Effect of Re-sintering on the morphological and thermoluminescence properties of the ALOX-520 detector.

Significant research is being conducted on new materials suitable for dosimetry in recent decades with particular focus on their luminescent properties. For instance, a new ceramic detector, aluminum oxide 520 (ALOX-520), was developed at CDTN in 2011 using the sol-gel method. The detectors were doped with C, Fe, Mg, Ca, Cr, Ni, and Mo impurities that generated the necessary dosimetric trap levels to enhance the luminescence effects. Consequently, the resultant material was appropriate for the quantification of ionizing radiation fields by both thermally and optically stimulated luminescence techniques. Originally, ALOX 520 was sintered at 2023 K under a highly reducing atmosphere. At the end of this process, it exhibited important dosimetric properties, as already described in existing literature. The objective of this study is to conduct tests at higher temperatures in vacuum to investigate the effect of thermal treatments under these conditions on the structural and dosimetric properties of the material. Accordingly, ALOX-520 was re-sintered at high temperatures and the changes in its physical, morphological, and dosimetric properties were analyzed. ALOX 520T exhibited better dosimetric properties in terms of homogeneity, reproducibility, linearity, and signal fading. Physically, an increase in the detection threshold value of ALOX-520T could be linked to a decrease in the sensitivity of this detector. The energy dependence, the thermal quenching correction, and kinetic studies for ALOX-520T conducted as part of this work are original. However, the obtained results are consistent with those reported in the literature for α-Al2O3 ceramic detectors. XRD and XRF analyses demonstrated that the thermal treatment did not change the crystalline structure or composition of the material. All the results indicate that an appropriate thermal treatment could improve the dosimetric properties of the ALOX-520 detector without causing significant changes in its crystalline structure.

Interleukin (IL)-22, IL-17, IL-23, IL-8, vascular endothelial growth factor and tumour necrosis factor-α levels in patients with psoriasis before, during and after psoralen-ultraviolet A and narrowband ultraviolet B therapy.

BACKGROUND: Several cross-sectional studies have shown that different cytokines and growth factors are enhanced in psoriasis. OBJECTIVES: We aimed to understand the role/relation of interleukin (IL)-22, IL-17, IL-23, IL-8, vascular endothelial growth factor (VEGF) and tumour necrosis factor (TNF)-α in psoriasis vulgaris, addressing their levels and changes before, during and after psoralen-ultraviolet A (PUVA) and narrowband ultraviolet B (NB-UVB) treatment. METHODS: A cross-sectional and a longitudinal study (n = 34) - before (T0) and at 3 (T3), 6 (T6) and 12 (T12) weeks of NB-UVB and PUVA therapy - were performed; 17 patients started NB-UVB and 17 PUVA, and IL-22, IL-17, IL-23, IL-8, TNF-α and VEGF levels were evaluated. RESULTS: At T0, compared with controls (n = 20), all the parameters were significantly higher in patients, except for TNF-α. Both NB-UVB and PUVA treatment gave, at T3, a significant decrease in TNF-α and IL-23; IL-22 and IL-17 decreased significantly at T6; all parameters and Psoriasis Area and Severity Index decreased significantly at T12. However, in both groups, at T12, VEGF was still significantly higher than control. CONCLUSIONS: Psoriasis seems to be a complex disease in which the cytokine network is disturbed, namely in levels of IL-22, IL-17, IL-23, IL-8, TNF-α and VEGF. NB-UVB and PUVA follow-up studies suggested that the reduction in the IL-23/Th17 axis might be important in the pathogenic mechanisms of psoriasis. Further follow-up studies of patients with psoriasis treated with these and other therapies could be very helpful for the understanding of the disturbance in the cytokine network in psoriasis and indirectly in its pathogenesis.

Circulating adipokine levels in Portuguese patients with psoriasis vulgaris according to body mass index, severity and therapy.

BACKGROUND: Psoriasis vulgaris is associated with overweight/obesity and with increased C-reactive protein (CRP), tumour necrosis factor (TNF)-α, interleukin (IL)-6, leptin and resistin levels and decreased adiponectin levels. OBJECTIVES: To understand the role/relationship of adipokines, as well as CRP, in a Portuguese psoriatic population, by assessing the relationship of their levels with psoriasis severity, defined by Psoriasis Area and Severity Index (PASI), with obesity, defined by body mass index (BMI), and psoriasis therapy. METHODS: A cross-sectional (n=66) and longitudinal study (before and after 12 weeks of therapy; n=44) was performed; 10 patients started topical treatment, 17 narrow-band ultraviolet B (NBUVB) and 17 psolaren associated with UVA (PUVA). RESULTS: Patients presented significantly higher BMI, leptin, resistin, TNF-α, IL-6 and CRP and significantly lower adiponectin values. CRP and IL-6 correlated with PASI. Adiponectin and leptin were more altered in patients with higher BMI. Concerning severity, CRP, resistin and adiponectin were more altered in the severer forms. After treatment, a significant reduction in PASI, CRP, resistin, TNF-α and IL-6, and a significant rise in adiponectin were observed. Nonetheless, CRP and adiponectin remained different from those of control. Concerning therapies, topical therapy was not associated with any significant change, except for TNF-α. After NBUVB, a significant reduction was observed in TNF-α and in CRP. For PUVA, we observed a significant reduction in TNF-α, IL-6 and CRP, and a significant increase in adiponectin. CONCLUSION: In psoriatic patients, increased overweight/obesity was associated with raised leptin levels and decreased adiponectin levels. Leptin may contribute to enhance the inflammatory process in overweight/obese psoriatic patients. Resistin, IL-6, CRP and adiponectin levels appear to be dependent on psoriasis severity. CRP, together with IL-6, appears to be a useful marker of psoriasis severity. Both NBUVB and PUVA were effective; however, PUVA results seem to be more successful. Nonetheless, after NBUVB and PUVA, a low-grade inflammation still persists.

C-reactive protein and leucocyte activation in psoriasis vulgaris according to severity and therapy.

BACKGROUND: Psoriasis vulgaris is a chronic recurrent inflammatory skin disease and psoriatic lesions have shown leucocyte infiltration. OBJECTIVES: We aimed to study C-reactive protein (CRP) and leucocyte activation markers/inhibitors as potential monitors of psoriasis vulgaris. METHODS: A cross-sectional (n = 73) and a longitudinal study (before, at 3, 6 and 12 weeks of therapy; n = 47) was performed; 10 patients started topical treatment, 17 narrow-band ultraviolet light B (NBUVB) and 20 psolaren associated to UVA (PUVA); psoriasis severity was defined by Psoriasis Area and Severity Index (PASI). RESULTS: Compared with control (n = 38), we found higher CRP levels, total leukocyte/neutrophil count, elastase, lactoferrin and alpha1-antitrypsin. Increasing PASI was linked to increasing CRP and a trend to higher elastase and lactoferrin, suggesting that worsening enhances inflammatory response with neutrophil activation. CRP correlated with PASI, total leucocytes, neutrophils, elastase, lactoferrin and alpha1-antitrypsin. NBUVB and PUVA presented similar effects. CONCLUSION: We propose CRP as a useful marker of psoriasis severity that could be used to monitor psoriasis and its treatment, and, together with PASI and elastase, could also be used as a global index of severity.

Characterization of a rat model of moderate chronic renal failure--focus on hematological, biochemical, and cardio-renal profiles.

The pathophysiological modifications underlying chronic renal failure seems to be dependent on the insufficiency degree, which will determine the moment to start therapy. As there is yet limited information about animal models of moderate chronic renal failure, we intended to perform a complete characterization of the hematological and cardio-renal alterations induced by partial nephrectomy. Blood samples from control and chronic renal failure rats were collected at 0, 3, 9, and 15 weeks in order to evaluate renal function, hematological parameters, iron metabolism, blood lipids, peripheral sympathetic nervous system, and inflammatory and redox status markers. BP, tissues trophy indexes, and kidney histomorphology were also assessed. Our data are consistent with a sustained moderate degree of chronic renal failure with a quickly compensated modest anaemia, though presenting iron metabolism disturbances. Despite the reasonable degree of functionality of the remnant kidney, as suggested by the anaemia correction and by the kidney hypertrophy and moderate lesions, several important cardiovascular modifications were developed. Our model presented hypertension, dyslipidemia, erythropoietic disturbances, sympathetic activation, and oxidative stress. This model might be a good tool to study the cellular/molecular mechanisms underlying moderate stages of chronic renal failure and to evaluate the therapeutic efficacy for prevention and treatment/correction of cardio-renal anaemia syndromes and complications in early stages.

Cross-talk between inflammation,coagulation/fibrinolysis and vascular access in hemodialysis patients.

This work aimed to study the association between fibrinolytic/endothelial cell function and inflammatory markers in chronic kidney disease (CKD) patients undergoing hemodialysis (HD) and recombinant human erythropoietin (rhEPO) therapies, and its relationship with the type of vascular access (VA) used for the HD procedure. As fibrinolytic/endothelial cell function markers we evaluated plasminogen activator inhibitor type-1 (PAI-1), tissue plasminogen activator (tPA) and D-dimers, and as inflammatory markers; C-reactive protein (CRP), soluble interleukin (IL)-2 receptor (s-IL2R), IL-6 and serum albumin levels. The study was performed in 50 CKD patients undergoing regular HD, 11 with a central venous dialysis catheter (CVC) and 39 with an arteriovenous fistula (AVF), and in 25 healthy controls. Compared to controls, CKD patients presented with significantly higher levels of CRP, s-IL2R, IL-6 and D-dimers, and significantly lower levels of PAI-1. The tPA/PAI-1 ratio was significantly higher in CKD patients. We also found statistical significant correlations in CKD patients between D-dimerslevels and inflammatory markers: CRP, albumin, s-IL2R and IL-6. When comparing the two groups of CKD patients, we found that those with a CVC presented statistically significant lower levels of hemoglobin concentration and albumin, and higher levels of CRP, IL-6, D-dimers and tPA. Our results showed an association between fibrinolytic/ endothelial cell function and increased inflammatory markers in CKD patients. The increased levels of Ddimer, tPA and inflammatory markers in CKD patients using a CVC, led us to propose a relationship between the type of VA chosen for HD, and the risk of thrombogenesis.

Protective effect of C. sativa leaf extract against UV mediated-DNA damage in a human keratinocyte cell line.

Toxic effects of ultraviolet (UV) radiation on skin include protein and lipid oxidation, and DNA damage. The latter is known to play a major role in photocarcinogenesis and photoaging. Many plant extracts and natural compounds are emerging as photoprotective agents. Castanea sativa leaf extract is able to scavenge several reactive species that have been associated to UV-induced oxidative stress. The aim of this work was to analyze the protective effect of C. sativa extract (ECS) at different concentrations (0.001, 0.01, 0.05 and 0.1 µg/mL) against the UV mediated-DNA damage in a human keratinocyte cell line (HaCaT). For this purpose, the cytokinesis-block micronucleus assay was used. Elucidation of the protective mechanism was undertaken regarding UV absorption, influence on (1)O2 mediated effects or NRF2 activation. ECS presented a concentration-dependent protective effect against UV-mediated DNA damage in HaCaT cells. The maximum protection afforded (66.4%) was achieved with the concentration of 0.1 µg/mL. This effect was found to be related to a direct antioxidant effect (involving (1)O2) rather than activation of the endogenous antioxidant response coordinated by NRF2. Electrochemical studies showed that the good antioxidant capacity of the ECS can be ascribed to the presence of a pool of different phenolic antioxidants. No genotoxic or phototoxic effects were observed after incubation of HaCaT cells with ECS (up to 0.1 µg/mL). Taken together these results reinforce the putative application of this plant extract in the prevention/minimization of UV deleterious effects on skin.

Leukocyte activation, erythrocyte damage, lipid profile and oxidative stress imposed by high competition physical exercise in adolescents.

BACKGROUND: The aim of this study was to evaluate and to compare the lipid profile and the levels of leukocyte activation, red blood cell (RBC) damage and of oxidative stress in two groups of adolescents, with similar body mass index: high competition swimmers and adolescents practising moderate regular physical exercise. METHODS: As markers of leukocyte activation, we measured plasma lactoferrin, elastase and granulocyte-monocyte colony stimulating factor. We studied RBC membrane band 3 profile and membrane-bound hemoglobin, as markers of RBC damage and aging; total and differential leukocyte count and RBC count, hematocrit, hemoglobin concentration and hematimetric indexes were also measured. Lipid profile included the evaluation of triglycerides (TG), total cholesterol (Chol), high-density lipoprotein cholesterol (HDLc), low-density lipoprotein cholesterol (LDLc), apolipoproteins AI and B (Apo AI and B), and lipoprotein (a) (Lp(a)). To evaluate oxidative stress, lipoperoxidation products and total antioxidant capacity were measured. RESULTS: We found that high competition adolescents presented increased plasma levels of leukocyte activation products, increased RBC damage suggesting aging and premature removal, and higher oxidative stress. Lipid profile showed some risk and some protective changes. CONCLUSIONS: Our data suggest that high competition exercise, by imposing a higher and sustained oxidative and proteolytic stress, may contribute in the future to a higher risk of cardiovascular disease. We believe these findings warrant a reevaluation of current views in the intensity, duration and regularity of physical exercise, and that the evaluation of leukocyte activation products, RBC damage, oxidative stress and lipid profile may represent good markers to establish putative protective thresholds.

Iron as the key modulator of hepcidin expression in erythroid antibody-mediated hypoplasia.

Erythroid hypoplasia (EH) is a rare complication associated with recombinant human erythropoietin (rHuEPO) therapies, due to development of anti-rHuEPO antibodies; however, the underlying mechanisms remain poorly clarified. Our aim was to manage a rat model of antibody-mediated EH induced by rHuEPO and study the impact on iron metabolism and erythropoiesis. Wistar rats treated during 9 weeks with a high rHuEPO dose (200 IU) developed EH, as shown by anemia, reduced erythroblasts, reticulocytopenia, and plasmatic anti-rHuEPO antibodies. Serum iron was increased and associated with mRNA overexpression of hepatic hepcidin and other iron regulatory mediators and downregulation of matriptase-2; overexpression of divalent metal transporter 1 and ferroportin was observed in duodenum and liver. Decreased EPO expression was observed in kidney and liver, while EPO receptor was overexpressed in liver. Endogenous EPO levels were normal, suggesting that anti-rHuEPO antibodies blunted EPO function. Our results suggest that anti-rHuEPO antibodies inhibit erythropoiesis causing anemia. This leads to a serum iron increase, which seems to stimulate hepcidin expression despite no evidence of inflammation, thus suggesting iron as the key modulator of hepcidin synthesis. These findings might contribute to improving new therapeutic strategies against rHuEPO resistance and/or development of antibody-mediated EH in patients under rHuEPO therapy.

Methodology for characterizing seeds under development for brachytherapy by means of radiochromic and photographic films.

The development of new medical devices possess a number of challenges, including designing, constructing, and assaying prototypes. In the case of new brachytherapy seeds, this is also true. In this paper, a methodology for rapid dosimetric characterization of (125)I brachytherapy seeds during the early stages of their development is introduced. The characterization methodology is based on the joint use of radiochromic and personal monitoring photographic films in order to determine the planar anisotropy due to the radiation field produced by the seed under development, by means of isodose curves. To evaluate and validate the process, isodose curves were obtained with both types of films after irradiation with a commercial (125)I brachytherapy seed.

Feasibility of EBT Gafchromic films for comparison exercises among standard beta radiation fields.

The feasibility of using radiochromic films to verify the metrological coherence among standard beta radiation fields was evaluated. Exercises were done between two Brazilian metrology laboratories in beta fields from (90)Sr/(90)Y, (85)Kr and (147)Pm radiation sources. Results showed that the radiochromic film was useful for field mapping aiming uniformity and alignment verification and it was not reliable for absorbed dose measurements only for (147)Pm beta field.

Cardiac antiapoptotic and proproliferative effect of recombinant human erythropoietin in a moderate stage of chronic renal failure in the rat.

OBJECTIVE: Recombinant human erythropoietin (rhEPO) therapy under circumstances of moderate chronic renal failure (CRF), with yet lower kidney and heart lesion, may have a protective cardiac effect beyond the correction of anemia, whose mechanism deserves better elucidation, namely by clarifying the impact on gene expression profile of markers of apoptosis, inflammation, proliferation, angiogenesis, and lesion/stress in the heart. MATERIALS AND METHODS: Four groups of rats were studied over a period of 15 weeks (n=7 each): control-without surgery and without drug treatment; rhEPO-treated with 50 IU/kg/week of rhEPO-beta; CRF-submitted to partial nephrectomy (3/4); CRF + rhEPO-CRF with rhEPO treatment after the 3rd week of surgery. The heart was collected in order to evaluate the gene expression, by real-time qPCR, of markers of apoptotic machinery, inflammation/immunology, proliferation/angiogenesis, and lesion/stress. RESULTS: The main findings obtained were (a) CRF rats have demonstrated overexpression of EPO-R in the heart without changes on EPO expression, together with overexpression of Bax/Bcl2 ratio, PCNA, and IL-2; (b) rhEPO therapy on the heart of the rats with CRF induced by partial 3/4 nephrectomy promoted nonhematopoietic protection, demonstrated by the apoptosis prevention, viewed by the Bax/Bcl2 balance, by the promotion of proliferation, due to PCNA increment, and by the immunomodulatory action, expressed by a trend to prevent the IL-2 increment. CONCLUSION: In this model of moderate CRF, rhEPO treatment showed important cardiac nonhematopoietic effects, expressed mainly by the antiapoptotic and the proproliferative action, suggesting that early rhEPO therapy in moderate stages of CRF might have further therapeutic benefits.

In vitro studies with 'acatalasemic-like' erythrocytes and hydrogen peroxide: attention to the formation of lysis resistant erythrocytes.

Hemolysis assays, using hydrogen peroxide as an oxidant injury agent and sodium azide as a catalase inhibitor, were performed to evaluate how assay conditions affect the development of lysis resistant erythrocytes. The concentration of hydrogen peroxide should be carefully selected for use in hemolysis assays, as it was found to affect the number of water resistant erythrocytes.

Erythropoietin levels in the different clinical forms of hereditary spherocytosis.

Erythropoietin (EPO), the main growth factor responsible for the regulation of red blood cell production, may be overproduced when blood loss or haemolysis occurs. Patients with mild hereditary spherocytosis (HS) are able to maintain normal haemoglobin concentration, whereas typical and severe HS patients develop an anaemic state. Splenectomy usually reverses anaemia. We aimed to clarify the role of EPO in the response to enhanced spherocyte destruction, and to look for a linkage with the broad clinical spectra of HS. EPO levels, reticulocyte count and production index (RPI), other parameters used to classify HS and the protein deficiencies underlying HS were evaluated in previously diagnosed unsplenectomised (n = 24) and splenectomised (n = 10) patients presenting mild, typical or severe HS. A significant increase in EPO was observed in all unsplenectomised HS patients. In the mild form, a significant correlation of EPO with reticulocyte count and RPI was observed; however, this correlation disappeared in typical HS patients. Splenectomised HS patients presented a correction in EPO levels in all forms of HS, although the reticulocyte count and RPI sustained slightly higher values. Our data show HS as a disease linked to an overproduction of EPO, according to the severity of the disease; however, a disturbance in erythropoiesis seems to occur in typical HS. Moreover, splenectomy leads to a correction in the EPO levels.

Protein deficiency balance as a predictor of clinical outcome in hereditary spherocytosis.

Vertical and horizontal interactions between membrane constituents account for integrity, strength and deformability of the erythrocyte. Disruption of vertical interactions caused by membrane protein deficiencies in hereditary spherocytosis (HS), favor membrane vesiculation with development of spherocytic cells. Our aim was to evaluate the hematological and clinical presentation of HS according to the type and amount of protein deficiency. We studied 81 Portuguese individuals, 71 belonging to 21 families plus 10 unrelated subjects, and found that 51 of them were HS patients. Patients were classified as presenting mild, typical or severe HS, according to laboratory results and clinical follow-up. We performed screening tests and the standardized electrophoretic membrane protein analysis to identify and quantify protein deficiencies. We found band 3 and ankyrin deficiencies as the major causes for HS. The ratios between the value of the primary and/or secondary protein deficiencies showed significantly different values according to the severity of HS, and a significant inverse correlation with the severity of HS was observed. In mild HS, the ratios between protein deficiencies reflected equivalent protein deficiencies, while an unbalance was observed in typical HS, which was enhanced in severe HS. Our data suggest that the relative quantification of each major membrane protein and of the ratios between the values of protein deficiencies may be helpful in providing additional data about the clinical outcome of HS.

Singular polarization eigenstates in anisotropic stratified structures.

A new optical element that displays singular polarization eigenstates is proposed. It consists of a planar stratified structure composed of alternate gyrotropic and birefringent layers. The orthogonality of the polarization eigenstates is lost because of anisotropic reflections at the interfaces, which are enhanced by the special condition chosen for the multiple-beam interference. First we show that the anisotropic reflection at the interface between the layers with linear and circular symmetries does produce strong enough dichroism to break the orthogonality of polarization eigenstates. Second, we investigate the behavior of these eigenstates with respect to their linearity and orthogonality as a function of the width of the layers. Our results concretely demonstrate that it is possible to control the effective optical parameters of such stratified structures by adjusting the thickness of each anisotropic layer. Finally, we obtain the necessary conditions for designing a double-layer system with singular eigenstates of linear polarization.

Helicobacter pylori genotypes may determine gastric histopathology.

The outcome of Helicobacter pylori infection has been associated with specific virulence-associated bacterial genotypes. The present study aimed to investigate the gastric histopathology in Portuguese and Colombian patients infected with H. pylori and to assess its relationship with bacterial virulence-associated vacA, cagA, and iceA genotypes. A total of 370 patients from Portugal (n = 192) and Colombia (n = 178) were studied. Corpus and antrum biopsy specimens were collected from each individual. Histopathological features were recorded and graded according to the updated Sydney system. H. pylori vacA, cagA, and iceA genes were directly genotyped in the gastric biopsy specimens by polymerase chain reaction and reverse hybridization. Despite the significant differences between the Portuguese and Colombian patient groups, highly similar results were observed with respect to the relation between H. pylori genotypes and histopathology. H. pylori vacA s1, vacA m1, cagA+ genotypes were significantly associated with a higher H. pylori density, higher degrees of lymphocytic and neutrophilic infiltrates, atrophy, the type of intestinal metaplasia, and presence of epithelial damage. The iceA1 genotype was only associated with epithelial damage in Portuguese patients. These findings show that distinct H. pylori genotypes are strongly associated with histopathological findings in the stomach, confirming their relevance for the development of H. pylori-associated gastric pathology.