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Tomato (Solanum lycopersicum L.) is the second most important horticultural crop after potato, one of the main problems in the cultivation of tomato is the presence of phytopathogenic nematodes that cause annual losses of millions of dollars worldwide. For that, a fast and simple way of nematode presence determination is desirable for timely disease control. Infection of tomatoes cultivated in soil inside greenhouses in two consecutive years of cultivation was analyzed by MIR. Leaves of healthy and Nacobbus aberrans nematode-infected tomato plants were evaluated for 112 and 54 days (first and second cultivation year, respectively) by mid infrared (MIR) spectroscopy, and spectral differences were found mainly in the 900-1200 cm−1 region, associated to CO bonds; in this region the behavior of four absorbance peaks were followed in time, finding that the first 20 days after infection was the main ones to determine nematode presence. Phenotypically infected plants had a lower height than control plants from 24 to 55 days post infection.By chemometric analysis applying Principal Component Analysis of the MIR spectra, it was possible to differentiate between healthy from Nacobbus aberrans infected plants since day 3 after infection, which correlated well with the experimental results. This study proved the efficacy of using infrared spectroscopy as a non-destructive tool for early detection of phytoparasitic nematodes in tomato plants.

Este artigo apresenta dados relativos à segmentação não convencional de palavras, especificamente o fenômeno de hipossegmentação, presente em produções escritas de estudantes do Ensino Fundamental. Tem-se o objetivo de analisar o fenômeno da hipossegmentação (junção indevida de palavras) e as possíveis motivações para a sua realização nas produções textuais dos estudantes. As reflexões fundamentam-se em autores da área da fonética, fonologia e variação linguística como Bisol (2000, 2005), Bortoni-Ricardo (2005), Busse (2013), Cagliari (2006, 2009), Mollica (2004) e Oliveira (2005). Com relação aos procedimentos metodológicos, destaca-se que este estudo pressupõe os processos qualitativos interpretativistas, desse modo, os resultados foram gerados a partir de uma perspectiva metodológica amparada na Linguística Aplicada. A partir da pesquisa realizada, constata-se que os desvios ortográficos presentes nas produções dos estudantes são resultantes do trânsito de práticas sociais orais para práticas sistematizadas de escrita, assim, evidenciam as hipóteses construídas pelos estudantes durante o processo de aquisição da modalidade escrita da língua portuguesa. Os dados reiteram a necessidade do trabalho sistêmico e permanente com os aspectos fonográficos da língua, cabendo ao professor a análise das produções textuais dos alunos com o intuito de atestar as eventuais dúvidas dos estudantes, e considerar os desvios como parte integrante do processo de aprendizagem.

Este artigo trata da relação entre a fala e a escrita em produções escritas de estudantes do Ensino Fundamental. A atividade escrita pode levar a inseguranças devido à complexa relação entre a fala e a representação gráfica de algumas palavras. Este estudo tem o objetivo de apresentar uma análise dos registros gráficos em produções escritas de alunos do Ensino Fundamental, a partir da descrição da natureza das ocorrências de escrita que infringem as regras ortográficas. Esta pesquisa insere-se na Sociolinguística Educacional, em que as reflexões partem dos estudos sobre variação linguística, escrita e ortografia realizados por Faraco (1994), Leal e Roazzi (2007), Morais (2007) (2009), Costa (2016), entre outros autores. Os dados analisados foram coletados em produções escritas desenvolvidas por alunos do 3º ano do Ensino Fundamental, visto que é nesse período que os estudantes têm os primeiros contatos com a ortografia da Língua Portuguesa. Observamos que os estudantes possuem dificuldades nas formas heterogêneas da língua, ou seja, no princípio de arbitrariedade que compõe a ortografia. Dessa forma, os dados reiteram que os índices de maior representatividade de desvios ortográficos são originários da influência da fala dos estudantes sobre a modalidade escrita, portanto, gerados devido à natureza fonético-fonológica.

Background: Bamboo species has been used for centuries in Asian traditional medicine to treat mental disorders resulting from the aging process. Brazil has the greatest diversity of bamboos in the Americas, with a high degree of endemism, but just a few of them has been studied for bioprospecting purposes. Purpose: Considering the previous report on the use of Asian bamboos to treat diseases affecting cognition and memory, a set of Brazilian bamboos species was investigated for similar properties. Methods: Leaves from Olyra glaberrima, Parodiolyra micrantha, Aulonemia aristulata, Filgueirasia arenicola, Filgueirasia cannavieira, and Merostachys pluriflora were investigated to their chemical profiles, free radical scavenging, anticholinesterase properties, toxicological effects on zebrafish larvae (Danio rerio), and protective effect on memory impairment assays (scopolamine-induced assay). Results: Based on HPLC-ESI-MS/MS data, 70 compounds had their putative structures assigned based on analysis of molecular formula and fragmentation pattern. The most abundant compounds were glycosylated flavonoids, followed by terpenoids and soluble sugars. Overall bamboo leaf extracts showed high antioxidant potential. A moderate potential as an inhibitor of the acetylcholinesterase activity was detected for M. pluriflora. The in vivo assays indicated that aqueous extracts at 0.1 mg/ml are not toxic for zebrafish embryos and do not alter the larval exploratory behavior. The extracts from O. glaberrima, P. micrantha, A. aristulata, and F. arenicola increased the cognitive capacity of zebrafish larvae against an aversive stimulus. In adult zebrafish, the extracts from O. glaberrima, F. cannavieira, and M. pluriflora prevented the cognitive deficit induced by scopolamine treatment. Conclusions: Aqueous extracts of the six Brazilian bamboo species showed high in vitro antioxidant potential. Some bamboo extracts increased the cognitive capacity of zebrafish larvae in the face of an aversive stimulus. Furthermore, some of them can reduce the memory loss induced by scopolamine in zebrafish adults. Moreover, many substances that were detected in this study had never been described for bamboos. This was the first study with herbaceous bamboo species; it is also the first study that used zebrafish as an experimental model to test bamboo extracts.

Este estudo teve por objetivo analisar as percepções de profissionais da saúde e da educação para a interdisciplinaridade no trabalho de promoção de saúde na escola, antes e depois da formação sobre autorregulação para o autocuidado e a promoção da saúde. Foi realizado um estudo exploratório e descritivo, de caráter qualitativo, no qual participaram 26 profissionais da saúde e da educação, distribuídos em dois grupos focais antes e dois depois da formação. Para a interpretação dos dados foi utilizada a análise temática. Os participantes perceberam que as ações de saúde nas escolas devem ser realizadas continuamente e de maneira interdisciplinar. Esta investigação destaca que a educação continuada é importante para a sensibilização dos profissionais para a interdisciplinaridade.

Human thymidine phosphorylase (hTP) is overexpressed in several solid tumors and is commonly associated with aggressiveness and unfavorable prognosis. 6-(((1,3-Dihydroxypropan-2-yl)amino)methyl)-5-iodopyrimidine-2,4(1H,3H)-dione (CPBMF-223) is a noncompetitive hTP inhibitor, which has been described as a tumor angiogenesis inhibitor. The present study investigated the effects of CPBMF-223 in a xenograft tumor induced by human colorectal carcinoma cells (HCT-116). Additionally, CPBMF-223 capacity to reduce cell migration, its toxicological profile, and pharmacokinetic characteristics, were also evaluated. The intraperitoneal treatment with CPBMF-223 markedly prevented the relative tumor growth with an efficacy similar to that observed for 5-fluorouracil. Interestingly, number of vessels were significantly decreased in the treated groups. Moreover, CPBMF-223 significantly reduced the migration of cell line HCT-116. In the Ames assay and in an acute oral toxicity test, the molecule did not alter any evaluated parameter. Using the zebrafish toxicity model, cardiac and locomotor parameters were slightly changed. Regarding the pharmacokinetics profile, CPBMF-223 showed clearance of 9.42 L/h/kg after intravenous administration, oral bioavailability of 13.5%, and a half-life of 0.75 h. Our findings shed new light on the role of hTP in colorectal cancer induced by HCT-116 cell in mice, pointing out CPBMF-223 as, hopefully, a promising drug candidate.

Pyriproxyfen is one of the most used larvicides and insecticides; it acts as an analog of juvenile insect hormone (a growth regulator). It is highly toxic during all stages of mosquito development, suppresses metamorphosis, and interferes in insect reproduction and proliferation. Pyriproxyfen and its main metabolite have been shown to affect brain development in rodents. This compound is employed mainly to eliminate outbreaks of the genus Aedes, even in potable water. Despite the increasing number of toxicological studies about larvicides and insecticides—with an indication of continuous use—there have been few studies about the effects of pyriproxyfen in non-target species such as fish. This study evaluated the effects of pyriproxyfen on behavioral, cognitive, and endocrine parameters in zebrafish. We exposed adult zebrafish to different pyriproxyfen (Pestanal®) concentrations (0.125, 0.675, and 1.75 mg/l) for 96 h. We analyzed behavioral parameters, memory, cortisol levels, and gene expression of glucocorticoid receptor (gr) and corticotrophin-releasing factor (crf) after pyriproxyfen exposure. This exposure did not alter locomotion (distance or mean speed), anxiety-like behavior (latency to enter to the top zone of the tank or time in the top zone of the tank), and social or aggressive behavior. However, there was impaired inhibitory avoidance memory at all tested pyriproxyfen concentrations. Cortisol levels were reduced in exposed groups when compared to control or vehicle. However, gr and crf gene expression in pyriproxyfen-treated animals were unaltered when compared to control or vehicle groups. Taken together, these findings indicate that pyriproxyfen may induce cognitive impairment and altered cortisol levels in zebrafish, a non-target species.

Aborda-se a temática da autorregulação da aprendizagem, no contexto da promoção do autocuidado em saúde. Trata-se de um estudo qualitativo. A pesquisa teve por objetivos: (a) realizar um programa de formação, com profissionais da Atenção Básica participantes do Programa Saúde na Escola e com professores de escolas de Educação Básica no Sul do Brasil, sobre a temática autocuidado em saúde; (b) acompanhar a intervenção em autorregulação em saúde, conduzida pelos professores e profissionais de saúde participantes da formação, junto a alunos do 5º ano, adotando-se como referencial a autorregulação da aprendizagem. Participaram do estudo 35 profissionais: dentistas, enfermeiros, técnicos de enfermagem, agentes comunitários de saúde, professores, supervisora, orientadoras educacionais e uma vice-diretora. O estudo desenvolveu-se em duas fases: (1) formação de professores e profissionais de saúde com vistas à promoção da autorregulação da saúde nos domínios de alimentação saudável e saúde bucal em escolares; (2) intervenção para a promoção da autorregulação em saúde, junto a alunos do 5º ano da Educação Básica, conduzida pelos professores e profissionais que realizaram a formação. Ambas as etapas estão descritas neste estudo. Os profissionais de ensino e de saúde envolvidos na formação e no desenvolvimento da intervenção engajaram-se no propósito de se tornarem autorreguladores e modeladores de práticas cotidianas na escola. Isso os subsidiou para o uso de metodologias que proporcionaram o aprender a aprender e o uso de estratégias autorregulatórias em sala de aula. As crianças participantes desse estudo mostraram-se capazes de planejar, executar e avaliar em outras situações do cotidiano, organizando objetivos coerentes com as atividades e desenvolvendo a competência de transpor para outros domínios as aprendizagens sobre os processos de autorregulação. O estudo mostra-se promissor para pensar a autorregulação no domínio da saúde e na formação de educadores, em especial na infância.

O presente artigo visa demonstrar um sistema de reaproveitamento de resíduos de construção civil na cidade de Curitiba, beneficiando com isso famílias de baixa. O objetivo do trabalho baseia-se no fato de que grande parte dos resíduos gerados é passível de reutilização e atualmente a maior parte deles é disposta incorretamente, acarretando em prejuízos ambientais, sociais e econômicos. Foi realizada uma pesquisa dos resíduos gerados em Curitiba através de um levantamento bibliográfico e de dados obtidos com os geradores, um estudo in loco junto à comunidade atingida pelo projeto e uma verificação de potenciais parcerias, para assim avaliar a viabilidade de implementação deste projeto neste município.

Alzheimer's disease (AD) is a devastating neurodegenerative disorder with no effective treatment and commonly diagnosed only on late stages. Amyloid-β (Aβ) accumulation and exacerbated tau phosphorylation are molecular hallmarks of AD implicated in cognitive deficits and synaptic and neuronal loss. The Aβ and tau connection is beginning to be elucidated and attributed to interaction with different components of common signaling pathways. Recent evidences suggest that non-fibrillary Aβ forms bind to membrane receptors and modulate GSK-3β activity, which in turn phosphorylates the microtubule-associated tau protein leading to axonal disruption and toxic accumulation. Available AD animal models, ranging from rodent to invertebrates, significantly contributed to our current knowledge, but complementary platforms for mechanistic and candidate drug screenings remain critical for the identification of early stage biomarkers and potential disease-modifying therapies. Here we show that Aβ1-42 injection in the hindbrain ventricle of 24 hpf zebrafish embryos results in specific cognitive deficits and increased tau phosphorylation in GSK-3β target residues at 5dpf larvae. These effects are reversed by lithium incubation and not accompanied by apoptotic markers. We believe this may represent a straightforward platform useful to identification of cellular and molecular mechanisms of early stage AD-like symptoms and the effects of neuroactive molecules in pharmacological screenings.

Abstract Idiopathic pulmonary fibrosis (IPF), the most common of the idiopathic interstitial pneumonias, is a devastating condition that carries a prognosis worse than that of many cancers. As such, it represents one of the most challenging diseases for chest physicians. The diagnostic process is complex and relies on the clinician integrating clinical, laboratory, radiologic, and/or pathologic data. Therefore, a close collaboration between chest physicians, radiologists, and pathologists experienced in the diagnosis of interstitial lung diseases (ILDs) is necessary in order to minimize diagnostic uncertainty. Similarly, the management of IPF continues to pose major difficulties. However, while there are no proven effective therapies for IPF beyond lung transplantation, recent trials of novel agents suggest that pharmacological treatment may retard the progression of the disease. In this regard, enrolment of patients into clinical trials is considered the “best current practice”by the most recent guidelines as it offers IPF patients the chance to receive new agents that may be more effective than current therapies. A more recent trend focusing on improving quality of life in IPF patients has also been gaining ground. The diagnosis and management of IPF remains a constant challenge for even the most experienced of clinicians. However, a multidisciplinary approach to this complex disease is steadily improving diagnostic accuracy, while recent advances in the pharmacological therapy offer the genuine promise of future treatments for this devastating disease.

Abstract Background Alterations in blood–brain barrier permeability have been proposed to represent a relevant factor contributing to Parkinson’s disease progression. However, few studies have addressed this issue in patients at different stages of disease. Methods Albumin was measured in cerebrospinal fluid and serum samples obtained from 73 non-demented subjects with idiopathic Parkinson’s disease and 47 age-matched control subjects. The albumin ratio (AR) was calculated to assess blood-cerebrospinal fluid and blood–brain barrier function. The group of patients with Parkinson’s disease included 46 subjects with Hoehn-Yahr staging between 1 and 2 and 27, with a score ranging from 2.5 to 4. Results Statistically significant differences in albumin ratio were found between patients with advanced disease, and both early-stage and unaffected groups. Conversely, early-phase patients did not differ from healthy subjects. Additionally, dopaminergic treatment seems to exert a possible effect on AR values. Conclusions Our study demonstrates that possible dysfunction of the blood-cerebrospinal fluid barrier, blood–brain barrier, or both, characterize Parkinson’s disease progression. The associations between clinical scores, treatments and biochemical findings suggest a progressive impairment of barrier integrity during the course of the disease.

Abstract Background Neuroacanthocytosis (NA) denotes a heterogeneous group of diseases that are characterized by nervous system abnormalities in association with acanthocytosis in the patients' blood. The 4.1R protein of the erythrocyte membrane is critical for the membrane-associated cytoskeleton structure and in central neurons it regulates the stabilization of AMPA receptors on the neuronal surface at the postsynaptic density. We report clinical, biochemical, and genetic features in four patients from four unrelated families with NA in order to explain the cause of morphological abnormalities and the relationship with neurodegenerative processes. Case presentation All patients were characterised by atypical NA with a novel alteration of the erythrocyte membrane: a 4.1R protein deficiency. The 4.1R protein content was significantly lower in patients (3.40 ± 0.42) than in controls (4.41 ± 0.40, P < 0.0001), reflecting weakened interactions of the cytoskeleton with the membrane. In patients IV:1 (RM23), IV:3 (RM15), and IV:6 (RM16) the 4.1 deficiency seemed to affect the horizontal interactions of spectrin and an impairment of the dimer self-association into tetramers was detected. In patient IV:1 (RM16) the 4.1 deficiency seemed to affect the skeletal attachment to membrane and the protein band 3 was partially reduced. Conclusion A decreased expression pattern of the 4.1R protein was observed in the erythrocytes from patients with atypical NA, which might reflect the expression pattern in the central nervous system, especially basal ganglia, and might lead to dysfunction of AMPA-mediated glutamate transmission.

Failed transfer of passive immunity (FTPI) in dairy calves - which is often due to the low amount of colostrum provided within a few hours after birth - remains a crucial issue. Enabling dairy calves to nurse colostrum from their dams could be useful in increasing intake and thus avoiding FTPI, but further potential effects on the health and welfare of both calves and dams should also be considered. In this study, 107 calf-dam pairs from two Italian dairy farms were alternately assigned to one of the following colostrum provision methods (CPMs): 'hand-fed method' (HFM) - the calf was separated from the dam immediately after birth and colostrum was provided by nipple-bottle (n = 50); 'nursing method' (NM) - the calf nursed colostrum from the dam for the first 12 h of life without farmer assistance (n = 30); and 'mixed method' (MM) - the nursing calf received a supplementary colostrum meal by nipple-bottle (n = 27). Serum of calves (1 to 5 days of age) and samples of their first colostrum meal were analysed by electrophoresis to assess immunoglobulin (Ig) concentration. Additionally, behavioural indicators of separation distress (calf and dam vocalisations; calf refusal of the first meal after separation; undesirable dam behaviour at milking) in the following 24 h were recorded as binary variables (Yes/No), and the health status of calves (disease occurrence and mortality) and dams (postpartum disorders and mastitis occurrence) were monitored for the first 3 months of life and 7 days after parturition, respectively. The lowest FTPI occurrence (calf serum Ig concentration <10.0 g/l) was found in the MM (11.1%) and the HFM (22.0%) compared with the NM (60.0%) (P<0.05), and the highest percentage of calves with optimal transfer of passive immunity (serum Ig concentration ≥16.0 g/l) was observed in the MM (55.6%). The lowest calf-dam separation distress was observed in the HFM (P<0.05). The highest calf disease occurrence was recorded in the HFM (64.0%) and the lowest in the NM (33.3%), with an intermediate value for the MM (44.4%) (P<0.05). No effect of the CPM was observed on dam health or calf mortality (P>0.05). The results of this study indicated that providing calves with a supplementary colostrum meal in addition to nursing from the dam (MM) is truly effective in maximizing passive immunity transfer. Anyway, specific strategies should be studied to minimise calf-dam separation distress.

During oestrus, fattening female pigs are more prone to lameness, fractures and wounds due to mounting and agonistic behaviours of penmates. This study assessed the effect of sexual maturity on the behaviour and welfare of heavy female pigs slaughtered at 36 weeks of age (180±10 kg) for dry-cured ham production. An immunocastrated control group was used for comparison. In all, 56 15-week-old female pigs, individually identifiable by back tattoos were equally distributed among four pens. All animals from two pens were subject to a three-dose immunocastration schedule at 16, 20 and 32 weeks of age. Skin lesions and behaviours were assessed at 18, 23, 28, 33 and 36 weeks of age. A blood sample was collected at 20, 24, 28 and 32 weeks of age for assessing health/stress parameters and GnRH antibodies. At slaughter, ovaries were weighed, measured and histologically examined; stomachs, carcasses and lungs were scored for lesions and a further blood sample was taken. Immunocastrated pigs did not significantly differ from controls in growth rate, feed efficiency and slaughter performances (lung score, gastric score, backfat thickness). However, they showed a lower frequency of aggressive interactions at 33 and 36 weeks, lower front lesions at 28 weeks, but higher at 30 weeks; a lower haptoglobin level at 28 weeks, a lower level of cortisol and back lesions at slaughter (36 weeks). These findings suggest a low, yet not negligible, impact of sexual maturity on the welfare of heavy female pigs.

Despite the well-known importance of an adequate colostral immunoglobulin (Ig) transfer to calf health and survival, failed transfer of passive immunity (FTPI) remains a widespread problem in dairy farming. The aim of this study was to investigate the management factors associated with FTPI in newborn calves, evaluating particularly the combined effect of delivery time, amount and quality of the first colostrum meal. The study was conducted from March to August 2014 on 21 Italian dairy farms. Farmers were asked as first to answer a farm-level questionnaire on calf management. Blood sampling was then performed on overall 244 calves (1 to 5 days of age) born from Holstein cows, and a sample of the first colostrum meal of each calf was collected. Individual information on calves and the respective colostrum management were recorded. Serum and colostrum Ig concentrations were assessed by electrophoresis. A mixed effects multivariable logistic regression model was used to investigate the association of the variables obtained from both the management questionnaire and the individual calf data with FTPI (calf serum Ig concentration 87.6 g/l) within 1.0 h from birth. Considerable improvements are still needed about colostrum management for newborn calves in dairy farms. The results of this study will help in developing farm-specific programs for reducing the occurrence of FTPI.

Limited information is available on suitable height of transport crates for turkeys. We compared behaviors and physiological indicators of four groups of 10 female turkeys each confined in either conventional (38.5 cm height) or experimental (77 cm height) crates during six commercial pre-slaughter transportations for 86 km (76 ± 4 min) along two tracts with one-lane streets, crossroads, bends, roundabouts (S1 and S2) and a highway tract (H) between S1 and S2. Only 36% of birds in the higher crates maintained a standing position. In conventional versus experimental crates, the frequency of rising attempts was five/bird/hour versus less than one/bird/hour, while wing flapping was seven/bird/hour versus 20/bird/hour, and balance loss was one versus four/bird/hour. The behaviors of both groups differed significantly according to the route tract, with a lower frequency of stress-related behaviors at H. No scratches, fractures or hematomas were detected in any birds after transportation. Crate height had no significant effect on hemato-biochemical markers. These results suggest that crates enabling a standing position may increase potentially dangerous behaviors. Moreover, busy and curvy routes should be avoided, as they may contribute to increasing the frequency of stress-related behaviors., (© 2017 Japanese Society of Animal Science.)

The aim of this study was to examine the concentrations of progesterone (P 4 ) and cholesterol (CHOL) in fluid of cavitary corpus luteum (CL) and in serum of dairy cattle. Cavitary corpora lutea, collected from cows at a local abattoir, were divided in four stages of development, based on days of the estrous cycle (stage I: 1-4days; stage II: 5-10days; stage III: 11-17days; stage IV: 18-20). Fluid of the their cavity was aspirated and P 4 and CHOL concentrations were evaluated. The concentrations of P 4 in CL cavity fluids were very high (1640-4666.67ng/mL) and showed a peak at the stage III. CHOL values were similar to those of serum and the highest levels were found in the stage I., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Neural transplantation is a promising therapeutic approach for neurodegenerative diseases; however, many patients receiving intracerebral fetal allografts exhibit signs of immunization to donor antigens that could compromise the graft. In this context, we intracerebrally transplanted mesencephalic pig xenografts into primates to identify a suitable strategy to enable long-term cell survival, maturation, and differentiation. Parkinsonian primates received WT or CTLA4-Ig transgenic porcine xenografts and different durations of peripheral immunosuppression to test whether systemic plus graft-mediated local immunosuppression might avoid rejection. A striking recovery of spontaneous locomotion was observed in primates receiving systemic plus local immunosuppression for 6 mo. Recovery was associated with restoration of dopaminergic activity detected both by positron emission tomography imaging and histological examination. Local infiltration by T cells and CD80/86+ microglial cells expressing indoleamine 2,3-dioxigenase were observed only in CTLA4-Ig recipients. Results suggest that in this primate neurotransplantation model, peripheral immunosuppression is indispensable to achieve the long-term survival of porcine neuronal xenografts that is required to study the beneficial immunomodulatory effect of local blockade of T cell costimulation., (© Copyright 2016 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Reference limits for metabolic profiles in Holstein late-pregnant heifers and dry cows were determined considering the effects of parity, days relative to calving, and season. Blood samples were collected from 104 pregnant heifers and 186 dry cows (68 primiparous and 118 pluriparous) from 60 to 10 d before the expected calving date in 31 dairy farms in northeastern Italy. Sampling was performed during summer (182 samples) and the following winter (108 samples). All the animals were judged as clinically healthy at a veterinary visit before sampling. Outliers were removed from data of each blood analyte, and variables that were not normally distributed were log transformed. A mixed model was used to test the fixed effects of parity (late-pregnant heifers, primiparous or pluriparous dry cows), class of days relative to calving (60-41 d, 40-21 d, 20-10 d), season (summer or winter), and the interactions between parity and class of days relative to calving and between parity and season, with farm as random effect. Single general reference limits and 95% confidence intervals were generated for analytes that did not vary according to fixed effects. Whenever a fixed effect included in the model significantly affected a given analyte, specific reference limits and 95% confidence intervals were generated for each of its levels. Albumin, urea, triglycerides, alanine aminotransferase, aspartate aminotransferase, creatinine kinase, conjugated bilirubin, calcium, phosphorus, magnesium, potassium, chloride, zinc, copper, and iron concentrations were not influenced by any of the fixed effects. Total protein, globulins, creatinine, glucose, alkaline phosphatase, gamma glutamyltransferase, lactate dehydrogenase, and sodium plasma concentrations were affected by parity. The class of days relative to calving had a significant effect on the concentrations of total protein, globulins, fatty acids, cholesterol, total bilirubin, and sodium. Season affected plasma concentrations of creatinine, glucose, fatty acids, lactate dehydrogenase, and sodium. Interactions between parity and class of days relative to calving and between parity and season did not significantly affect any of the blood analytes tested. The reference limits and the 95% confidence intervals for blood analytes determined in the study could help dairy practitioners to improve the accuracy of metabolic profile interpretation in Holstein late-pregnant cattle., (Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

The pronounced fragility that characterizes swine erythrocytes is likely to produce a variable degree of hemolysis during blood sampling, and the free hemoglobin may then unpredictably bias the quantification of several analytes. The aim of this study was to evaluate the degree of acceptability of values obtained for several biochemical parameters at different levels of hemolysis. Progressively increased degrees of physical hemolysis were induced in 3 aliquots of 30 nonhemolytic sera, and the relative effects on the test results were assessed. To define the level of hemolysis, we used both visual estimation (on a scale of 0 to 3+) and analytical assessment (hemolytic index) and identified the best analytical cutoff values for discriminating the visual levels of hemolysis. Hemolysis led to a variable and dose-dependent effect on the test results that was specific for each analyte tested. In mildly hemolyzed specimens, C-reactive protein, haptoglobin, β1-globulin, β2-globulin, α1-globulin, γ-globulin, sodium, calcium, and alkaline phosphatase were not significantly biased, whereas α2-globulin, albumin, urea, creatinine, glucose, total cholesterol, aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transferase, nonesterified fatty acids, bilirubin, phosphorus, magnesium, iron, zinc, copper, lipase, triglycerides, lactate dehydrogenase, unbound iron-binding capacity, and uric acid were significantly biased. Chloride and total protein were unbiased even in markedly hemolyzed samples. Analytical interference was hypothesized to be the main source of this bias, leading to a nonlinear trend that confirmed the difficulty in establishing reliable coefficients of correction for adjusting the test results., (© 2015 The Author(s).)

The study compared the effects of enriching a basic solid feed mixture made of corn grain and straw with a protein source (extruded pea) or with urea on growth, health, behavior, and carcass quality of veal calves. Seventy-nine calves, divided according to their initial body weight (59.8 ± 6.9 kg) into 3 groups (5 pens of 5 or 6 animals per group), were allotted to 1 of 3 experimental feeding treatments: milk replacer plus an 85:15 (as-fed basis) mixture of corn grain and wheat straw (CGS); milk replacer plus a 72:15:13 mixture of corn grain, wheat straw, and extruded pea (CGS-EP); or milk replacer plus an 83.3:16:0.7 mixture of corn grain, wheat straw, and urea (CGS-U). All feeding treatments were targeted to provide 140 kg of dry matter (DM)/calf of solid feed during the 201-d fattening cycle, and the greater crude protein content of the mixtures supplemented with protein or urea was balanced by restricting to 96% the daily amount of milk replacer delivered to CGS. Results did not differ among feeding treatments for average daily gain or solid feed intake but, net of meal refusal events, the average daily intake of milk replacer was 1.73, 1.66, and 1.60 kg of DM/calf for CGS, CGS-EP, and CGS-U, respectively. The overall mean hemoglobin values from samples taken at d 11, 40, 83, 126, and 196 were lower for CGS-U calves (9.1 ± 0.2 g/dL) compared with CGS (9.8 ± 0.2 g/dL), whereas those of CGS-EP were intermediate (9.4 ± 0.2 g/dL). Behavioral observations showed a frequency of oral stereotypes <1.2% for all feeding treatments. Longer eating and chewing or ruminating time was recorded for CGS-U calves compared with CGS and CGS-EP calves. All carcasses had satisfactory color for the veal market and none of the carcass traits were affected by the feeding treatments. The proportions of tongues and lungs with signs of lesions, forestomach development, abomasal lesions, and rumen plaques did not differ among feeding treatments. Hyperkeratinization of rumen papillae was observed only in CGS-U calves with a prevalence of 11.3%. Based on these findings, providing a corn grain and straw solid feed mixture enriched with extruded pea or urea was an effective strategy to reduce milk replacer consumption, lowering total feeding cost per calf by 3.0 to 3.4% and 6.9 to 7.2%, respectively. This economic advantage was supported by the lack of detrimental effects on calf growth performance, behavior, and carcass quality. However, the occurrence of rumen papillae hyperkeratosis may raise some concerns about the use of urea., (Copyright © 2014 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

The particle size of cereal grains has been found to modulate the rate of passage from the rumen and the digestibility of starch and neutral detergent fibre (NDF), but few studies have examined its impact on reticular pH. The study aimed to evaluate the effect of feeding finely ground maize on the risk of ruminal acidosis, milk yield and composition. Twelve Holstein-Friesian cows were assigned to one of two experimental groups and fed according to a cross-over design. Diets were isoenergetic and isonitrogenous and were characterised by the same NDF and ADF, differing only in maize particle size. In the control diet (Ct), the maize meal was ground to 1.0 mm, whereas in the experimental diet, it was finely ground (Fg) to 0.5 mm. The pH and temperature of the reticulum were continuously measured in eight cows throughout the trial using indwelling sensors. Dry matter intake was higher in cows offered Fg diet than in Ct (19.0 vs. 20.3 kg/day; p = 0.067). However, milk yield (p = 0.855) and the 3.5% fat-corrected milk (FCM) (p = 0.724) did not show any differences between the diets. Casein (2.48 vs. 2.57%; p = 0.035) and crude protein (CP) (3.18 vs. 3.31%; p = 0.021) resulted higher in Fg. Similarly, starch digestibility increased in animals offered Fg diet versus Ct (0.94 vs. 0.98; p = 0.078). Among the reticular parameters, the Fg-fed cows spent a significantly higher time below the 5.5 pH threshold (15 vs. 61 min/day; p = 0.047) and had an average daily variation in reticular pH characterised by a lower nadir pH (5.95 vs. 5.72; p < 0.001) and a higher pH range (0.79 vs. 0.94; p = 0.003). In this study, grain particle size affected the risk of the onset of ruminal acidosis. Therefore, it should be carefully considered when formulating rations., (Journal of Animal Physiology and Animal Nutrition © 2013 Blackwell Verlag GmbH.)

Adopting a 2 × 2 × 2 factorial design, this study evaluated whether continuous straw provision by racks, tail docking and gender (barrows vs. females) have an effect on the prevalence of lung lesions and oesophago-gastric ulcer (OGU) visually scored at slaughter in 635 Italian heavy pigs (169 ± 4 kg). The lung lesions were very low (72% of pigs with score 0), and were not significantly different among the experimental groups. Overall, OGU was diagnosed in 47% of the pigs. The consumption of small amounts of straw (70 g/day/pig) represented a protective factor against the onset of OGU (OR: 0.27). Barrows were more likely than females to have OGU (OR: 1.52), while no significant differences between docked and undocked pigs were detected. Nevertheless, the presence of straw acted as a protective factor particularly in undocked pigs (OR: 0.16), suggesting that in this group the absence of rooting material may have a stronger effect on welfare., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

This study evaluated whether the specific heavy pig rearing context allowed the fattening of undocked pigs without an outbreak of tail biting. At the same time, gender and straw availability (small amounts) were considered to understand their possible interactions with tail presence in the display of tail biting. A 2 × 2 × 2 factorial design was adopted to test the effects of these factors on blood parameters, behaviour and tail/ear lesions. Few interactions among factors were detected. Undocked pigs showed lower cortisol (P<0.02), lying behaviour (P<0.001), and higher risk of tail/ear biting (weeks 3 and 9), but lower risk of tail lesions (week 14). Straw increased the motivation for exploring (P<0.001), reduced serum haptoglobin (P<0.001) and the risk for tail biting (weeks 3, 9, 18) and ear biting (weeks 3, 9). Results highlight the importance of straw as an environmental enrichment and seem to indicate that fattening undocked heavy pigs is possible., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Background: Ruminal acidosis is responsible for the onset of different pathologies in dairy and feedlot cattle, but there are major difficulties in the diagnosis. This study modelled the data obtained from various blood variables to identify those that could indicate the severity of ruminal acidosis. Six heifers were fed three experimental rations throughout three periods. The diets were characterised by different starch levels: high starch (HS), medium starch (MS) and low starch, as the control diet (CT). Ruminal pH values were continuously measured using wireless sensors and compared with pH measurements obtained by rumenocentesis. Blood samples were analysed for complete blood count, biochemical profile, venous blood gas, blood lipopolysaccharide (LPS) and LPS-binding proteins (LBP)., Results: The regression coefficient comparing the ruminal pH values, obtained using the two methods, was 0.56 (P = 0.040). Feeding the CT, MS and HS led to differences in the time spent below the 5.8, 5.5 and 5.0 pH thresholds and in several variables, including dry matter intake (7.7 vs. 6.9 vs. 5.1 kg/d; P = 0.002), ruminal nadir pH (5.69 vs. 5.47 vs. 5.44; P = 0.042), mean ruminal pH (6.50 vs. 6.34 vs. 6.31; P = 0.012), haemoglobin level (11.1 vs. 10.9 vs. 11.4 g/dL; P = 0.010), platelet count (506 vs. 481 vs. 601; P = 0.008), HCO3(-) (31.8 vs. 31.3 vs. 30.6 mmol/L; P = 0.071) and LBP (5.9 vs. 9.5 vs. 10.5 μg/mL; P < 0.001). A canonical discriminant analysis (CDA) was used to classify the animals into four ruminal pH classes (normal, risk of acidosis, subacute ruminal acidosis and acute ruminal acidosis) using haemoglobin, mean platelet volume, β-hydroxybutyrate, glucose and reduced haemoglobin., Conclusions: Although additional studies are necessary to confirm the reliability of these discriminant functions, the use of plasma variables in a multifactorial model appeared to be useful for the evaluation of ruminal acidosis severity.

The glucocorticoid dexamethasone (DEX), when used as a growth promoter, cause morphological and functional alterations in cattle lymphoid organs and cells. In the present experiment, the transcriptional effects of an illicit DEX protocol upon six target genes were investigated in cattle neutrophils (NEU) and lymphocytes (LFC). Blood samples were taken before (T(0)) and 2, 3, 10, 19, 31 and 43 days from the beginning of DEX administration (T(1)-T(6)). Leukocytes were counted and cells isolated by gradient centrifugation; then, glutathione peroxidase 1 and 3 (GPX1 and GPX3), glucocorticoid receptor alpha (GRα), l-selectin, nuclear factor κB, subunit p65 (NFκB) and tumor necrosis factor alpha (TNFα) mRNA amounts were measured through a quantitative Real Time RT-PCR approach. A significant change vs controls in NEU/LFC ratio was noticed from T(3) forward. Compared to T(0), DEX significantly increased to a variable extent all candidate gene mRNAs abundances in NEU; in contrast, only l-selectin, GRα and GPX1 were significantly up-regulated in LFC. Present results suggest that illicit DEX affects transcription in cattle immune cells, that might be considered as a promising surrogate tissue for the screening of DEX abuse in cattle farming., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

The study aimed at comparing three strategies of supplementing selenium (Se) during the finishing period of Charolais young bulls: (1) administration of sodium selenite throughout the finishing (NaSe); (2) administration of an Se-enriched yeast strain (Saccharomyces cerevisiae NCYC R397) throughout the finishing (Se-Y); (3) administration of sodium selenite for 140 days replaced by Se-enriched yeast during the last 70 days of finishing (Switch). Eighty-four young bulls (mean initial BW=434.2±31.9 kg; mean age=382±52 days) were stratified by live weight and equally assigned to one of three Se treatments. Experimental groups were fed the same diets and the inclusion rate of the different treatments was targeted to achieve 0.3 mg of Se/kg of dry matter (DM) in the complete feed. The average daily gain of bulls was 1.36 kg/d and no differences due to Se treatment were recorded. Dry matter intake and feed conversion ratio were not affected by Se treatment resulting in, on average, 10.3 kg/d and 7.65, respectively. Repeated blood samples were taken at days 0, 120, 180 and 210 of finishing to assess the Se status of the animals. As compared to NaSe, both organic Se treatments (Se-Y and Switch) increased plasma Se in the last two sampling sessions according to a significant treatment×time interaction (P<0.001). A similar trend was observed for serum total antioxidant status of the young bulls, whereas there was only a significant time effect (P<0.001) on glutathione peroxidase activity that was raised by all Se treatments. The finishing period lasted 210 days and at the abattoir there were no differences across Se treatments in carcass weight and dressing percentage. A higher Se content in the Longissimus thoracis (LT) muscle was instead observed in Se-Y samples as compared with NaSe (0.85 v. 0.47 mg/kg DM; P<0.05). Meat quality evaluation was carried out on LT samples after 6 and 11 days of ageing under a vacuum package. Regardless of ageing time, meat from young bulls supplemented with Se yeast had higher colour lightness (L*) values than those receiving NaSe (38.1 v. 36.6; P<0.01) and showed a significant decrease in shear force (3.69 v. 4.22 kg/cm2; P<0.01). The outcomes of the study suggest that the provision of Se yeast throughout the finishing period is a strategy to increase the benefits of the replacement of sodium selenite with organic selenium in beef cattle.

Confidence intervals for blood parameters used for nutritional and metabolic profile testing in cattle were calculated for clinically normal lactating Holstein cows, taking into account the effects of parity, stage of lactation, and season. Blood samples were collected from 740 cows in 33 Italian dairy herds according to a predefined protocol. Herds were visited during summer and the following winter, sampling 12 lactating cows at each visit (4 primiparous and 8 multiparous). Six cows were selected from the early-lactation group (days in milk: 10 to 89) and the other 6 were selected from the mid-lactation group (days in milk: 90 to 215). Cow selection criteria excluded animals clinically exposed to periparturient diseases as well as animals not considered in good health by a veterinary clinical examination. For each blood variable, outliers were identified and discarded. Data were then analyzed for their Gaussian distribution and variables with not normal distribution were log-transformed to adjust for lack of normality. Herd mean values were calculated for each blood parameter according to 3 main classification factors: parity (primiparous vs. multiparous), stage of lactation (early vs. mid) and season of production (summer vs. winter). The resulting data set was statistically analyzed using a mixed model with the fixed effects of these factors, their interactions, and the random effect of herd. General 95% confidence intervals were calculated for blood variables that showed a relevant herd variance component such as albumin, triglycerides, aspartate, urea, glucose, alanine aminotransferase, lactate dehydrogenase, direct and total bilirubin, calcium, magnesium, and potassium. For the remaining parameters, specific confidence intervals were calculated for each level of the significant main factors. Parity affected blood concentration of total protein, globulin, creatinine, alkaline phosphatase, gamma glutamyl transferase, creatinine kinase, and phosphorus. Blood nonesterified fatty acids, aspartate aminotransferase, gamma glutamyl transferase, creatinine kinase and cholesterol were influenced by stage of lactation. The season of production had a significant effect on total protein, globulin, creatinine, alkaline phosphatase, phosphorus, sodium, and chlorine. The outcomes of this work will improve the accuracy of the biochemical profile as a tool for dairy practitioners to assess the metabolic status of lactating Holstein cows., (Copyright © 2011 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

A set of hormonal, haematological and biochemical parameters was used to evaluate the physiological response and welfare status of 14 finishing Marchigiana bulls treated for 49 days with a low daily dosage (0.75 mg/head per day) of dexamethasone per os. Compared to the Control group, dexamethasone decreased cortisol concentrations (42.3 v. 5.7 nmol/l; s.e.d. = 4.17; P < 0.001), and led to the reversal of the leukocyte formula in the animals treated (P < 0.05). Total serum proteins (70.2 v. 73.9 g/l; s.e.d. = 1.55; P < 0.05), in particular β1 globulins (7.5 v. 9.1 g/l; s.e.d. = 0.24; P < 0.01) and fibrinogen (199 v. 258 mg/dl; s.e.d. = 32.70; P < 0.05), increased as a consequence of treatment. Prolonged dexamethasone administration led the bulls to an apparently chronic stress condition. Moreover, the study indicated various blood parameters that might be used by health officials as effective tools in identifying beef cattle suspected of being illegally treated with dexamethasone.

Background/aims: Gene therapy might be a promising therapeutic approach for advanced hepatocellular carcinoma (HCC) not amenable to any effective traditional treatment. The aim of the study was to evaluate the in vitro and in vivo efficacy of combined gene therapy of HCC with two different MoMLV-derived retroviral vectors, an MFG- and a LXSN-derived vector, both containing HSV-TK and hIL-2., Results: In vitro experiments on HCC cells showed efficient killing of transduced cells and efficient bystander effect after ganciclovir (GCV) treatment, with higher antitumor activity when the MFG-based vector was used. In vivo studies in a murine syngenic model of HCC demonstrated that treatment with GCV led to complete regression of tumors composed of transduced cells and regression of distant non-transduced tumors. Tumor transduction and efficacy of treatment was also demonstrated after in vivo delivery of vectors. Microarray analysis of tumor samples in mice receiving gene therapy showed up-regulation of genes involved in immune response and signal transduction., Conclusions: We demonstrated the in vitro and in vivo efficacy of combined retroviral-mediated gene therapy for HCC, with significant systemic therapeutic efficacy in vivo.

Several viruses have been engineered for gene therapy applications, and the specific properties of each viral vector have been exploited to target a variety of inherited and acquired diseases. Preclinical and clinical studies demonstrated that viral vectors are highly versatile tools capable of efficient transfer of foreign genetic information into almost all cell types and tissues. Gene therapy applications depend on vector characteristics, such as host range, cell- or tissue-specific targeting, genome integration, efficiency and duration of transgene expression, packaging capacity, and suitability for scale-up production. This review discusses the advances in the development of viral vectors, with particular emphasis on how knowledge of virus biology has been exploited to design a variety of vectors with improved safety characteristics and efficiency, potentially suitable for a large number of gene therapy applications.

Objective and Methods: Quantitative analysis of mRNA expression of ghrelin and its receptors GHS-R1a and -R1b in a large series of normal and neoplastic human adrenocortical tissues. Evaluation of the effects of ghrelin on GHS-R expression and proliferation of human adrenocortical carcinoma (ACC) cell lines., Results: Ghrelin and GHS-R transcripts are expressed in normal adrenal cortex, with GHS-R1b mRNA levels being 5- to 10-fold higher than GHS-R1amRNA. A significant increase in ghrelin expression was observed in adrenocortical adenomas, but not in carcinomas. GHS-R1a was undetectable in about 60% of both benign and malignant tumor samples, except for cortisol-producing adenomas, which showed increased receptor expression. At variance, GHS-R1b was overexpressed in both benign and malignant adrenocortical tumors. In vitro studies in human ACC cell lines demonstrated that GHS-R1a is downregulated and GHS-R1bmRNA expression is upregulated by ghrelin, while inhibiting cell proliferation., Conclusion: Downregulation ofGHS-R1a in adrenal tumors and the presence of high levels of GHS-R1b transcripts in adrenocortical tissue suggest a role for these receptors in adrenal function and growth. In this regard, ghrelin inhibits cell proliferation and modulates GHS-R expression in ACC cells in vitro., ((c) 2005 S. Karger AG, Basel)

Aims: The aims of this study were 1) to investigate the mRNA pattern of CD44 variants in three primary (MIA PaCa 2, PANC-1, PSN-1) and two metastatic (CAPAN-1, SUIT-2) pancreatic cancer (PC) cell lines; 2) to ascertain whether the genetic transfer of CD44s and CD44v10 modifies the adhesion of PC cells to the extracellular matrix (ECM) in vitro and their metastatic behavior in vivo., Methods: CD44 mRNA analysis was done by means of RT-PCR. Adhesion to ECM the was assessed using coated microtiter plates. For the study of CD44v10 insertion in the CAPAN-1 line, liposome-mediated DNA transfer was used. SCID mice were employed for in vivo experiments., Results: CD44v10 mRNA was not expressed by the CAPAN-1 nor by four of the six SUIT-2-derived clones. The stable expression of CD44v10 by modified CAPAN-1 significantly enhanced fibronectin adhesion. Mice without either liver or pancreatic metastases were more frequently found among the animals injected with modified (CD44v10 expressing) than with non-modified CAPAN-1., Conclusions: 1) It is possible to differentiate between metastatic and non-metastatic PC cells on the basis of CD44v10 expression; 2) CD44v10 seems to be involved in mediating fibronectin adhesion in vitro and in counteracting metastases in vivo.

Introduction: The transfer of drug-susceptible (suicide) genes to tumor cells by retroviral or adenoviral vectors is a novel approach to the treatment of human tumors., Aims: To ascertain the antitumor effect of retroviral transduction of the pancreatic cancer cell lines MIA PaCa 2, CAPAN-1, PANC1, and PSN1 with the herpes simplex virus thymidine kinase (HSV-TK) gene., Methodology: The vector carried a neoselectable marker gene, the human interleukin-2 gene, an internal ribosome entry coding site, and the region coding HSV-TK., Results: Twenty micromoles or less of ganciclovir did not modify nontransduced TK- cell growth, whereas > or =100 micromol completely inhibited TK- cell growth, indicating that this dosage is cytotoxic per se. The 4 TK- and the 4 transduced cell lines were treated daily with 0.001, 0.01, 0.1, 1, 10, and 20 micromol of ganciclovir for 13 days. CAPAN-1 cell growth was completely inhibited by 0.1 micromol of ganciclovir; higher doses were required to kill PANC1 (10 micromol) and PSN1 (20 micromol). MIA PaCa 2 cell growth decreased following a 20-micromol ganciclovir dosing. The bystander effect was great in the CAPAN-1 cell line and moderate in PANC1; no bystander effect was recorded in MIA PaCa 2 and PSN1 cell lines., Conclusion: Gene therapy with HSV-TK for pancreatic cancer seems effective in only a limited number of tumor-derived cell lines, and this limits its application in vivo.

Variations in cancer cell adhesion to extracellular matrix (ECM) proteins might underlie an enhanced metastatic potential. ECM binding is mediated by cell-adhesion molecules, the membrane expression of which might be influenced by soluble mediators, such as cytokines. The aims of our study were to ascertain whether epidermal growth factor (EGF), transforming growth factor beta1 (TGF-beta1), interleukin 1alpha (IL-1alpha), or interleukin 1beta (IL-1beta) can modify MIA PaCa 2 (pancreatic cancer cell line) and CAPAN-1 (metastatic pancreatic cancer cell line) adhesion to fibronectin, laminin, or type I collagen, and whether these cytokines can shift the membrane expression of the hyaluronic acid receptor (CD44). EGF significantly enhanced MIA PaCa 2, but not CAPAN-1, adhesion to fibronectin, laminin, and type I collagen. TGF-beta1 reduced MIA PaCa 2 adhesion to type I collagen, but enhanced CAPAN-1 adhesion to fibronectin and laminin. IL-1alpha was found to enhance MIA PaCa 2 adhesion to fibronectin, while reducing adhesion to type I collagen, whereas IL-1beta reduced the adhesion to laminin. IL-1alpha enhanced CAPAN-1 adhesion to laminin in a dose-dependent manner; IL-1beta slightly increased the adhesion of these cells to laminin at low dosage, and to type I collagen at high dosage. Both IL-1alpha and IL-1beta reduced CD44 membrane expression of MIA PaCa 2, while TGF-beta1 increased the percentage of CD44-positive CAPAN-1 cells. We suggest that the effects on cell adhesion induced by different cytokines depend on the status of the target pancreatic cancer cell. EGF and, in part, IL-1alpha can favor nonmetastatic pancreatic cancer cell adhesion to ECM, possibly favoring tumor spread. Metastatic cells seem to lose the responsiveness to EGF, while becoming hyperresponsive to IL-1alpha. TGF-beta1 might exert an antidiffusive effect on primary, and a prodiffusive effect on metastatic pancreatic cancer cells. Only IL-1alpha, IL-1beta, and TGF-beta1 seem to influence CD44 membrane expression. All the results presented in this study were obtained in vitro, and in vivo studies are needed to verify whether the studied cytokines can favor or counteract pancreatic cancer spread.

The serum determination of pepsinogen A (PGA) and pepsinogen C (PGC) might indicate gastric mucosal inflammation and atrophy. Body gastric mucosa produces both PGA and PGC, while antral mucosa produces only PGC. Therefore, diseases involving mainly the antrum, such as H. pylori infection, are mainly indicated by the variations in serum PGC than in serum PGA. In agreement, when the antral mucosa is infected by the more virulent cagA positive H. pylori strains, which cause severe inflammation, serum PGC significantly increases. Another indirect indicator of gastric inflammation is polymorphonuclear (PMN) oxidative burst after the stimulation with water extracts from H. pylori culture: this parameter is significantly increased in infected if compared to non-infected subjects. The higher oxidative burst response of peripheral PMN in infected patients, possibly consequent to the release of specific cytokines able to prime PMN towards H. pylori products, is unable to eliminate the infection, but it might concur in damaging the gastric mucosa.