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.

Copper formulations in bacterial blight control and toxic effects on coffee seedlings

Bacterial blight of coffee (Pseudomonas syringae pv. garcae) is an important coffee disease and can be controlled using antibiotics and copper-based compounds. However, copper-based compounds raise doubts among coffee growers regarding bacterial blight control efficiency and phytotoxic potential. In this work, coffee plants were sprayed with different copper molecules in order to study their efficiency on bacterial blight control and the phytotoxic potential. Seven copper formulations, cuprous oxide, copper oxychloride, copper nitrate, copper hydroxide 1 (water-dispersible granules) and 2 (concentrated suspension), copper sulfate 1 (complexed with gluconic acid) and 2 (Bordeaux mixture) were studied. The copper formulations efficiency was compared with the antibiotic kasugamycin, saline solution, and control. In controlled environmental conditions of temperature, relative humidity, and photoperiod, coffee seedlings were sprayed with the treatments and after 24 hours they were inoculated with Pseudomonas syringae pv. garcae suspension. Disease incidence and severity assessments were performed in a 2-day interval during a 16-day period. Phytotoxicity incidence and severity, mapping, and quantification of copper on the leaf tissue surface, dried leaves weight, and total copper leaf content were assessed 16 days after pathogen inoculation. Data were submitted to the Scott-Knott test (p < 0.05). Cuprous oxide and copper sulfate 2 proved most efficient to bacterial blight control, causing lower phytotoxicity effect, best covering, and persistence on leaf tissues. Copper nitrate and copper sulfate complexed with gluconic acid were more phytotoxicity compared to other copper formulations.

DNA damage in a solution containing copper(II) ions and ascorbic acid: Effect of the presence of sulfite

Some antioxidant compounds have a pro-oxidant effect in the presence of transition metal ions, due to the reduction of Mn+ to M(n-1)+ with simultaneous formation of free radicals, which then promote DNA damage. In the present study, we evaluated the pUC19 DNA damage in a solution containing Cu(II) and ascorbic acid (AA) or S(IV) saturated with air by agarose gel electrophoresis. Our results showed that this damage decreases if AA and S(IV) are simultaneously added. This study also illustrates the importance of Cu(II) in this process, as no DNA damage was observed when AA or S(IV) were present in the absence of this metallic ion. Our data showed that DNA preservation depends on the concentration of AA and S(IV) and occurs when the [S(IV)]:[AA] ratio ranges from 1:1 to 20:1. Absorbance measurements and thermodynamic data show that no reaction occurs between AA and S(IV) when this mixture (pH 5.5) is added to pUC-19 DNA. The presence of dissolved oxygen may be the cause of AA consumption in the mixture of these two antioxidants, which subsequently decreases DNA damage.

Antibacterial effect of titanium alloys with copper nanoparticles: in vitro study

Objective: To evaluate the in-vitro antimicrobial effect of Titanium alloys with Copper Nanoparticles (CuNP) against Streptococcus mutans and Phorphyromonas gingivalis. Materials and Methods: An in vitro study was carried out. The unit of analysis corresponded to 10 healing abutments. In 5 abutments Copper nanoparticles (CuNP) electrodeposition was applied. The remaining 5 abutments corresponded to control. The healing abutments were then immersed in culture medium for S. mutans and P. gingivalis for 14 days. Results: The agar plates with CuNP-coated abutments showed a lower growth, statistically significant for both bacterial strains. Conclusion: There is a statistically significant lower growth of S. mutans and P. gingivalis in healing abutments with CuNP.

Copper stress induces antioxidant responses and accumulation of sugars and phytochelatins in Antarctic Colobanthus quitensis (Kunth) Bartl

BACKGROUND: In field, C. quitensis Is subjected to many abiotic extreme environmental conditions, such as low temperatures, high UV-B, salinity and reduced water potentials, but not metal or metalloid high concentrations in soil, however, other members of Caryophyllaceae family have tolerance to high concentrations of metals, this is the case of Silene genre. In this work, we hypothesize that C. quitensis have the same mechanisms of Silene to tolerate metals, involving accumulation and induction of antioxidant systems, sugar accumulation and the induction of thiols such as phytochelatins to tolerate. RESULTS: The results showing an effective antioxidant defensive machinery involving non-enzymatic antioxidants such as phenolics, GSH and ascorbic acid, in another hand, GSH-related oligomers (phytochelatins) and sugars was induced as a defensive mechanism. CONCLUSIONS: Colobanthus quitensis exhibits certain mechanisms to tolerate copper in vitro demonstrating its plasticity to tolerate several abiotic stress conditions.

Antimicrobial effect of copper surfaces on bacteria isolated from poultry meat

Abstract Poultry meat is a food product that usually carries high rates of microbial contamination, including foodborne pathogens. The poultry industry has established different systems to minimize these hazards. In recent years, extensive literature has demonstrated the antimicrobial activity of different contact surfaces made of copper to effectively reduce microbial loads. The aim of the present study was to evaluate the antibacterial effect of copper surfaces on the transmission of two foodborne pathogens - Salmonella enterica and Listeria monocytogenes - and a poultry native microbiota bacterial species - Enterobacter cloacae. We also evaluated the impact of the poultry meat matrix on the antimicrobial activity of a copper surface. Our results indicated that copper surfaces reduced the bacterial load quickly (<than 4 min) when the microorganisms were exposed to polished copper surfaces. Even when bacteria were inoculated on copper surfaces soiled with the organic matrix (washing water from poultry carcasses) and survival rates were significantly higher, an antimicrobial effect was still observed. Survival rates of two microorganisms simultaneously exposed to copper did not show significant differences. We found an antimicrobial effect over pathogenic and non-pathogenic microorganisms. Results suggest a potential role for copper surfaces in the control of microbiological hazards in the poultry industry.

Copper nanoparticles as potential antimicrobial agent in disinfecting root canals: a systematic review / Nanopartículas de cobre como potencial agente antimicrobiano en la desinfección de canales radiculares: revisión sistemática

Copper was registered as the first solid antimicrobial material. Its availability makes it an important option as an antibacterial agent. At nanoparticle size it does not exceed 100 nm, allowing close interaction with microbial membranes, enhancing its effect even more. Copper generates toxic hydroxyl radicals that damage cell membranes of Gram-negative and Gram-positive bacteria, among the latter, Enterococcus faecalis, which are present in infected radicular canals. Synthesis of metal nanoparticles with antimicrobial properties has become a viable alternative and has promising applications in the fight against pathogenic microorganisms. Furthermore, the use of some polymers to stabilize nanoparticles increases their release time and may as well decrease the risk of bacterial recolonization and biofilm formation within the ducts, enhancing the antimicrobial properties of these compounds.The aim of this article is to conduct a systematic review of the literature on antimicrobial copper nanoparticles, their current applications and their potential use in the area of oral health, specifically in the field of endodontics.

El cobre fue registrado como el primer material antimicrobiano sólido y su disponibilidad permite que constituya una importante opción como agente antibacteriano. Al tamaño de nanopartícula no supera los 100 nm, lo que permite una interacción estrecha con las membranas microbianas, potenciando aún más su efecto. Genera radicales hidroxilos tóxicos que provocan daño en la membrana celular de bacterias Gram negativas y Gram positivas, entre estas últimas, Enterococcus faecalis, presente en conductos radiculares infectados. Por lo que la síntesis de nanopartículas metálicas con propiedades antimicrobianas se ha vuelto una alternativa viable con aplicaciones prometedoras en la lucha contra microorganismos patógenos. Además, utilizando algunos polímeros para estabilizar las nanopartículas se aumenta el tiempo de liberación de éstas y se disminuye el riesgo de recolonización bacteriana y la formación de biopelículas al interior de los conductos, mejorando las propiedades antimicrobianas de estos compuestos. El propósito de este artículo es realizar una revisión sistemática de la literatura acerca de nanopartículas de cobre como antimicrobiano, sus aplicaciones actuales y su potencial uso en el área de la salud oral, específicamente en el campo de la Endodoncia.

Comportamiento antibacteriano de partículas de cobre frente a microorganismos obtenidos de úlceras crónicas infectadas y su relación con la resistencia a antimicrobianos de uso común / Antibacterial activity of copper salts against microorganisms isolated from chronic infected wounds

Background: The antimicrobial activity of copper (Cu+2) is recognized and used as an antimicrobial agent. Aim: To evaluate the antimicrobial activity of copper against microorganisms obtained from chronic cutaneous wound infections. Material and Methods: Five chemical products that contained copper particles in their composition were tested (zeolite, silica, acetate, nitrate and nanoparticle of copper). The antimicrobial activity against antibiotic resistant strains usually isolated from chronic cutaneous wound infections was determined for two of the products with better performance in copper release. Results: The minimal inhibitory and minimal bactericidal concentrations of copper acetate and nitrate were similar, fluctuating between 400-2,000 µg/ml. Conclusions: The studied copper salts show great potential to be used to control both gram positive and gram negative, antibiotic resistant bacteria isolated from wound infections.

Actividad de cobre sobre cocáceas grampositivas multi-resistentes a los antibióticos aisladas en hospitales chilenos / Copper activity against multiresistant Gram-positive cocci isolated in Chilean hospitals

Background: Nosocomial infections caused by multiresistant Gram-positive cocci are a serious problem for public health systems worldwide. The use of copper surfaces in hospital environments has proven to be an effective alternative for the control of various microorganisms, including multiresistant nosocomial pathogens. Aim: To determine the association between antibiotic multiresistance and higher levels of copper tolerance in Gram-positive cocci isolated from Chilean hospitals, which might confer a selective advantage in environments with copper. Methods: The ionic copper tolerance levels were evaluated using the Mueller Hinton agar dilution method, in S. aureus and Enterococcus spp. strains with different levels of susceptibility to clinically relevant antibiotics. Results: A statistically significant association between higher levels of tolerance to copper ion and multi-resistance to antibiotics in Enterococcus spp. was observed.

Introducción: Las infecciones nosocomiales, producidas por bacterias cocáceas grampositivas multi-resistentes constituyen un serio problema para los sistemas de salud pública mundial. El uso de superficies de cobre en ambientes hospitalarios ha demostrado ser una alternativa efectiva para el control de diversos microorganismos, incluyendo patógenos nosocomiales multi-resistentes. Objetivo: Determinar la asociación entre la multi-resis-tencia a antimicrobianos y mayores niveles de tolerancia a cobre en bacterias cocáceas grampositivas aisladas de hospitales chilenos, que podrían conferir una ventaja selectiva en ambientes cobrizados. Material y Métodos: Se evaluó los niveles de tolerancia a cobre iónico en grupos de cepas de Staphylococcus aureus y Enterococcus spp. con distintos grados de susceptibilidad a antimicrobianos de relevancia clínica, mediante el método de dilución en agar Mueller Hinton. Resultados: Se observó una asociación estadísticamente significativa entre mayores niveles de tolerancia a cobre iónico y la multi-resistencia a antimicrobianos en Enterococcus spp.

Optimization of laccase production by two strains of Ganoderma lucidum using phenolic and metallic inducers / Optimización de la producción de lacasa por dos cepas de Ganoderma lucidum utilizando inductores fenólicos y metálicos

Ganoderma lucidum (Curtis) P. Karst es un hongo causante de pudrición blanca, capaz de degradar la lignina de la madera y otros sustratos en los que crece. En este trabajo se evaluó la capacidad de dos cepas de esta especie de producir la enzima ligninolítica lacasa. Asimismo, se ensayó la inducción de esta enzima con diferentes compuestos fenólicos e iones metálicos, y se encontró que el ácido ferúlico y el cobre fueron los mejores inductores de la lacasa entre los agentes evaluados. También se encontró que los dos tipos de inductores (fenólicos y metálicos) producen distintos patrones electroforéticos de actividad lacasa. Las concentraciones óptimas de los inductores fueron establecidas mediante un diseño factorial. Se estimó la estabilidad térmica de la lacasa en un amplio rango de pH ácidos, y se comprobó que a pH más altos la enzima es más termoestable.

Ganoderma lucidum (Curtis) P. Karst is a white rot fungus that is able to degrade the lignin component in wood. The ability of two strains of this species to produce the ligninolytic enzyme laccase was assessed. After the evaluation of induction with heavy metals and phenolic compounds, it was found that among the tested substances, copper and ferulic acid are the best laccase inducers. It was also observed that the two types of inducers (phenolic and metallic) produce different electrophoretic patterns of laccase activity. Optimized concentrations of inducers were obtained through a factorial design and the thermal stability of optimized supernatants was studied at a wide range of acidic pH. We found that the enzyme is more thermostable at higher pH values.

Controvérsias acerca do dispositivo intrauterino: uma revisão / Controversies about the intrauterine device: a review

O dispositivo intrauterino (DIU) é atualmente o método contraceptivoreversível mais usado no mundo, sobretudo nos países em desenvolvimento, com maior número de usuáriasna Ásia oriental. Entretanto, ainda há controvérsias envolvendo o seu uso. Por esse motivo, consultamos sitescom bancos de dados eletrônicos como Medline, Lilacs, Wholis e Biblioteca Cochrane, sem restrição linguística,à procura de artigos que abordassem controvérsias sobre o DIU e selecionamos 32, os quais foram incluídos napresente revisão. O mecanismo de ação se deve à reação inflamatória, citotóxica, comprometendo a qualidade,viabilidade e a migração do esperma pela ação do DIU com cobre sobre o muco cervical. A inserção imediatamenteapós uma gestação apresenta várias vantagens, como prevenção de gravidez indesejada, porém não há consensose é tão segura e eficaz quando comparada à inserção fora desse período. O uso profilático de antibióticos nãodiminui o risco de infecções do trato genital, podendo ser indicada para mulheres que vivem em regiões comalta prevalência de doenças sexualmente transmissíveis (DST). Menorragia e dismenorreia são os efeitos colateraismais frequentes referidos pelas usuárias de DIU e as principais causas de sua remoção. O uso de anti-inflamatóriosnão hormonais para tratá-los é motivo de controvérsias na literatura. Sobre o uso de DIU em nulíparas, existemrelativamente poucos estudos na literatura e as conclusões não são seguras. Apesar dos dados sobre adolescentesquanto à segurança, eficácia e aceitação, serem escassos, há pressa no que diz respeito ao uso nesse grupo,tendo em vista a prevenção de gravidez indesejada, tão comum entre elas. As contraindicações são limitadas àgravidez, neoplasias malignas uterinas e efeitos adversos aos componentes do DIU. Apesar de o DIU ser usadohá muitos anos, existe ainda questionamentos de como a fertilidade subsequente é afetada...

The intrauterine device (IUD) is nowadays the most widely used reversiblecontraceptive method in the world, particularly in developing countries, with the highest use in Eastern Asia.Nevertheless, there are still controversies involving its use. For this reason, we searched Medline, Lilacs, Wholisand Cochrane Collaboration databases for articles in any language, addressing controversies about the IUD, selecting 32 for inclusion in this review. The mechanism of action is due to cytotoxic and inflammatory reaction,compromising the quality, viability and sperm migration, by the action of the IUD with cupper on the cervicalmucus. Insertion immediately after a pregnancy ends has several potential advantages, like preventing an unwantedpregnancy. However, there is no consensus if the insertion in this period is as safe and effective as the intervalinsertion. The prophylactic use of antibiotics has not decreased the risk of upper genital tract infection, but itmay be justified for women living in regions with high prevalence for sexually transmitted diseases (STD). Themost frequent side effects reported by users of IUD are menorrhagia and dysmenorrhea, considered the mostcommon reasons for its removal. Non-steroidal anti-inflammatory drugs used for these associated symptoms arecause for controversy in the literature. Concerning the utilization of IUDs in nuliparous women, there are relativelyfew studies in the medical literature and the conclusions are no definitive. There are little data regarding safety,efficacy, and acceptability of IUDs in teenagers. However, this should be countered with the pressing need toprevent unintended pregnancy in this group of women. Contraindications are restricted to pregnancy, malignantuterine neoplasms and adverse effects of the IUD components in the user...

THE COPPER INTERFERENCE WITH THE MELANOGENESIS OF Cryptococcus neoformans / A interferência de cobre na melanogênese de Cryptococcus neoformans

Melanin is a pigment produced by laccase, a phenoloxydase enzyme, and is related to the virulence of Cryptococcus neoformans as it is also considered an adaption mechanism to environmental conditions and protection against UV radiation, phagocytic system attack and antifungal drugs. Laccase synthesis is stimulated by several factors, including copper metabolism. The current study shows C. neoformans strains with higher melanization intensity when grown in L-dopa medium supplemented with different concentrations of copper sulfate. This increase shows that melanization rates may be enhanced in the presence of copper ions and may also enhance the virulence of C. neoformans in infected patients that present increasing copper concentrations in serum, such as those with HIV. The virulence of these strains may also be increased in the environment, where this metal is available as CuSO4 in algicidal and fungicidal compounds.

A melanina é um pigmento produzido pela enzima lacase, uma fenoloxidase, e está associada à virulência de Cryptococcus neoformans sendo considerada mecanismo de adaptação às condições ambientais e proteção contra a radiação UV, ataque do sistema fagocítico e antifúngicos. A lacase tem sua síntese estimulada por diversos fatores, incluindo o metabolismo de cobre. Este estudo mostra linhagens de C. neoformans com maior intensidade de melanização quando cultivadas em meio L-dopa suplementado com diferentes concentrações de sulfato de cobre. Este aumento demonstra que as taxas de melanização podem ser aumentadas na presença de íons cobre e também aumentar a virulência de C. neoformans em pacientes infectados que apresentam aumento nas concentrações séricas de íons cobre tais como pacientes com HIV. A virulência destas linhagens também pode ser incrementada no meio ambiente, onde este metal está disponível como CuSO4 em compostos algicidas e fungicidas.

Actividad de cobre sobre bacilos gramnegativos multi-resistentes aislados en hospitales chilenos / Copper activity against multiresistant Gram negative bacilli isolated from Chilean hospitals

Introduction: Multiresistant nosocomial pathogens, especially Gram-negative bacilli (GNB), are a serious problem for public health systems worldwide. Due to their antimicrobial properties, copper alloys have been suggested as an alternative for the control of bacterial burden in surfaces in hospital environment. However, antibiotic multiresistance and copper resistance could be associated in GNB, and there is evidence that both kind of resistance genes (antibiotic and copper) can be located on the same genetic structures. For this reason antibiotic-multiresistant strains could survive in the presence of copper, selecting for bacterial phenotypes resistant to both antibacterial agents. Aim: To evaluate antibacterial activity of copper against nosocomial extended-spectrum β-lactamases (ESBL) (+) and ESBL (-) GNB, and carbapenems resistant or susceptible strains. Material and Method: This study included 390 strains of GNB isolated from Chilean hospitals: Acinetobacter baumannii and Pseudomonas aeruginosa resistant (CAR R) and susceptible (CAR S) to carbapenem antibiotics, and Klebsiella pneumoniae and Escherichia coli producers and non-producers of ESBL. Susceptibility levels to cupric sulphate were determined by agar dilution method and statistical analysis were used to determine the significance of the differences in the copper tolerance levels between the strains groups. Results: Statistically superior copper tolerance levels were found in the CAR R and ESBL producing strains of A. baumannii and K. pneumoniae, in relation with the CAR S and ESBL not-producing strains. Conclusion: A relation between a diminished susceptibility to ionic copper and to recent generation antimicrobial agents was observed in K. pneumoniae y A. baumannii strains.

Introducción: Los patógenos intrahospitalarios multi-resistentes constituyen un grave problema mundial de salud pública, especialmente los bacilos gramnegativos (BGN). El uso de cobre como antimicrobiano de superficie en hospitales se postula como una alternativa para el control de microorganismos en estos ambientes. Sin embargo, la multi-resistencia a antimicrobianos en BGN hospitalarios puede asociarse con la tolerancia a cobre, ya que existe evidencia que genes que codifican tolerancia a este metal pueden encontrarse en elementos genéticos que confieren resistencia a antimicrobianos. Por esta razón, cepas multi-resistentes a antimicrobianos podrían sobrevivir en presencia de cobre, seleccionando bacterias resistentes a ambos agentes antibacterianos. Objetivo: Investigar la actividad de cobre sobre BGN hospitalarios productores y no productores de β-lactamasas de espectro extendido (BLEE), y resistentes o susceptibles a antimicrobianos carbapenémicos. Material y Métodos: Se estudió 390 cepas de BGN aisladas en hospitales chilenos: Acinetobacter baumannii y Pseudomonas aeruginosa resistentes (CAR R) y susceptibles (CAR S) a carbapenémicos y Klebsiella pneumoniae y Escherichia coli productoras y no productoras de BLEE. Se investigó los niveles de susceptibilidad a sulfato cúprico, mediante dilución seriada en agar y se evaluó la significancia estadística de la diferencia de estos niveles entre los distintos grupos de cepas. Resultados: Se encontraron niveles de tolerancia a cobre superiores en cepas de A. baumannii y K. pneumoniae, CAR R y productoras de BLEE respectivamente, con respecto a sus pares CAR S y no productoras de BLEE. Conclusión: Observamos una relación entre la disminución de la susceptibilidad a cobre iónico y a antimicrobianos de última generación en K. pneumoniae y A. baumannii.

Aplicación de la capacidad bactericida del cobre en la práctica médica / Application of copper bactericidal properties in medical practice

Background: Copper is essential for cell metabolism in animals and plants and thus for life. Along centuries, copper has been identified as a metal containing antimicrobial properties. In recent years, laboratory assays and clinical studies have revealed that surfaces of metallic copper or its alloys, containing at least 70% copper, eliminate in a few hours several pathogenic organisms including bacterial strains associated with nosocomial infections, influenza virus, HIV, and fungi such as Candida albicans. In March 2008, the American Environmental Protection Agency (EPA), supported by scientific evidence gathered to date, registered copper as the first and only metal with antimicrobial properties. We herein review certain mechanisms proposed for the antibacterial, antiviral and antifungal activity of copper. We also discuss in vitro and clinical efficacy studies developed world wide and in Chile, focusing on bactericidal activity of copper surface areas in comparison to materials typically used in hospital environments such as stainless steel and polymers. Scientific evidence gathered to date, consistently shows that the use of copper surface areas in high contact critical points in hospitals, significantly reduces environmental bacterial load. This is associated with a decreased risk of pathogen transmission to patients and represents therefore an interesting complement to infection control programs.

El cobre en la neurofisiología del hipocampo / Copper and hippocampus neurophysiology

Copper is an oligoelement essential for various enzymatic processes both in pathology and in human physiology. Its excessive accumulation in the liver and brain, particularly in the basal ganglia drives to the pathological syndrome known as Wilson's disease, on the other hand, this metal absence in the newborn provokes brain and cerebellar degeneration, pathology recognized as Menkes' disease. Currently its role in Parkinson, Alzheimer and lateral amyotrophic sclerosis is discussed. Our studies in rats about the copper effects in the hippocampus excitability, long term potentiation (LTP) and learning have shown a suppressor action on LTP, without memory alteration nor on the animal learning in the Morris' aquatic maze, a physiological paradoxical result and in its clinical inference also.

El cobre es un elemento esencial en diversos procesos fisiológicos y patológicos. Su acumulación excesiva en hígado, cerebro y particularmente en los ganglios basales, conduce al cuadro patológico conocido como la enfermedad de Wilson. Por otra parte, la ausencia de este metal en el recién nacido provoca degeneración cerebral y cerebelosa patología reconocida como enfermedad de Menkes. Actualmente se discute su papel en el Parkinson, Alzheimer y esclerosis lateral amiotrófica. Nuestros estudios en ratas han mostrado los efectos del cobre en la excitabilidad del hipocampo; su acción supresora de la LTP hipocámpica, sin alterar el aprendizaje y la memoria estudiados en el laberinto acuático de Morris, resultados paradójicos tanto desde la perspectiva neurofisiológica como en su inferencia clínica.

Inhibitory effect of zinc, copper and selenium on telomerase activity in tumor tissues and t47d breast cancer cell line

The present study was performed to investigate the effects of trace elements particularity Se, Zn and Cu on tumor genesis in breast cancer. The inhibitory effect of Se, Zn and Cu, on telomerase activity was analyzed in human breast tumor tissues and breast cancer [T47D] cells. Tissue specimens from 24 women with benign breast disease and 32 women with breast cancer specimens [ductal carcinoma, lobular carcinoma] were collected during surgery. In addition venous blood samples were obtained for assessing the trace elements. T47D cell line was cultured and treated with trace elements. Telomerase activity then was measured with TRAP assay in cell line and tissue extracts. There was a significant difference between tissue and serum levels of Cu, Se and the ratio of Cu/Zn in patients and controls [P<0.001]. After treating with 100 microm/L Zn So4, 10 um /L Cu So4 for 6 hours, telomerase activity of T47D cells was markedly increased. But after treating with 10, and 30 um /L selenium-L- methionin, telomerase activity was markedly inhibited. Telomerase activity of T47D cells for 24 hours were 0.93, 0.60 and for 48 hours were 0.76, 0.12 respectively [control 49.2%]. There were variations in serum level of Zn and Cu in breast cancer patients. Association between trace elements level and telomerase activity level can be exploited as prognostic and diagnostic marker for breast cancer

DNA degradation by aqueous extract of Aloe vera in the presence of copper ions.

The plant Aloe vera has long been used in medicine, as dietary supplements and for cosmetic purposes. Aloe vera extracts are a rich source of polyphenols, such as aloin and aloe emodin and have shown a wide range of pharmacological properties, including anti-inflammatory and anti-cancer properties. The bioactive component aloe emodin has been reported to induce apoptosis in various cancer cell lines. Many of the biological activities of Aloe vera have been attributed to its antioxidant properties. However, most plant-derived polyphenols that are also present in Aloe vera may exhibit pro-oxidant properties either alone or in the presence of transition metals, such as copper. Previous reports from this laboratory have implicated the pro-oxidant action as one of the mechanisms for their anti-cancer properties. In the present paper, we show that aqueous extract of Aloe vera is also able to cause DNA degradation in the presence of copper ions. Further, the extract is also able to reduce Cu(II) to Cu(I) and generate reactive oxygen species, such as superoxide anion and hydroxyl radicals in a dose-dependent manner, which correlates with ability of the extract to cause DNA breakage. Thus, the study shows that in addition to antioxidant activity, Aloe vera extract also possess pro-oxidant properties, leading to oxidative DNA breakage.

Hormesis response of marine and freshwater luminescent bacteria to metal exposure

The stimulatory effect of low concentrations of toxic chemicals on organismal metabolism, referred to as hormesis, has been found to be common in the widely used luminescence bioassay. This paper aims to study the hormesis phenomenon in both marine and freshwater luminescent bacteria, named Photobacterium phosphorem and Vibrio qinghaiensis. The effects of Cu (II), Zn (II), Cd (II) and Cr (VI) on luminescence of these two bacteria were studied for 0 to 75 minutes exposure by establishing dose- and time-response curves. A clear hormesis phenomenon was observed in all four testing metals at low concentrations under the condition of luminescence assays.

Permeability of different groups of maxillary teeth after 38 percent hydrogen peroxide internal bleaching

This study evaluated the influence of internal tooth bleaching with 38 percent hydrogen peroxide (H2O2) on the permeability of the coronal dentin in maxillary anterior teeth and premolars. Seventy teeth (14 per group) were used: central incisors (CI), lateral incisor (LI), canines (C), first premolars (1PM) and second premolars (2PM). Pulp chamber access and transversal sectioning at 2 mm from the cementoenamel junction were performed and the specimens were divided into 2 groups (n= 7): a) no treatment and b) bleaching with 38 percent H2O2. The bleaching agent was applied to the buccal surface and to the pulp chamber for 10 min. This procedure was repeated 3 times. The specimens were processed histochemically with copper sulfate and rubeanic acid, sectioned longitudinally, and digitalized in a scanner. The area of stained dentin was measured using Image Tool software. Data were analyzed statistically by ANOVA and Tukey's HSD test (?=0.05). There was statistically significant difference (p<0.001) among the untreated groups, CI (0.23 ± 0.26) having the lowest permeability and LI (10.14 ± 1.89) the highest permeability. Among the bleached groups, dentin permeability was increased in all groups of teeth except for 2PM. It may be concluded that bleaching with 38 percent H2O2 affected dentin permeability near the pulp chamber in maxillary anterior teeth and in first and second premolars.

Este estudo avaliou a influência do clareamento interno com peróxido de hidrogênio (H2O2) a 38 por cento na permeabilidade da dentina coronária de dentes anteriores superiores e pré-molares superiores. Quatorze incisivos centrais (IC), incisivos laterais (IL), caninos (C), primeiros (1PM) e segundos (2PM) pré-molares foram seccionados transversalmente e distribuídos em 2 grupos (n=7) sendo: G1: não receberam tratamento e, G2: clareados com aplicação de gel na face vestibular e câmara pulpar por 10 min, repetido 3 vezes. Os espécimes foram processados histoquimicamente por meio de imersão em sulfato de cobre e ácido rubeânico e digitalizados em escaner. A área corada foi aferida (Programa Image Tool). Os dentes que não receberam tratamento, apresentaram diferença estatisticamente significante (p<0,001), sendo o ICS (0,23 ± 0,26) e o ILS (10,14 ± 1,89) os grupo com os menores e os maiores valores de permeabilidade, respectivamente. Quando clareados, a permeabilidade coronária dos grupos dentais foi aumentada, exceto no grupo do 2PM. Concluiu-se que a permeabilidade da dentina coronária nos dentes anteriores superiores e primeiros pré-molares foi alterada pelo clareamento dental interno.

Efeito de íons Cu2+ e Zn2+ em atividade Ca-ATPásica isolada de larvas de Pachymerus nucleorum (Fabricius) (Coleoptera: Chrysomelidae, Bruchinae) / Effect of Cu2+ and Zn2+ ions in Ca-ATPase activity isolated from Pachymerus nucleorum (Fabricius) (Coleoptera: Chrysomelidae, Bruchinae) larvae

As ATPases, um importante alvo de inseticidas, são enzimas que hidrolisam o ATP e utilizam a energia liberada no processo para realizar algum tipo de trabalho celular. A larva de Pachymerus nucleorum (Fabricius) possui uma ATPase que apresenta alta atividade Ca-ATPásica, mas não expressa atividade Mg-ATPásica. Nesse trabalho, foi testado o efeito de íons zinco e cobre na atividade Ca-ATPásica dessa enzima. Mais de 90 por cento da atividade Ca-ATPásica foi inibida em 0,5 mM de íons cobre ou 0,25 mM de íons zinco. Na presença de EDTA, mas não na sua ausência, a inibição por zinco foi revertida pelo aumento da concentração de cálcio. A inibição por íons cobre, não foi revertida nem na presença e nem na ausência de EDTA. O tratamento da fração ATPase com cobre, previamente ao ensaio de atividade ATPásica, não inibiu a atividade Ca-ATPásica sugerindo que o íon cobre não liga diretamente a enzima. Os resultados sugerem que íons zinco e cobre formam complexo com o ATP e se ligam à enzima inibindo sua atividade Ca-ATPásica.

ATPases, an important target of insecticides, are enzymes that hydrolyze ATP and use the energy released in that process to accomplish some type of cellular work. Pachymerus nucleorum (Fabricius) larvae possess an ATPase, that presents high Ca-ATPase activity, but no Mg-ATPase activity. In the present study, the effect of zinc and copper ions in the activity Ca-ATPase of that enzyme was tested. More than 90 percent of the Ca-ATPase activity was inhibited in 0.5 mM of copper ions or 0.25 mM of zinc ions. In the presence of EDTA, but not in the absence, the inhibition by zinc was reverted with the increase of calcium concentration. The inhibition by copper ions was not reverted in the presence or absence of EDTA. The Ca-ATPase was not inhibited by treatment of the ATPase fraction with copper, suggesting that the copper ion does not bind directly to the enzyme. The results suggest that zinc and copper ions form a complex with ATP and bind to the enzyme inhibiting its Ca-ATPase activity.