Uptake by breast carcinoma of a lipidic nanoemulsion after intralesional injection into the patients: A new strategy for neoadjuvant chemotherapy

Objective. Previously we showed that after intravenous injection a lipidic nanoemulsion concentrates in breast carcinoma tissue and other solid tumors and may carry drugs directed against neoplastic tissues. Use of the nanoemulsion decreases toxicity of the chemotherapeutic agents without decreasing the anticancer action. Currently, the hypothesis was tested whether the nanoemulsion concentrates in breast carcinoma tissue after locoregional injection. Methods. Three different techniques of injection of the nanoemulsion were tested in patients scheduled for surgical treatment: G1 (n=4) into the mammary tissue 5 cm away from the tumor; G2 (n=4) into the peritumoral mammary tissue; G3 (n=6) into the tumoral tissue. The nanoemulsion labeled with radioactive cholesteryl oleate was injected 12 h before surgery; plasma decay of the label was determined from blood samples collected over 24 h and the tissue fragments excised during the surgery were analyzed for radioactivity uptake. Results. Among the three nanoemulsion injection techniques, G3 showed the greatest uptake (data expressed in c.p.m/g of tissue) by the tumor (44,769 +/- 54,749) and by the lymph node (2356 +/- 2966), as well as the greatest concentration in tumor compared to normal tissue (844 +/- 1673). In G1 and G2, uptakes were, respectively, tumor: 60 +/- 71 and 843 +/- 1526; lymph node: 263 +/- 375 and 102 +/- 74; normal tissue: 139 +/- 102 and 217 +/- 413. Conclusions. Therefore, with intralesional injection of the nanoemulsion, a great concentration effect can be achieved. This injection technique may be thus a promising approach for drug-targeting in neoadjuvant chemotherapy in breast cancer treatment. (C) 2008 Published by Elsevier Inc.

Evaluation of the cytogenetic effects of I-131 preceded by recombinant human thyrotropin (rhTSH) in peripheral lymphocytes of Wistar rats

The present study was carried out to investigate the cytogenetic effects of therapeutic exposure to radioiodine preceded by rhTSH in an animal model. Three groups of Wistar rats (n = 6) were used: one group was treated only with I-131 (11.1 MBq/animal); the other two groups received rhTSH (1.2 mu g/rat of either Thyrogen or rhTSH-IPEN, respectively) 24 h before administration of radioiodine. The percentage of lymphocytes with chromosome aberrations and the average number of aberrations and of dicentrics per cell were determined on blood samples collected 24 h, 7 and 30 days after administration of I-131. The data show that the treatment with radioiodine alone or associated with rhTSH resulted in a greater quantity of chromosome alterations in relation to basal values after 24 h, with a gradual decline after 7 and 30 days of treatment. An increase in chromosome alterations was also seen after rhTSH treatment alone. Neither of the treatments, i.e., with I-131 alone or associated with hormone, resulted in an aneugenic effect or influenced the kinetics of cellular proliferation in rat blood lymphocytes. There was no significant difference between the cytogenetic effects of Thyrogen and rhTSH-IPEN treatment. These data suggest that the treatment with radioiodine, associated or not with rhTSH, affects to a limited extent a relatively small number of cells although the occurrence of late stochastic effects could not be discarded.

Metabolism of triglyceride-rich lipoproteins and lipid transfer to high-density lipoprotein in young obese and normal-weight patients with polycystic ovary syndrome

Objective: To clarify whether the metabolism of triglyceride-rich lipoproteins and lipid transfer to high-density lipoprotein (HDL) are altered in patients with polycystic ovary syndrome (PCOS). Design: Case control study. Setting: Endocrinology clinics. Patient(s): Eight normal-weight (NW) and 15 obese (013) patients with PCOS were compared with 10 NW and 10 Ob women without PCOS paired for age and body mass index. Intervention(s): Determination of triglyceride-rich lipoprotein metabolism and lipid transfer to HDL. Main Outcome Measure(s): Participants were injected triglyceride-rich emulsions labeled with (14)C-cholesteryl esters and (3)H-triglycerides and the fractional clearance rate (FCR, in min(-1)) of labels was determined. Lipid transfer from artificial nanoemulsions to HDL was performed by incubating radioactively labeled lipid nanoemulsions with plasma during 1 hour, followed by radioactive counting of HDL-containing supernatant after chemical precipitation. Result(s): Lipolysis estimated by triglyceride FCR was equal in PCOS groups (NW = 0.043 +/- 0.032, Ob = 0.033 +/- 0.009) and respective controls (NW = 0.039 +/- 0.015, Ob = 0.044 +/- 0.019). However, the remnant removal as estimated by cholesteryl ester FCR was reduced in both PCOS groups (NW = 0.005 +/- 0.006, Ob = 0.005 +/- 0.005) compared with controls (NW = 0.016 +/- 0.006, Ob = 0.011 +/- 0.072). Lipid transfer rates were not different among groups, but triglyceride transfer rates were positively correlated with homeostasis model assessment estimate of insulin resistance in PCOS. Conclusion(s): PCOS patients showed decreased removal of atherogenic remnants even when fasting glucose was <100 mg/dL. This reinforces the usefulness of the measures taken to prevent cardiovascular events in PCOS patients. (Fertil Steril (R) 2010;93:1948-56. (C)2010 by American Society for Reproductive Medicine.)

HDL concentration, lipid transfer to HDL, and HDL size in normolipidemic nonobese menopausal women

Objective: To determine the impact of menopause on lipid transfer from donor lipoproteins to high-density lipoproteins (HDLs)-a process that is related to the protective function of HDL-and the size of HDL particles. Method: Plasma from 22 prernenopausal and 18 postmenopausal nonobese, normolipidemic women paired for age (40-50 years) was incubated in an artificial nanoemulsion labeled with radioactive lipids. Then the HDL fraction was assessed for radioactivity; the percentage of radioactive lipids transferred from the nanoemulsion to HDL was determined; and the size of HDL particles was measured by laser light scattering. Results: There were no differences between the 2 groups in serum concentration of HDL cholesterol (61 12 mg/dL vs 61 +/- 14 mg/dL) or apolipoprotein A(1) (1.5 +/- 0.3 g/L vs 1.5 +/- 0.2 g/L); lipid transfer to HDL; or size of HDL particles (8.8 +/- 0.8 vs 9.0 +/- 0.5 nm). Conclusion: Menopause was not found to affect HDL cholesterol plasma concentration, lipid transfer to HDL, or size of HDL particles in normolipidemic nonobese women. (C) 2008 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd.All rights reserved.

Integrating toxicity testing in the wastewater management of chemical storage terminals - A proposal based on a ten-year study

Wastewater control at storage terminals of liquid chemical products in bulk is very difficult because of the variety of products handled in the facilities generating effluents of variable composition. The main objective of this work was to verify if the Vibrio fischeri acute toxicity test could be routinely included in the wastewater management of those facilities along with physical and chemical analysis in order to evaluate and improve the quality of the generated effluents. The study was performed in two phases before and after the implementation of better operational practices/treatment technologies. Chemical oxygen demand (COD) and toxicity of treated effluents did not correlate showing that effluents with low COD contain toxic substances and non-biodegradable organic matter, which may be not degraded when discharged into the aquatic environment. Segregation of influents or pre-treatment based on toxicity results and biodegradability index were implemented in the facilities generating significant improvements in the quality of final effluents with reduction of Biochemical oxygen demand (BOD) and toxicity. The integration of physical and chemical analysis with the V.fischeri toxicity test turned out to be an excellent tool for wastewater management in chemical terminals allowing rapid decision making for pollution control and prevention measures. Reuse of rain water was also proposed and when implemented by the facilities resulted in economical and environmental benefits. (C) 2010 Elsevier B.V. All rights reserved.

The role of PKA and PKC epsilon pathways in prostaglandin E(2)-mediated hypernociception

Background and purpose: Protein kinase (PK) A and the epsilon isoform of PKC (PKC epsilon) are involved in the development of hypernociception (increased sensitivity to noxious or innocuous stimuli) in several animal models of acute and persistent inflammatory pain. The present study evaluated the contribution of PKA and PKC epsilon to the development of prostaglandin E(2) (PGE(2))-induced mechanical hypernociception. Experimental approach: Prostaglandin E(2)-induced mechanical hypernociception was assessed by constant pressure rat paw test. The activation of PKA or PKC epsilon was evaluated by radioactive enzymic assay in the dorsal root ganglia (DRG) of sensory neurons from the hind paws. Key results: Hypernociception induced by PGE(2) (100 ng) by intraplantar (i.pl.) injection, was reduced by i.pl. treatment with inhibitors of PKA [A-kinase-anchoring protein St-Ht31 inhibitor peptide (AKAPI)], PKC epsilon (PKC epsilon I) or adenylyl cyclase. PKA activity was essential in the early phase of the induction of hypernociception, whereas PKC activity was involved in the maintenance of the later phase of hypernociception. In the DRG (L4-L5), activity of PKA increased at 30 min after injection of PGE(2) but PKC activity increased only after 180 min. Moreover, i.pl. injection of the catalytic subunit of PKA induced hypernociception which was markedly reduced by pretreatment with an inhibitor of PKC epsilon, while the hypernociception induced by paw injection of PKC epsilon agonist was not affected by an inhibitor of PKA (AKAPI). Conclusions and implications: Taken together, these findings are consistent with the suggestion that PKA activates PKC epsilon, which is a novel mechanism of interaction between these kinases during the development of PGE(2)-induced mechanical hypernociception.

Decay chain differential equations: Solution through matrix algebra

A matricial method to solve the decay chain differential equations system is presented. The quantity of each nuclide in the chain at a time t may be evaluated by analytical expressions obtained in a simple way using recurrence relations. This method may be applied to problems of radioactive buildup and decay and can be easily implemented computationally. (C) 2009 Elsevier B.V. All rights reserved.

Phosphorus kinetics in calves experimentally submitted to a trickle infection with Cooperia punctata

Ten male Holstein calves (74.3 +/- 3.2 kg LW) were used for a trial with trickle infection with Cooperia punctata to evaluate phosphorus (P) kinetics. Five calves were inoculated with 10,000 L(3) stage larvae per week during 35 days, while the other group of five calves was kept as a control. On the 29th day each calf was intravenously injected with 29.6 MBq of a (32)p solution. Blood samples were taken at 24 h periods for 7 days, after which all calves were slaughtered and worms burdens. Faeces, urine and tissue samples were taken for analysis using isotopic dilution and modeling techniques. The number of eggs per gram of faeces (EPG)was 1920 +/- 168 on 28th day and the total number of worms burdens was 11,131 +/- 1500. Infected calves showed lower feed intake and live weight gain, as well as lower P intake, absorption and retention than control calves. The P flows between body compartments were lower for blood to gastrointestinal tract (TGI), TGI to blood, blood to soft tissues, bone balance and soft tissue balance in infected calves when compared to the control. The trickle infection of C punctata affected P metabolism due to the decrease in P retained and live weight due to fall in feed intake. (C) 2009 Elsevier B.V. All rights reserved.

LC-MS/MS quantitation of plasma progesterone in cattle

Quantitation of progesterone (P(4)) in biological fluids is often performed by radioimmunoassay (RIA), whereas liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) has been used much less often. Due to its autoconfirmatory nature, LC-MS/MS greatly minimizes false positives and interference. Herein we report and compare with RIA an optimized LC-MS/MS method for rapid, efficient, and cost-effective quantitation of P(4) in plasma of cattle with no sample derivatization. The quantitation of plasma P(4) released from three nonbiodegradable, commercial, intravaginal P(4)-releasing devices (IPRD) over 192 h in six ovariectomized cows was compared in a pairwise study as a test case. Both techniques showed similar P(4) kinetics (P > 0.05) whereas results of P(4) quantitation by RIA were consistently higher compared with LC-MS/MS (P < 0.05) due to interference and matrix effects. The LC-MS/MS method was validated according to the recommended analytical standards and displayed P(4) limits of detection (LOD) and quantitation (LOQ) of 0.08 and a 0.25 ng/mL, respectively. The high selective LC-MS/MS method proposed herein for P(4) quantitation eliminates the risks associated with radioactive handling; it also requires no sample derivatization, which is a common requirement for LC-MS/MS quantitation of steroid hormones. Its application to multisteroid assays is also viable, and it is envisaged that it may provide a gold standard technique for hormone quantitation in animal reproductive science studies. (C) 2011 Elsevier Inc. All rights reserved.

The efficiency and condition of oysters and macroalgae used as biological filters of shrimp pond effluent

Current shrimp pond management practices generally result in elevated concentrations of nutrients, suspended solids, bacteria and phytoplankton compared with the influent water. Concerns about adverse environmental impacts caused by discharging pond effluent directly into adjacent waterways have prompted the search for cost-effective methods of effluent treatment. One potential method of effluent treatment is the use of ponds or raceways stocked with plants or animals that act as natural biofilters by removing waste nutrients. In addition to improving effluent water quality prior to discharge, the use of natural biofilters provides a method for capturing otherwise wasted nutrients. This study examined the potential of the native oyster, Saccostrea commercialis (Iredale and Roughley) and macroalgae, Gracilaria edulis (Gmelin) Silva to improve effluent water quality from a commercial Penaeus japonicus (Bate) shrimp farm, A system of raceways was constructed to permit recirculation of the effluent through the oysters to maximize the filtration of bacteria, phytoplankton and total suspended solids. A series of experiments was conducted to test the ability of oysters and macroalgae to improve effluent water quality in a flow-through system compared with a recirculating system. In the flow-through system, oysters reduced the concentration of bacteria to 35% of the initial concentration, chlorophyll a to 39%, total particulates (2.28-35.2 mum) to 29%, total nitrogen to 66% and total phosphorus to 56%. Under the recirculating flow regime, the ability of the oysters to improve water quality was significantly enhanced. After four circuits, total bacterial numbers were reduced to 12%, chlorophyll a to 4%, and total suspended solids to 16%. Efforts to increase biofiltration by adding additional layers of oyster trays and macroalgae-filled mesh bags resulted in fouling of the lower layers causing the death of oysters and senescence of macroalgae. Supplementary laboratory experiments were designed to examine the effects of high effluent concentrations of suspended particulates on the growth and condition of oysters and macroalgae. The results demonstrated that high concentrations of particulates inhibited growth and reduced the condition of oysters and macroalgae. Allowing the effluent to settle before biofiltration improved growth and reduced signs of stress in the oysters and macroalgae. A settling time of 6 h reduced particulates to a level that prevented fouling of the oysters and macroalgae.

Variation of bulk properties of anaerobic granules with wastewater type

Development of a granular sludge with high strength, high biological activity and a narrow settling distribution is necessary for optimal operation of high-rate upflow anaerobic treatment systems. Several studies have compared granules produced from different wastewaters but these have largely been from laboratory-fed reactors or compared granules from full-scale reactors fed similar wastewater types. Though two authors have commented on the inferiority of granules produced by a protein-based feed, the properties of these granules have not been characterised. In this paper, granules from full-scale reactors treating fruit and vegetable cannery effluent, two brewery effluents and a pig abattoir (slaughterhouse) were compared in terms of basic composition, size distribution, density, settling velocity, shear strength, and EPS content. The results supported previous qualitative observations by other researchers that indicate granule properties depend more on wastewater type rather than reactor design or operating conditions such as pre-acidification level. The cannery-fed granules bad excellent shear strength, settling distribution and density. Granules from the two brewery-fed reactors had statistically the same bulk properties, which were still acceptable for upflow applications. The protein-grown granule had poor strength and settling velocity. (C) 2001 Elsevier Science Ltd. All rights reserved.

Perfis de tensão residual do aço duplex UNS S32304 submetido a diferentes processos de soldagem TIG e condições de tratamento térmico

Visando a aplicação do aço UNS S32304 em embalados para transporte de material radioativo, amostras soldadas por processo TIG, com diferentes gases de proteção, foram submetidas a tratamentos térmicos nas temperaturas de 475°C, 600°C e 750°C por 8 horas, seguidas de resfriamento ao ar, a fim de analisar o efeito de temperaturas críticas no perfil de tensões residuais e microestrutura. A difratometria de raios X foi utilizada para determinação das tensões residuais, em diferentes condições (amostras como recebidas e apenas tratadas termicamente) e o perfil de tensões residuais total das amostras soldadas é apresentado para cada fase (austenita e ferrita). As tensões residuais das fases foram determinadas pela técnica sen2ψ, utilizando um difratômetro com fonte de radiação CuKα (<λ

Analysis of constructed wetland performance for irrigation reuse

Most of the wastewater treatment systems in small rural communities of the Cova da Beira region (Portugal) consist of constructed wetlands (CW) with horizontal subsurface flow (HSSF). It is believed that those systems allow the compliance of discharge standards as well as the production of final effluents with suitability for reuse. Results obtained in a nine-month campaign in an HSSF bed pointed out that COD and TSS removal were lower than expected. A discrete sampling also showed that removal of TC, FC and HE was not enough to fulfill international irrigation goals. However, the bed had a very good response to variation of incoming nitrogen loads presenting high removal of nitrogen forms. A good correlation between mass load and mass removal rate was observed for BOD5, COD, TN, NH4-N, TP and TSS, which shows a satisfactory response of the bed to the variable incoming loads. The entrance of excessive loads of organic matter and solids contributed for the decrease of the effective volume for pollutant uptake and therefore, may have negatively influenced the treatment capability. Primary treatment should be improved in order to decrease the variation of incoming organic and solid loads and to improve the removal of COD, solids and pathogenic. The final effluent presented good physical-chemical quality to be reused for irrigation, which is the most likely application in the area.

Eliminação do Cr(VI) na fase de neutralização de um efluente industrial proveniente de processos de galvanoplastia

A presente tese teve por base a identificação e resolução de um problema existente no tratamento de efluentes provenientes dos processos de tratamento de superfícies por galvanoplastia, na OGMA – Indústria Aeronáutica de Portugal S.A.. Observou-se a ocorrência, esporádica, de crómio hexavalente, (Cr (VI)), em valor superior ao valor limite de emissão (VLE). Os resultados foram monitorizados e os dados recolhidos no decorrer da actividade de tratamento de efluentes, durante o período de, aproximadamente, 5 anos (2006 a 2011). A recolha de resultados decorreu no âmbito da actividade profissional da mestranda, que, para além da responsabilidade técnica dos processos de galvanoplastia na empresa, é também responsável pelo suporte técnico ao processo de tratamento de efluentes resultantes da actividade de tratamento de superficies por processos de galvanoplastia. A empresa OGMA – Indústria Aeronáutica de Portugal S.A., é uma empresa de actividade aeronáutica dedicada à Fabricação e Manutenção de aeronaves, nomeadamente a prestação de serviços de Manutenção, Revisão e Modernização de, Aeronaves, Motores e Componentes, bem como Fabricação e Montagem de Aeroestruturas. Integrada na OGMA, S.A. encontra-se a área de tratamentos electroquímicos, onde são realizados processos de tratamento de materiais metálicos por electrodeposição, deposição química e conversão química. Desta actividade resulta uma quantidade considerável de efluentes líquidos que necessitam de tratamento adequado previamente à sua descarga em cursos de água. Devido ao tipo de contaminantes que estes efluentes possuem, o tratamento dos mesmos é realizado em várias etapas, passando pela oxidação de cianetos, a redução de cromatos e a neutralização. Posteriormente segue-se uma sedimentação e a remoção de lamas. De modo a garantir um controlo dos parâmetros de descarga dos efluentes tratados, de acordo com a legislação ambiental em vigor, o efluente obtido é analisado periodicamente em laboratório acreditado. Na perspectiva de solucionar o problema em questão, procedeu-se à realização de ensaios experimentais utilizando os efluentes provenientes dos tanques de reacção da redução de cromatos e da oxidação de cianetos da linha com cádmio, com especial incidência na variação dos intervalos de pH recomendados para cada uma das fases do tratamento de efluentes, e observação do comportamento das misturas em termos de presença de Cr (VI), quando sujeitos a variações de pH. Após análise dos dados disponíveis e realização de todos os ensaios, conclui-se que, o processo de oxidação de cianeto da linha com cádmio e o processo de redução de cromatos na mesma linha estão a funcionar adequadamente. Concluiu-se que o reaparecimento de Cr (VI) ocorre devido à existência de hipoclorito de sódio, em excesso, no tanque de oxidação de cianeto que, quando passa para o tanque de neutralização e entra em contacto com o efluente proveniente do tanque de redução de cromatos, oxida parte do crómio trivalente, (Cr (III)), existente, a Cr (VI). Para impedir a ocorrência deste fenómeno separou-se todo o efluente contendo crómio que passou a ser tratado na linha de tratamento de efluentes isenta de cádmio, não entrando assim em contacto com o efluente que contém hipoclorito não reagido, evitando a oxidação do Cr (III) a Cr (VI).

Evaluation of the respiratory motion effect in small animal PET images with GATE Monte Carlo simulations

The rapid growth in genetics and molecular biology combined with the development of techniques for genetically engineering small animals has led to increased interest in in vivo small animal imaging. Small animal imaging has been applied frequently to the imaging of small animals (mice and rats), which are ubiquitous in modeling human diseases and testing treatments. The use of PET in small animals allows the use of subjects as their own control, reducing the interanimal variability. This allows performing longitudinal studies on the same animal and improves the accuracy of biological models. However, small animal PET still suffers from several limitations. The amounts of radiotracers needed, limited scanner sensitivity, image resolution and image quantification issues, all could clearly benefit from additional research. Because nuclear medicine imaging deals with radioactive decay, the emission of radiation energy through photons and particles alongside with the detection of these quanta and particles in different materials make Monte Carlo method an important simulation tool in both nuclear medicine research and clinical practice. In order to optimize the quantitative use of PET in clinical practice, data- and image-processing methods are also a field of intense interest and development. The evaluation of such methods often relies on the use of simulated data and images since these offer control of the ground truth. Monte Carlo simulations are widely used for PET simulation since they take into account all the random processes involved in PET imaging, from the emission of the positron to the detection of the photons by the detectors. Simulation techniques have become an importance and indispensable complement to a wide range of problems that could not be addressed by experimental or analytical approaches.