Animal Models to Study Cancer and Its Microenvironment.

Cancers are complex tissues composed by genetically altered cancer cells and stromal elements such as inflammatory/immune cells, fibroblasts, endothelial cells and pericytes, neuronal cells, and a non-cellular component, the extracellular matrix. The complex network of interactions and crosstalk established between cancer cells and the supportig cellular and non-cellular components of the microenvironment are of extreme importance for tumor initiation and progression, strongly impacting the course and the outcome of the disease. Therefore, a better understanding of the tumorigenic processes implies the combined study of the cancer cell and the biologic, chemical and mechanic constituents of the tumor microenvironment, as their concerted action plays a major role in the carcinogenic pathway and is a key determinant of the efficacy of anti-cancer treatments. The use of animal models (e.g. Mouse, Zebrafish and Drosophila) to study cancer has greatly impacted our understanding of the processes governing initiation, progression and metastasis and allowed the discovery and pre-clinical validation of novel cancer treatments as it allows to recreate tumor development in a more pathophysiologic environment.

A dinosaur community composition dataset for the Late Cretaceous Nemegt Basin of Mongolia.

Dinosaur community composition data for eleven fossil localities in the Late Cretaceous Nemegt Basin of Mongolia are compiled from field observations and records in the literature. Counts were generated from skeletons and represent numbers of individuals preserved in each locality. These data were used in the analyses of Funston et al. [1] "Oviraptorosaur anatomy, diversity, and ecology in the Nemegt Basin" in the Nemegt Ecosystems Special Issue of Palaeogeography, Palaeoclimatology, Palaeoecology, where the results are discussed.

Impact of systemic lupus erythematosus on oral health-related quality of life.

Oral symptoms in systemic lupus erythematosus (SLE) patients are often unexplored and affect the health-related quality of life. The aims of this study were: (a) to evaluate the oral health condition of SLE patients compared to control subjects without rheumatic diseases; (b) to determine the consequences of oral health condition in the quality of life of these two groups. Individuals with SLE ( n = 75) and without SLE ( n = 78) (control group), paired for gender and age, underwent complete oral examination. Sociodemographic and clinical information was obtained, and interviews were conducted using the Brazilian version of the oral health impact profile. The activity and damage of SLE disease were assessed, respectively, by the systemic lupus erythematosus disease activity index 2000 and the Systemic Lupus International Collaborating Clinics/American College of Rheumatology damage index for systemic lupus erythematosus. When we analysed the oral health condition and hygiene habits of the participants, SLE patients exhibited an increased number of missing teeth despite their higher frequency of tooth brushing. No significant differences were verified in other habits and clinical parameters evaluated such as smoking, flossing, salivary flux, periodontitis, decayed and filled teeth. Patients with SLE presented with worse oral health-related quality of life than controls ( P = 0.011). The significant difference was on individuals' physical disability ( P = 0.002). The determinant of the negative impact on the oral health-related quality of life was prosthesis wearing ( P < 0.05). Overall, the oral health impact profile score was higher in individuals with moderate SLE damage compared to SLE individuals with no damage ( P = 0.043). Patients with SLE had a negative impact of oral condition on their quality of life. The evaluation of the oral health-related quality of life might be useful to monitor the effects of SLE on oral condition.

Variation in 'fast-track' referrals for suspected cancer by patient characteristic and cancer diagnosis: evidence from 670 000 patients with cancers of 35 different sites.

BACKGROUND: In England, 'fast-track' (also known as 'two-week wait') general practitioner referrals for suspected cancer in symptomatic patients are used to shorten diagnostic intervals and are supported by clinical guidelines. However, the use of the fast-track pathway may vary for different patient groups. METHODS: We examined data from 669 220 patients with 35 cancers diagnosed in 2006-2010 following either fast-track or 'routine' primary-to-secondary care referrals using 'Routes to Diagnosis' data. We estimated the proportion of fast-track referrals by sociodemographic characteristic and cancer site and used logistic regression to estimate respective crude and adjusted odds ratios. We additionally explored whether sociodemographic associations varied by cancer. RESULTS: There were large variations in the odds of fast-track referral by cancer (P<0.001). Patients with testicular and breast cancer were most likely to have been diagnosed after a fast-track referral (adjusted odds ratios 2.73 and 2.35, respectively, using rectal cancer as reference); whereas patients with brain cancer and leukaemias least likely (adjusted odds ratios 0.05 and 0.09, respectively, for brain cancer and acute myeloid leukaemia). There were sex, age and deprivation differences in the odds of fast-track referral (P<0.013) that varied in their size and direction for patients with different cancers (P<0.001). For example, fast-track referrals were least likely in younger women with endometrial cancer and in older men with testicular cancer. CONCLUSIONS: Fast-track referrals are less likely for cancers characterised by nonspecific presenting symptoms and patients belonging to low cancer incidence demographic groups. Interventions beyond clinical guidelines for 'alarm' symptoms are needed to improve diagnostic timeliness.

La Autoenografía como un instrumento de (trans)formación profesional en la práctica del Pharmaceutical Care / Autoethnography as an Instrument for Professional (Trans) Formation in Pharmaceutical Care Practice

La inclusión reciente de farmacéuticos en atención primaria en Brasil a través del Equipo de Apoyo de Salud Familiar los ha alentado a reflexionar sobre la necesidad de dejar de ser un profesional enfocado en los medicamentos a un profesional enfocado en las personas. La autoetnografía le permitió a una farmacéutica confrontar sus perspectivas sobre la práctica clínica entre 2014 y 2016, período en el que ella decidió desafiar, como farmacéutica, su formación tradicional centrada en los medicamentos. Utilizando como marco teórico la práctica del Pharmaceutical Care que había impulsadoa la profesión farmacéutica a cambiar su enfoque hacia el paciente, los autores colaboraron en la construcción de un monólogo sobre lo que significa centrarse en el paciente,de manera que éste cautivara a los lectores. Los hallazgos de la investigación también respaldan la versatilidad de la aplicación del proceso reflexivo proporcionado por la autoetnografía. Durante el trabajo de campo, a través de una redacción reflexiva y la realización de entrevistas, la farmacéutica descubrió una nueva forma de relacionarse con el "cuidado" y los "pacientes" en su rutina diaria

The recent inclusion of pharmacists in primary healthcare in Brazil through the Family Health Support Team has encouraged them to reflect on the need to change from a professional focused on medications to one focusedon individuals. This autoethnography allowed a pharmacist to confront her perspectives on clinical practice between 2014 and 2016, a period when she decided to challenge her traditional training as a pharmacist centered on medications. Using pharmaceutical care practice as the theoretical framework that prompted the profession of pharmacy to change its focus to the patient, the authors collaborated to construct a monologue that engages readers in the meanings of becoming patient centered. The research findings also support the versatility of application of the reflective process provided by autoethnography. Through fieldwork, reflective writing and interviews, the pharmacist discovered a new way to relate to "caring" and "patients" in her daily routine

Warfarin related acute kidney injury: A case report.

Warfarin is an oral anticoagulant used extensively in clinical practice; However, its side-effect of causing renal damage has been recently detected. The mechanism leading to renal damage is glomerular hemorrhage and red blood cell tubular casts prothrombin time. Recently, it was found that warfarin causes renal damage in patients with chronic kidney disease and is also associated with progression of renal disease. Warfarin causing acute kidney injury in patients with normal renal function is a rare manifestation. It is important to be aware of this condition as its innocuous presence can lead to chronic kidney disease if not corrected in time. Further studies have also found that novel oral anticoagulants such as dabigatran also cause a similar syndrome and hence a new term called anticoagulant-related nephropathy is now in vogue.

Artepillin C and phenolic compounds responsible for antimicrobial and antioxidant activity of green propolis and Baccharis dracunculifolia DC.

AIMS: This study investigates the antimicrobial activity in Staphylococcus aureus isolates (methicillin-sensitive S. aureus (MSSA) and methicillin-resistant S. aureus (MRSA)) and antioxidant activity of green propolis, Baccharis dracunculifolia DC extracts and Artepillin C™. METHODS AND RESULTS: The amount of Artepillin C in different extracts was determined by high performance liquid chromatography analysis. Minimum inhibitory concentration 90 (MIC90) was determined using 40 isolates of S. aureus inoculated in Müeller-Hinton agar culture medium containing the green propolis and B. dracunculifolia DC extracts. PVEE (green propolis ethanolic extract) and BDEH (B. dracunculifolia hexanic extract) showed the greatest antimicrobial activity with MIC90 values of 246·3 and 295·5 µg ml-1 respectively. Green propolis ethanolic and hexanic extracts (PVEE and PVEH respectively) showed the greatest antioxidant activity assessed by DPPH (1,1-diphenyl-2-picryl hydrazyl radical) with IC50 values of 13·09 and 95·86 µg ml-1 respectively. CONCLUSIONS: Green propolis ethanolic displays better antimicrobial and antioxidant activities compared to other extracts. These activities may be related to the presence of Artepillin C in synergism with the other constituents of the extracts. SIGNIFICANCE AND IMPACT OF THE STUDY: In this study, the antimicrobial activity of the extracts of green propolis and B. dracunculifolia DC demonstrated in MRSA and MSSA clinical isolates indicated that they can be important tools to treat infections caused by these bacteria.

Pre-referral general practitioner consultations and subsequent experience of cancer care: evidence from the English Cancer Patient Experience Survey.

Prolonged diagnostic intervals may negatively affect the patient experience of subsequent cancer care, but evidence about this assertion is sparse. We analysed data from 73 462 respondents to two English Cancer Patient Experience Surveys to examine whether patients with three or more (3+) pre-referral consultations were more likely to report negative experiences of subsequent care compared with patients with one or two consultations in respect of 12 a priori selected survey questions. For each of 12 experience items, logistic regression models were used, adjusting for prior consultation category, cancer site, socio-demographic case-mix and response tendency (to capture potential variation in critical response tendencies between individuals). There was strong evidence (P < 0.01 for all) that patients with 3+ pre-referral consultations reported worse care experience for 10/12 questions, with adjusted odds ratios compared with patients with 1-2 consultations ranging from 1.10 (95% confidence intervals 1.03-1.17) to 1.68 (1.60-1.77), or between +1.8% and +10.6% greater percentage reporting a negative experience. Associations were stronger for processes involving primary as opposed to hospital care; and for evaluation than report items. Considering 1, 2, 3-4 and '5+' pre-referral consultations separately a 'dose-response' relationship was apparent. We conclude that there is a negative association between multiple pre-diagnostic consultations with a general practitioner and the experience of subsequent cancer care.

Adequacy of twice weekly hemodialysis in end stage renal disease patients at a tertiary care dialysis centre.

Hemodialysis has improved the morbidity and mortality associated with end stage renal disease. In India, hemodialysis prescription is empiric, which leads to complications related to under-dialysis. Hence, adequacy of hemodialysis in Indian setting was analyzed in this study. A total of 50 patients on twice per week hemodialysis were assessed for 1 month. The number of sessions meeting standards laid out by Kidney Diseases Outcome Quality Initiatives (KDOQI) guidelines were calculated. They were divided into two groups: one in whom dialysis was monitored and session length enhanced to meet the minimum standard Kt/V of 2 and second control group; where Kt/V was not monitored. Hemoglobin (Hb) levels, albumin levels, mean arterial pressure and World Health Organization (WHO) quality of life (QoL) score were compared in the two groups after 6 months. Only 28% of hemodialysis sessions were adequate as per KDOQI guidelines. There was significant improvement in Hb levels (1.47 vs. 0.15 g/dl), mean arterial pressure levels (15.2 vs. 3.16 mm Hg), serum albumin levels (0.82 vs. 0.11 g/dl) and WHO QoL score (17.2 vs. 2.24) in study group as compared to control group. Standard Kt/V can be used as an important tool to modify twice weekly dialysis sessions to provide better QoL to the patients. However, studies with larger sample size are required to conclusively prove our results.

Nutritional value of high moisture corn silage in the diet of Holstein cows / Valor nutritivo da silagem de grãos úmidos de milho na alimentação de vacas da raça Holandesa

Five Holstein cows were distributed in a 5x5 latin square design to assess the effect of replacement levels of dry ground corn grain (DGCG) by high moisture corn silage (HMCS) on intake, total nutrient digestibility and plasma glucose, according to the following treatments: 1) 100% DGCG; 2) 75% DGCG and 25% HMCS; 3) 50% DGCG and 50% HMCS; 4) 25% DGCG and 75% HMCS; 5) 100% HMCS. The experiment lasted 70 days, divided into five phases of 14 days each. The digestibility was obtained using chromic oxide (Cr2O3) as the indicator. Fecal samples were collected twice daily and blood samples were collected on the last day of each period before the first meal (0h) and 2h, 4h, 6h and 12h after the meal. There was no effect (P>0.05) on the intake of dry matter (DM), neutral detergent fiber (NDF), acid detergent fiber (ADF) and starch. The total apparent digestibility of DM, crude protein (CP), NDF and ADF were not affected (P>0.05) by the treatments, as well as the plasma glucose concentration. However, there was a decreased linear effect (P<0.05) for the protein intake and increased linear effect (P<0.05) for starch digestibility, as the level of HMCS was increased in the diets...

Cinco vacas da raça Holandesa foram distribuídas em quadrado latino 5x5 com o objetivo de se avaliar o efeito de níveis de substituição do grão seco de milho (GSM) pela silagem de grãos úmidos de milho (SGUM) sobre consumo, digestibilidade total dos nutrientes e glicose plasmática, o que constituiu os tratamentos: 1) 100% GSM; 2) 75% GSM e 25% SGUM; 3) 50% GSM e 50% SGUM; 4) 25% GSM e 75% SGUM; 5) 100% SGUM. O período experimental durou 70 dias, divididos em cinco fases de 14 dias. A digestibilidade foi obtida utilizando-se óxido crômico (Cr2O3) como indicador. Foram colhidas amostras fecais duas vezes por dia, bem como amostras de sangue no último dia dos períodos, antes da primeira refeição (zero hora), duas, quatro, seis e 12 horas após a refeição. Não houve efeito (P>0,05) sobre o consumo de matéria seca (MS), fibra em detergente neutro (FDN), fibra em detergente ácido (FDA) e amido. A digestibilidade aparente total da MS, a proteína bruta (PB), a FDN e a FDA não foram afetadas (P>0,05), assim como a concentração de glicose plasmática. Houve efeito linear decrescente (P<0,05) para consumo de PB e linear crescente (P<0,05) para digestibilidade do amido, à medida que se aumentou a inclusão de SGUM...

Food preferences of middle aged and elderly subjects in a Brazilian city.

OBJECTIVES: The objectives of this study were to assess data on the consumption frequency of some food items and the places they are purchased, especially by adults and elderly subjects, and finally to determine their food preference using cluster and correspondence analyses as a diagnosis and prevention factor. DESIGN: Cross-sectional study. SETTING: Town of Serranópolis do Iguaçú, State of Paraná, Brazil, city with 4,854 inhabitants of which 22% are over 50 years old. PARTICIPANTS: Two hundred and ninety five randomly selected subjects (96 men and 199 women), between 51 and 91 years old. MEASUREMENTS: A socio-demographic and food frequency questionnaire was applied via home visits including questions on socioeconomic, anthopometric and health characteristics concerning the consumption frequency of 45 food items and the places they were purchased, using a five point category scale to obtain consumption data as well. The body mass index (BMI) was calculated using the Quetelet Index and compared with the World Health Organization Report Consultation on obesity. The cluster and correspondence statistical analysis were used to determine their food preference. RESULTS: From the correspondence mapping (which explained 89.1 % of the variance), it was possible to determine aspects regarding the non-consumption of instant soups, frozen vegetables, cookies, crystallized fruits, canned fruit, distilled drinks and beer. CONCLUSIONS: The dimensional representation structure demonstrated that the population of Serranópolis, who were 62 % overweight, preferred high fat content products, suggesting a reevaluation of their eating habits in the expectation of preventing non transmissible chronic diseases. The value given to farm production in Serranópolis do Iguaçú was also observed.

Toxicidade do pericarpo da Jatropha curcas em ovinos / Jatropha curcas pericarp toxicity in sheep

O pinhão manso (Jatropha curcas) é uma planta cultivada para a produção de biocombustível. O pericarpo é um coproduto com potencial para alimentação animal, e a presença de componentes tóxicos, principalmente ésteres de forbol, pode limitar sua utilização. Assim, objetivou-se avaliar a toxicidade do pericarpo. Vinte ovinos foram distribuídos em quatro grupos - um grupo-controle, que não recebeu a planta, e três experimentais, que receberam o pericarpo nas concentrações de 15% (G15), 30% (G30) e 45% (G45), durante 23 dias. Após o 10º dia, a ingestão do pericarpo promoveu redução do consumo de alimento, diarreia, desidratação e caquexia. Todos os grupos tratados apresentaram redução na concentração de fosfatase alcalina. Animais do G30 apresentaram redução na concentração de ureia e proteínas totais e elevação de potássio e sódio. No G45, houve aumento de aspartato aminotransferase, albumina, creatinina bilirrubina indireta e total. A avaliação anatomo-histopatológica revelou ascite, hidropericárdio, congestão no trato gastrintestinal e nos pulmões, edema pulmonar, aderências à parede torácica, degeneração hepática centrolobular e das células tubulares renais, pneumonia linfo-histiocitica e enterite linfoplasmocitária e histiocítica. À análise fitoquímica, constatou-se 0,3845mg de ésteres de forbol/g de pericarpo. Conclui-se que o pericarpo de J. curcas é tóxico, não sendo recomendado para alimentação de ovinos.

Physic nut (Jatropha curcas) is a plant cultivated for biofuel production. Pericarp is a potential livestock food source by-product. However, its use may be limited due to the presence of toxic compounds, mainly phorbol esters. Thus, this study aimed to evaluate pericarp toxicity. Twenty sheep were divided in four groups, one control group which did not receive the plant and three experimental groups which received pericarp in 15% (G15), 30% (G30) and 45% (G45) concentrations for 23 days. After 10 days of treatment, pericarp ingestion produced food intake decrease, diarrhea, dehydration and loss of body condition. All treated groups showed decrease in alkaline phosphatase activity. G30 animals presented reductions in urea and total protein concentrations, and increase in potassium and sodium levels. G45 animals showed increase in serum aspartate aminotransferase activity and in albumin, creatinin, total and indirect bilirubin levels. Anatomohistopathologic findings included ascites, hydropericardium, congestion of the gastintestinal tract and lungs, pulmonary edema and adhesions in the thoracic cavity, renal tubular cells and centrilobular cytoplasmic vacuolation and lymphohistiocytic pneumonia and lymphoplasmacytic and histiocytic enteritis. On the physiochemical analysis 0.3845mg of phorbol esters/g of pericarp were detected. It is concluded that J. curcas pericarp is toxic and is not recommended for sheep feeding.

Interleukin-10-dependent down-regulation of interferon-gamma response to Leishmania by Mycobacterium leprae antigens during the clinical course of a coinfection.

We have described a case of a patient with an intriguing association of mucocutaneous leishmaniasis with lepromatous leprosy, two opposite polar forms of these spectral diseases. In the present follow-up study, we investigated the effect of the addition of Mycobacterium leprae antigens on interferon-gamma (IFN-γ) production in Leishmania antigen-stimulated cultures of peripheral blood mononuclear cells (PBMC) from this patient. For this purpose, PBMC cultures were stimulated with crude L. braziliensis and/or M. leprae whole-cell antigen extracts or with concanavalin A. In some experiments, neutralizing anti-human interleukin (IL)-10 antibodies were added to the cultures. IFN-γ and IL-10 levels in culture supernatants were measured by ELISA. During active leprosy, M. leprae antigens induced 72.3% suppression of the IFN-γ response to L. braziliensis antigen, and this suppression was abolished by IL-10 neutralization. Interestingly, the suppressive effect of M. leprae antigen was lost after the cure of leprosy and the disappearance of this effect was accompanied by exacerbation of mucosal leishmaniasis. Considered together, these results provide evidence that the concomitant lepromatous leprosy induced an IL-10-mediated regulatory response that controlled the immunopathology of mucosal leishmaniasis, demonstrating that, in the context of this coinfection, the specific immune response to one pathogen can influence the immune response to the other pathogen and the clinical course of the disease caused by it. Our findings may contribute to a better understanding of the Leishmania/M. leprae coinfection and of the immunopathogenesis of mucosal leishmaniasis.

Multifunctional CD4⁺ T cells in patients with American cutaneous leishmaniasis.

Leishmaniasis is a group of important parasitic diseases affecting millions worldwide. To understand more clearly the quality of T helper type 1 (Th1) response stimulated after Leishmania infection, we applied a multiparametric flow cytometry protocol to evaluate multifunctional T cells induced by crude antigen extracts obtained from promastigotes of Leishmania braziliensis (LbAg) and Leishmania amazonensis (LaAg) in peripheral blood mononuclear cells from healed cutaneous leishmaniasis patients. Although no significant difference was detected in the percentage of total interferon (IFN)-γ-producing CD4(+) T cells induced by both antigens, multiparametric flow cytometry analysis revealed clear differences in the quality of Th1 responses. LbAg induced an important proportion of multifunctional CD4(+) T cells (28% of the total Th1 response evaluated), whereas LaAg induced predominantly single-positive cells (68%), and 57% of those were IFN-γ single-positives. Multifunctional CD4(+) T cells showed the highest mean fluorescence intensity (MFI) for the three Th1 cytokines assessed and MFIs for IFN-γ and interleukin-2 from those cells stimulated with LbAg were significantly higher than those obtained after LaAg stimulation. These major differences observed in the generation of multifunctional CD4(+) T cells suggest that the quality of the Th1 response induced by L. amazonensis antigens can be involved in the mechanisms responsible for the high susceptibility observed in L. amazonensis-infected individuals. Ultimately, our results call attention to the importance of studying a Th1 response regarding its quality, not just its magnitude, and indicate that this kind of evaluation might help understanding of the complex and diverse immunopathogenesis of American tegumentary leishmaniasis.

Description of embryonic stages in Melanosuchus niger(Spix, 1825) (Crocodylia: Alligatoridae)

The determination of embryonic stages is very useful in comparative and evolutionary anatomy, experimentalresearch and ecological studies. Although tables of development stages already exist for some crocodilianspecies, no table has yet been published for Melanosuchus niger. Therefore, the aim of this work is to monitorthe development of this species of Alligatoridae and characterize its stages based on the main morphologicaltransformations the embryo undergoes during the incubation process. Under natural conditions, two sampleswere collected daily in the Lake Cuniã Extractive Reserve in Rondônia, Brazil, making a total of 186 eggs.The incubation period was 90 days at an ambient temperature varying from 25.2 to 31.7 °C. We established24 embryonic stages between the formation of the pharyngeal arch and hatching. Primordia for the sensoryorgans and somites were observed in the early stages. The buds of the pelvic and thoracic limbs emergedsimultaneously, also in the early stages. An analysis of these structures showed evidence of considerableevolutionary modifications when compared with embryos of different species. In stage 12 we observed subtlepigmentation in the region of the head and, in stage 25, the pigmentation and striped pattern were typical ofthe newly hatched specimen. The eyetooth was visible in stage 18, disappearing within the first few weeks afterhatching. The vitellus was completely absorbed in the penultimate stage. Direct comparisons of the table ofembryonic stages were made between M. niger and other crocodilian taxa, and the main differences identifiedwere chronological variations.

4D XCAT phantom for multimodality imaging research.

PURPOSE: The authors develop the 4D extended cardiac-torso (XCAT) phantom for multimodality imaging research. METHODS: Highly detailed whole-body anatomies for the adult male and female were defined in the XCAT using nonuniform rational B-spline (NURBS) and subdivision surfaces based on segmentation of the Visible Male and Female anatomical datasets from the National Library of Medicine as well as patient datasets. Using the flexibility of these surfaces, the Visible Human anatomies were transformed to match body measurements and organ volumes for a 50th percentile (height and weight) male and female. The desired body measurements for the models were obtained using the PEOPLESIZE program that contains anthropometric dimensions categorized from 1st to the 99th percentile for US adults. The desired organ volumes were determined from ICRP Publication 89 [ICRP, "Basic anatomical and physiological data for use in radiological protection: reference values," ICRP Publication 89 (International Commission on Radiological Protection, New York, NY, 2002)]. The male and female anatomies serve as standard templates upon which anatomical variations may be modeled in the XCAT through user-defined parameters. Parametrized models for the cardiac and respiratory motions were also incorporated into the XCAT based on high-resolution cardiac- and respiratory-gated multislice CT data. To demonstrate the usefulness of the phantom, the authors show example simulation studies in PET, SPECT, and CT using publicly available simulation packages. RESULTS: As demonstrated in the pilot studies, the 4D XCAT (which includes thousands of anatomical structures) can produce realistic imaging data when combined with accurate models of the imaging process. With the flexibility of the NURBS surface primitives, any number of different anatomies, cardiac or respiratory motions or patterns, and spatial resolutions can be simulated to perform imaging research. CONCLUSIONS: With the ability to produce realistic, predictive 3D and 4D imaging data from populations of normal and abnormal patients under various imaging parameters, the authors conclude that the XCAT provides an important tool in imaging research to evaluate and improve imaging devices and techniques. In the field of x-ray CT, the phantom may also provide the necessary foundation with which to optimize clinical CT applications in terms of image quality versus radiation dose, an area of research that is becoming more significant with the growing use of CT.

Anti-secretory, anti-inflammatory and anti-Helicobacter pylori activities of several fractions isolated from Piper carpunya Ruiz & Pav.

ETHNOPHARMACOLOGICAL RELEVANCE: The leaves of Piper carpunya Ruiz & Pav. (syn Piper lenticellosum C.D.C.) (Piperaceae), are widely used in folk medicine in tropical and subtropical countries of South America as an anti-inflammatory, anti-ulcer, anti-diarrheal and anti-parasitical remedy as well as an ailment for skin irritations. AIMS OF THE STUDY: To study the anti-inflammatory, anti-secretory and anti-Helicobacter pylori activities of different fractions isolated from an ethanolic extract of the leaves of Piper carpunya, in order to provide evidence for the use of this plant as an anti-ulcer remedy. Moreover, to isolate the main compounds of the extract and relate their biological activity to the experimental results obtained with the fractions. MATERIALS AND METHODS: Sixteen fractions were obtained from the ethanolic extract (F I-XVI) and 16 pure compounds were isolated and identified from these fractions. We studied the effects of the fractions (0.1-400microg/mL) on the release of myeloperoxidase (MPO) enzyme from rat peritoneal leukocytes, on rabbit gastric microsomal H(+), K(+)-ATPase activity and anti-Helicobacter pylori anti-microbial activity using the microdilution method (MM). The main compounds contained in the fractions were isolated and identified by (1)H- and (13)C NMR spectra analysis and comparison with the literature data. RESULTS: Eight fractions showed inhibition of MPO enzyme (F I-IV, X, XII, XIV and XV). The highest inhibition was observed with F XIV (50microg/mL, 60.9%, p<0.001). F X and XII were the most active ones, inhibiting the gastric H(+), K(+)-ATPase activity with IC(50) values equal to 22.3microg/mL and 28.1microg/mL, respectively. All fractions, except F XV, presented detectable anti-Helicobacter pylori activity, with a diameter of inhibition zones ranging from 11mm up to 50mm. The best anti-Helicobacter pylori activity was obtained with F III and V. Both fractions killed Helicobacter pylori with lowest concentration values, about 6.25mug/mL. Sixteen pure compounds were isolated, five of them are flavonoids that possess strong anti-oxidant and free radical scavenging activity, e.g. vitexin, isovitexin, and rhamnopyranosylvitexin. Terpenoids like sitosterol, stigmasterol and phytol, which have shown gastroprotective activity, and dihydrochalcones, like asebogenin, with anti-bacterial activity, were also isolated. Furthermore, the rare neolignan 1, that is a DNA polymerase beta lyase inhibitor, and (6S, 9S)-roseoside, that shows strong anti-bacterial activity, were isolated, for the first time, from the genus Piper. CONCLUSIONS: We suggest that the flavonoids isolated from F I and II (vitexin, isovitexin, rhamnopyranosylvitexin and isoembigenin) contribute to the anti-MPO activity, as well as to their anti-Helicobacter pylori activity. These flavonoids may also be responsible for the important inhibition of H(+), K(+)-ATPase activity. Also the phytosterols and phytol obtained from F XIV and XV could be involved in these gastroprotective activities. These results encourage us to continue phytochemical studies on these fractions in order to obtain full scientific validation for this species.

Cholesterol-lowering properties of whole cowpea seed and its protein isolate in hamsters.

Hypercholesterolemic hamsters were fed for 4 wk on diets rich in saturated fatty acids and cholesterol, differing only in protein source (20 %): casein (control group, HC), whole cowpea seed (HWS), and cowpea protein isolate (HPI). Hamsters fed on HWS and HPI presented significant reductions in plasma total cholesterol and non-HDL cholesterol. HPI and HC presented similar protein digestibility, which were significantly higher than that of HWS. Animals fed on HWS presented significantly higher levels of bile acids and cholesterol in feces than did the animals fed on casein or HPI diets. Histological analyses of the liver showed that HC diet resulted in steatosis widely distributed throughout the hepatic lobule, while HWS and HPI diets promoted reductions in liver steatosis. The effectiveness of HWS for modulating lipid metabolism was greater than that of HPI, as measured by plasma cholesterol reduction and liver steatosis.

Contrasting human cytokine responses to promastigote whole-cell extract and the Leishmania analogue receptor for activated C kinase antigen of L. amazonensis in natural infection versus immunization.

It is known that the same antigen can induce different immune responses, depending upon the way that it is presented to the immune system. The objective of this study was to compare cytokine responses of peripheral blood mononuclear cells (PBMC) from cutaneous leishmaniasis patients and subjects immunized with a first-generation candidate vaccine composed of killed Leishmania amazonensis promastigotes to a whole-cell promastigote antigen extract (La) and to the recombinant protein LACK (Leishmania analogue receptor for activated C kinase), both from L. amazonensis. Thirty-two patients, 35 vaccinees and 13 healthy subjects without exposure to Leishmania, were studied. Cytokine production was assessed by enzyme-linked immunosorbent assay and enzyme-linked immunospot assay. The interferon (IFN)-gamma levels stimulated by La were significantly higher and the levels of interleukin (IL)-10 significantly lower than those stimulated by LACK in the patient group, while LACK induced a significantly higher IFN-gamma production and a significantly lower IL-10 production compared with those induced by La in the vaccinated group. LACK also induced a significantly higher frequency of IFN-gamma-producing cells than did La in the vaccinated group. The contrast in the cytokine responses stimulated by LACK and La in PBMC cultures from vaccinated subjects versus patients indicates that the human immune response to crude and defined Leishmania antigens as a consequence of immunization differs from that induced by natural infection.