Evaluación de accesiones cubanas de papaya (Carica papaya L.) ante la mancha anular

Se colectaron en diferentes regiones de Cuba semillas de las accesiones de papayo Tallo Morado de Nava, Amarilla de Duaba, Amarilla de Nava y Sapote de Pilón. Estas se plantaron en condiciones de campo en Jagüey Grande, Matanzas - Cuba, donde se evaluó la presencia e intensidad de síntomas de mancha anular, siguiendo una escala graduada del 1 al 5. Los resultados mostraron un incremento temporal de la proporción de plantas afectadas en todas las accesiones. La accesión Amarilla de Duaba mostró los síntomas a los dos meses después de la primera evaluación (MDPE), mientras que el resto lo hizo a los cinco MDPE, aunque con proporciones que variaron entre ellas. A los siete MDPE las accesiones Amarilla de Duaba y Amarilla de Nava mostraron proporciones idénticas de plantas enfermas, mientras que Tallo morado de Nava y Sapote de Pilón mostraron proporciones inferiores. La intensidad de los síntomas se incrementó en los diferentes órganos siguiendo el siguiente orden: tallo (1,7 a 2,66), pecíolos (2,21 a 3,03) y follaje (3,44-4,03). En los frutos la intensidad de los síntomas observados fue inferior a 2,5, considerados como leves de acuerdo a su intensidad y distribución. Se ofrecen los primeros resultados sobre la susceptibilidad a la mancha anular de estas accesiones, siendo de gran utilidad para los productores, así como para los programas de mejoramiento genético en el país.

Atributos químicos e estoques de carbono e nitrogênio em argissolo vermelho-amarelo sob sistemas agroflorestais e agricultura de corte e queima no norte do Piauí

A prática da agricultura de corte e queima tem causado a degradação do solo no Estado do Piauí, e isso tem estimulado a adoção de alternativas sustentáveis de uso da terra, como os Sistemas Agroflorestais. Este trabalho objetivou avaliar as mudanças nas características químicas e nos estoques de carbono (COT) e nitrogênio (NT) de um Argissolo Vermelo-Amarelo sob sistemas agroflorestais com seis (SAF6) e 10 (SAF10) anos de adoção, sistema com base ecológica com três anos de adoção (SE3), agricultura de corte e queima (ACQ) e floresta nativa (FN), no Norte piauiense. Foram coletadas amostras de solo nos períodos seco e chuvoso na profundidade de 0-10 cm, para a avaliação dos atributos químicos do solo e dos estoques totais de carbono (COT) e nitrogênio (NT). O SAF10 apresentou menor teor de Al+3 (0,02 cmol c dm-3). O teor de P no SAF10 (12,27 mg dm-3), no período seco, foi seis a sete vezes maior do que ACQ e FN, respectivamente. Os maiores estoques de COT e NT foram observados no período seco, respectivamente no SAF10 (48,54 Mg ha-1 e 4,43 Mg ha-1) e SAF6 (43,30 Mg ha-1 e 3,45 Mg ha-1). Os sistemas agroflorestais melhoraram a qualidade do solo e podem ser considerados como estratégia conservacionista para o Norte do Piauí.

Fatores de risco associados à infecção pelo herpesvírus bovino 1 em rebanhos bovinos da região Oeste do Estado do Paraná

O objetivo deste estudo foi determinar a prevalência de rebanhos positivos (focos) e identificar os fatores de risco que possam estar associados com a infecção pelo herpesvírus bovino 1 (BoHV-1) em rebanhos bovinos com atividade reprodutiva, na região Oeste do Estado do Paraná. O delineamento estatístico, amostras de soro e informações referentes às propriedades foram as empregadas para o estudo da brucelose bovina no Estado do Paraná dentro do contexto do Programa Nacional de Controle e Erradicação da Brucelose e Tuberculose. Foram avaliadas 1930 fêmeas com idade igual ou superior a 24 meses, provenientes de 295 rebanhos não vacinados contra o BoHV-1. Para o diagnóstico sorológico da infecção pelo BoHV-1, foi utilizado um ensaio imunoenzimático (ELISA) indireto. Em cada propriedade foi aplicado um questionário epidemiológico, afim de obter informações epidemiológicas e práticas de manejo empregadas. Dos 295 rebanhos analisados, 190 foram considerados positivos para o BoHV-1, com a prevalência de rebanhos de 64,41% (I.C.95% = 58,65-69,87%). As variáveis consideradas fatores de risco para a infecção pelo BoHV-1 na análise de regressão logística multivariada foram: i) número (>23) fêmeas com idade >24 meses (OR=2,22; IC: 1,09-4,51); ii) compra de reprodutores (OR=2,68; IC: 1,48-4,82); iii) uso de pastagens comuns (OR=5,93; IC: 1,31-26,82); iv) histórico de abortamento nos últimos 12 meses (OR=2,37; IC: 1,09-5,16); v) presença de animais silvestres (OR=8,86; IC: 1,11-70,73). Estes resultados indicam que a infecção pelo BoHV-1 está amplamente distribuída na região estudada e que fatores relacionados às características das propriedades e ao manejo estão associados à infecção.

Efeitos do Foscarnet sobre a infecção pelos herpesvírus bovino tipos 1 e 5 em coelhos

O efeito antiviral do Foscarnet (PFA) foi demonstrado anteriormente em células de cultivo infectadas com três herpesvírus bovino (BoHV). No presente estudo, investigaram-se os seus efeitos sobre a infecção e doença causadas pelo BoHV-1 e BoHV-5 em coelhos infectados experimentalmente. Coelhos inoculados com o BoHV-5 pela via intraconjuntival (IC) e tratados com o PFA (100mg/kg/dia) a partir do dia 1 pós-inoculação (pi) apresentaram uma redução nos títulos de vírus excretados entre os dias 2 e 6 pi em comparação com o grupo não-tratado; essa diferença foi significativa no dia 3 pi [F(9,108) = 2,23; P<0,03)]. Os coelhos inoculados com o BoHV-5 e tratados com o PFA apresentaram uma redução significativa nos índices de morbidade e mortalidade (95,4% [21/22] nos controles; 50% [11/22] nos tratados; [P<0,0008]). Em coelhos inoculados com o BoHV-1 pela via IC, o tratamento com o PFA resultou em redução nos títulos de vírus excretados, entre os dias 1 e 4, e 6 e 7 pi. Esses animais apresentaram um período de incubação mais curto e um curso clínico mais longo comparando-se com o grupo controle não tratado (P<0,005 e P<0,04, respectivamente). O PFA também reduziu a freqüência e severidade da doença ocular nos coelhos inoculados com o BoHV-1. Esses resultados demonstram que o PFA possui atividade frente ao BoHV-1 e BoHV-5 in vivo e são promissores para o uso desse fármaco em terapias experimentais das infecções herpéticas dos animais domésticos.

Degradação luminosa e retenção foliar dos corantes azul brilhante FDC-1 e amarelo tartrasina FDC-5 utilizados como traçadores em pulverizações

Três estudos foram conduzidos no Núcleo de Pesquisas Avançadas em Matologia (NUPAM) pertencente à UNESP/FCA - campus de Botucatu-SP, com o objetivo de avaliar a estabilidade dos corantes Azul Brilhante FDC-1 e Amarelo Tartrasina FDC-5 quanto a diferentes períodos de exposição à luz solar e contato com folhas de Eichhornia crassipes. No primeiro estudo, soluções de 0,3125, 0,625, 1,25, 2,5, 5, 10 e 20 ppm dos corantes Azul Brilhante FDC-1 e Amarelo Tartrasina FDC-5 foram acondicionadas em tubos de quartzo hermeticamente fechados e submetidos a 0, 0,5, 1, 2, 4, 6 e 10 horas de exposição à luz solar e ao escuro. Ao final de cada período, amostras de 10 mL foram retiradas dos tubos e analisadas. No segundo estudo, os tratamentos foram dispostos no esquema fatorial 2x7: duas condições luminosas (escuro e pleno sol) e sete períodos de exposição (0, 0,5, 1, 2, 4, 6 e 10 horas), com seis repetições. Com o auxílio de micropipeta, oito gotas de 5 µL das soluções Azul Brilhante e Amarelo Tartrasina a 4.000 ppm foram depositadas em placas de Petri de vidro. Após o término dos períodos de exposição, as placas foram lavadas com 50 mL de água destilada, com o objetivo de extrair o corante depositado sobre elas. No terceiro estudo, adotaram-se os mesmos tratamentos do segundo experimento, com quatro repetições, porém as soluções foram depositadas sobre as folhas de plantas de Eichhornia crassipes. Foram adotados também os mesmos procedimentos de extração dos corantes após o término dos períodos de exposição. As soluções finais obtidas nos três estudos foram submetidas à leitura óptica de absorbância em espectrofotômetro UV-visível nos comprimentos de onda de 630 e 427 nm, para os corantes Azul Brilhante FDC-1 e Amarelo Tartrasina FDC-5, respectivamente. As várias concentrações das soluções de ambos os corantes não sofreram degradação pela luz solar quando submetidas aos vários períodos de incidência luminosa nos tubos de quartzo (ambiente fechado), visto que as curvas de recuperação apresentaram equações semelhantes àquelas concentrações que foram mantidas no escuro. A mesma estabilidade também foi observada quando os corantes foram submetidos à luz solar em ambiente aberto, ou seja, nas placas de Petri. O corante Amarelo Tartrasina também se apresentou muito estável quando depositado sobre as folhas de E. crassipes, independentemente da exposição ou não à luz solar. Para o corante Azul Brilhante, ocorreram significativas perdas de 7,8 e 18,6% quando esteve depositado na superfície da folha de aguapé pelo período de 10 horas sob condições de escuro e plena luz solar, respectivamente.

Effect of selective angiotensin antagonists on the antidiuresis produced by angiotensin-(1-7) in water-loaded rats

In the present study we evaluated the nature of angiotensin receptors involved in the antidiuretic effect of angiotensin-(1-7) (Ang-(1-7)) in water-loaded rats. Water diuresis was induced in male Wistar rats weighing 280 to 320 g by water load (5 ml/100 g body weight by gavage). Immediately after water load the rats were treated subcutaneously with (doses are per 100 g body weight): 1) vehicle (0.05 ml 0.9% NaCl); 2) graded doses of 20, 40 or 80 pmol Ang-(1-7); 3) 200 nmol Losartan; 4) 200 nmol Losartan combined with 40 pmol Ang-(1-7); 5) 1.1 or 4.4 nmol A-779; 6) 1.1 nmol A-779 combined with graded doses of 20, 40 or 80 pmol Ang-(1-7); 7) 4.4 nmol A-779 combined with graded doses of 20, 40 or 80 pmol Ang-(1-7); 8) 95 nmol CGP 42112A, or 9) 95 nmol CGP 42112A combined with 40 pmol Ang-(1-7). The antidiuretic effect of Ang-(1-7) was associated with an increase in urinary Na+ concentration, an increase in urinary osmolality and a reduction in creatinine clearance (CCr: 0.65 ± 0.04 ml/min vs 1.45 ± 0.18 ml/min in vehicle-treated rats, P<0.05). A-779 and Losartan completely blocked the effect of Ang-(1-7) on water diuresis (2.93 ± 0.34 ml/60 min and 3.39 ± 0.58 ml/60 min, respectively). CGP 42112A, at the dose used, did not modify the antidiuretic effect of Ang-(1-7). The blockade produced by Losartan was associated with an increase in CCr and with an increase in sodium and water excretion as compared with Ang-(1-7)-treated rats. When Ang-(1-7) was combined with A-779 there was an increase in CCr and natriuresis and a reduction in urine osmolality compared with rats treated with Ang-(1-7) alone. The observation that both A-779, which does not bind to AT1 receptors, and Losartan blocked the effect of Ang-(1-7) suggests that the kidney effects of Ang-(1-7) are mediated by a non-AT1 angiotensin receptor that is recognized by Losartan.

Limited-sampling strategy models for estimating the pharmacokinetic parameters of 4-methylaminoantipyrine, an active metabolite of dipyrone

Bioanalytical data from a bioequivalence study were used to develop limited-sampling strategy (LSS) models for estimating the area under the plasma concentration versus time curve (AUC) and the peak plasma concentration (Cmax) of 4-methylaminoantipyrine (MAA), an active metabolite of dipyrone. Twelve healthy adult male volunteers received single 600 mg oral doses of dipyrone in two formulations at a 7-day interval in a randomized, crossover protocol. Plasma concentrations of MAA (N = 336), measured by HPLC, were used to develop LSS models. Linear regression analysis and a "jack-knife" validation procedure revealed that the AUC0-¥ and the Cmax of MAA can be accurately predicted (R²>0.95, bias <1.5%, precision between 3.1 and 8.3%) by LSS models based on two sampling times. Validation tests indicate that the most informative 2-point LSS models developed for one formulation provide good estimates (R²>0.85) of the AUC0-¥ or Cmax for the other formulation. LSS models based on three sampling points (1.5, 4 and 24 h), but using different coefficients for AUC0-¥ and Cmax, predicted the individual values of both parameters for the enrolled volunteers (R²>0.88, bias = -0.65 and -0.37%, precision = 4.3 and 7.4%) as well as for plasma concentration data sets generated by simulation (R²>0.88, bias = -1.9 and 8.5%, precision = 5.2 and 8.7%). Bioequivalence assessment of the dipyrone formulations based on the 90% confidence interval of log-transformed AUC0-¥ and Cmax provided similar results when either the best-estimated or the LSS-derived metrics were used.

Simultaneous changes in the function and expression of beta 1 integrins during the growth arrest of poorly differentiated colorectal cells (LISP-1)

Cells usually lose adhesion and increase proliferation and migration during malignant transformation. Here, we studied how proliferation can affect the other two characteristics, which ultimately lead to invasion and metastasis. We determined the expression of ß1 integrins, as well as adhesion and migration towards laminin-1, fibronectin, collagens type I and type IV presented by LISP-1 colorectal cancer cells exposed to 2.5% dimethyl sulfoxide (DMSO), an agent capable of decreasing proliferation in this poorly differentiated colorectal cell line. Untreated cells (control), as shown by flow cytometry and monoclonal antibodies, expressed alpha2 (63.8 ± 11.3% positive cells), alpha3 (93.3 ± 7.0%), alpha5 (50.4 ± 12.0%) and alpha6 (34.1 ± 4.9%) integrins but not alpha1, alpha4, alphav or ß4. Cells adhered well to laminin-1 (73.4 ± 6.0%) and fibronectin (40.0 ± 2.0%) substrates but very little to collagens. By using blocking monoclonal antibodies, we showed that alpha2, alpha3 and alpha6 mediated laminin-1 adhesion, but neither alpha3 nor alpha5 contributed to fibronectin adherence. DMSO arrested cells at G0/G1 (control: 55.0 ± 2.4% vs DMSO: 70.7 ± 2.5%) while simultaneously reducing alpha5 (24.2 ± 19%) and alpha6 (14.3 ± 10.8%) expression as well as c-myc mRNA (7-fold), the latter shown by Northern blotting. Although the adhesion rate did not change after exposure to DMSO, alpha3 and alpha5 played a major role in laminin-1 and fibronectin adhesion, respectively. Migration towards laminin-1, which was clearly increased upon exposure to DMSO (control: 6 ± 2 cells vs DMSO: 64 ± 6 cells), was blocked by an antibody against alpha6. We conclude that the effects of DMSO on LISP-1 proliferation were accompanied by concurrent changes in the expression and function of integrins, consequently modulating adhesion/migration, and revealing a complex interplay between function/expression and the proliferative state of cells.

Endothelin-1 receptors play a minor role in the protection against acute Trypanosoma cruzi infection in mice

Chagas' disease, caused by the protozoan Trypanosoma cruzi, is a major cause of cardiovascular disability in countries where it is endemic. Damage to the heart microvasculature has been proposed to be an important factor in the pathogenesis of heart dysfunction. Endothelin-1 (ET-1) is a potent vasoconstrictor and exerts its effects via specific ET A and ET B receptors. A few studies have suggested a role for ET-1 and its receptors in the pathogenesis of Chagas' disease. We investigated the effects of treatment with bosentan, an ET A/ET B receptor antagonist, on the course of T. cruzi infection (Y strain) in C57Bl/6 mice. Treatment with bosentan (100 mg kg-1 day-1) was given per os starting day 0 after infection until sacrifice. Bosentan significantly increased myocardial inflammation, with no effects on parasitemia. Although the total number of nests was similar, a lower number of intact amastigote nests was found in the heart of bosentan-treated animals. Bosentan failed to affect the infection-associated increase in the cardiac levels of the cytokines IFN-g and TNF-a and the chemokines CCL2/MCP-1, CCL3/MIP-1a and CCL5/RANTES. In vitro, pre-incubation with ET-1 (0.1 µM) 4 h before infection enhanced the uptake of the parasites by peritoneal macrophages, and this effect was abrogated when macrophages were pre-treated with bosentan (1 µM) 15 min before incubation with ET-1. However, ET-1 did not alter killing of intracellular parasites after 48 h of in vitro infection. Our data suggest that bosentan-treated mice have a delay in controlling parasitism which is compensated for exacerbated inflammation. Infection is eventually controlled in these animals and lethality is unchanged, demonstrating that ET-1 plays a minor role in the protection against acute murine T. cruzi infection.

Sleep deprivation reduces the lymphocyte count in a non-obese mouse model of type 1 diabetes mellitus

The objective of the present study was to determine whether sleep deprivation (SD) would promote changes in lymphocyte numbers in a type 1 diabetes model (non-obese diabetic, NOD, mouse strain) and to determine whether SD would affect female and male NOD compared to Swiss mice. The number of lymphocytes in peripheral blood after 24 and 96 h of SD (by multiple platform method) or equivalent period of time in home-cage controls was examined prior to the onset of diabetes. SD for 96 h significantly reduced lymphocytes in male Swiss mice compared to control (8.6 ± 2.1 vs 4.1 ± 0.7 10³/µL; P < 0.02). In male NOD animals, 24- and 96-h SD caused a significant decrease of lymphocytes compared to control (4.4 ± 0.3 vs 1.6 ± 0.5; P < 0.001 and 4.4 ± 0.3 vs 0.9 ± 0.1 10³/µL; P < 0.00001, respectively). Both 24- and 96-h SD induced a reduction in the number of lymphocytes in female Swiss (7.5 ± 0.5 vs 4.5 ± 0.5, 4.4 ± 0.6 10³/µL; P < 0.001, respectively) and NOD mice (4 ± 0.6 vs 1.8 ± 0.2, 1.2 ± 0.4 10³/µL; P < 0.01, respectively) compared to the respective controls. Loss of sleep induced lymphopenia in peripheral blood in both genders and strains used. Since many cases of autoimmunity present reduced numbers of lymphocytes and, in this study, it was more evident in the NOD strain, our results suggest that SD should be considered a risk factor in the onset of autoimmune disorders.

Historia Bibliothecae Regiae Academiae Aboensis 1

Invokaatio: D.A.G.

Coronary artery calcification is associated with insulin resistance index in patients with type 1 diabetes

The objective of the present study was to evaluate the risk factors associated with the presence of coronary artery calcification (CAC) in patients with type 1 diabetes (T1D). A cross-sectional study was conducted on 100 consecutive T1D patients without coronary artery disease, with at least 5 years of diabetes and absence of end-stage renal disease. Mean age was 38 ± 10 years and 57% were males. CAC score was measured by multidetector computed tomography (Siemens Sensation 64 Cardiac). The insulin resistance index was measured using the estimated glucose disposal rate (eGDR). The eGDR was lower among CAC-positive patients than among CAC-negative patients, suggesting an increased insulin resistance. In a logistic regression model adjusted for age (at 10-year intervals), eGDR, diabetic nephropathy and gender, CAC was associated with age 1;OR = 2.73 (95%CI = 1.53-4.86), P = 0.001] and with eGDR 1;OR = 0.08 (95%CI = 0.02-0.21), P = 0.004]. In T1D subjects, insulin resistance is one of the most important risk factors for subclinical atherosclerosis.

MMP-1/PAR-1 signal transduction axis and its prognostic impact in esophageal squamous cell carcinoma

The matrix metalloprotease-1 (MMP-1)/protease-activated receptor-1 (PAR-1) signal transduction axis plays an important role in tumorigenesis. To explore the expression and prognostic value of MMP-1 and PAR-1 in esophageal squamous cell carcinoma (ESCC), we evaluated the expression of two proteins in resected specimens from 85 patients with ESCC by immunohistochemistry. Sixty-two (72.9%) and 58 (68.2%) tumors were MMP-1- and PAR-1-positive, respectively, while no significant staining was observed in normal esophageal squamous epithelium. MMP-1 and PAR-1 overexpression was significantly associated with tumor node metastasis (TNM) stage and regional lymph node involvement. Patients with MMP-1- and PAR-1-positive tumors, respectively, had poorer disease-free survival (DFS) than those with negative ESCC (P = 0.002 and 0.003, respectively). Univariate analysis showed a significant relationship between TNM stage [hazard ratio (HR) = 2.836, 95% confidence interval (CI) = 1.866-4.308], regional lymph node involvement (HR = 2.955, 95%CI = 1.713-5.068), MMP-1 expression (HR = 2.669, 95%CI = 1.229-6.127), and PAR-1 expression (HR = 1.762, 95%CI = 1.156-2.883) and DFS. Multivariate analysis including the above four parameters identified TNM stage (HR = 2.035, 95%CI = 1.167-3.681), MMP-1 expression (HR = 2.109, 95%CI = 1.293-3.279), and PAR-1 expression (HR = 1.967, 95%CI = 1.256-2.881) as independent and significant prognostic factors for DFS. Our data suggest for the first time that MMP-1 and PAR-1 were both overexpressed in ESCC and are novel predictors of poor patient prognosis after curative resection. The MMP-1/PAR-1 signal transduction axis might be a new therapeutic target for future therapies tailored against ESCC.

Specimen explicationis dicti Hebr. XI:1

Invokaatio: D.D.

Peroxiredoxin isoforms are associated with cardiovascular risk factors in type 2 diabetes mellitus

The production of oxygen free radicals in type 2 diabetes mellitus contributes to the development of complications, especially the cardiovascular-related ones. Peroxiredoxins (PRDXs) are antioxidant enzymes that combat oxidative stress. The aim of this study was to investigate the associations between the levels of PRDX isoforms (1, 2, 4, and 6) and cardiovascular risk factors in type 2 diabetes mellitus. Fifty-three patients with type 2 diabetes mellitus (28F/25M) and 25 healthy control subjects (7F/18M) were enrolled. We measured the plasma levels of each PRDX isoform and analyzed their correlations with cardiovascular risk factors. The plasma PRDX1, -2, -4, and -6 levels were higher in the diabetic patients than in the healthy control subjects. PRDX2 and -6 levels were negatively correlated with diastolic blood pressure, fasting blood sugar, and hemoglobin A1c. In contrast, PRDX1 levels were positively correlated with low-density lipoprotein and C-reactive protein levels. PRDX4 levels were negatively correlated with triglycerides. In conclusion, PRDX1, -2, -4, and -6 showed differential correlations with a variety of traditional cardiovascular risk factors. These results should encourage further research into the crosstalk between PRDX isoforms and cardiovascular risk factors.