Tal derivaria, em grande parte,

de alterações havidas na «bolsa de ácido», suscetíveis de favorecerem a ocorrência de refluxo patológico, bem tipificadas, aliás, no que habitualmente sucede no contexto da hérnia hiatal por deslizamento (HHD)9 and 10. De facto, e para além de se associar com uma diminuição da função do EEI e da clearance esofágica, a HHD poderia ainda contribuir para a patogénese da DRGE através das modificações que provoca Ibrutinib concentration no tamanho e localização da «bolsa de ácido» 9 and 11. Efetivamente, foi demonstrado que os doentes com DRGE apresentam uma «bolsa de ácido» mais extensa comparativamente aos voluntários saudáveis, facto atribuível à migração proximal da junção gastroesofágica, o mesmo é dizer, à presença de HHD 9. Contudo, mais importante que a extensão

parece ser o posicionamento da «bolsa de ácido», já que, quando ela se situa acima do diafragma, 74-85% dos episódios de relaxamento transitório do EEI são acompanhados de refluxo ácido, contra apenas 7-20% nos casos de localização infradiafragmática 5. Estes dados foram reforçados pelas conclusões duma análise de regressão logística multivariada, as quais confirmaram a presença de HHD e o posicionamento supradiafragmático da «bolsa de ácido» como fatores independentes majores STI571 in vitro para a ocorrência de refluxo ácido no decurso dum episódio de relaxamento transitório do EEI 5. Pesquisas ulteriores sugerem que a HHD plenamente constituída representaria o ponto de chegada de um processo de degradação progressiva da anatomia da junção gastroesofágica, mas não necessariamente o ponto de partida da relevância clínica 11. Com efeito, qualquer modificação estrutural, ainda que subtil (maior abertura do ângulo da incisura cárdica,

por exemplo), que altere a dinâmica da «bolsa de ácido», contribuindo para a migração proximal da mesma, pode resultar na produção triclocarban de refluxo patológico 11 and 12. À luz dos conceitos patogénicos atrás expandidos, a atuação dos agentes farmacológicos na DRGE visaria um, ou mais, dos 3 objetivos terapêuticos seguintes: migração distal, redução do tamanho e/ou elevação do pH da «bolsa de ácido». Assim, os fármacos procinéticos, ao incrementarem o tónus do estômago proximal e acelerarem o esvaziamento gástrico, procurariam atingir os 2 primeiros objetivos13. Isto foi conseguido, pelo menos em parte, quer pela eritromicina quer pela azitromicina, nomeadamente, neste último caso, em indivíduos com HHD de pequenas dimensões13 and 14.

The inclusion of sedimentation dynamics in this study provides an improved context for interpreting the temporal trends and the evaluation of spatial distribution patterns of contaminants supplied to the western

Barents Sea. We thank the captain and crew of r/v ‘Jan Mayen’ for their support and assistance at sea during the CABANERA project ‘Carbon flux and ecosystem feedback in the northern Barents Sea in an era of BGJ398 mouse climate change’. Oddmund Isaksen provided essential logistical support for the benthos group. Special thanks go to the laboratory personnel at IO PAS, especially to Anna Malenga and Ewa Kamińska, who assisted in all phases of the analytical work. Our thanks also go to Paul Wassmann, Michael Carroll and other members

of the CABANERA project for their assistance during the fieldwork and for sharing their ideas and data. Finally, we wish to thank the Norwegian Research Council Project for its financial support of CABANERA (project number: 155936/700) with additional funding provided by the Polish State Committee for Scientific Research (Grant No. 2PO4E 007 28), Institute of Oceanology and Akvaplan-niva. “
“The Vistula Spit’s marine coastal zone is a complex and changeable morpho-lithodynamic system. The main sources of bed load for the study area are the Vistula River mouth (0.4–1.4 × 106 t per year), the Sambian Peninsula (22 × 103 m3 per year from the western coast and 1.5 × 106 m3 per year from the northern coast), the eroded Vistula palaeodelta, and abrasive platforms located in the Gulf of Gdańsk (Passchier et al. 1997, Ryabkova 2002). buy PF-562271 Earlier studies conducted in the Vistula Spit provided important information about coastal processes (Musielak 1980, Rosa

tuclazepam & Wypych 1980, Solovieva & Badiukova 1997, Zawadzka-Kahlau 1999, Boldyrev & Bobykina 2001, Babakov 2008, Chechko et al. 2008, Bobykina & Karmanov 2009). These studies, however, focused mostly on certain western or eastern stretches of the coast. Particularly with respect to the lithological studies, the time and methodology of the research differed significantly. As a result, comparison of these studies is difficult, and the questions of morphometric structure and lithodynamic conditions still need to be addressed. The study presented in this paper includes the results of transborder morphological and lithological onshore and nearshore research, performed by unified methods in cooperation between the Department of Marine Geology, Institute of Oceanography, University of Gdańsk (Gdynia, Poland) and the Laboratory of Coastal Systems, Atlantic Department of the P. P. Shirshov Institute of Oceanology of the Russian Academy of Sciences (RAS) (Kaliningrad, Russia) (Bobykina et al. 2009). A lithodynamic interpretation of the collected data was carried out, and two different methods of shore sediment sampling were compared.

Biorąc pod uwagę PARP inhibitor powyższe doniesienia o immunogenności, skuteczności klinicznej i efektywności populacyjnej szczepionek przeciw ospie wietrznej oraz aktualną sytuację epidemiologiczną w Polsce, Grupa Ekspertów rekomenduje przyspieszony schemat szczepień przeciw ospie wietrznej, który przedstawiono w tabeli 1. “
“W ostatnich latach wiele uwagi poświęcono bakteriom probiotycznym, znajdując coraz

więcej korzyści z ich zastosowania w medycynie. Wzrasta liczba gatunków dobrze poznanych probiotyków, a także przeprowadzonych badań dotyczących ich skuteczności w określonych sytuacjach klinicznych oraz bezpieczeństwa w różnych grupach pacjentów. Lactobacillus reuteri (L. reuteri) jest jedną z dobrze już poznanych bakterii probiotycznych, o udokumentowanym działaniu w wielu sytuacjach klinicznych. Wykryto ją już na początku XX wieku, jednak wówczas nie postrzegano jej jako odrębny gatunek, lecz, wraz z innymi bakteriami o podobnych właściwościach, zaliczano do tzw. bakterii kwasu mlekowego [1]. W latach 60. XX wieku niemiecki mikrobiolog Gerhard Reuter wyizolował tę pałeczkę z kału ludzkiego i wycinków z jelit i

zaczął klasyfikować. Odróżnił ją od L. fermentum i nazwał Lactobacillus fermentum biotype II [2]. Ribociclib solubility dmso Jako odrębny gatunek Antidiabetic Compound Library wyróżniono i sklasyfikowano L. reuteri w latach 80. XX w. [3]. W dalszych badania wykazano, że istnieje ponad 160 odmian L. reuteri, które ewoluowały wraz z gatunkami gospodarzy [4]. Odmiany bytujące u człowieka cechują się wysoką konserwatywnością. L. reuteri wyizolowano z wielu naturalnych środowisk, w tym wielu pokarmów, zwłaszcza mięsa

i produktów mlecznych [2, 5, 6]. Bakterie te kolonizują przewód pokarmowy człowieka po zjedzeniu przetworów mlecznych; są zdolne do kolonizacji przewodu pokarmowego także noworodków, w tym wcześniaków. Wykazano, że u wielu gatunków zwierząt, a także u człowieka, L. reuteri jest głównym składnikiem wszystkich pałeczek Lactobacillus bytujących w przewodzie pokarmowym, tak więc uznano go za najbardziej uniwersalną bakterię jelitową. L. reuteri należy do naturalnych mikrobiontów mleka kobiecego [7]. Znajduje się głównie w początkowej porcji mleka wypływającej z piersi podczas karmień. Niedawno wykazano jednak, że te bakterie można wyizolować z mleka tylko u około 15% kobiet karmiących [8]. W mleku kobiet zamieszkujących tereny wiejskie występują one częściej niż w mleku kobiet z miast. Chociaż L. reuteri jest naturalnym mikrobiontem przewodu pokarmowego, to nie kolonizuje w sposób naturalny jelit 100% ludzi.

The modified beam model uses the interpolated eigenvectors of the 3-D FE model in motion analysis. Linear computations are performed on the three structural models coupled with the 3-D Rankine panel method. In Fig. 11, all responses are shown to be almost identical. The sharp peak of roll motion is observed near the frequency of 1.2 rad/s, which corresponds to the natural frequency of roll motion. The smooth peak of Etoposide solubility dmso roll motion is due to the relationship between the wave and ship length. A small difference between the models is found in the resonant response of the

7th mode near 3.7 rad/s. The difference is acceptable because a resonant response is very sensitive to frequency. Resonant responses to linear and nonlinear wave excitations are compared in the following sections concerning the 6500 TEU and 10,000 TEU containerships. In Fig. 12, the time series of sectional forces in the regular wave are compared. The still water loads are not included. The high-frequency oscillations in the front part of the torsional moment and vertical bending moment are transient motions of 2-node vertical bending and 2-node torsion modes. Good agreement is obtained for both wet mode natural frequencies and

responses to waves. The natural frequency of 2-node vertical bending decreases from 0.92 Hz in dry mode to 0.61 Hz in wet mode. The added mass can be calculated from the wet mode natural frequency. Fig. 13 shows the longitudinal distribution of the sectional forces. It is confirmed clonidine that the system is balanced in each time step. Fig. 14 shows the time series of normal stresses in the longitudinal selleck compound direction. The stress is evaluated on the top at the mid-ship section, the coordinates of which are 30.0 m from AP, 0.0 m from the center line, 2.0 m from the water line. The stress including both quasi-static and dynamic contribution is calculated as follows: equation(73) σx=MyIyz+FzA equation(74)

σx=∑j=7kσxjξjwhere the normal stress of jth mode obtained by eigenvalue analysis of the 3-D FE model. Eq. (73) is used in the beam theory model, and Eq. (74) is used in the modified beam and 3-D FE models. The results show good agreement between the stresses of the different models. In Eq. (74), the stress converges when k=14. If stress is evaluated at the location far from the mid-ship, k must be larger than 14. In order to obtain the converged stress at every location, quasi-static stresses of higher modes should be calculated, which are not included in the coupled-analysis. The most rigorous method is to perform FE analysis with applying all the inertial and external forces. In addition, the mesh of the 3-D FE model should be finer than that for eigenvalue analysis. The stress evaluation is not discussed more than the above because it is too complicated to be fully handled in this study. However, the method for stress evaluation will be thoroughly discussed in the near future because stress evaluation is the final goal of the hydroelastic analysis.

Reassuringly, there was no reliable interaction between the affordance effect and the particular toolbox exemplar presented [congruency × object interaction: F(4, 239) = 1.20, p = .31]. Furthermore, we repeated the analysis of correct RTs after removing those trials which contained the relatively infrequent exemplar (the chisel). The affordance effect shown for the remaining toolbox items remains very large and statistically significant (incongruent mean = 1122 msec; congruent mean = 1064 msec; congruency effect = 58 msec, p = .03). Errors were very infrequent (an above-threshold response

was made by the erroneous hand on only 10/512 trials – approximately 2% of all trials). This error rate is similar to that which we observed in young (approximately 5%), and elderly (approximately 3%) healthy controls. Of these errors E7080 made

by Patient SA, 8/10 were made by the right (alien) hand when the task required a response with the left hand. Six errors were detected by the alien limb in response to affordance incongruent trials (in other words, when the object presented required a left hand response, but was oriented such that it afforded a right-hand response), and 2 errors in response to affordance congruent trials. Errors were not confined to one particular Selleck ERK inhibitor stimulus, and instead were spread across 7 different exemplars. As errors were so infrequent, they were not analysed any further. In Experiment 2, we used a backwards masked priming task (adapted from Sumner et al., 2007) to investigate automatic inhibition of responses that had been automatically primed in the alien and non-alien hands. In order to be sure of producing automatic priming and inhibition of responses, it was necessary to change the interval between masked-prime and target. There are several methods reported in the literature to achieve this. One possibility would be to present the target stimulus once the mask had offset, and Obeticholic Acid change the duration of the mask. However, shorter masks would be expected

to mask the prime stimulus less well, which could have strong effects on the priming of responses. Alternatively, some researchers have used meta-contrast masking – that is, to use a stimulus which masks the prime by surrounding it. However, such masks are problematic because masks can act as prime stimuli in their own right – as masks of this type typically contain elements of both possible primes, any NCE obtained using such a mask may not be produced by response inhibition, but by mask-induced priming of the response opposite that evoked by the prime (see “object updating” e.g., Lleras and Enns, 2004; Sumner, 2008). As we were interested in the effects of automatic response inhibition, we sought to avoid this possibility.

The patient underwent an upper gastrointestinal endoscopy, which showed a slight loss of folds in the second portion of the duodenum. Multiple biopsies were obtained in this

location, revealing a complete villous atrophy, crypt lengthening and markedly increased number of intraepithelial lymphocytes (Fig. 1), histopathological findings typical of celiac disease (with a destructive pattern, 3c type according to the Marsh–Oberhuber classification). Since the differential diagnosis of AIH versus celiac hepatitis was unclear, it was decided to perform a liver biopsy. The biopsy revealed minimal macrovesicular steatosis and hepatocellular selleck chemicals llc reactive changes, with no evidence of interface hepatitis ( Fig. 2), all nonspecific findings, not consistent with AIH. At this point, the simplified AIH score was 6, indicating a probable diagnosis of AIH. According to the overall clinicopathological data, the liver abnormalities were primarily attributed to celiac disease. The patient received dietary counseling and started on a gluten-free C59 wnt purchase diet alone. After 6 months the laboratory reassessment evidenced

a complete normalization of aminotransferases (AST 25 U/L, ALT 22 U/L) and decreasing IgG anti-transglutaminase levels (342 U/mL); antinuclear and anti-smooth muscle antibodies remained positive. Her BMI was 21 kg/m2. Hepatic abnormalities are common extraintestinal manifestations of CD. They may arise in patients with the classical malabsorption syndrome or may be the sole presentation in some cases.2 Approximately 27% of adult patients with untreated classic CD have elevated transaminases. Conversely, CD is the potential cause for cryptogenic hypertransaminasemia in 3–4% of cases.5 CD not only may itself injure the liver but it may also coexist with other chronic liver diseases and modify their clinical impact.2 Two main forms of liver damage are recognized: the nonspecific celiac hepatitis and the autoimmune mediated. It is not clearly defined if these two forms are distinct entities or only different ends of a continuous spectrum

of liver injury. 6 and 7 Fatty liver disease, viral hepatitis and iron overload liver disease have also been described in patients with CD. 3 and 6 A Anidulafungin (LY303366) nonspecific form of liver disease, the so-called celiac hepatitis, is the most common form of hepatic involvement in CD. The pathogenesis remains poorly understood. Malnutrition, with its metabolic effects, is one of the proposed hypothesis, although nowadays this is an uncommon feature of CD patients. 5 An alternative possible mechanism is the direct effect of antigens absorbed from the gut, as a result of an increased permeability of the inflamed intestinal mucosa. 8 and 9 Against this hypothesis is the absence of correlation between intestinal histological changes and the severity of hepatic dysfunction.

PDT of C. albicans planktonic cultures reduced cell viability in a statistically significant manner at the lowest erythrosine concentration used (0.39 μM), whilst the lowest suitable concentration for reduction of C. dubliniensis was 1.56 μM. Both strains were reduced completely at concentrations of erythrosine 3.12 μM and higher with LED irradiation of 3 min and a fluence of 42.63 J cm−2. Candida were previously shown to be completely inactivated when a blue LED (37.5 J cm−2) was used in association with Photogem

(25 mg/mL) on planktonic cultures of reference and fluconazole-resistant strains of C. albicans and C. glabrata. 19 In contrast, the present study resulted in a greater microbial reduction at lower concentrations of photosensitizer than that reported by Peloi et al.25 These authors assessed the photodynamic action of a methylene blue photosensitizer at a concentration of 35.2 μM irradiated check details by a red LED (2–12 J cm−2) for 10–60 min against planktonic cultures of Staphylococcus aureus, Escherichia coli and C. albicans, obtaining reductions of 2.34–3.71, 1.61–3.41 and 2.77–3.87 log10, respectively. However, the fluence of the LED used by Peloi et al. 25 was approximately 3.5 times smaller than the fluence of the LED used here. We demonstrated greater microbial reductions with a smaller fluence of LED, irradiation time and dye concentration than

that reported by Soares et al.,26 who used a red LED with a fluence of 180 J cm−2 and an irradiation time of 15 min in association with 25 μM toluidine blue to achieve a 3.41 log10

Enzalutamide datasheet reduction in fluconazole-resistant and -sensitive Candida learn more strains. These authors also demonstrated that PDT inhibited 55% of the adhesion of the Candida strains to buccal epithelial cells, highlighting the important impact of LED in association with toluidine blue on the inhibition of growth and virulence factors of the fluconazole-resistant and -sensitive Candida strains. The biofilms of C. albicans and C. dubliniensis exposed to PDT mediated by 400 μM erythrosine and a green LED exhibited statistically significant reductions in CFU/mL of 0.74 log10 and 0.21 log10, respectively. The result obtained for the C. dubliniensis biofilms corroborates those described by Dovigo et al. 19 for the PDT of biofilms of C. albicans and C. glabrata, which were reduced 0.24 log and 0.16 log respectively. The biofilms of C. albicans and C. dubliniensis were less susceptible to PDT than their planktonic counterparts, which could be due to the heterogeneity of the biofilm population, the restriction of antimicrobial penetration by the extracellular matrix material, the slower growth rate of the cells in the biofilms and differences in gene expression levels. 11 and 29 Chabrier-Roselló et al.30 evaluated the effects of Photofrin- and Hg arc lamp-mediated PDT on biofilms and germ tubes of C. albicans.

In the hypothalamus binding was localized to the

PVN and SON (Fig. 4A). No binding of other structures throughout the brain was observed. High densities of APJ were present in the anterior lobe of the pituitary with moderate levels of binding sites seen in the posterior lobe. Little to no binding above background levels was seen in the intermediate lobe (Fig. 4B). [125I]-(Pyr1)apelin-13 binding was also seen in the adrenal cortex with the highest receptor densities seen in the zona glomerulosa and no APJ binding sites were found in the medulla (Fig. 4C). No binding was detected in the adrenal gland in the presence of unlabeled ligand (inset Fig. 4C). In the kidney the most Dabrafenib mouse dense localization of [125I]-(Pyr1)apelin-13 binding sites was found in the outer medulla with patches of binding found in the cortex (Fig. 5A). The lung showed uniform binding to the parenchyma with no binding sites detected in connective tissue or blood vessels (Fig. 5B). High densities of APJ binding sites were localized to the mucosal layer of the pyloric region of the stomach (Fig. 5C) as well as in the mucosa and villi of the ileum (Fig. 5D). The density of APJ binding sites

in the heart was uniform throughout the myocardium (Fig. 5E). No specific binding was detected in the presence of unlabeled ligand (Fig. 5E, inset) not in the heart of APJ KO mice (Fig. 5F). In the uterus very high levels of binding were present in the endometrium but totally absent from the myometrium (Fig. 6A). The ovary displayed strong binding in the theca cells of follicles and in corpus lutea (Fig. 6B) while no binding occurred in the presence of unlabeled (Pyr1)apelin-13 GSK126 (Fig. 6B, inset), Specific labeling of (Pyr1)apelin-13 binding sites was absent in the APJ KO ovary (Fig. 6C). Previous studies mapping APJ distribution have focused primarily on APJ mRNA expression in rat brain and peripheral tissues and few studies have investigated the distribution of APJ protein in any species. The present study provides the first detailed

characterization of APJ mRNA and I125[Pyr1]apelin-13 binding Buspirone HCl site distribution in the mouse. We have found that APJ mRNA and I125[Pyr1]apelin-13 binding site localization appear to be unaffected by gender and that there is a clear correlation between the expression of APJ mRNA and I125[Pyr1]apelin-13 binding. A summary of our findings is shown in Table 1. We report a restricted localization of both APJ mRNA and I125[Pyr1]apelin-13 binding sites in the mouse CNS, with discernable levels found only in the hypothalamic PVN and SON. While we cannot discount that the level of APJ in additional regions of the mouse CNS is too low to allow detection by the techniques used in our study, comparable studies in rats have revealed high levels of APJ mRNA in the cerebroventricular system, hypothalamus, the pineal gland, olfactory bulb and hippocampus [9], [17] and [34], suggesting a species difference in central APJ distribution.

v.) administered through the caudal vein with a sterile PBS solution (1 mL/100 g of body weight) or ALS (1 mL/100 g of body weight). Additional control groups (n = 6/group) were injected only with PBS or ALS under the same conditions.

At 24 h after the treatments, blood was collected to measure biochemical and hematological markers of tissue damage. The dose of ALS used here is sufficient to completely neutralize the in vitro pro-coagulant activity of the LOBE. Moreover, the same dose was used in a previous study to compare the efficacy between ALS and antifibrinolytic drugs ( Gonçalves et al., 2007). After treatment, animals from the different groups were anesthetized intraperitoneally (i.p.) with a mixture of ketamine (75 mg/kg) (Syntec, São Paulo, Brazil) and xylazine (10 mg/kg) (Syntec, São Paulo, Neratinib nmr Brazil), and blood was collected by cardiac

puncture. For the coagulation and hematological assays, the blood samples were collected in 1:10 (v/v) 3.8% trisodium citrate (Merck, Darmstadt, Germany) or 1:16 VE-821 clinical trial (v/v) 10% Na2-EDTA (Merck, Darmstadt, Germany), respectively, while for the biochemical assays, no anticoagulants were used. All samples had 2% (v/v) ALS added to block the activity of the toxin after blood collection. Plasma and serum were obtained by centrifugation Exoribonuclease at 1500 × g for 10 min and stored at −80 °C prior to use. Serum samples were used to measure several biochemical markers of tissue injury. Blood urea nitrogen (BUN), creatinine (Cr), uric acid (UA), creatine kinase (CK), creatine kinase – MB fraction (CK-MB), aspartate aminotransferase (AST), alanine aminotransferase (ALT), γ-glutamyl transferase (γ-GT), lactate dehydrogenase (LDH), plasma free hemoglobin

(Hb) and bilirubin (BIL) levels were determined using commercially available kits (BioClin/Quibasa, Belo Horizonte, Brazil), following the manufacturer’s recommended instructions. The absorbance was read using a SP-220 spectrophotometer (BioSpectro, Paraná, Brazil), or the protocol was adapted for use in 96-well plates and the reads were performed using a SpectraMAX microplate reader (Molecular Devices Co., Sunnyvale, USA). Free hemoglobin (Hb) was measured in the plasma samples that had been collected with Na2-EDTA. In these cases, plasma Hb levels were determined directly by spectrophotometry using a standard curve made with known concentrations of purified Hb (Sigma–Aldrich, Saint Louis, MO, USA). Samples with levels of free Hb higher than 180 mg/dL due to LOBE-induced intravascular hemolysis were diluted to avoid interference during the determination of other parameters. Complete blood cell counts were carried out on plasma samples containing the anticoagulant Na2-EDTA.

To perform atomic absorption experiments

high purity water provided by a Milli-Q water purification system (Millipore, Bedford, MA, USA), nitric acid (Merck) and analytical solutions containing 1000 mg L−1 of Cu (CuCl2) (Titrisol®, Merck) were used. Calibrations curves were obtained by using reference solutions containing 0.5–5 mg L−1 of Cu2+ in 0.1% vol/vol HNO3. Direct analysis of cells was performed by weighing masses around 0.25 mg directly onto the graphite boat-type platform. A ZEEnit® 60 atomic absorption spectrometer (Analytik Jena AG, Jena, Germany) equipped with a manual HKI-272 datasheet solid sampling accessory, pyrolytic graphite tube atomizer and boat-type platform and hollow cathode lamp (wavelength = 216.5 nm, bandpass = 0.8 nm and lamp current = 4.0 mA) was used. A stainless steel

microspatula was used to transfer the samples to the pyrolytic boat-type platform. Microbalance Auto Balance AD-4 (Perkin-Elmer, Norwalk, USA) with a precision of 0.001 mg was used to weight samples. The heating program used for the direct determination of Cu in cells was adapted from a previous program developed by our group (step: temperature/°C, ramp/°C s− 1, hold/s): (drying: 180, 50, and 10), (pyrolysis: 1200, 100, and 15), (atomization: 2500, 2500, and 5) and (cleaning: 2600, Fulvestrant cost 1200, and 3) [49]. All experiments were repeated at least five times (except where otherwise stated) and data expressed as mean values and standard deviation. Differences between means were assessed by ANOVA with Bonferroni’s correction, and those with p values < 0.05 were considered significant. The aim of the study was to gain an insight into the mechanism by which the bicarbonate/carbon dioxide pair influences the generation of reactive species from hydrogen peroxide in the presence of different Cu(II) ions and complexes thereof. For this purpose, we have investigated the effect

on oxygen-derived radical formation of Cu(II) complexed with four different stable imine ligands [41], [42] and [43], cycling the metal between Glutamate dehydrogenase the 2+ and 1+ redox states, and with three low molecular weight peptide ligands known to form stable Cu(III) complexes in solution [44], [45], [46] and [47]. Assay of the rates of the copper-catalysed H2O2/HCO3− or H2O2-induced oxidation of DHR and NADH in vitro revealed that the generation of oxygen-derived radicals was much higher in the presence of Cu(II) sulphate than when Cu(II) imine complexes were present ( Fig. 2 and Fig. 3). This unexpected finding indicates that imine complexes generate lower levels of reactive oxygen species (ROS) than the free Cu(II) ion and Cu(II) peptide ligands, except Cu(GlyGlyHis). Such a result challenges the use of these complexes in cancer cell therapy to induce apoptosis in mammalian tumour cells in vitro on the basis of their facility to generate free radical and reactive species [35], [36], [37], [38] and [39].