosis is complicated by the rarity and diversity of manifestations. Objective To describe the diagnostic features and response to treatment in our cohort of WD patients. Methods This was a retrospective analysis of 262 WD patients stratified by clinical presentation, complementary exams, ATP7B genotyping, and response to treatment. Results Symptoms occurred at an average age of 17.4 (7-49) years, and patients were followed up for an average of 9.6 (0-45) years. Patients presented mainly with hepatic (36.3%), neurologic (34.7%), and neuropsychiatric (8.3%) forms. Other presentations were hematologic, renal, or musculoskeletal, and 16.8% of the patients were asymptomatic. Kayser-Fleischer rings occurred in 78.3% of the patients, hypoceruloplasminemia in 98.3%, and elevated cupruria/24h in 73.0%, with an increase after D-penicillamine in 54.0%. Mutations of the ATP7B gene were detected in 84.4% of alleles. Brain magnetic resonance imaging showed abnormalities in the basal ganglia in 77.7% of patients. D-penicillamine was the first choice in 93.6% of the 245 patients, and 21.1% of these patients were switched due to adverse effects. The second-line therapies were zinc and trientine. The therapeutic response did not differ significantly between the drugs (p= 0.2). Nine patients underwent liver transplantation and 82 died. Conclusion Wilson disease is diagnosed at a late stage, and therapeutic options are limited. In people under 40 years of age with compatible manifestations, WD could be considered earlier in the differential diagnosis. There is a need to include ATP7B genotyping and therapeutic alternatives in clinical practice.

Resumo Antecedentes A doença de Wilson (DW) é um distúrbio autossômico recessivo caracterizado por acúmulo de cobre lesivo aos órgãos. O diagnóstico precoce é dificultado pela raridade e diversidade de apresentações. Objetivo Descrever características ao diagnóstico e resposta ao tratamento em uma coorte de DW. Métodos Análise retrospectiva de 262 casos de DW quanto à apresentação clínica, exames complementares, genotipagem e resposta ao tratamento. Resultados Os sintomas surgiram em uma média aos 17,4 (7-49) anos, e os pacientes foram acompanhados por uma média de 9,6 (0-45) anos. Os pacientes apresentaram principalmente formas hepáticas (36,3%), neurológicas (34,7%) e neuropsiquiátricas (8,3%). Outras apresentações foram hematológicas, renais e musculoesqueléticas. Apenas 16,8% eram assintomáticos. Anéis de Kayser-Fleischer ocorreram em 78,3% dos pacientes, hipoceruloplasminemia em 98,3%, e cuprúria elevada/24h em 73,0%, com aumento após D-penicilamina em 54,0%. Mutações do gene ATP7B foram detectadas em 84,4% dos alelos pesquisados. A ressonância magnética cerebral mostrou alterações em gânglios da base em 77,7% dos pacientes. O tratamento com D-penicilamina foi a escolha inicial em 93,6% dos 245 casos e foi trocado em 21,1% devido a efeitos adversos. Terapias de segunda linha foram zinco e trientina. A resposta terapêutica não diferiu significativamente entre os medicamentos (p= 0,2). Nove pacientes receberam transplante hepático e 82 faleceram. Conclusão O diagnóstico da DW ainda ocorre em estágios tardios, e as opções terapêuticas são limitadas. A DW deve ser considerada precocemente no diagnóstico diferencial de pessoas com menos de 40 anos com manifestações compatíveis. É necessário incorporar na prática clínica a genotipagem do ATP7B e alternativas terapêuticas à penicilamina.

Studies on bioaccumulation patterns, biochemical and genotoxic effects of copper on freshwater fish, Catla catla: an in vivo analysis / Estudos sobre padrões de bioacumulação, efeitos bioquímicos e genotóxicos do cobre em peixes de água doce, Catla catla: uma análise in vivo

During present study, the copper (Cu) mediated oxidative stress was measured that induced DNA damage by concentrating in the tissues of fish, Catla catla (14.45±1.24g; 84.68±1.45mm) (Hamilton,1822). Fish fingerlings were retained in 5 groups for 14, 28, 42, 56, 70 and 84 days of the exposure period. They were treated with 2/3, 1/3, 1/4 and 1/5 (T1-T4) of 96h lethal concentration of copper. Controls were run along with all the treatments for the same durations. A significant (p < 0.05) dose and time dependent concentration of Cu was observed in the gills, liver, kidney, muscles, and brain of C. catla. Among organs, the liver showed a significantly higher concentration of Cu followed by gills, kidney, brain, and muscles. Copper accumulation in these organs caused a significant variation in the activities of enzymes viz. superoxide dismutase (SOD), catalase (CAT) and peroxidase (POD). The SOD activity varied significantly in response to the exposure time of Cu as 56 > 70 > 42 > 84 > 28 > 14 days while CAT activity exhibited an inverse relationship with the increase in Cu concentration. POD activity showed a significant rise with an increase in Cu exposure duration. Comet assay exhibited significant DNA damage in the peripheral erythrocytes of Cu exposed C. catla. Among four exposure concentrations, 2/3rd of LC50 (T1) caused significantly higher damage to the nuclei compared to control. Increased POD and SOD activity, as well as a decrease in CAT activity in response to Cu, demonstrates the involvement of a protective mechanism against reactive oxygen species (ROS), whereas increased ROS resulted in higher DNA damage. These above-mentioned molecular markers can be efficiently used for the biomonitoring of aquatic environments and conservation of edible fish fauna.

Durante o presente estudo, o estresse oxidativo mediado pelo cobre (Cu) foi medido que induziu danos ao DNA por concentração nos tecidos de peixes, Catla catla (14,45 ± 1,24g; 84,68 ± 1,45mm) (Hamilton, 1822). Os alevinos foram retidos em 5 grupos por 14, 28, 42, 56, 70 e 84 dias do período de exposição. Eles foram tratados com 2/3, 1/3, 1/4 e 1/5 (T1-T4) de 96h de concentração letal de cobre. Os controles foram executados junto com todos os tratamentos para as mesmas durações. Uma significativa (p <0,05) concentração dependente do tempo e da dose de Cu foi observada nas brânquias, fígado, rim, músculos e cérebro de C. catla. Entre os órgãos, o fígado apresentou uma concentração significativamente maior de cobre, seguido por guelras, rins, cérebro e músculos. O acúmulo de cobre nesses órgãos causou uma variação significativa nas atividades das enzimas viz. superóxido dismutase (SOD), catalase (CAT) e peroxidase (POD). A atividade de SOD variou significativamente em resposta ao tempo de exposição de Cu como 56> 70> 42> 84> 28> 14 dias, enquanto a atividade de CAT exibiu uma relação inversa com o aumento na concentração de Cu. A atividade POD mostrou um aumento significativo com um aumento na duração da exposição ao Cu. O ensaio do cometa exibiu dano significativo ao DNA induzido por Cu nos eritrócitos periféricos de C. catla. Entre as quatro concentrações de exposição, 2/3 do LC50 (T1) causou danos significativamente maiores aos núcleos em comparação com o controle. O aumento da atividade de POD e SOD, bem como uma diminuição na atividade de CAT em resposta ao Cu, demonstra o envolvimento de um mecanismo protetor contra espécies reativas de oxigênio (ROS), enquanto o aumento de ROS resultou em maior dano ao DNA. Esses marcadores moleculares mencionados acima podem ser usados ​​de forma eficiente para o biomonitoramento de ambientes aquáticos e conservação da ictiofauna comestível.

Headache as the sole manifestation of Wilson’s disease

Wilson’s disease (WD) is an inborn error of copper metabolism caused by a mutation to the copper-transporting gene ATP7B. In the first decade of life, hepatic involvement predominates but neurological manifestations occur in the third or fourth decades. Studies showed Indian children with neuro WD present with behavior abnormality, speech and cognitive impairment, sub-clinical affection of visual pathway, and autonomic function. As a treatable disease, WD should be detected early in the course of the disease by any health professional at any care level, but the rare prevalence of the disease explains the lack of awareness of this disease. Even a high index of suspicion about this entity gets more difficult when the rare and atypical symptom is the only presentation of the disease. Here, we present the case of a 15-year-old girl with worsening headache for the past 3 months as the only neurological manifestation of WD, and that also without any evidence of hepatic involvement.