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1.
Mutagenesis ; 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38606763

RESUMO

Pleiotropic variants (i.e., genetic polymorphisms influencing more than one phenotype) are often associated with cancer risk. A scan of pleiotropic variants was successfully conducted ten years ago in relation to pancreatic ductal adenocarcinoma susceptibility. However, in the last decade, genetic association studies performed on several human traits have greatly increased the number of known pleiotropic variants. Based on the hypothesis that variants already associated with a least one trait have a higher probability of association with other traits, 61,052 variants reported to be associated by at least one genome wide association study (GWAS) with at least one human trait were tested in the present study consisting of two phases (discovery and validation), comprising a total of 16,055 pancreatic ductal adenocarcinoma (PDAC) cases and 212,149 controls. The meta-analysis of the two phases showed two loci (10q21.1-rs4948550 (P=6.52×10-5) and 7q36.3-rs288762 (P=3.03×10-5) potentially associated with PDAC risk. 10q21.1-rs4948550 shows a high degree of pleiotropy and it is also associated with colorectal cancer risk while 7q36.3-rs288762 is situated 28,558 base pairs upstream of the Sonic Hedgehog (SHH) gene, which is involved in the cell differentiation process and PDAC etiopathogenesis. In conclusion, none of the single nucleotide polymorphisms (SNPs) showed a formally statistically significant association after correction for multiple testing. However, given their pleiotropic nature and association with various human traits including colorectal cancer, the two SNPs showing the best associations with PDAC risk merit further investigation through fine mapping and ad hoc functional studies.

2.
Br J Surg ; 108(10): 1251-1258, 2021 10 23.
Artigo em Inglês | MEDLINE | ID: mdl-34240110

RESUMO

BACKGROUND: The purpose of this study was to investigate the prevalence of ypN+ status according to ypT category in patients with locally advanced rectal cancer treated with chemoradiotherapy and total mesorectal excision, and to assess the impact of ypN+ on disease recurrence and survival by pooled analysis of individual-patient data. METHODS: Individual-patient data from 10 studies of chemoradiotherapy for rectal cancer were included. Pooled rates of ypN+ disease were calculated with 95 per cent confidence interval for each ypT category. Kaplan-Meier and Cox regression analyses were undertaken to assess influence of ypN status on 5-year disease-free survival (DFS) and overall survival (OS). RESULTS: Data on 1898 patients were included in the study. Median follow-up was 50 (range 0-219) months. The pooled rate of ypN+ disease was 7 per cent for ypT0, 12 per cent for ypT1, 17 per cent for ypT2, 40 per cent for ypT3, and 46 per cent for ypT4 tumours. Patients with ypN+ disease had lower 5-year DFS and OS (46.2 and 63.4 per cent respectively) than patients with ypN0 tumours (74.5 and 83.2 per cent) (P < 0.001). Cox regression analyses showed ypN+ status to be an independent predictor of recurrence and death. CONCLUSION: Risk of nodal metastases (ypN+) after chemoradiotherapy increases with advancing ypT category and needs to be considered if an organ-preserving strategy is contemplated.


When patients are diagnosed with rectal cancer and the tumour grows beyond the rectal wall there is a high risk that the tumour has spread to nearby lymph nodes. This study showed that this relationship between tumour invasion depth and lymph node involvement is similar after treatment with (chemo)radiotherapy. Patients who have tumour cells remaining in the lymph nodes after (chemo) radiotherapy have a worse prognosis than patients who do not have cancer cells remaining in the lymph nodes. When an organ-preserving treatment is considered as an alternative therapy, this should be kept in mind during patient counselling.


Assuntos
Linfonodos/patologia , Metástase Linfática , Neoplasias Retais/patologia , Neoplasias Retais/terapia , Idoso , Idoso de 80 Anos ou mais , Quimiorradioterapia Adjuvante , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Recidiva Local de Neoplasia , Protectomia , Neoplasias Retais/cirurgia , Análise de Regressão
3.
Int J Cancer ; 145(3): 686-693, 2019 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-30672594

RESUMO

Rare truncating BRCA2 K3326X (rs11571833) and pathogenic CHEK2 I157T (rs17879961) variants have previously been implicated in familial pancreatic ductal adenocarcinoma (PDAC), but not in sporadic cases. The effect of both mutations in important DNA repair genes on sporadic PDAC risk may shed light on the genetic architecture of this disease. Both mutations were genotyped in germline DNA from 2,935 sporadic PDAC cases and 5,626 control subjects within the PANcreatic Disease ReseArch (PANDoRA) consortium. Risk estimates were evaluated using multivariate unconditional logistic regression with adjustment for possible confounders such as sex, age and country of origin. Statistical analyses were two-sided with p values <0.05 considered significant. K3326X and I157T were associated with increased risk of developing sporadic PDAC (odds ratio (ORdom ) = 1.78, 95% confidence interval (CI) = 1.26-2.52, p = 1.19 × 10-3 and ORdom = 1.74, 95% CI = 1.15-2.63, p = 8.57 × 10-3 , respectively). Neither mutation was significantly associated with risk of developing early-onset PDAC. This retrospective study demonstrates novel risk estimates of K3326X and I157T in sporadic PDAC which suggest that upon validation and in combination with other established genetic and non-genetic risk factors, these mutations may be used to improve pancreatic cancer risk assessment in European populations. Identification of carriers of these risk alleles as high-risk groups may also facilitate screening or prevention strategies for such individuals, regardless of family history.


Assuntos
Proteína BRCA2/genética , Carcinoma Ductal Pancreático/genética , Quinase do Ponto de Checagem 2/genética , Genes BRCA2 , Neoplasias Pancreáticas/genética , Idoso , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença , Mutação em Linhagem Germinativa , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único
5.
Stem Cell Rev Rep ; 12(5): 604-612, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27503204

RESUMO

Inflammatory bowel diseases (IBDs) are the result of pathological immune responses due to environmental factors or microbial antigens into a genetically predisposed individual. Mainly due to their trophic properties, a mounting interest is focused on the use of human mesenchymal stem/stromal cells (hMSCs) to treat IBD disease in animal models. The aim of the study is to test whether the secreted molecules, derived from a specific population of second trimester amniotic fluid mesenchymal stem/stromal cells, the spindle-shaped MSCs (SS-AF-MSCs), could be utilized as a novel therapeutic, cell free approach for IBD therapy. Induction of colitis was achieved by oral administration of dextran sulphate sodium (DSS) (3 % w/v in tap water), for 5 days, to 8-week-old NOD/SCID mice. The progression of colitis was assessed on a daily basis through recording the body weight, stool consistency and bleeding. Conditioned media (CM) derived from SS-AF-MSCs were collected, concentrated and then delivered intraperitoneally into DSS treated mice. To evaluate and determine the inflammatory cytokine levels, histopathological approach was applied. Administration of CM derived from SS-AF-MSCs cells reduced the severity of colitis in mice. More importantly, TGFb1 protein levels were increased in the mice received CM, while TNFa and MMP2 protein levels were decreased, respectively. Accordingly, IL-10 was significantly increased in mice received CM, whereas TNFa and IL-1b were decreased at mRNA level. Our results demonstrated that CM derived from SS-AF-MSCs cells is able to ameliorate DSS-induced colitis in immunodeficient colitis mouse model, and thus, it has a potential for use in IBD therapy.


Assuntos
Líquido Amniótico/metabolismo , Colite/terapia , Células-Tronco Mesenquimais/metabolismo , Animais , Células Cultivadas , Meios de Cultivo Condicionados/metabolismo , Sulfato de Dextrana/metabolismo , Modelos Animais de Doenças , Humanos , Doenças Inflamatórias Intestinais/terapia , Interleucina-10/metabolismo , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , RNA Mensageiro/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
6.
Poult Sci ; 95(7): 1598-1608, 2016 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-26944970

RESUMO

The aim of this work was to assess the effect of dietary viable or heat inactivated probiotic forms (PF) combined or not with avilamycin (AV) used as a growth promoter, on broiler growth performance, nutrient digestibility, digestive enzyme activities, and expression of immune response related genes.Depending on the type of PF (i.e., no addition, viable, inactivated) and AV addition (no/yes), 450 one-day-old Cobb male broilers were allocated in the following 6 treatments according to a 3 × 2 factorial arrangement with 5 replicates of 15 broilers each for 6 wk: CoN: diet without any addition; CoN+A: combination of CoN with AV; ViP: viable PF - no AV; ViP+A: combination of ViP with AV; InP: inactivated PF - no AV; InP+A: combination of InP with AV.There were no interactions (P > 0.05) for overall performance parameters. In contrast, PF or AV addition improved BW gain (PPF= 0.015; PAV < 0.001), FCR (PPF < 0.001; PAV < 0.001) and production efficiency factor (PPF= 0.001; PAV= 0.001).Significant (PPF×AV ≤ 0.05) interaction effects regarding ileal digestibility (IAD) of DM and total tract apparent digestibility (TTAD) of DM and ether extracts (EE) were noted. In addition, PF affected IAD and TTAD of CP (PPF < 0.001, PPF= 0.004, respectively). Inactivated PF increased (PPR= 0.024) lipase activity in jejunal digesta.At spleen level InP and ViP+A down-regulated TGF-ß4 (PPF × AV = 0.035) compared to CoN and ViP, whereas ViP+A up-regulated iNOS (PPF × AV = 0.022). An anti-inflammatory effect of live and inactive PF and/or AV addition at cecal tonsils was shown by iNOS down-regulation (PPF × AV= 0.015) compared to CoN. Furthermore, AV down-regulated IFN-γ (PAV= 0.002).In conclusion, viable probiotic, as well as inactivated probiotic alone or in combination with avilamycin, improved nutrient digestibility. All dietary additives affected growth performance positively and induced an anti-inflammatory response at cecal level.


Assuntos
Fenômenos Fisiológicos da Nutrição Animal , Galinhas/fisiologia , Dieta/veterinária , Substâncias de Crescimento/farmacologia , Probióticos , Ração Animal/análise , Fenômenos Fisiológicos da Nutrição Animal/efeitos dos fármacos , Animais , Proteínas Aviárias/genética , Proteínas Aviárias/metabolismo , Biomarcadores , Galinhas/crescimento & desenvolvimento , Galinhas/imunologia , Digestão/efeitos dos fármacos , Digestão/imunologia , Trato Gastrointestinal/efeitos dos fármacos , Trato Gastrointestinal/enzimologia , Trato Gastrointestinal/imunologia , Expressão Gênica/efeitos dos fármacos , Expressão Gênica/imunologia , Substâncias de Crescimento/administração & dosagem , Temperatura Alta , Imunidade Inata/efeitos dos fármacos , Imunidade Inata/imunologia , Masculino , Oligossacarídeos/farmacologia , Distribuição Aleatória
7.
Cancer Biomark ; 15(6): 843-50, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26406410

RESUMO

BACKGROUND: Bevacizumab, an angiogenesis inhibitor is used in regimens for metastatic colorectal cancer (CRC). A minority of cancer cells with characteristics of cancer stem cells (CSC) may be responsible for progression and development of chemotherapy resistance in this disease. CD133 is a well-known CSC marker and is associated with angiogenesis, poor prognosis and resistance to chemotherapy. OBJECTIVE: The purpose of our study was to evaluate the association between the rs3130 and rs2286455 polymorphisms of the CD133 gene and the response, toxicity, and overall survival of patients with CRC on bevacizumab-based treatment. METHODS: Forty-three patients receiving bevacizumab, irinotecan and capecitabine and 15 patients receiving bevacizumab, irinotecan and 5-FU were included. Efficacy and toxicity were evaluated. KRAS mutation analysis and rs3130 and rs2286455 polymorphisms genotyping in the tumors and peripheral blood respectively were performed with PCR-RFLP. RESULTS: No association between KRAS mutated alleles and response was found. The rs3130 CC genotype was associated with reduced toxicity of treatments (p= 0.0017), and with lower overall survival on bevacizumab (p= 0.002). CONCLUSIONS: The CC genotype of rs3130 polymorphism in the CD133 gene can predict poorer overall survival in patients with metastatic CRC on bevacizumab which cannot be attributed to increased treatment toxicity.


Assuntos
Antígenos CD/genética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/genética , Neoplasias Colorretais/genética , Glicoproteínas/genética , Neoplasias Hepáticas/genética , Peptídeos/genética , Polimorfismo Genético/genética , Antígeno AC133 , Adulto , Idoso , Idoso de 80 Anos ou mais , Bevacizumab/administração & dosagem , Camptotecina/administração & dosagem , Camptotecina/análogos & derivados , Cetuximab/administração & dosagem , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Feminino , Fluoruracila/administração & dosagem , Seguimentos , Humanos , Irinotecano , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/secundário , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Taxa de Sobrevida
8.
Poult Sci ; 94(10): 2445-55, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26286998

RESUMO

The dietary supplementation of Saccharomyces cerevisiae var. boulardii was evaluated in broilers challenged or not challenged with Salmonella Enteritidis (SE) using a 2 × 2 factorial arrangement. Depending on yeast inclusion at 0 (C) or 1 × 109 cfu/kg diet (Y) and SE challenge (0 or log 6.3 cfu/bird) on d 15, the experiment had four treatments C, Y, C-SE, and Y-SE, respectively. Each treatment had seven replicate floor pens with 15 broilers. Growth performance responses were determined weekly and overall for the 5 week experimental period. Salmonella levels and prevalence in ceca, cloacae, and carcass skin were determined by culture procedures, while cecal microbiota was determined by real time PCR. Yeast supplementation had no effect (PY > 0.05) on growth performance. For the overall post SE-challenge period (i.e., wk 3 to wk 5), Salmonella reduced body weight gain (BWG) (PSE < 0.001), feed intake (FI) (PSE = 0.032), and the European production efficiency (EPEF) factor (PSE = 0.005). Broilers Y-SE had higher (P < 0.001) overall BW gain compared to C-SE ones. Overall mortality was 2.14% and did not differ (P > 0.05) between treatments. Reduced Salmonella levels in the cloacae (P = 0.014) and on the breast skin (P = 0.006) and lower prevalence on the neck skin (P = 0.007) were noted for treatment Y-SE compared to C-SE. Yeast supplementation did not have an effect (P > 0.05) on cecal microbiota composition at d 1 and d 21 post SE-challenge. On the contrary, SE-challenge reduced cecal levels of total bacteria (PSE = 0.002), E. coli (PSE = 0.006), Bifidobacterium spp. (PSE = 0.006), Bacteroides spp. (PSE = 0.010), and Clostridial populations belonging to cluster I and cluster XIVa, (PSE = 0.047 and PSE = 0.001, respectively) on d 1 post SE-challenge. At 21 d post SE-challenge, only the levels of cecal Lactobacillus spp. (PSE = 0.001) and Bifidobacterium spp. (PSE = 0.049) were reduced compared to the non SE-challenged groups. In conclusion, yeast supplementation in SE challenged broilers (Y-SE) was beneficial for growth performance and reduced Salmonella presence compared to C-SE ones. The disturbance of cecal microbiota balance by SE merits further investigation for potential implications in gut and overall bird health.


Assuntos
Galinhas , Doenças das Aves Domésticas/dietoterapia , Salmonelose Animal/dietoterapia , Salmonella enteritidis/isolamento & purificação , Fermento Seco/farmacologia , Ração Animal/análise , Animais , Ceco/microbiologia , Cloaca/microbiologia , Dieta/veterinária , Suplementos Nutricionais/análise , Conteúdo Gastrointestinal/microbiologia , Masculino , Microbiota/efeitos dos fármacos , Doenças das Aves Domésticas/microbiologia , Distribuição Aleatória , Salmonelose Animal/microbiologia , Pele/microbiologia , Fermento Seco/administração & dosagem
9.
Vet Parasitol ; 211(3-4): 216-22, 2015 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-26073108

RESUMO

The epidemiological, clinical, and biochemical profile of non-cerebral coenurosis in goats and the morphological characteristics of the responsible metacestodes (cysts) were examined in a cross-sectional survey of slaughtered goats in abattoirs of the United Arab Emirates (U.A.E.) originating from Abu Dhabi and various tropical countries. The age, country of origin, and location of each cyst in the body of goats were recorded. Blood samples collected from infected and matching healthy goats were subjected to biochemical analysis. Data on the morphological characteristics of the cysts as well as the clusters, scoleces, and rostellar hooks in one cyst from each affected carcass were collected. The data collected were subjected to statistical analysis. A total of 2,284 slaughtered goats were examined and 40 goats were diagnosed as infected with non-cerebral coenurus cysts. The prevalence of non-cerebral coenurosis was 1.75% and the degree of parasite aggregation (k) was 0.003, which is indicative of overdispersion (k<1). The only abnormalities observed in the infected goats were palpation of large single cysts in thigh muscles and higher serum aspartate aminotransferase (AST) value. A total of 76 non-cerebral coenurus cysts from 14 different body locations were collected. No cysts were found in the brain or spinal cord. Cysts located in psoas muscles had on average significantly bigger volumes and higher numbers of scoleces and clusters compared to cysts located in other body parts (P-value=0.000). Significant differences in the morphometric measurements of the rostellar hooks were observed between cysts found in goats from different countries of origin (P-value<0.05) perhaps due to initial steps of allopatric speciation by geographic isolation. A significant positive correlation was found between number of scoleces and volume of cysts (b=6.37>5; R-Sq=89.4%; P-value=0.000) and between number of clusters and number of scoleces (b=25.13>1; R-Sq=79.8%; P-value=0.000) indicative of following a positive allometric growth as well as between number of clusters and volume of cysts (b=0.25<0.5; R-Sq=69.4%; P-value=0.000) indicative of following a negative allometric growth. The biological significance of the observed allometries is not known, but perhaps for evolutionary reasons the parasite is investing its resources more on the growth of scoleces, less on the growth of cyst volume, and even less on the number of clusters.


Assuntos
Infecções por Cestoides/veterinária , Doenças das Cabras/parasitologia , Animais , Cestoides/classificação , Cestoides/isolamento & purificação , Infecções por Cestoides/epidemiologia , Infecções por Cestoides/parasitologia , Doenças das Cabras/epidemiologia , Cabras , Clima Tropical , Emirados Árabes Unidos/epidemiologia
10.
Vet Parasitol ; 205(3-4): 653-65, 2014 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-25182211

RESUMO

Trichinella spp. and Toxoplasma gondii are important zoonotic parasites that infect warm blooded animals and humans worldwide. Among domesticated food animals, pigs are the main host for Trichinella spiralis. Pigs, chickens, sheep, and goats are known to be infected with T. gondii at varying rates, depending on husbandry. Infections in wildlife with these parasites are generally higher than in domesticated species. Feral swine act as reservoirs of infection in the sylvatic ecosystem for Trichinella spp. and T. gondii, acting as sources of infection for peridomestic carnivores whose home ranges overlap with domestic pigs. Feral swine can have direct contact with non-biosecure domestic pigs, presenting opportunity for direct disease transmission through cannibalistic behavior. Determination of the prevalence of Trichinella spp. and T. gondii infection in feral swine is needed to understand the risk of transmission of these parasites to domestic pigs. A cross-sectional serological survey was conducted between 2006 and 2010 to estimate the antibody prevalence of Trichinella spp. and T. gondii and risk factors associated with infection in feral swine in the USA. Serum samples were tested from 3247 feral pigs from 32 states; results are reported from 26 states. Maximum entropy ecological niche modeling and spatial scan statistic were utilized to predict the geographic range and to examine clusters of infection of Trichinella spp. and T. gondii in feral pigs. The seroprevalence of antibodies to Trichinella spp. and T. gondii was 3.0% and 17.7%, respectively. Species distribution modeling indicated that the most probable distribution areas for both parasites was similar, concentrated primarily in the South and the Midwest regions of the USA. A follow up survey conducted during 2012-2013 revealed that 2.9% of 984 sampled feral swine were seropositive for Trichinella spp., and 28.4% were seropositive for T. gondii. Three hundred and thirty (330) tongues were collected from the 984 sampled animals during 2012-2013; 1.81% were tissue positive for T. spiralis muscle larvae; no other genotypes were found. The potential exists for introduction of these pathogens into domestic herds of non-biosecure domestic pigs as a result of increasing overlap of the range of feral pigs with non-biosecure domestic pigs production facilities in the USA.


Assuntos
Doenças dos Suínos/epidemiologia , Toxoplasma/imunologia , Toxoplasmose Animal/epidemiologia , Trichinella/imunologia , Triquinelose/veterinária , Animais , Animais Selvagens , Anticorpos Anti-Helmínticos/sangue , Anticorpos Antiprotozoários/sangue , Estudos Transversais , Feminino , Geografia , Humanos , Masculino , Estudos Soroepidemiológicos , Sus scrofa , Suínos , Doenças dos Suínos/parasitologia , Toxoplasma/isolamento & purificação , Toxoplasmose Animal/parasitologia , Trichinella/isolamento & purificação , Trichinella spiralis/imunologia , Trichinella spiralis/isolamento & purificação , Triquinelose/epidemiologia , Triquinelose/parasitologia , Estados Unidos/epidemiologia , Zoonoses
11.
J BUON ; 18(1): 86-97, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23613393

RESUMO

PURPOSE: Laparoscopic colectomy has been reported as a safe and oncologically similar operation to open colectomy. A number of expensive surgical instruments are necessary for the procedure which should be applied if it is cost-effective for the patient and the health system in general. The purpose of the current study was the economic evaluation of laparoscopic compared to open colectomy for the treatment of colon cancer in the Greek national health system. METHODS: Fifty patients undergoing open colectomy and 42 undergoing laparoscopic colectomy were enrolled in this case-control study. Length of hospital stay, duration of operation, complication rates, cost of equipment used, total costs and three questionnaires measuring quality of life /QoL (EQ-5D, SF-36 and QLQ-C30) at baseline, 1 and 3 months after the operation were recorded. RESULTS: No statistically significant difference in QoL measured by QALYs between laparoscopic and open colectomy was observed. On the other hand, cost utility analysis revealed that laparoscopic colectomy was more expensive considering the advantages it offers. CONCLUSIONS: Laparoscopic colectomy is not superior to open colectomy on a QoL basis in the Greek public hospital system and is less cost-effective compared to the open procedure. Since the expensive equipment used in laparoscopic colectomy seems to be the causative factor for the high cost of this type of operation, an effort should be made to reduce it either by using reusable instruments or by implementing policies aiming at suppliers cutting down equipment charges.


Assuntos
Colectomia/economia , Neoplasias Colorretais/economia , Neoplasias Colorretais/cirurgia , Custos Hospitalares , Hospitais Públicos/economia , Laparoscopia/economia , Programas Nacionais de Saúde/economia , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , Colectomia/efeitos adversos , Colectomia/métodos , Análise Custo-Benefício , Feminino , Grécia , Humanos , Laparoscopia/efeitos adversos , Tempo de Internação/economia , Modelos Lineares , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Complicações Pós-Operatórias/economia , Qualidade de Vida , Inquéritos e Questionários , Fatores de Tempo , Resultado do Tratamento
12.
Infect Genet Evol ; 17: 8-15, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23567820

RESUMO

Johne's disease or paratuberculosis is a chronic, progressive intestinal disease of ruminants caused by Mycobacterium avium subsp. paratuberculosis (MAP). One of the genes that have been targeted with regard to resistance or sensitivity to paratuberculosis is the SLC11A1 (solute carrier family 11 member A1). Here we extend our previous work to the sequence and structure analysis of the caprine SLC11A1 gene and we assess the functional impact of the most frequent polymorphisms of the 3' UTR region of the SLC11A1 gene to its expression in goat macrophages exposed in vitro to MAP. The role of these polymorphisms in primary immune response is also investigated with connection to gene expression of two interleukins (IL), one of which pro (IL-1a), and the other anti-inflammatory (IL-10). In order to assess gene response, quantitative detection of the SLC11A1, IL-10 and IL1a mRNA was performed by real time PCR before, and at 1, 3 and 24h after exposure of primary cultures of peripheral blood monocyte-derived macrophages to MAP, collected from 54 goats of the Greek native goat breed. Sequence analysis of the 3' UTR end of the caprine SLC11A1 gene determined its full length to be 522 bases. Structure analysis confirmed the presence of two microsatellites consisted of a variable number of guanine-thymine repeats (regions A and B). The homozygous B7 genotype [B(GTn)7/7] was associated at a statistically significant level with increased expression of the SLC11A1 and IL-1α genes indicating increased in vitro responsiveness and therefore resistance of mononuclear derived macrophages to MAP infection.


Assuntos
Proteínas de Transporte de Cátions/genética , Expressão Gênica , Macrófagos/metabolismo , Macrófagos/microbiologia , Mycobacterium avium subsp. paratuberculosis , Regiões 3' não Traduzidas , Alelos , Animais , Sequência de Bases , Proteínas de Transporte de Cátions/química , Células Cultivadas , Genótipo , Cabras , Interleucina-10/genética , Interleucina-1alfa/genética , Dados de Sequência Molecular , Polimorfismo Genético
13.
Tech Coloproctol ; 17(5): 525-36, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23605189

RESUMO

BACKGROUND: Anatomical changes after intestinal resection and the effects of adjuvant treatment for colorectal cancer may lead to gastrointestinal disturbances. The aim of our study was to assess gastrointestinal function using validated health-related quality of life (HRQoL) questionnaires that are able to reliably quantify patients' symptoms. METHODS: Two hundred and eighty-nine colorectal cancer patients underwent HRQoL assessment preoperatively and at 3,6 and 12 months postoperatively. They were evaluated with the Gastrointestinal Quality of Life Index (GIQLI) ["global" and "symptoms" scales and questions 3 ("bloating"), 4 ("excessive gas"), 6 ("gurgling noises"), 7 ("frequent bowel movements (BMs)"), 30 ("urgent BMs"), 31 ("diarrhea"), 32 ("constipation"), 36 ("uncontrolled stools")] and the European Organization for Research and Treatment of Cancer (EORTC) modules QLQ-C30 (symptom scales: "constipation" and "diarrhea") and QLQ-CR29 (symptom scales: "defecation problems," "incontinence," and "bloating"). RESULTS: GIQLI "global" and "symptom" indices and the majority of single-item scores and the EORTC QLQ-C30 "constipation" and "diarrhea" subscales showed significant postoperative improvement (p < 0.05). Females and younger age (<70 years) patients appeared to have worse postoperative gastrointestinal function. Rectal cancer patients had more "urgent BMs," "uncontrolled stools" and worse "global" and "symptom" scores at 3 months and more "diarrhea" at 3 and 6 months than colon cancer patients (p < 0.03). Right colectomy patients had less "excessive passage of gas," "constipation," and "uncontrolled stools" than left colectomy patients (3 months, p < 0.01). Anterior resection patients faced more gastrointestinal difficulties, especially in the first 6 months after surgery. Adverse effects related to stage and adjuvant treatment were predominant only at baseline (p < 0.05). GIQLI "diarrhea" and "constipation" scores were correlated with the respective EORTC QLQ-C30 domains (p = 0.0001). CONCLUSIONS: Overall, gastrointestinal function is improved after colorectal cancer surgery. However, women and younger patients are at higher risk of postoperative gastrointestinal dysfunction.


Assuntos
Colectomia/efeitos adversos , Neoplasias Colorretais/cirurgia , Trato Gastrointestinal/fisiopatologia , Complicações Pós-Operatórias/fisiopatologia , Qualidade de Vida , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Colectomia/métodos , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Constipação Intestinal/epidemiologia , Constipação Intestinal/etiologia , Diarreia/epidemiologia , Diarreia/etiologia , Incontinência Fecal/epidemiologia , Incontinência Fecal/etiologia , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Estudos Prospectivos , Distribuição por Sexo , Perfil de Impacto da Doença , Estatísticas não Paramétricas , Inquéritos e Questionários , Análise de Sobrevida , Resultado do Tratamento
14.
J Helminthol ; 87(1): 125-7, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22260813

RESUMO

This study reports seven rare cases of non-cerebral coenurosis in sheep. The sheep were slaughtered in abattoirs of Abu Dhabi (United Arab Emirates) but originated from India, Iran, Oman and Sudan. The prevalence of infection with non-cerebral coenurosis was 0.008%. The locations of the cysts were the triceps brachii muscle, the diaphragm, the infraspinatus muscle of the shoulder, the muscles of the thigh and the abdomen, and the ommentum. The Coenurus cysts were surrounded by a fibrous, semi-opaque membrane, cloudy white in colour. Altogether, 12 cysts were recovered and all contained a single bladderworm. Cysts had a volume of 7.3 ± 1.30 cm3 (ml), with 7.3 ± 4.0 clusters of scolices, and an average number of scolices 75.3 ± 24.4. These features in sheep were similar to those reported for non-cerebral Coenurus cysts in goats. No cysts were found in the brain or spinal cord of any of the infected sheep. No clinical evidence of non-cerebral coenurosis had been recorded during the antemortem veterinary inspection of the infected sheep.


Assuntos
Cestoides/isolamento & purificação , Infecções por Cestoides/veterinária , Doenças dos Ovinos/epidemiologia , Doenças dos Ovinos/parasitologia , Animais , Infecções por Cestoides/epidemiologia , Infecções por Cestoides/parasitologia , Infecções por Cestoides/patologia , Músculos/parasitologia , Músculos/patologia , Prevalência , Ovinos , Doenças dos Ovinos/patologia , Emirados Árabes Unidos
15.
Epidemiol Infect ; 141(1): 81-90, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22370223

RESUMO

Maximum entropy ecological niche modelling and spatial scan statistic were utilized to predict the geographical range and to investigate clusters of infections for Neospora caninum and Coxiella burnetii in dairy cattle farms in Catalonia, northeastern Spain, using the Maxent and SaTScan programs, respectively. The geographical distribution of Neospora and Coxiella with the highest level of probability (P > 0·60) covers central Catalonia and spreads towards northeastern Catalonia which contains a high concentration of dairy cattle farms. The most important environmental factor that contributed to the ecological niche modelling was precipitation of driest month followed by elevation. Significant clusters (P < 0·001) were detected for Neospora and Coxiella infections in the western and eastern regions of Catalonia, respectively.


Assuntos
Doenças dos Bovinos/epidemiologia , Coccidiose/veterinária , Febre Q/veterinária , Topografia Médica , Animais , Bovinos , Doenças dos Bovinos/microbiologia , Doenças dos Bovinos/parasitologia , Análise por Conglomerados , Coccidiose/epidemiologia , Coxiella burnetii/isolamento & purificação , Neospora/isolamento & purificação , Prevalência , Febre Q/epidemiologia , Fatores de Risco , Espanha/epidemiologia , Tempo (Meteorologia)
16.
Tech Coloproctol ; 17(1): 27-38, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23065134

RESUMO

BACKGROUND: The aim of the present study was to prospectively determine health-related quality of life (HRQoL) changes and affecting factors after elective laparoscopic colectomy for cancer. METHODS: The SF-36, EORTC QLQ-C30 and QLQ-CR29, and Gastrointestinal Quality of life Index (GIQLI) were used to assess 85 patients preoperatively and at 1, 3, 6, and 12 months. RESULTS: An initial drop form baseline values was observed in 3 of 8 SF-36 domains, 3 of 5 QLQ-C30 functional scales and 1 of 5 GIQLI subscales. Emotional functioning (EF) was better postoperatively even from the first month (p = 0.03). Most functional domains were improved compared to baseline. The statistically significant changes (p < 0.05) were in the SF-36: general health (GH) (3 months), physical function (PF) (12 months) and role limitations due to emotional problems (12 months); in the QLQ-C30: EF (12 months); in the GIQLI: the global score and PF at 12 months and EF (3, 6, 12 months). From the first month after surgery, most QLQ-C30 "symptom" items were better than baseline. QLQ-CR29 "anxiety" and the "defecation problems" scales were significantly better than baseline at 1, 12 and at 6, 12 months (p < 0.05). Advanced stage (III) and chemotherapy were linked to worse EF, social function (SF), GH and global quality of life (QOL) at 3 and 6 months (p < 0.01). Males appeared to have a worse HRQoL than females at 3 and 6 months, and in 5 of 8 SF-36 domains and 3 of 5 GIQLI subscales at 12 months (p < 0.05). According to the QLQ-CR29, rectal surgery was associated more often with "impotence," "stoma problems" and "incontinence" up to 6 months, and ostomies with "embarrassment" and "stoma problems" (p < 0.05). CONCLUSIONS: HRQoL generally improved over the first year after laparoscopic colectomy reaching even better levels than before surgery. There was an early postoperative improvement in patients' emotional status. The main factors affecting HRQoL seem to be tumor stage, chemotherapy and male sex.


Assuntos
Colectomia/psicologia , Neoplasias do Colo/psicologia , Neoplasias do Colo/cirurgia , Qualidade de Vida/psicologia , Neoplasias Retais/psicologia , Neoplasias Retais/cirurgia , Idoso , Ansiedade/etiologia , Quimioterapia Adjuvante/psicologia , Colectomia/efeitos adversos , Neoplasias do Colo/patologia , Colostomia/efeitos adversos , Constipação Intestinal/etiologia , Emoções , Disfunção Erétil/etiologia , Feminino , Nível de Saúde , Humanos , Laparoscopia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Prospectivos , Neoplasias Retais/patologia , Fatores Sexuais , Participação Social , Estatísticas não Paramétricas , Inquéritos e Questionários , Fatores de Tempo
17.
Tech Coloproctol ; 16(3): 237-41, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22562595

RESUMO

BACKGROUND: The isolated application of Doppler-guided haemorrhoidal artery ligation (DGHAL) may fail due to the increased reprolapse rate for high-grade haemorrhoids. DGHAL has been combined with a proctoscopic-assisted transanal rectal mucopexy of the prolapsing tissue. The technique is called rectoanal repair (RAR) and is an evolution of various mucopexy and suture haemorrhoidopexy (SHP) techniques. A prominent external component may require minimal (muco-) cutaneous excision (MMCE) of protruding anoderm or minor cutaneous excision of skin tags. METHODS: Fifty-seven patients with symptomatic Goligher grade III and IV haemorrhoids underwent DGHAL followed by either RAR or SHP. In 26 cases, the addition of MMCE was necessary. RESULTS: No significant differences were observed between the two approaches with regards to pain scores measured with visual analogue scale (VAS). On postoperative day 1, mean pain score at rest was 5.81 (±2.23 SD) after SHP versus 5.08 (±2.35 SD) after RAR, while mean pain score at first defecation was 7.31 (±1.6 SD) versus 7.52 (±1.83 SD). There was no difference in the duration of analgesic requirements, postoperative complications and residual prolapse between the 2 procedures. The addition of MMCE did not affect postoperative pain nor analgesic requirements. With the exception of 8 patients who still had with skin tags or minimal protrusion, the remaining of patients (86 %) were asymptomatic and recurrence-free at an average follow-up of 20 months. Overall, 94.8 % of patients stated that they were satisfied with the results, and 91.2 % that they would repeat it if necessary. CONCLUSIONS: Performance of either SHP or RAR after DGHAL is a safe and effective surgical tactic for advanced grade haemorrhoids. Our initial results do not confirm any superiority of RAR over traditional SHP.


Assuntos
Canal Anal/cirurgia , Hemorroidas/cirurgia , Dor Pós-Operatória/etiologia , Canal Anal/irrigação sanguínea , Analgésicos/uso terapêutico , Artérias/cirurgia , Feminino , Hemorroidas/diagnóstico por imagem , Humanos , Ligadura , Masculino , Pessoa de Meia-Idade , Dor Pós-Operatória/tratamento farmacológico , Satisfação do Paciente , Técnicas de Sutura , Resultado do Tratamento , Ultrassonografia Doppler , Ultrassonografia de Intervenção
18.
Prev Vet Med ; 99(2-4): 148-60, 2011 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-21377747

RESUMO

Each year, more than 167 million pigs in the European Union (EU) are tested for Trichinella spp. under the current meat hygiene regulations. This imposes large economic costs on countries, yet the vast majority of these pigs test negative and the public health risk in many countries is therefore considered very low. This work reviewed the current Trichinella status across the EU as well as the national level of monitoring and reporting. It also reviewed which animal species were affected by Trichinella and in which species it should be surveyed. This information was used to design a cost-effective surveillance programme that enables a standardised monitoring approach within the EU. The proposed surveillance programme relies on identifying sub-populations of animals with a distinct risk. Low-risk pigs are finisher pigs that originate from so-called controlled housing. All other pigs are considered high-risk pigs. Controlled housing is identified by the application of a specific list of management and husbandry practices. We suggest that member states (MS) be categorised into three classes based on the confidence that Trichinella can be considered absent, in the specified sub-population of pigs above a specified design prevalence which we set to 1 per million pigs. A simple and transparent method is proposed to estimate this confidence, based on the sensitivity of the surveillance system, taking into account the sensitivity of testing and the design prevalence. The probability of detecting a positive case, if present, must be high (>95 or >99%) to ensure that there is a low or negligible risk of transmission to humans through the food chain. In MS where the probability of a positive pig is demonstrated to be negligible, testing of fattening pigs from a sub-population consisting of pigs from controlled housing can be considered unnecessary. Furthermore, reduced testing of finishers from the sub-population consisting of pigs from non-controlled housing might even be considered, if conducted in conjunction with a proportionate sampling scheme and a risk-based wildlife surveillance programme where applicable. The proposed surveillance programme specifies the required number of samples to be taken and found negative, in a MS. A MS with no data or positive findings will initially be allocated to class 1, in which all pigs should be tested. When a MS is able to demonstrate a 95% or 99% confidence that Trichinella is absent, the MS will be allocated to class 2 or 3, in which the testing requirement is lower than in class 1.


Assuntos
Criação de Animais Domésticos/normas , Vigilância de Evento Sentinela/veterinária , Doenças dos Suínos/epidemiologia , Trichinella/isolamento & purificação , Triquinelose/veterinária , Animais , Análise Custo-Benefício , União Europeia , Feminino , Higiene , Masculino , Saúde Pública , Suínos , Doenças dos Suínos/economia , Doenças dos Suínos/prevenção & controle , Triquinelose/economia , Triquinelose/epidemiologia , Triquinelose/prevenção & controle
19.
Infect Genet Evol ; 11(1): 109-15, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-20937412

RESUMO

The genetic diversity of liver fluke populations in three different countries from Eastern Europe (Greece, Bulgaria, and Poland) was determined and compared with available data from other countries. Specifically, SNPs from regions of two nuclear genes, 28S rDNA, ß-tubulin 3 and an informative region of the mitochondrial genome were examined. Two major lineages for the 28S rDNA gene based on the highly polymorphic 105th nucleotide position were found. These lineages were widely and almost equally spread not only through the countries studied but also in other investigated geographical areas. Two basic lineages and additional haplotypes were defined for the mtDNA gene region which consisted of the cytochrome c oxidase subunit III gene, transfer RNA histidine gene and cytochome b gene. The basic lineages were observed within Greek, Bulgarian, and Polish Fasciola hepatica populations but the distribution of additional haplotypes differed between the populations from the three countries. For the ß-tubulin 3 gene multiple polymorphic sites were revealed but no explicit clades. The SNPs were spread unequally in all studied geographical regions with an evident distinction between the Greek and Polish specimens. Additional genotypes for the 28S rDNA region as well as haplotypes of the mtDNA region that were typical for the Greek or Polish populations were observed. Significant polymorphisms for ß-tubulin 3 gene were displayed with decreasing percentage of presence within populations from Greece to Poland. There was an amino acid substitution in ß-tubulin 3 protein found only among Polish specimens. It is hypothesized that genotypic differences between Greek, Bulgarian, and Polish liver fluke populations are due to territorial division and genetic drift in past epochs.


Assuntos
Fasciola hepatica/genética , Variação Genética , Animais , Sequência de Bases , Primers do DNA , DNA Mitocondrial/genética , DNA Ribossômico/genética , Europa Oriental , Genes de Helmintos , Reação em Cadeia da Polimerase , Polimorfismo de Nucleotídeo Único , RNA Ribossômico 28S/genética , Tubulina (Proteína)/genética
20.
Parasitology ; 138(7): 926-38, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24650359

RESUMO

Risk factors related to herd and farmer status, farm and pasture management, and environmental factors derived by satellite data were examined for their association with the prevalence of F. hepatica in sheep and goat farms in Thessaly, Greece. Twelve farms (16.2%) and 58 farms (78.4%) of 74 had evidence of infection using coproantigen and serology respectively. The average normalized difference vegetation index (NDVI) of farm location for 12 months before sampling was the most significant environmental risk factor for F. hepatica infection based on high seropositivity. The risk of infection increased by 1% when the value of NDVI increased by 0.01 degree. A geospatial map was constructed to show the relative risk (RR) of Fasciola infection in sheep and goat farms in Thessaly. In addition, geospatial maps of the model-based predicted RR for the presence of Fasciola infection in farms in Thessaly and the entire area of Greece were constructed from the developed model based on NDVI. In conclusion, this study demonstrated that Thessaly should be regarded as an endemic region for Fasciola infection and it represents the first prediction model of Fasciola infection in small ruminants in the Mediterranean basin.


Assuntos
Meio Ambiente , Fasciola hepatica/fisiologia , Fasciolíase/veterinária , Doenças das Cabras/epidemiologia , Modelos Teóricos , Doenças dos Ovinos/epidemiologia , Animais , Fasciolíase/epidemiologia , Cabras , Grécia , Prevalência , Fatores de Risco , Ovinos
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