Pan-cancer genomic analysis shows hemizygous PTEN loss tumors are associated with immune evasion and poor outcome.

In tumors, somatic mutations of the PTEN suppressor gene are associated with advanced disease, chemotherapy resistance, and poor survival. PTEN loss of function may occur by inactivating mutation, by deletion, either affecting one copy (hemizygous loss) leading to reduced gene expression or loss of both copies (homozygous) with expression absent. Various murine models have shown that minor reductions in PTEN protein levels strongly influence tumorigenesis. Most PTEN biomarker assays dichotomize PTEN (i.e. presence vs. absence) ignoring the role of one copy loss. We performed a PTEN copy number analysis of 9793 TCGA cases from 30 different tumor types. There were 419 (4.28%) homozygous and 2484 (25.37%) hemizygous PTEN losses. Hemizygous deletions led to reduced PTEN gene expression, accompanied by increased levels of instability and aneuploidy across tumor genomes. Outcome analysis of the pan-cancer cohort showed that losing one copy of PTEN reduced survival to comparable levels as complete loss, and was associated with transcriptomic changes controlling immune response and the tumor microenvironment. Immune cell abundances were significantly altered for PTEN loss, with changes in head and neck, cervix, stomach, prostate, brain, and colon more evident in hemizygous loss tumors. These data suggest that reduced expression of PTEN in tumors with hemizygous loss leads to tumor progression and influences anticancer immune response pathways.

Fatores de influência sobre o desempenho reprodutivo em vacas leiteiras / [Influence factors on reproductive performance in dairy cows]

O objetivo deste estudo foi avaliar os efeitos das estações do parto e da inseminação, da retenção de placenta, da natimortalidade e da ordem de parto sobre o desempenho reprodutivo de vacas leiteiras. Utilizou-se a regressão logística, em que as variáveis dependentes foram concepção à primeira inseminação pós-parto e percentual de vacas prenhes no rebanho aos 100, 150 ou 200 DEL e as variáveis independentes foram a estação do parto e a estação da inseminação, a retenção de placenta, a natimortalidade e a ordem de parto. A estação do parto e a estação da inseminação influenciaram o desempenho reprodutivo, reduzindo a fertilidade das vacas nas estações quentes do ano. O atraso na primeira inseminação aumentou a concepção na primeira inseminação, mas reduziu o percentual de vacas prenhes ao longo da lactação. O desempenho reprodutivo da vaca leiteira foi afetado por vários fatores, relacionados à vaca, ao ambiente e ao manejo a ela imposto.(AU)

The objective of this study was to evaluate the effects of the calving season, insemination, placenta retention, stillbirth and birth order on the reproductive performance of dairy cows. Logistic regression was used, where the dependent variables were conception at the first postpartum insemination and the percentage of cows pregnant in the herd at 100, 150 and 200 DEL. The independent variables were delivery season and insemination season, placenta retention, stillbirth and delivery order. The calving season and the insemination season influenced reproductive performance, and in the hot seasons of the year the fertility of the cows was reduced. The delay in the first insemination increased conception in the first insemination but reduced the percentage of pregnant cows during lactation. The reproductive performance of the dairy cow was affected by several factors, related to the cow, the environment and the management imposed on it.(AU)

Targeted uptake of folic acid-functionalized polymeric nanoparticles loading glycoalkaloidic extract in vitro and in vivo assays.

Solanum lycocarpum fruits contain two major glycoalkaloids (GAs), solamargine (SM) and solasonine (SS). These compounds are reported as cytotoxic. However, they have poor water solubility and low bioavailability. To overcome these disadvantages and getting an efficient formulation the current study aimed to develop, characterize, and test the effectiveness of a nanotechnology-based strategy using poly(D,L-lactide) (PLA) nanoparticles functionalized with folate as delivery system of glycoalkaloidic extract (AE) for bladder cancer therapy. The strategic of adding folic acid into nanoformulations can increase the selectivity of the compounds to the cancer cells reducing the side effects. Our results revealed the successful preparation of AE-loaded folate-targeted nanoparticles (NP-F-AE) with particle size around 177 nm, negative zeta potential, polydispersity index <0.20, and higher efficiency of encapsulation for both GAs present in the extract (>85 %). To investigate the cellular uptake, the fluorescent dye coumarin-6 was encapsulated into the nanoparticle (NP-F-C6). The cell studies showed high uptake of nanoparticles by breast (MDA-MB-231) and bladder (RT4) cancer cells, but not for normal keratinocytes cells (HaCaT) indicating the target uptake to cancer cells. The cytotoxicity of nanoparticles was evaluated on RT4 2D culture model showing 2.16-fold lower IC50 than the free AE. Furthermore, the IC50 increased on the RT4 spheroids compared to 2D model. The nanoparticles penetrated homogeneously into the urotheliumof porcine bladder. These results showed that folate-conjugated polymeric nanoparticles are potential carriers for targeted glycoalkaloidic extract delivery to bladder cancer cells.

Supplementation with different non-fiber carbohydrate sources in dairy cow diets with high or low rumen-undegradable protein content / Suplementação com diferentes fontes de carboidratos não fibrosos em dietas para vacas leiteiras com alto ou baixo teor de proteína não degradável no rúmen

The objective for this study was to evaluate the supplementation with different non-fibrous carbohydrate (NFC) sources for grazing dairy cows in diets with high or low concentrations of rumen undegradable protein (RUP). Twelve multiparous cows averaging 30kg/d of milk production and 45±23 days in milk in a 4x4 Latin square design with 2 × 2 factorial arrangement were used. The difference in NFC content of the diets was achieved using ground corn (GC) or dried citrus pulp (DCP). Dietary RUP was altered by the partial replacement of soybean meal (LRUP) by roasted whole soybean and corn gluten meal (HRUP). Greater dry matter intake (DMI) was observed in DCP treatments compared to GC treatments (19.2 and 17.7kg/day of DM, respectively). Milk fat concentration was lower for LRUP treatments (3.4%) when compared to HRUP (3.6%). The milk protein concentration was greater for GC treatments (2.9%) in relation to DCP treatments (2.8%). Lower milk ureic nitrogen was observed when DCP diets were fed compared to those with GC (17.8 and 21.2mg/dL, respectively). The use of DCP as CNF source increased dry matter intake as well as milk fat concentration, although no differences in milk production were observed for RUP level.(AU)

Objetivou-se avaliar a suplementação com diferentes fontes de carboidratos não fibrosos (CNF) em vacas manejadas a pasto em dietas com alta ou baixa concentração de proteína não degradável no rúmen (PNDR). Doze vacas multíparas com média de 30kg leite/ dia e 45±23 dias em lactação foram utilizadas em delineamento quadrado latino 4x4 com arranjo fatorial 2 × 2. As fontes de CNF foram milho moído (MM) e polpa cítrica seca (PC). A PNDR da dieta foi alterada pela substituição parcial do farelo de soja da dieta de baixa PNDR (BPNDR) por grão de soja tostado e farelo de glúten de milho dieta de alta PNDR (APNDR). Foi observado maior consumo de matéria seca (CMS) nos tratamentos com PC quando comparado aos tratamentos com MM (19,2 e 17,7kg / dia de MS, respectivamente). O teor de gordura do leite foi menor para os tratamentos com BPNDR (3,4%) em comparação aos tratamentos com APNDR (3,6%). O teor de proteína do leite foi maior nos tratamentos com MM (2,9%) em relação aos tratamentos com PC (2,8%). Foram observados menores teores de nitrogênio ureico no leite dos animais alimentados com PC em relação aos com MM (17,8 e 21,2mg / dL, respectivamente). O uso de PC como fonte de CNF aumentou o consumo de matéria seca, bem como o teor de gordura do leite, embora não tenham sido observadas diferenças na produção de leite relacionada a alteração nos teores de PNDR.(AU)

Hypoenhancing prostate cancers on dynamic contrast-enhanced MRI are associated with poor outcomes in high-risk patients: results of a hypothesis generating study.

PURPOSE: To investigate the association of hypoenhancement on dynamic Contrast enhanced (DCE) with prostate cancer patient outcomes. MATERIAL AND METHODS: This was a single-institution retrospective Institutional Review Board (IRB)-approved cohort study of 54 men who had prostate Magnetic Resonance Imaging (MRI) within 6 months of cancer diagnosis between 01/2012 to 03/2014. Two readers independently identified the dominant MRI-lesions utilizing Prostate Imaging-Reporting and Data System-version2- guidelines. These lesions were classified as hypoenhancing or hyperenhancing, compared to normal peripheral zone using quantitative DCE analysis. The t test for unequal sample sizes and the two-sample Wilcoxon rank-sum tests were used to compare groups. Logistic regression determined if DCE characteristics predict the development of metastases or prostate cancer death. RESULTS: Time-to-progression was significantly shorter for hypoenhancing tumors (6.2 vs. 24.8 months, p = 0.05). Men with these lesions had a higher odds of having poor outcome (univariate logistic regression, odds ratio (OR) 6.79, 95% confidence interval (CI) 1.45-31.72, p = 0.02; multivariate analysis, OR 2.05, 95% CI 0.30-13.72, p = 0.47). Hypoenhancing tumors were larger (33.1 vs. 19.1 mm, p < 0.001) and more likely to be intermediate (Gleason scores 3 + 4 and 4 + 3) and high-grade (Gleason scores ≥ 4 + 4) prostate cancers (p = 0.05). Men in the hypoenhancing group had a higher mean prostate-specific antigen (PSA) value (87.6 vs. 24.8 ng/dL, p = 0.01) and PSA density (1.54 vs. 0.72, p = 0.03). The mean Ktrans and kep of hypoenhancing lesion were lower when compared to hyperenhancing lesions (p = 0.03 and p = 0.04). Ve values did not differ (p = 0.25). CONCLUSION: Men with hypoenhancing prostate cancers may have a worse prognosis than men with hyperenhancing tumors.

PTEN loss in Gleason grade 7 prostate tumors exhibits intratumoral heterogeneity and is associated with unfavorable pathological features

Background: PTEN loss is observed in 20­30% of prostate cancers and is associated with a poor outcome, but clinical details of the impact of this biomarker are unclear for intermediate grade tumors. Methods: We investigated 43 radical prostatectomy-derived grade 7 prostate tumors from the Clinics Hospital of Ribeirão Preto. Tissue microarray (TMA) blocks were constructed and PTEN copy number status was determined for all patients through fluorescence in situ hybridization (FISH). To determine the presence of PTEN protein loss in our study cohort, we performed immunohistochemistry (IHC) in TMA sections. We then developed an automated algorithm in HALO™ to identify regions of PTEN protein loss in whole prostate scanned sections from ten patients with known PTEN deletion status by FISH. Clinical analyses were conducted to determine the associations between PTEN loss and patient outcome. All statistical analyses were conducted in R v3.4.3 with P-values below 0.05 being considered statistically significant. Results: In this study of 43 grade 7 tumors, we found PTEN deletions by FISH in 18.9% of tumors, and PTEN protein loss by IHC in 16.3% of tumors. Both techniques were highly concordant and complementary. Clinical analysis demonstrated that PTEN deletion by FISH was significantly associated with positive margin invasion (P = 0.04) and Gleason score upgrade (P = 0.001). Digital image analysis of ten representative tumors demonstrated distinct intratumoral heterogeneity for PTEN protein loss in four tumors. Conclusions: This study shows that PTEN loss in Gleason grade 7 tumors can be heterogeneous and that a systematic analysis of this biomarker using a combination of FISH, IHC, and digital imaging may identify patients with a greater risk of poor outcome (AU)

Mitochondrial genome analysis in penile carcinoma.

Penile cancer is a rare neoplasm that seems to be linked to socio-economic differences. Mitochondrial genome alterations are common in many tumors types and are reported as regulating oxidative metabolism and impacting tumorigenesis. In this study, we evaluate for the first time the mitochondrial genome in penile carcinoma (PeCa), aiming to evaluate heteroplasmy, mitochondrial DNA (mtDNA) mutational load and mtDNA content in Penile tumors. Using next generation sequencing (NGS), we sequenced the mitochondrial genome of 13 penile tumors and 12 non-neoplastic tissue samples, which allowed us to identify mtDNA variants and heteroplasmy. We further evaluated variant's pathogenicity using Mutpred predictive software and calculated mtDNA content using quantitative PCR. Mitochondrial genome sequencing revealed an increase number of non-synonymous variants in the tumor tissue, along with higher frequency of heteroplasmy and mtDNA depletion in penile tumors, suggesting an increased mitochondrial instability in penile tumors. We also described a list of mitochondrial variants found in penile tumor and normal tissue, including five novel variants found in the tumoral tissue. Our results showed an increased mitochondrial genome instability in penile tumors. We also suggest that mitochondrial DNA copy number (mtDNAcn) and mtDNA variants may act together to imbalance mitochondrial function in PeCa. The better understanding of mitochondrial biology can bring new insights on mechanisms and open a new field for therapy in PeCa.

Desempenhos produtivo e reprodutivo de um rebanho F1 Holandês x Gir em Minas Gerais / Productive and reproductive performances of F1 Holstein x Gir cows in the state of Minas Gerais

Objetivou-se avaliar os desempenhos produtivo e reprodutivo de vacas F1 Holandês x Gir Minas Gerais, as quais foram mantidas em sistema de produção a pasto no verão, com suplementação de concentrado, e, no inverno, alimentadas com cana-de-açúcar, polpa de citros e concentrado. As características avaliadas foram: idade ao primeiro parto, intervalo parto-primeiro serviço, período de serviço, intervalo de partos, permanência da matriz no rebanho, produção de leite total por lactação, duração da lactação, produção média diária, produções ajustadas a 280 dias e a 305 dias de lactação, produção de leite por intervalo de partos e curvas de lactação conforme ordem de partos, época de partos e período de serviço. A função gama incompleta foi utilizada para estimação dos parâmetros das curvas de lactação. As demais características foram analisadas utilizando-se modelos lineares mistos. O rebanho apresentou ótimo desempenho (6271,56kg de leite por lactação). As fêmeas F1 Holandês x Gir são boa alternativa para a produção de leite, desde que garantidas boas condições de manejo, alimentação do rebanho e utilização de matrizes oriundas de programas de cruzamento direcionados empregando-se critérios de melhoramento genético.(AU)

The objective was to evaluate the productive and reproductive performances of F1 Holstein x Gir cows in the state of Minas Gerais. The herd during the summer was managed in a pasture based production system with supplementation of concentrate according to milk production and in the winter it was fed with sugar cane, citrus pulp and concentrate. The characteristics evaluated were: age at first calving, calving to first service interval, service period, calving interval, permanence the cows in the herd, total milk production per lactation, lactation length, average milk daily, productions adjusted to 280 and to 305 days of lactation, milk production per calving interval, and lactation curves. The Incomplete Gamma function was used to estimate the parameters of lactation curves at parturition order, parturition epoch and service period. The other characteristics were analyzed using linear mixed models. The herd showed great performance (6271,56 kg of milk per lactation). F1 Holstein x Gir cows are a good alternative to milk production, as long as good conditions of handling and feeding are guaranteed, and the use of cows derived from breeding programs targeted using genetic improvement criteria.(AU)

Comparison of PI-RADS 2, ADC histogram-derived parameters, and their combination for the diagnosis of peripheral zone prostate cancer.

PURPOSE: The purpose of this study was to compare the PI-RADS V2 scores, ADC histogram-derived parameters, and their combination for the diagnosis of clinically significant peripheral zone prostate cancer (PCa). MATERIALS AND METHODS: The IRB approved this retrospective study of 47 men who underwent 1.5 Tesla endorectal prostate magnetic resonance imaging (MRI). Informed consent was waived. Two readers identified and scored MRI lesions using PI-RADS V2. Their mean, median, 10th, 25th, 75th percentile ADC values, and normalized ratio were also calculated. Multilevel logistic regression and receiver-operating characteristic (ROC) curve analyses assessed their diagnostic performance. Clinically significant PCa was defined as tumor volume over 0.5 cc and Gleason grade of 4 or 5 on prostatectomy. RESULTS: The area under the ROC curve (A z) of the overall and diffusion-weighted imaging (DWI) PI-RADS V2 scores were 0.69 and 0.84 (reader-1), and 0.68 and 0.73 (reader-2). The A z of ADC parameters ranged from 0.68 to 0.75 for both readers. Compared to other predictors, DWI PI-RADS V2 yielded the highest A z for identification of significant cancer; but, except for reader-1 75th percentile ADC, the differences were not statistically significant (P > 0.05). Adding ADC parameters to PI-RADS V2 scores did not improve their diagnostic ability. CONCLUSION: DWI PI-RADS V2 score may a better predictor of clinically significant PCa than the overall PI-RADS V2 score, but its diagnostic performance was not significantly improved by the addition of objective ADC value measurements.

Effects of bovine mammary gland biopsy and increased milking frequency on post-procedure udder health, histology, and milk yield.

Sixteen cows in early lactation were randomly distributed into two groups in order to evaluate the effects of mammary biopsies and increased milking frequency on tissue characteristics, post-biopsy udder health and histology. One group was milked twice a day (2×) starting on the 2nd day after calving, until 28 days in milk (DIM). The other group was milked four times a day (4×) from two to 21 DIM, and twice a day (2×) from 22 to 28 DIM. On days 2, 7, 14, 21, and 28 postpartum, one fragment of secretory tissue was collected from one mammary quarter at a time. Collections were alternated between the four mammary quarters per collection day. A total of 80 mammary tissue samples were collected. Qualitative and quantitative analyses of the tissues were conducted by histologic examination. Animal health was assessed by observation of feed intake behavior immediately after biopsy, and weight and body condition score before and one week after biopsy. Udder health was assessed daily from calving to 60 DIM with California Mastitis Test (CMT) and by noting alterations in the milk such as blood, milk clots, blood clots, clinical signs of mastitis. Milk composition and somatic cell count (SCC) were analyzed before and after the biopsies. Milk production was evaluated before biopsy, on the day of biopsy, and after the biopsy. An average of 10 fields at 40× magnification was obtained from each sample. There were no evident changes in mammary morphology as a result of milking two or four times/day at any of the evaluated time points. Biopsy wounds healed rapidly without infection. Intramammary bleeding and CMT alterations were observed in 96% and 75% of the biopsied mammary quarters, respectively. Clinical mastitis was diagnosed in 12% of the biopsied quarters. Different milking frequencies had no effect on the frequency and duration of post-biopsy alterations. Milk production decreased after biopsies done on days 2 for 2× and 4× groups, but it returned to pre-biopsy values within 1 day. Milk composition and SCC were affected transiently. Increased milking frequency did not influence udder health. Post-biopsy recovery was rapid and the procedure proved effective without damaging the cows' health.

Perfil de ácidos graxos do leite de vacas holandês x Gir em pastagem de capim-marandu suplementado com quantidades crescentes de grão de soja tostado / Milk fatty acid profile of holstein x Gyr cows grazing on marandugrass supplemented with increasing levels of roasted soybeans

O experimento foi realizado na Embrapa Gado de Leite, em delineamento quadrado latino (QL) 4x4, com o objetivo de avaliar o perfil de ácidos graxos (AG) e os índices de qualidade nutricional da gordura do leite de vacas Holandês x Gir (n = 16) sob pastejo em Brachiaria brizantha cv. Marandu suplementada com concentrado (6kg/vaca/dia) contendo 0; 1,3; 2,6 e 3,9kg (base matéria natural) de grão de soja tostado (GST). Foram observados decréscimos lineares (P<0,0001) nas concentrações e nas secreções dos AG láurico, mirístico e palmítico e dos AG de cadeia ímpar linear e ramificada, bem como incrementos lineares (P<0,0001) nas concentrações e secreções dos AG α-linolênico, linoleico, oleico e esteárico na gordura do leite, com a inclusão do GST no concentrado. As concentrações e as secreções dos AG vacênico e rumênico apresentaram comportamento quadrático (P<0,001) em resposta à inclusão de quantidades crescentes de GST na dieta. As alterações observadas no perfil de AG do leite com o aumento da inclusão de GST no concentrado resultaram em reduções lineares (P<0,0001) nos índices de aterogenicidade e de trombogenicidade e em incrementos lineares (P<0,0001) nas relações entre AG hipo:hipercolesterolêmicos e entre AG ω-6:ω-3 da gordura do leite. Os resultados deste estudo mostraram que a inclusão de quantidades crescentes de GST na dieta de vacas Holandês x Gir pastejando capim-marandu apresenta potencial para a secreção de leite com gordura enriquecida com ácidos graxos benéficos à saúde humana.

The experiment was carried out at Embrapa Dairy Cattle in order to evaluate the milk fatty acid (FA) composition and indices of nutritional quality of milk fat from Holstein x Gyr cows (n = 16) grazing on Brachiaria brizanta cv. Marandu supplemented with concentrate (6 kg/cow/d) containing 0, 1.3, 2.6 and 3.9 kg (as-fed basis) of roasted soybeans (RS). A linear decrease (P<0.0001) in the content and secretion of lauric, myristic and palmitic FA, and odd- and branched-chain FA was observed, whereas the content and secretion of α-linolenic, linoleic, oleic, and stearic FA in milk fat increased linearly (P<0.0001) as the amount of RS increased in the diet. The milk fat content and secretion of vaccenic and rumenic FA increased quadratically (P<0.001) in response to dietary RS level. As a consequence of the above-mentioned changes in milk FA composition, both atherogeniticy and trombogenicity indices of milk fat were reduced linearly (P<0.0001), whereas hypo:hypercholesterolemic and ω-6:ω-3 FA ratios increased linearly (P<0.0001) in milk fat from cows fed increasing levels of RS. The results showed that dietary supplementation with increasing amounts of RS have the potential to secrete fat milk enriched fatty acids beneficial to human health.

Efeito da adição de teores crescentes de ureia na cana-de-açúcar em dietas de vacas em lactação sobre a produção e composição do leite e viabilidade econômica / The effect of increasing urea in sugarcane diet of lactating cows on milk production and composition and its economic viability

Avaliou-se o efeito da adição de teores crescentes de ureia (0,0; 0,5 e 1,0%) na matéria natural da cana-de-açúcar sobre a produção e composição do leite, eficiência alimentar e viabilidade econômica. Foram utilizadas 18 vacas em lactação, com produção média inicial de 21,3±0,8kg/dia de leite e com 83±7 dias em lactação, distribuídas em delineamento ensaio de reversão do tipo switch-back, 3x3. As dietas experimentais foram constituídas de cana-de-açúcar como volumoso único e concentrado, na relação de 50:50 (base MS). Não houve efeito da suplementação dos diferentes teores de ureia sobre a produção e composição do leite. Contudo, a eficiência alimentar (produção de leite/consumo de matéria seca) foi melhor nas dietas em que se utilizou ureia, sendo 1,14; 1,17 e 1,17, respectivamente, para as dietas com 0,0; 0,5 e 1,0% de ureia (P<0,05). Considerando-se apenas o custo alimentar, todas as dietas apresentaram saldo positivo, sendo que a dieta com 1,0% de ureia apresentou o melhor saldo.(AU)

We studied the effect of increasing 0.0, 0.5 and 1.0% urea in natural sugar cane on cow milk production and composition, food productivity and economic viability. Eighteen lactating cows were studied, they had avarage milk production of 21.3±0.8kg/day and were 83±7 days in lactation in a switch-back, 3 x 3 design. The experimental diets consisted of a unique concentrated sugar cane portion with the 50:50 relation (MS base). The results showed no effect of different urea concentrations on the milk production or composition. However, food productivity (milk production/dry matter consumption) was 1.14; 1.17, and 1.17 respectively on urea diets of 0.0; 0.5 and 1.0% (P<0.05). Considering only the alimentary cost, all diets had a positive balance, and the 1.0% urea concentration was the best.(AU)

Processamento do milho para vacas leiteiras em pastejo / Processing of corn for grazing dairy cows

Doze vacas lactantes Holandês-Gir (1/2), em sistema de pasto rotativo de Panicum maximum cv. Mombaça, foram suplementadas com concentrados contendo milho seco finamente moído (MM), milho expandido (ME), milho floculado a vapor (MF) ou milho moído reidratado e ensilado (MU). O delineamento experimental adotado foi o de quadrado latino 4 x 4, com três repetições. O consumo de pasto foi maior quando as vacas foram suplementadas com MF, o que se refletiu em maior consumo de MS, PB, FDN para o mesmo tratamento. A digestibilidade aparente da MS foi maior para as dietas de MF e MM. A digestibilidade aparente da FDN foi menor para MU. A produção e composição do leite das vacas não diferiram entre os tratamentos, entretanto a eficiência alimentar foi menor para MF...

Twelve lactating Holstein-Gyr (1/2) cows in a rotational grazing system with Panicum maximum cv. Mombasa were supplemented with different concentrates containing finely ground dried corn (MM), expanded corn (ME), steam flaked corn (MF) or silage of re-hydrated ground corn (MU). The experiment was arranged in a 4 x 4 Latin square design with three replications. Pasture intake was higher when cows were supplemented with MF, which resulted in higher DM, CP, and NDF. The apparent digestibility of DM was higher for MF and MM diets. The NDF apparent digestibility was lower for MU. Milk yield and composition did not differ between treatments; however, feed efficiency was lower for MF...

Suplementação de lisina e metionina em associação ou não com o óleo de soja na dieta de vacas leiteiras / Supplementation of lysine and methionine in association or not with soybean oil in dairy cow diets

O objetivo do estudo foi avaliar a suplementação de lisina e metionina em associação ou não ao óleo de soja na dieta de vacas leiteiras e seus efeitos sobre a produção e a composição do leite. Doze vacas Holandesas foram distribuídas em quadrado latino 4x4, com as dietas O+LM (dieta acrescida de óleo de soja, lisina e metionina misturados na dieta total), OLM (dieta com o complexo óleo de soja/lisina e metionina fornecido separadamente da dieta total), OS (dieta acrescida de óleo de soja fornecido separadamente da dieta total) e LM (dieta acrescida de lisina e metionina fornecidos separadamente da dieta total). A produção de leite, a de proteína e a de gordura não foram afetadas pela adição de lisina e metionina associadas ou não com óleo de soja. O percentual de gordura do leite, a produção de leite corrigida para 3,5% de gordura e a produção de leite corrigida para sólidos totais reduziram-se com a adição de óleo de soja na dieta. O percentual de proteína aumentou 0,14% (p<0,05) com a adição de óleo na presença de lisina e metionina na dieta. Os resultados sugerem efeito protetor do complexo óleo/lisina e metionina da degradação ruminal na condição experimental proposta...

The aim of this study was to evaluate the effects of lysine and methionine supplementation with or without soybean oil in the diet of dairy cows on milk production and composition. Twelve Holstein cows were randomly distributed in a 4x4 latin square where the diets were O+LM (diet with soybean oil, lysine and methionine added in the total mixed ration), OLM (diet with complex soybean oil/ lysine and methionine provided as top dressed), OS (diet with soybean oil provided as top dressed) and LM (diet with lysine and methionine provided as top dressed). The milk production, milk protein and milk fat production were not affected by the addition of lysine and methionine in association or not with soybean oil in the diet. The milk fat percentage, 3.5% fat-corrected milk and solids corrected milk were reduced with increasing soybean oil in the diet. The milk protein percentage increased in 0.14% (P < 0.05) when soybean oil was added to the diet in the presence of the lysine and methionine. The results suggest a protection effect of oil/lysine and methionine complex from the rumen degradation in this experimental condition...

Cyclin D1 expression in prostate carcinoma

The purpose of this study was to investigate the relationship between cyclin D1 expression and clinicopathological parameters in patients with prostate carcinoma. We assessed cyclin D1 expression by conventional immunohistochemistry in 85 patients who underwent radical prostatectomy for prostate carcinoma and 10 normal prostate tissue samples retrieved from autopsies. We measured nuclear immunostaining in the entire tumor area and based the results on the percentage of positive tumor cells. The preoperative prostate-specific antigen (PSA) level was 8.68±5.16 ng/mL (mean±SD). Cyclin D1 staining was positive (cyclin D1 expression in REPLACE_GT5% of tumor cells) in 64 cases (75.4%) and negative (cyclin D1 expression in ≤5% of tumor cells) in 21 cases (including 15 cases with no immunostaining). Normal prostate tissues were negative for cyclin D1. Among patients with a high-grade Gleason score (≧7), 86% of patients demonstrated cyclin D1 immunostaining of REPLACE_GT5% (PREPLACE_LT0.05). In the crude analysis of cyclin D1 expression, the high-grade Gleason score group showed a mean expression of 39.6%, compared to 26.9% in the low-grade Gleason score group (PREPLACE_LT0.05). Perineural invasion tended to be associated with cyclin D1 expression (P=0.07), whereas cyclin D1 expression was not associated with PSA levels or other parameters. Our results suggest that high cyclin D1 expression could be a potential marker for tumor aggressiveness.

Cyclin D1 expression in prostate carcinoma.

The purpose of this study was to investigate the relationship between cyclin D1 expression and clinicopathological parameters in patients with prostate carcinoma. We assessed cyclin D1 expression by conventional immunohistochemistry in 85 patients who underwent radical prostatectomy for prostate carcinoma and 10 normal prostate tissue samples retrieved from autopsies. We measured nuclear immunostaining in the entire tumor area and based the results on the percentage of positive tumor cells. The preoperative prostate-specific antigen (PSA) level was 8.68±5.16 ng/mL (mean±SD). Cyclin D1 staining was positive (cyclin D1 expression in >5% of tumor cells) in 64 cases (75.4%) and negative (cyclin D1 expression in ≤5% of tumor cells) in 21 cases (including 15 cases with no immunostaining). Normal prostate tissues were negative for cyclin D1. Among patients with a high-grade Gleason score (≥7), 86% of patients demonstrated cyclin D1 immunostaining of >5% (P<0.05). In the crude analysis of cyclin D1 expression, the high-grade Gleason score group showed a mean expression of 39.6%, compared to 26.9% in the low-grade Gleason score group (P<0.05). Perineural invasion tended to be associated with cyclin D1 expression (P=0.07), whereas cyclin D1 expression was not associated with PSA levels or other parameters. Our results suggest that high cyclin D1 expression could be a potential marker for tumor aggressiveness.

Alimentação de vacas F1 Holandês x Zebu com suplementos nitrogenados e monensina sódica: avaliação do consumo, parâmetros ruminais e produção de leite / Feeding F1 Holstein x Zebu cows with nitrogenated supplements and sodic monensin: feed intake, ruminal parameters and milk production

Avaliaram-se suplementos nitrogenados contendo ou não monensina sódica, adicionados à silagem, sobre o consumo de matéria seca (CMS), a digestibilidade da MS (DMS) e a produção de vacas F1 Holandês x Zebu. Vacas (n=15) com 21 dias em lactação, produzindo 19,2kg/dia, foram distribuídas em um delineamento quadrado latino 5X5, com três vacas por tratamento (T). Os T foram: 1- concentrado durante as ordenhas e silagem de milho após as ordenhas (C.SM); 2- C.SM + nitromineral (C.SMNM); 3- C.SM + nitroproteico (C.SMNP), 4- C.SMNM + monensina (C.SMNM+MO) e 5- C.SMNP + monensina (C.SMNP+MO). Os suplementos NP e NM adicionados à SM, (C.SMNP e C.SMNM) aumentaram o CMS (P<0,05). A adição de monensina não alterou o CMS nem a DMS (P>0,05). A suplementação proteica não aumentou o acetato (P>0,05), mas aumentou o propionato e o butirato (P<0,05). A adição de MO ao T C.SMNP reduziu o propionato e o butirato (P<0,05) em relação ao T C.SMNP. A concentração de nitrogênio amoniacal aumentou (P<0,05) no T C.SMNM em relação ao T C.SM e não diferiu dos demais. As produções de leite nos T C.SMNP e C.SMNPMO foram maiores do que no T C.SM (P<0,05). Vacas do T C.SM foram mais eficientes produzindo leite do que as do T C.SMNM (P<0,05).

The objectives of this study were to evaluate consumption, ruminal parameters and milk production of F1 Holstein x Zebu milking cows fed nitrogenated supplements with or without monensin added to the silage. Cows with 21 days on milk and producing initially 19.2kg of milk/day were distributed in a 5X5 Latin square design with three replicates per treatment. The treatments (T) were: 1- concentrate fed during the milking time and corn silage fed after milking (C.SM); 2- C.SM + nitromineral(NM) (C.SMNM); 3- C.SM + nitroproteico (NP) (C.SMNP); 4- C.SMNM + monensin (C.SMNM+MO) e 5- C.SMNP + monensin (C.SMNP+MO). The addition of NP e NM to the T C.SM increased the DMI when compared to C.SM (P<0.05). The addition of monensin did not change the DMI (P>0,05). The protein supplementation did not alter acetate (P>0,05), but increased propionate and butyrate concentrations. (P<0.05) The N-NH3 concentration increased (P<0.05) only in T C.SMNM (P<0.05). The addition of monensin to T C.SMNP decreased propionate and butyrate concentrations (P<0.05) related to T C.SMNP. The milk production was greater in the C.SMNP treatments than T C.SM (P<0.05). Cows in T C.SM produced milk more efficiently than cows fed C.SMNM (P<0.05), but did not differ from the others.

Gene expression study related with the intrinsic pathway of apoptosis in bladder cancer by real-time PCR technique.

We examined the expression of anti-apoptotic genes (XIAP and Bcl-2) and apoptotic genes (cytochrome c, caspase-9, Apaf-1) in tissue samples of patients with superficial bladder cancer. Thirty-two bladder cancer tissue samples (8 papillary urothelial neoplasm of low malignant potential, 10 low-grade, and 14 high-grade) and 8 normal bladder tissue samples from necropsy were used for the study of gene expression by real-time PCR analysis. Analysis of the expression of apoptotic gene constituents of an apoptosome demonstrated an increase in Apaf-1 expression in the three tumor grades when compared with the control (P < 0.01, P < 0.05, and P < 0.01), low expression of caspase-9 in all groups (P < 0.05), and an increase in cytochrome c expression in all tumor grades in relation to the control, although without statistically significant difference. The expression of anti-apoptotic genes revealed an increase in XIAP expression in all tumor grades in relation to the control, although without statistically significant difference, and low expression of Bcl-2 in all tumor grades and the control (P < 0.05). The results proved that there is low evidence of apoptotic activity by the intrinsic pathway, demonstrated by the low expression of caspase-9 and considerable increase in XIAP expression, which may render these genes potential therapeutic targets in bladder cancer treatment.

Desempenho, composição do leite e metabólitos sanguíneos de vacas Holandês x Gir manejadas em pastagem de Brachiaria brizantha cv. Marandu e suplementadas com grão de soja tostado / Performance milk composition and blood metabolites of Holstein x Gir cows grazing Brachiaria brizantha cv. Marandu grass supplemented with roasted soybeans

Avaliaram-se o consumo, metabólitos sanguíneos e a produção e composição do leite de 16 vacas Holandês x Gir, manejadas em pastagem de Brachiaria brizantha cv. Marandu, suplementadas com 6kg/vaca/dia (base matéria natural) de concentrado contendo 0; 1,3; 2,6 e 3,9kg/vaca/dia de grão de soja tostado (GST). Foi utilizado o delineamento com quatro quadrados latinos (QL) 4 x 4, sendo cada fase do QL constituída de 10 dias de período de adaptação à dieta e de cinco para coleta de amostras. A suplementação da dieta com GST resultou em redução linear (P<0,05) nos consumos de matéria seca e de fibra insolúvel em detergente neutro do pasto e total. A concentração de glicose não foi afetada (P>0,05), porém a de ácidos graxos não esterificados aumentou com a inclusão do GST na dieta (P<0,05). Não houve efeito (P>0,05) da adição do GST sobre a produção e composição do leite, exceto para o teor (P=0,10) e produção (P=0,08) de gordura no leite.

Feed intake, blood metabolites, and milk yield and composition of Holstein x Gir cows grazing Brachiaria brizantha cv. Marandu receiving 6kg/cow/day (natural matter based) of concentrate containing 0, 1.3, 2.6, 3.9kg/cow/day of roasted soybean seeds (RSS) were evaluated. The experimental design was four 4 x 4 latin square (LS) in wich each phase consisted of 10 days for diet adaptation period and 5 days for samples collection. Diet supplementation with RSS decreased linearly (P<0.05) the intake of pasture, total diet dry matter and neutral detergent fiber. The plasma glucose concentration was unaffected (P>0.05), but nonesterified fatty acids increased with RSS supplementation (P<0.05). There was no effect (P>0.05) of RSS supplement on milk production and composition, except the linear reduction on the content (P=0.10) and yield (P=0.08) milk fat, which can present positive financial implication to farmers, knowing that most of the Brazilian dairy use payment programs by milk composition.