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1.
Arthritis Rheum ; 63(5): 1452-8, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21538322

RESUMO

OBJECTIVE: The current treatment options for systemic-onset juvenile idiopathic arthritis (JIA) are methotrexate, steroids, and biologic agents. This study was undertaken to evaluate the safety of the orally active histone deacetylase inhibitor givinostat (ITF2357) and its ability to affect the disease. METHODS: Givinostat was administered orally, for up to 12 weeks at a dosage of 1.5 mg/kg/day, to 17 patients with systemic-onset JIA who had had active disease for ≥1 month. Disease activity was clinically assessed using the American College of Rheumatology Pediatric 30 (ACR Pedi 30), ACR Pedi 50, or ACR Pedi 70 criteria for improvement and a systemic feature score. The primary goal was safety and the primary efficacy end point was the number of patients completing 12 weeks of treatment who were responders. RESULTS: Givinostat was safe and well tolerated, with adverse events (AEs) being mild or moderate, of short duration, and self-limited. The 17 patients from the intent-to-treat population reported a total of 44 AEs, and the 9 patients in the per-protocol population reported a total of 25. Six AEs in 3 patients (nausea, vomiting, and fatigue) were related to the study drug, but each resolved spontaneously and no patient was withdrawn from the study due to drug-related AEs. In the per-protocol population at week 4, the improvement as measured by the ACR Pedi 30, ACR Pedi 50, and ACR Pedi 70, respectively, was 77.8%, 55.6%, and 22.2%, and this increased further to 77.8%, 77.8%, and 66.7% at week 12. The most consistent finding was the reduction in the number of joints with active disease or with limited range of motion. CONCLUSION: After 12 weeks, givinostat exhibited significant therapeutic benefit in patients with systemic-onset JIA, particularly with regard to the arthritic component of the disease, and showed an excellent safety profile.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Juvenil/tratamento farmacológico , Inibidores de Histona Desacetilases/uso terapêutico , Ácidos Hidroxâmicos/uso terapêutico , Adolescente , Antirreumáticos/administração & dosagem , Criança , Feminino , Inibidores de Histona Desacetilases/efeitos adversos , Humanos , Ácidos Hidroxâmicos/efeitos adversos , Análise de Intenção de Tratamento , Masculino , Resultado do Tratamento
2.
Diagnostics (Basel) ; 12(6)2022 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-35741256

RESUMO

Clinical evidence has emphasized the importance of coronary plaques' characteristics, rather than lumen stenosis, for the outcome of cardiovascular events. Coronary computed tomographic angiography (CCTA) has a well-established role as a non-invasive tool for assessing plaques. The aim of this study was to compare clinical characteristics and CCTA-derived information of stable patients with non-severe plaques in predicting major adverse cardiac events (MACEs) during follow-up. We retrospectively selected 371 patients (64% male) who underwent CCTA in our center from March 2016 to January 2021 with Coronary Artery Disease­Reporting and Data System (CAD-RADS) 0 to 3. Of those, 198 patients (53% male) had CAD-RADS 0 to 1. Among them, 183 (49%) had normal pericoronary fat attenuation index (pFAI), while 15 (60% male) had pFAI ≥ 70.1 Hounsfield unit (HU). The remaining 173 patients (76% male) had CAD-RADS 2 to 3 and were divided into patients with at least one low attenuation plaque (LAP) and patients without LAPs (n-LAP). Compared to n-LAP, patients with LAPs had higher pFAI (p = 0.005) and had more plaques than patients with n-LAP. Presence of LAPs was significantly higher in elderly (p < 0.001), males (p < 0.001) and patients with traditional risk factors (hypertension p = 0.0001, hyperlipemia p = 0.0003, smoking p = 0.0003, diabetes p = <0.0001, familiarity p = 0.0007). Among patients with CAD-RADS 0 to 1, the ones with pFAI ≥ 70.1 HU were more often hyperlipidemic (p = 0.05) and smokers (p = 0.007). Follow-up (25,4 months, range: 17.6−39.2 months) demonstrated that LAP and pFAI ≥ 70.1 significantly and independently (p = 0.04) predisposed to outcomes (overall mortality and interventional procedures). There is an added value of CCTA-derived features in stratifying cardiovascular risk in low- to intermediate-risk patients with non-severe, non-calcified coronary plaques. This is of utmost clinical relevance as it is possible to identify a subset of patients with increased risk who need strengthening in therapeutic management and closer follow-up even in the absence of severe CAD. Further studies are needed to evaluate the effect of medical treatments on pericoronary inflammation and plaque composition.

3.
Mol Med ; 17(5-6): 353-62, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21365126

RESUMO

ITF2357 (givinostat) is a histone deacetylase inhibitor with antiinflammatory properties at low nanomolar concentrations. We report here a phase I safety and pharmacokinetics trial in healthy males administered 50, 100, 200, 400 or 600 mg orally. After 50 mg, mean maximal plasma concentrations reached 104 nmol/L 2 h after dosing, with a half-life of 6.9 h. After 100 mg, maximal concentration reached 199 nmol/L at 2.1 h with a half-life of 6.0 h. Repeat doses for 7 consecutive days of 50, 100 or 200 mg resulted in nearly the same kinetics. There were no serious adverse effects (AEs) and no organ toxicities. However, there was a dose-dependent but transient fall in platelets. After 7 daily doses of 50 or 100 mg, the mean decrease in platelets of 17 and 25% was not statistically significant and returned to baseline within 14 d. Blood removed from the subjects after oral dosing was cultured ex vivo with endotoxin, and the release of tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6, IL-1Ra, interferon (IFN)-γ and IL-10 was determined. Maximal reduction in IL-1ß, TNFα, IL-6 and IFNγ was observed 4 h after dosing but returned to baseline at 12 h. There was no significant reduction in IL-1Ra or IL-10. With daily dosing, the fall in cytokine production in blood cultures observed on day 7 was nearly the same as that of the first day. We conclude that dosing of 50 or 100 mg ITF2357 is safe in healthy humans and transiently but repeatedly reduces the production of proinflammatory cytokines without affecting production of antiinflammatory cytokines.


Assuntos
Anti-Inflamatórios/efeitos adversos , Anti-Inflamatórios/farmacocinética , Citocinas/sangue , Ácidos Hidroxâmicos/efeitos adversos , Ácidos Hidroxâmicos/farmacocinética , Adulto , Anti-Inflamatórios/administração & dosagem , Feminino , Humanos , Ácidos Hidroxâmicos/administração & dosagem , Interferon gama/sangue , Proteína Antagonista do Receptor de Interleucina 1/sangue , Interleucina-10/sangue , Interleucina-1beta/sangue , Interleucina-6/sangue , Masculino , Fator de Necrose Tumoral alfa/sangue , Adulto Jovem
4.
Poult Sci ; 100(1): 147-158, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33357677

RESUMO

An experiment was conducted to estimate the nutritional requirements of calcium (Ca) and available phosphorus (aP) for Japanese quails (Coturnix coturnix japonica) in the egg-laying stage (64-168 D). The experiment was an entirely randomized design, in a factorial scheme (Ca = 1.70, 2.40, 3.10, and 3.80% and aP = 0.15, 0.30, 0.45, and 0.60%), with 3 replicates and 10 quails per experimental unit. No interactions were found for quail body weight and daily feed intake (DFI) (P > 0.05). However, body weight decreased linearly (P < 0.05) as the levels of Ca increased, whereas DFI exhibited a quadratic effect (P < 0.05) for both Ca and aP. The lowest values of DFI were estimated in 2.79 and 0.36% for Ca and aP, respectively. Egg production, egg mass, and feed conversion ratio per egg dozen presented significant interaction in which all of them had a quadratic effect (P < 0.05), with estimations for maximum yield in feed containing 2.74, 2.71, 2.75, and 2.74% Ca and 0.40, 0.39, 0.39, and 0.40% aP. The concentration of Ca in the eggshell increased linearly as per the levels of Ca studied, having a quadratic effect for aP levels, with a maximum point of 0.44%. In relation to the bone parameters, there was a linear interaction for Ca and aP in bone density and bone resistance (BR) of the femur, with a quadratic effect in BD estimating 2.84 and 0.50% for Ca and aP, respectively. In BR, the estimation was 3.27% Ca, with linear increase for aP. The BR of the tibiotarso increased linearly as per the Ca levels, obtaining the same Ca concentration response in this bone. As conclusion, when considering the estimations obtained through overlapped contour plots, the best responses to the effects of Ca and aP on productive characteristics were estimated at 2.68% Ca and 0.38% aP to produce feed for egg-laying Japanese quails.


Assuntos
Cálcio , Coturnix , Necessidades Nutricionais , Fósforo , Ração Animal/análise , Fenômenos Fisiológicos da Nutrição Animal , Animais , Cálcio/metabolismo , Coturnix/fisiologia , Dieta/normas , Dieta/veterinária , Necessidades Nutricionais/fisiologia , Oviposição/fisiologia , Fósforo/metabolismo , Distribuição Aleatória
5.
Anim Sci J ; 90(7): 870-879, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31099149

RESUMO

Three experiments were carried out to determine the crude protein requirements for maintenance (CPm) and weight gain (CPg) of meat quail and to develop protein-requirement prediction models. Experiment 1 was conducted to determine CPm by the nitrogen-balance technique. The regression of nitrogen balance on nitrogen intake revealed a CPm requirement of 2.94 g/kg0.75 /day. Experiment 2 was aimed at determining CPm by the comparative-slaughter technique. Retained nitrogen (RN) and nitrogen intake (NI) were quantified considering the metabolic weight of the birds. The linear regression of RN on NI provided a CPm estimate of 6.63 g/kg0.75 /day. Experiment 3 was conducted to determine CPg. The regression of body nitrogen from the carcasses on fasted body weight revealed CPg estimates of 407.68 (0-7 days), 501.76 (8-14 days), 470.40 (0-14 days), 517.44 (15-21 days), 627.20 (22-28 days), 423.36 (29-35 days), and 517.44 mg/g (15-35 days). The protein-requirement prediction models developed for meat quail aged 0-7, 8-14, 0-14, 15-21, 22-28, 29-35, and 15-35 days were CP = 2.94.W0.75  + 0.408.G; CP = 2.94.W0.75  + 0.502.G; CP = 2.94.W0.75  + 0.470.G; CP = 2.94.W0.75  + 0,517.G; CP = 2.94.W0.75  + 0.627.G; CP = 2.94.W0.75  + 0.423.G; CP = 2.94.W0.75  + 0.517.G, respectively, where: W0.75  =  metabolic weight (kg), and G =  daily weight gain (g).


Assuntos
Fenômenos Fisiológicos da Nutrição Animal/fisiologia , Dieta/veterinária , Proteínas Alimentares/administração & dosagem , Modelos Estatísticos , Necessidades Nutricionais , Codorniz/fisiologia , Fatores Etários , Ração Animal , Animais , Manutenção do Peso Corporal , Proteínas Alimentares/metabolismo , Nitrogênio/metabolismo , Fatores de Tempo , Aumento de Peso
6.
J Ultrasound ; 21(4): 309-314, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30324460

RESUMO

PURPOSE: To investigate the frequency of thickening of pulleys for flexor tendons in patients with early arthritis in their hands, and to evaluate it as a predictive sign of PsA. METHODS: A prospective observational study involving 228 consecutive patients presenting with recent onset of arthritis in their hands was conducted at rheumatology outpatient clinics in the Veneto region of Italy between October 2014 and September 2017. Diabetic patients were excluded because of the high frequency of trigger finger. The final diagnosis of the rheumatologist delivered after 12 months of follow-up, was considered as the gold standard for the analysis of diagnostic accuracy. RESULTS: Twenty-two patients were excluded from the study because of diabetes. A total of 86 patients with thickening of A1 pulleys in flexor tendons and 120 without were evaluated. Pulley thickness was significantly associated with a family history of psoriasis (18/86 vs 3/120, p Ë‚ 0.001) and diabetes (9/86 vs 4/120, p = 0.036), and with a personal history of cutaneous psoriasis (25/86 vs 10/120, p Ë‚ 0.001), psoriatic onychopathy (7/86 vs 2/120, p = 0.028), lower back pain (22/86 vs 11/120, p = 0.001), Dupuytren's disease (7/86 vs 2/120 p = 0.028) and De Quervain tenosynovitis (4/86 vs 0/120, p = 0.028). In isolation, this sign had a good sensitivity rate (80%). The specificity rate for the disease was barely significative (71%), with an LR+ of 2.71 for PsA. CONCLUSIONS: The thickening of the pulleys in the flexor tendons is an easy-to-detect sign with good sensitivity for the diagnosis of PsA. Its specificity and positive predictive value are not very high; however, if it is included in a complete classification process, sonographers should report it during hand evaluations of patients with arthritis.


Assuntos
Artrite Psoriásica/diagnóstico por imagem , Mãos/diagnóstico por imagem , Tendões/diagnóstico por imagem , Ultrassonografia , Diagnóstico Diferencial , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Sensibilidade e Especificidade
8.
Joint Bone Spine ; 78(2): 171-4, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-20620090

RESUMO

OBJECTIVES: To study and compare the clinical and serological features of patients with elderly versus adult and younger onset of primary Sjögren's syndrome (pSS). METHODS: We analyzed retrospectively 336 consecutive pSS patients followed at our unit. They were subdivided into three groups according to the age at disease onset: elderly (>65 years), adult (>40 and ≤65 years), and young (≤40 years). Clinical and immunological features of the disease, labial salivary glands biopsy, ocular and oral tests were collected at time of diagnosis and then compared among the three groups. RESULTS: In 21 (6%) patients, disease onset occurred after the age of 65 years. At the time of diagnosis, 15 (71.4%) of these patients reported symptoms of dry mouth and 16 (76.1%) of dry eye. The most common extraglandular manifestation were arthralgias in 14 (66.7%), Raynaud's phenomenon in five (23.8%) and purpura in three (14.2%) cases. Ocular diagnostic tests (Schirmer's I and Rose-Bengal staining) were positive respectively in 17 (80%) and nine (44.4%) patients. In eight (38%) cases, unstimulated whole salivary flow showed normal values, while 12 patients (57.1%) showed positivity for salivary sialography. A focus score greater or equal to 1 per 4mm(2) was demonstrated in 11 (53.3%) of the 21 cases. CONCLUSION: Elderly onset of pSS was associated with similar incidence of the diagnostic tests positivity (parotid sialography, ocular tests, minor salivary gland biopsy) in comparison with adult and younger onset. Moreover, no statistical differences were found among the three groups concerning sex, disease duration, as well as ocular and oral symptoms.


Assuntos
Testes Diagnósticos de Rotina , Síndrome de Sjogren/diagnóstico , Síndrome de Sjogren/epidemiologia , Adolescente , Adulto , Fatores Etários , Idade de Início , Idoso , Idoso de 80 Anos ou mais , Autoanticorpos/sangue , Biópsia , Estudos de Coortes , Olho/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Boca/patologia , Estudos Retrospectivos , Glândulas Salivares/patologia , Adulto Jovem
10.
J Acquir Immune Defic Syndr ; 54(1): 1-9, 2010 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-20300007

RESUMO

OBJECTIVES: Chromatin-associated repression is one mechanism that maintains HIV-1 latency. Inhibition of histone deacetylases (HDAC) reverses this repression resulting in viral expression from quiescently infected cells. Clinical studies with the HDAC inhibitor valproic acid (VPA) failed to substantially decrease the latent pool within resting CD4(+) cells. Here we compared the efficacy of ITF2357, an orally active and safe HDAC inhibitor, with VPA for HIV-1 expression from latently infected cells in vitro. We also evaluated the effect of ITF2357 on the surface expression of CXCR4 and CCR5. METHODS: Latently infected cell lines were incubated with either ITF2357 or VPA and p24 levels were measured. Peripheral blood mononuclear cells of uninfected donors were treated with ITF2357 and HIV-1 coreceptors expression was assessed by flow cytometry. RESULTS: At clinically relevant concentrations, ITF2357 increased p24 by 15-fold in ACH2 cells and by 9-fold in U1 cells, whereas VPA increased expression less than 2-fold. Analogues of ITF2357 primarily targeting HDAC-1 increased p24 up to 30-fold. In CD4(+) T cells treated with ITF2357, CXCR4 expression decreased by 54% (P < 0.001). CONCLUSION: ITF2357 is superior to VPA in inducing HIV-1 from latently infected cells. Safely used in humans, ITF2357 is an attractive candidate for HIV-1 clinical purging.


Assuntos
Antagonistas dos Receptores CCR5 , Linfócitos T CD4-Positivos/virologia , HIV-1/crescimento & desenvolvimento , Inibidores de Histona Desacetilases/farmacologia , Ácidos Hidroxâmicos/farmacologia , Monócitos/virologia , Receptores CXCR4/antagonistas & inibidores , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linhagem Celular , Células Cultivadas , Proteína do Núcleo p24 do HIV/biossíntese , Humanos , Monócitos/efeitos dos fármacos , Ácido Valproico/farmacologia
11.
Rev. MVZ Córdoba ; 20(1): 4406-4414, ene.-abr. 2015. ilus, tab
Artigo em Inglês | LILACS, COLNAL | ID: lil-743924

RESUMO

Objective. Determine the nutritional values of ground (SCI) or extruded (SCE) canola seed and evaluate its use in the performance of piglets from 15 to 30 kg. Materials and methods. Two experimental diets with canola seed were evaluated in a digestibility trial. We used 15 barrows with an initial weight of 19.79±1.43kg, distributed in a completely randomized design. In the performance, four experimental diets were evaluated consisting of a diet with soybean oil added (RAS), one with the of addition of canola oil (RAC) and two oil-free; one with 11% SCI included and one with 6% SCE (RSCE) included. 40 commercial hybrid piglets were used that had 15.25±1.5kg initial body weight, randomly distributed, in four treatments and five replicates; two animals per experimental unit. Results. The digestible energy values for SCI and SCE were 4.197 kcal/kg and 5.234 kcal/kg, respectively. The extrusion process improved the digestibility coefficients. Piglets fed with RSCI showed less daily weight gain (DWG) and F:G ratio. Conclusion. Results suggest that SCE can be included in diets of piglets from 15 to 30 kg until 6% without negatively affecting performance.


Objetivo. Determinar los valores nutricionales de las semillas de canola integral molida (SCI) y extrusada (SCE) y evaluar su influencia sobre el desempeño de lechones de 15 a 30 kg. Material y métodos. Se evaluaron dos dietas experimentales con semilla de canola en un ensayo de digestibilidad. Fueron utilizados 15 lechones machos, castrados, con peso inicial de 19.79±1.43kg, distribuidos en un diseño completamente al azar. En el desempeño se evaluaron cuatro dietas experimentales que consistieron de una dieta con adición de aceite de soya (RAS), una con adición de aceite de canola (RAC) y otras dos exentas de aceite; siendo una con la inclusión de 11% de SCI (RSCI) y otra con la inclusión de 6% de SCE (RSCE). Fueron utilizados 40 lechones híbridos comerciales, con peso vivo medio inicial de 15.25±1.5kg, distribuidos en un diseño experimental completamente al azar, con cuatro tratamientos, cinco repeticiones; siendo dos animales por unidad experimental. Resultados. Los valores de energía digestible para SCI y SCE en base seca fueron de 4.197 kcal/kg y 5.234 kcal/kg, respectivamente. El proceso de extrusión mejoró los coeficientes de digestibilidad. Los lechones alimentados con RSCI presentaron menor ganancia de peso (GPD) y peor conversión alimentaria (CA). Conclusiones. Los resultados indicaron que la SCE puede ser incluida en la dieta de lechones de 15 a 30 kg, hasta un nivel de 6% sin afectar el desempeño.


Assuntos
Ciências da Nutrição
12.
Autoimmun Rev ; 8(3): 228-32, 2009 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-18718560

RESUMO

Blau syndrome (BS) is a rare familial disease transmitted as an autosomal dominant trait, characterized by arthritis, uveitis, skin rash and granulomatous inflammation. Until now BS has been observed in 136 persons belonging to 28 families as well as in 4 sporadic cases. The gene responsible for BS has recently been identified in the nucleotide-binding domain (NBD) of caspase recruitment domain (CARD15/NOD2), also involved in the pathogenesis of Crohn's disease. In addition to three missense mutations (R334Q, R334W and L469F) previously identified, a new CARD 15 mutation (E383K) has recently been described in a family followed by us for the past 25 years. The characteristics of this family which, to our knowledge, is the only one affected with BS in Italy, are the object of this manuscript. Both the proband and her daughter were originally affected with a papulonodular skin eruption and then with mild arthritis of the hands and feet. The proband, but not the daughter, complained of severe chronic bilateral uveitis, followed by glaucoma and, a few years later, by cataracts. Histological examination of skin biopsies from both subjects and a joint biopsy (daughter only), showed non-caseating granulomas with multinucleated giant cells which, at electron microscopy, revealed "comma-shaped bodies" in epithelioid cells, thought to be a marker for BS. The disease is presently well controlled with low doses of prednisone for the mother and non-steroidal anti-inflammatory drugs (NSAIDs) plus low doses of prednisone, when necessary, for the daughter. As in Crohn's disease, CARD15/NOD2 mutation is believed to be responsible for the granulomatous autoinflammatory reactions probably triggered by microorganisms in BS.


Assuntos
Artrite/genética , Proteínas de Transporte/metabolismo , Exantema/genética , Uveíte/genética , Anti-Inflamatórios não Esteroides/uso terapêutico , Artrite/patologia , Artrite/fisiopatologia , Artrite/terapia , Proteínas de Transporte/genética , Proteínas de Transporte/imunologia , Transtornos Cromossômicos/genética , Transtornos Cromossômicos/imunologia , Doença de Crohn/genética , Doença de Crohn/imunologia , Exantema/patologia , Exantema/fisiopatologia , Exantema/terapia , Feminino , Seguimentos , Genes Dominantes/imunologia , Predisposição Genética para Doença , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Itália , Masculino , Mutação de Sentido Incorreto , Proteína Adaptadora de Sinalização NOD2/imunologia , Proteína Adaptadora de Sinalização NOD2/metabolismo , Linhagem , Polimorfismo Genético , Síndrome , Fatores de Tempo , Uveíte/patologia , Uveíte/fisiopatologia , Uveíte/terapia
13.
Vasc Health Risk Manag ; 5: 775-81, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19774219

RESUMO

OBJECTIVES: Sepsis remains a disease with a high mortality in neonates. Microcirculatory impairment plays a pivotal role in the development of multiorgan failure in septic newborns. The hemodynamic effects of recombinant activated protein C (rhAPC) were tested in an animal model of neonatal septic shock focusing on intestinal microcirculation. MATERIALS AND METHODS: Endotoxic shock was triggered by intravenous application of Escherichia coli lipopolysaccarides in newborn piglets. Thereafter, five animals received a continuous infusion of 24 microg/kg/h rhAPC, and five received vehicle for control. Over the course of three hours, intestinal microcirculation was assessed by intravital microscopy every 30 min. Macrocirculation and blood counts were monitored simultaneously. RESULTS: After a short hypotensive period in all animals, the arterial blood pressure returned to baseline in the rhAPC-treated piglets, whereas the hypotension became increasingly severe in the controls. By 90 min, mean blood pressure in the controls was significantly lower than in the treatment group. Similar observations were made regaring microcirculation. After an early impairment in all study animals, functional capillary density and intestinal microcirculatory red blood cell velocity and red blood cell flow recovered in the rhAPC group, but deteriorated further in the control piglets. CONCLUSION: Recombinant activated protein C protects macro- and microcirculation from endotoxic shock.


Assuntos
Intestinos/irrigação sanguínea , Microcirculação/efeitos dos fármacos , Proteína C/administração & dosagem , Choque Séptico/tratamento farmacológico , Circulação Esplâncnica/efeitos dos fármacos , Animais , Animais Recém-Nascidos , Velocidade do Fluxo Sanguíneo/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos , Modelos Animais de Doenças , Humanos , Hipotensão/tratamento farmacológico , Hipotensão/fisiopatologia , Infusões Intravenosas , Lipopolissacarídeos , Microscopia de Vídeo , Proteínas Recombinantes/administração & dosagem , Fluxo Sanguíneo Regional/efeitos dos fármacos , Choque Séptico/sangue , Choque Séptico/induzido quimicamente , Choque Séptico/fisiopatologia , Suínos , Fatores de Tempo
14.
J Rheumatol ; 36(8): 1575-9, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19567627

RESUMO

OBJECTIVE: Tumor necrosis factor-alpha (TNF-alpha) is a proinflammatory cytokine involved in the pathogenesis of several rheumatic diseases, including rheumatoid arthritis (RA), associated with systemic bone loss and subchondral bone erosions. TNF-alpha-blocking agents such as infliximab have been successful in treatment of disease-modifying antirheumatic drug-resistant rheumatic diseases. Infliximab therapy in RA also had beneficial effects on local bone destruction and bone mineral density. We assessed effects of infliximab treatment on the bone tissue compartment and cytokine profile expression in vitro. METHODS: Osteoblast-like cells were exposed for 24 h to sera of RA patients collected at baseline and after 1 month (T1) and 3 years (T2) of infliximab treatment. Total RNA was extracted, and expression of interleukin 1beta (IL-1beta), IL-6, and osteoprotegerin (OPG) was measured by RT-PCR. RESULTS: IL-1beta gene expression was significantly reduced by the T1 serum, and the same decrease was elicited by the T2 serum. IL-6 downregulation was evident with the T2 serum. OPG was unaffected. CONCLUSION: The finding of downregulation of inflammatory cytokines was interesting, particularly IL-6, which plays a crucial role in arthritis-related bone loss due to its involvement in osteoclast recruitment and activation. These results may represent a biological explanation and a link for the clinical observation of the beneficial effects of anti-TNF-alpha agents on the progression of rheumatic diseases at the bone level.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Antirreumáticos/uso terapêutico , Interleucina-1beta/genética , Interleucina-6/genética , Osteoblastos/fisiologia , Fator de Necrose Tumoral alfa/efeitos adversos , Proteínas Sanguíneas/farmacologia , Linhagem Celular , Expressão Gênica/efeitos dos fármacos , Expressão Gênica/imunologia , Humanos , Técnicas In Vitro , Infliximab , Interleucina-18/genética , Osteoblastos/citologia , Osteoprotegerina/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Soro
15.
Ciênc. rural ; 41(3): 507-512, mar. 2011. tab
Artigo em Português | LILACS | ID: lil-579674

RESUMO

Dois experimentos foram realizados para determinar o valor nutritivo da silagem de grãos úmidos de milho (SGUM) e avaliar os efeitos da substituição gradativa do milho seco das rações pela SGUM sobre o desempenho e características quantitativas de carcaça de coelhos, no período de 36 a 70 dias de idade. No ensaio de digestibilidade, foram utilizados 22 coelhos da raça Nova Zelândia Branco, com 50 dias de idade, alojados individualmente em gaiolas de metabolismo, em delineamento inteiramente ao acaso, com dois tratamentos e 11 repetições. Os valores da matéria seca digestível, proteína bruta digestível, energia bruta digestível, fibra em detergente neutro digestível, fibra em detergente ácido digestível e amido digestível da SGUM foram, respectivamente, 94,42 por cento; 7,94 por cento; 3973kcal kg-1, 6,74 por cento; 2,61 por cento e 68,73 por cento. No experimento de desempenho, foram utilizados 110 coelhos, distribuídos em um delineamento inteiramente casualizado, com cinco tratamentos, 11 repetições e dois animais por unidade experimental. Os tratamentos consistiram de uma dieta referência e outras quatro com 25, 50, 75 e 100 por cento de substituição do milho pela SGUM, com base na matéria seca do milho incluído na dieta referência. Não foram observadas diferenças entre os tratamentos no desempenho, tanto no período de 36 a 50 dias como no período total do experimento, de 36 a 70 dias de idade. Nenhuma diferença foi observada no peso e rendimento de carcaça entre os tratamentos. Diante dos resultados, a SGUM substitui eficientemente o milho seco em dietas para coelhos.


Digestibility and performance experiments were carried out to evaluate the nutrients digestibility coefficients of high moisture corn silage (HMCS) and the gradative replacing (0, 25, 50, 75 and 100 percent) of dry grain corn by HMCS on performance and carcass yield of growing rabbits from 36 to 70 days old. In the digestibility experiment 22 rabbits were used allocated on a completely randomized design, with two treatments and 11 replicates. The values of digestible dry matter, digestible crude protein, digestible crude energy, digestible neutral fiber detergent, digestible acid fiber detergent and digestible starch were, respectively, 94.42 percent; 7.94 percent; 3973kcal kg-1; 6.74 percent; 2.61 percent and 68.73 percent. In the performance experiment, 110 rabbits were allocated on a completely randomized design, with five treatments, 11 replications and two rabbits per experimental unit. The HMCS replaced the dry grain corn in levels of 0, 25, 50, 75 and 100 percent, on dry matter basis. No differences were observed on performance in the period from 36 to 50 and the period from 36 to 70 days old. No difference was observed also on weight and carcass yield. The results showed that the HMCS replaces efficiently the dry grain corn in rabbit diets.

16.
Braz. arch. biol. technol ; 53(1): 141-152, Jan.-Feb. 2010. tab, ilus
Artigo em Inglês | LILACS | ID: lil-543201

RESUMO

The nuclear ribosomal DNA internal transcribed spacers (ITS1 and ITS2) from leaves of Drosera (Droseraceae) were amplified using "universal" primers. The analysis of the products demonstrated most samples were a molecular mixture as a result of unsuccessful and non-specific amplifications. Among the obtained sequences, two were from Basidiomycota fungi. Homologous sequences of Basidiomycota were obtained from GenBank database and added to a data set with sequences from Drosera leaves. Parsimony analysis demonstrated that one sequence was amplified from an Ustilaginomycetes fungus, and another from a Heterobasidiomycetes. Possibly these fungi were associated to leaves of Drosera, and not because of samples contamination. In order to provide optimization and a better specificity of PCR (polymerase chain reaction), a very successful method was demonstrated using dimethyl sulfoxide (DMSO) and bovine serum albumin (BSA) in reactions.


Os espaçadores internos transcritos do DNA nuclear ribossomal (ITS1 e ITS2) de folhas de Drosera (Droseraceae) foram amplificados com o emprego de iniciadores "universais". A análise demonstrou que a maior parte das amostras continha uma mistura resultante de amplificações não-específicas. Dentre as sequências de DNA obtidas, duas delas foram de fungos basidiomicetos. Sequências homólogas foram obtidas do GenBank e analisadas junto às sequências obtidas de folhas de Drosera. Através das análises filogenéticas de máxima parcimônia foi possível identificar uma seqüência como sendo de um Ustilaginomycetes e outra de Heterobasidiomycetes (Basidiomycota). Possivelmente esses organismos estavam associados às folhas de Drosera e assim não sejam resultantes de contaminação. Com o objetivo de otimizar e buscar uma melhor especificidade das reações de PCR, um protocolo bem sucedido foi demonstrado com o uso de dimetilsulfóxido (DMSO) e soroalbumina bovina (BSA).

18.
Ciênc. rural ; 38(2): 463-469, mar.-abr. 2008. tab
Artigo em Português | LILACS | ID: lil-474514

RESUMO

O experimento foi conduzido com o objetivo de verificar o efeito da inclusão de diferentes níveis de casca (CS) de soja em dietas isoenergéticas para suínos em crescimento e terminação. Quarenta suínos híbridos, machos castrados e fêmeas, com peso inicial de 27,8 ± 2,1kg, foram bloqueados por peso e distribuídos ao acaso em cinco tratamentos, com quatro repetições de dois animais/baia (unidade experimental). Os tratamentos consistiram da inclusão de 0; 4; 8; 12 e 16 por cento de CS moída (2,5mm) em dietas isoenergéticas (16,4 e 15,0 por cento PB e 3.385 e 3.390kcal ED kg-1) para as fases de crescimento e terminação, respectivamente. Nenhuma variável de desempenho foi influenciada pela inclusão de CS nas dietas. Os níveis crescentes de CS promoveram redução linear da espessura de toucinho (ET), do rendimento de carcaça quente (RCQ) e do rendimento de carcaça fria (RCF) e aumento da quebra por resfriamento (QR). Para as variáveis peso de carcaça quente (PCQ) e peso de carcaça fria (PCF), foram observados efeitos quadráticos, sendo os menores valores observados com 8,0 por cento de inclusão de CS. O aumento do nível de CS na dieta elevou a QR, que piorou o rendimento de carcaça e diminuiu a ET. Não houve diferença para comprimento de carcaça, peso de pernil, área de olho de lombo e relação carne: gordura. Os resultados sugerem que a inclusão de até 16 por cento de CS nas dietas dos suínos em crescimento/terminação não altera seu desempenho e pode produzir carcaças mais magras.


The experiment was carried out to verify the effect of different soybean hull (SH) inclusion levels on isoenergetic growing-finishing pig diets. Forty crossbred pigs, barrows and gilts, with 27.8 ± 2.1kg of BW, were blocked according to the weight and distributed in a randomized way in five treatments, with four replicates of two pigs per pen (experimental unit). The treatments consisted of the inclusion of 0; 4; 8; 12 and 16 percent of ground SH (2.5mm) on isoenergetic diets (16.4 and 15.0 percent CP and 3,385 and 3,390 kcal DE kg-1 for growing and finishing phases, respectively. None of the performance parameters were influenced by SH inclusion on diets. The crescent SH levels promoted linear reduction on the back fat thickness (BT) and an increase of shrinkage chilling (SCh), hot carcass yield (HCY) and cold carcass yield (CCY). To the variables hot carcass weight (HCW) and cold carcass weight (CCW) were observed quadratic effects and smaller values were observed with 8.0 percent of SH inclusion. The SH increase level also increase the SCh, worst the carcass yield and decrease the BT. No difference was observed to the length carcass, ham weight, loin muscle area and meat: fat ratio. The results suggest that the inclusion up to 16 percent of SH on growing-finishing pigs diets does not change their performance and can produce leaner carcasses.

19.
Braz. arch. biol. technol ; 51(1): 49-56, Jan.-Feb. 2008. tab
Artigo em Inglês | LILACS | ID: lil-482053

RESUMO

A trial was carried out to determine the lysine requirement for starting barrows fed on ideal protein concept-based diets. Thirty-two pigs from a commercial crossbred genetic group (CCGG, BW=15.9 ± 1.4 kg) and 32 pigs from a dam line one (DLGG, BW= 14.8 ± 1.0 kg) were used. Pigs were allotted to 4 treatments with diets containing increasing levels of total lysine (0.80, 1.00, 1.20 and 1.40 percent). Methionine+cystine, threonine and tryptophan were adjusted according to ideal protein profile. Data from performance, plasma urea nitrogen (PUN) and carcass composition were analyzed. CCGG showed higher daily feed intake, daily weight gain, PUN and protein:fat ratio in carcass, while DLGG showed higher fat carcass content and nitrogen retention. Fat content and protein:fat ratio in carcass for CCCGG and PUN and crude protein carcass content for DLGG showed quadratic response to increasing total lysine levels. Derivations of the quadratic equations indicated the total lysine requirement for CCGG starting barrows is 1.15 percent and for DLGG starting barrows is 1.09 percent.


Foi realizado um trabalho com o objetivo de determinar a exigência em lisina para suínos castrados em fase inicial, alimentados com dietas formuladas de acordo com o conceito de proteína ideal. Trinta e dois suínos provenientes de cruzamento comercial (CC, PV = 15,9 kg) e 32 suínos provenientes de linhagem materna (LM, PV= 14,8 kg) foram alimentados com quatro dietas contendo níveis crescentes de lisina total (0,80; 1,00; 1,20 e 1,40 por cento). Metionina + cistina, triptofano e treonina foram adicionados às dietas para manter constante o padrão de proteína ideal. Foram analisados dados de desempenho, nitrogênio da uréia plasmática (NUP) e carcaça. Suínos do grupo CC apresentaram maior consumo diário de ração, ganho diário de peso, NUP e relação proteína: gordura na carcaça, enquanto que os animais do grupo LM apresentaram maiores teores de gordura na carcaça e retenção de nitrogênio. Teor de gordura e relação proteína:gordura na carcaça para o grupo CC e NUP e teor de proteína bruta na carcaça para o grupo LM apresentaram resposta quadrática aos níveis de lisina. Derivações das equações indicaram a exigência de lisina total de suínos machos castrados do grupo cruzamento industrial de 1,15 por cento e do grupo linhagem materna de 1,09 por cento.

20.
Ciênc. rural ; 34(4): 1213-1217, jul.-ago. 2004. tab
Artigo em Português | LILACS | ID: lil-383000

RESUMO

Este estudo foi realizado para determinar o coeficiente de digestibilidade aparente (CDA) da energia bruta e proteína bruta da silagem de sorgo de baixo tanino (SSBT) e da silagem de sorgo de alto tanino (SSAT) para a tilápia do Nilo (Oreochromis niloticus). A ração referência foi misturada aos ingredientes-teste na proporção de 60:40. Os peixes (53,26 ± 12,94g) foram alimentados até a saciedade aparente e as fezes foram coletadas após sedimentação. A fibra em detergente neutro foi utilizada como indicador endógeno. Os CDA da energia bruta e proteína bruta da SSBT e SSAT variaram entre 70,17 e 68,37 por cento e 84,94 e 82,40 por cento, respectivamente. Os valores de energia digestível foram de 3049,81 e 2954,74kcal kg-1 para SSBT e SSAT, respectivamente. A SSBT apresentou valores significa-tivamente (P<0,05) maiores de energia e proteína digestíveis em relação ao SSAT. Os resultados indicaram que a tilápia do Nilo pode utilizar a energia bruta e proteína bruta da silagem de sorgo eficientemente.

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