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The occurrence and severity of osteonecrosis in sickle cell anaemia (SCA) vary due to risk factors, including genetic modifiers. Bone morphogenetic proteins (BMPs), particularly BMP6, and the vitamin D receptor (VDR) play key roles in cartilage and bone metabolism, making them potential contributors to orthopaedic outcomes in SCA. Here, we evaluated the association of polymorphisms in BMP6 (rs3812163, rs270393 and rs449853) and VDR (FokI rs2228570 and Cdx2 rs11568820) genes with osteonecrosis risk in a Brazilian SCA cohort. A total of 177 unrelated SCA patients were selected. The AA genotype of BMP6 rs3812163 was independently associated with a lower osteonecrosis risk (p = 0.015; odds ratio (OR): 0.38; 95% confidence interval (CI): 0.18-0.83) and with the long-term cumulative incidence of osteonecrosis (p = 0.029; hazard ratio: 0.56, 95% CI: 0.34-0.94). The VDR rs2228570 TT genotype was independently associated with a lower osteonecrosis risk (p = 0.039; OR: 0.14; 95% CI: 0.02-0.90). In summary, our results provide evidence that BMP6 rs3812163 and the VDR rs2228570 might be implicated in osteonecrosis pathophysiology in SCA and might help identify individuals at high risk.
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Anemia de Células Falciformes , Osteonecrosis , Humanos , Predisposición Genética a la Enfermedad , Polimorfismo de Nucleótido Simple , Factores de Riesgo , Osteonecrosis/genética , Anemia de Células Falciformes/complicaciones , Anemia de Células Falciformes/genética , Genotipo , Estudios de Casos y Controles , Proteína Morfogenética Ósea 6/genética , Receptores de Calcitriol/genéticaRESUMEN
OBJECTIVE: To compare blind and endoscopic-guided techniques for orotracheal intubation in rabbits and the number of intubation attempts with laryngeal/tracheal damage. STUDY DESIGN: Prospective, randomized experimental study. ANIMALS: A total of 24 healthy, intact female New Zealand White rabbits, weighing 2.2 ± 0.2 kg (mean ± standard deviation). METHODS: Rabbits were randomly assigned to blind (group B) or endoscopic-guided (group E) orotracheal intubation with a 2.0 mm internal diameter uncuffed tube. Intramuscular (IM) alfaxalone (7 mg kg-1), hydromorphone (0.1 mg kg-1) and dexmedetomidine (0.005 mg kg-1) were administered, and additional IM alfaxalone (3-5 mg kg-1) and dexmedetomidine (0.025 mg kg-1) were administered to rabbits with strong jaw tone. An intubation attempt was defined as the advancement of the endotracheal tube from the incisors to the laryngeal entrance. Tracheal intubation was confirmed via capnography and anesthesia was maintained with isoflurane for 2 hours. Following euthanasia, laryngeal and tracheal tissues were submitted for histopathology. Quality of anesthesia for orotracheal intubation, intubation procedure and tissue damage were numerically scored. Data were analyzed using Poisson regression, Spearman's correlation, t test, mixed anova, Mann-Whitney U test, Friedman and Chi square tests as appropriate. RESULTS: Median (range) intubation attempts were 2 (1-8) and 1 (1-3) for groups B and E, respectively. More rabbits in group E (91.6%) required additional alfaxalone and dexmedetomidine than in group B (16.7%). Median (range) cumulative histopathology scores were 6 (3-10) and 6 (2-9) for groups B and E, respectively. Scores were highest in the cranial trachea, but there was no difference between groups and no correlation between laryngeal/tracheal damage and the number of intubation attempts. CONCLUSIONS AND CLINICAL RELEVANCE: Both orotracheal intubation techniques were associated with laryngeal/tracheal damage. Although blind orotracheal intubation was associated with a higher number of attempts, the tissue damage was similar between groups.
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Dexmedetomidina , Máscaras Laríngeas , Laringe , Animales , Dexmedetomidina/farmacología , Femenino , Intubación Intratraqueal/métodos , Intubación Intratraqueal/veterinaria , Máscaras Laríngeas/veterinaria , Estudios Prospectivos , Conejos , Tráquea/cirugíaRESUMEN
Xylanases are hemicellulases that break down xylan to soluble pentoses. They are used for industrial purposes, such as paper whitening, beverage clarification, and biofuel production. The second-generation bioethanol production is hindered by the enzymatic hydrolysis step of the lignocellulosic biomass, due to the complex arrangement established among its constituents. Xylanases can potentially increase the production yield by improving the action of the cellulolytic enzyme complex. We prospected endo-ß-1,4-xylanases from meta-transcriptomes of the termite Heterotermes tenuis. In silico structural characterization and functional analysis of an endo-ß-1,4-xylanase from a symbiotic protist of H. tenuis indicate two active sites and a substrate-binding groove needed for the catalytic activity. No N-glycosylation sites were found. This endo-ß-1,4-xylanase was recombinantly expressed in Pichia pastoris and Escherichia coli cells, presenting a molecular mass of approximately 20 kDa. Enzymatic activity assay using recombinant endo-ß-1,4-xylanase was also performed on 1% xylan agar stained with Congo red at 30 °C and 40 °C. The enzyme expressed in both systems was able to hydrolyze the substrate xylan, becoming a promising candidate for further analysis aiming to determine its potential for application in industrial xylan degradation processes.
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The fermented beverage industry is always pursuing alternatives to make products that delight consumers with special or unique characteristics. The identification and improvement of new yeast strains emerge as an opportunity; however, wild strains usually have a limitation in maltose fermentation and/or off-flavors production. Here we report the production of a Blond-style ale beer using a bioethanol isolated strain (LBGA-287) with flavor complexity approved in sensorial panels. LBGA-287 also showed an increase in maltose consumption, growth and fermentation rates when compared to the commercial yeast. Using qPCR analysis, genes related to the (i) efficiency of fermentation (ii) production of aromas/off-flavors, and (iii) metabolization of carbohydrates were found as differentially expressed in the isolated strains when compared to industrial yeast. This suggests that LBGA-287 could have an important impact on beer production, improving brewing efficiency, quality and diversity of this beverage, and most importantly satisfying the final consumer.
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Cerveza , Saccharomyces cerevisiae , Cerveza/análisis , Etanol/análisis , Fermentación , Bebidas Fermentadas , Saccharomyces cerevisiae/genéticaRESUMEN
Local anesthetics provide analgesia and can be incorporated into multimodal anesthetic protocols. They work by blocking the voltage-dependent sodium ion channels along neurons that mediate nociception. Systemically, these drugs can be cardiotoxic in a dose-dependent manner. Lidocaine and bupivacaine are the most commonly used local anesthetics and their use has been reported in all classes of vertebrates. Despite anecdotal reports to the contrary, zoologic companion animals are unlikely to be more susceptible to the cardiotoxic effects of local anesthetics than domestic small animals. Local anesthetics can be clinically useful for analgesia and anesthesia in zoologic companion animal practice.
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Anestesia de Conducción , Mascotas , Anestesia de Conducción/veterinaria , Anestésicos Locales/efectos adversos , Animales , Bupivacaína , Lidocaína/efectos adversosRESUMEN
BACKGROUND: Alzheimer's disease (AD) is the main cause of dementia and it is a progressive neurogenerative disease characterized by the accumulation of neurofibrillary tangles and senile plaques. There is currently no cure; however, some treatments are available to slow down the progression of the disease, including gene therapy, which has been investigated to have great potential for the treatment of AD. OBJECTIVE: The aim of this review was to identify the efficacy of gene therapy to restore cognition in AD. METHODS: A systematic review was carried out using papers published up to May 2020 and available in the Web of Science, Scopus, and Medline/PUBMED databases. Articles were considered for inclusion if they were original researches that investigated the effects of gene therapy on cognition in AD. The methodological quality of the selected studies was evaluated using the Risk of Bias Tool for Animal Intervention Studies (SYRCLE's Rob tool) and the Jadad Scale. RESULTS: Most preclinical studies obtained positive results in improving memory and learning in mice that underwent treatment with gene therapy. On the other hand, clinical studies have obtained inconclusive results related to the delivery methods of the viral vector used in gene therapy. CONCLUSION: Gene therapy has shown a great potential for the treatment of AD in preclinical trials, but results should be interpreted with caution since preclinical studies presented limitations to predict the efficacy of the treatment outcome in humans.
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Envejecimiento/genética , Enfermedad de Alzheimer/terapia , Cognición , Terapia Genética/métodos , Vectores Genéticos/uso terapéutico , Animales , Progresión de la Enfermedad , Humanos , Memoria , RatonesRESUMEN
BACKGROUND: The use of thermotolerant yeast strains can improve the efficiency of ethanol fermentation, allowing fermentation to occur at temperatures higher than 40 °C. This characteristic could benefit traditional bio-ethanol production and allow simultaneous saccharification and fermentation (SSF) of starch or lignocellulosic biomass. RESULTS: We identified and characterized the physiology of a new thermotolerant strain (LBGA-01) able to ferment at 40 °C, which is more resistant to stressors as sucrose, furfural and ethanol than CAT-1 industrial strain. Furthermore, this strain showed similar CAT-1 resistance to acetic acid and lactic acid, and it was also able to change the pattern of genes involved in sucrose assimilation (SUC2 and AGT1). Genes related to the production of proteins involved in secondary products of fermentation were also differentially regulated at 40 °C, with reduced expression of genes involved in the formation of glycerol (GPD2), acetate (ALD6 and ALD4), and acetyl-coenzyme A synthetase 2 (ACS2). Fermentation tests using chemostats showed that LBGA-01 had an excellent performance in ethanol production in high temperature. CONCLUSION: The thermotolerant LBGA-01 strain modulates the production of key genes, changing metabolic pathways during high-temperature fermentation, and increasing its resistance to high concentration of ethanol, sugar, lactic acid, acetic acid, and furfural. Results indicate that this strain can be used to improve first- and second-generation ethanol production in Brazil.
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OBJECTIVE: To investigate the effects of a priming dose of alfaxalone on the total anesthetic induction dose for and cardiorespiratory function of sedated healthy cats. ANIMALS: 8 healthy adult cats. PROCEDURES: For this crossover study, cats were sedated with dexmedetomidine and methadone administered IM. Cats next received a priming induction dose of alfaxalone (0.25 mg/kg, IV) or saline (0.9% NaCl) solution (0.025 mL/kg, IV) over 60 seconds and then an induction dose of alfaxalone (0.5 mg/kg/min, IV) until orotracheal intubation was achieved. Cardiorespiratory variables were recorded at baseline (immediately prior to priming agent administration), immediately after priming agent administration, after orotracheal intubation, and every 2 minutes until extubation. The total induction dose of alfaxalone was compared between the 2 priming agents. RESULTS: Mean ± SD total anesthetic induction dose of alfaxalone was significantly lower when cats received a priming dose of alfaxalone (0.98 ± 0.28 mg/kg), compared with when cats received a priming dose of saline solution (1.41 ± 0.17 mg/kg). Mean arterial blood pressure was significantly higher when alfaxalone was used as the priming dose. No cats became apneic or had a hemoglobin oxygen saturation of < 90%. Expired volume per minute was not significantly different between the 2 priming agents. CONCLUSIONS AND CLINICAL RELEVANCE: Administration of a priming dose of alfaxalone to healthy sedated cats reduced the total dose of alfaxalone needed to achieve orotracheal intubation, maintained mean arterial blood pressure, and did not adversely impact the measured respiratory variables.
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Anestésicos , Enfermedades de los Gatos , Pregnanodionas , Anestésicos/farmacología , Animales , Apnea/veterinaria , Gatos , Estudios Cruzados , Pregnanodionas/farmacologíaRESUMEN
Serratia marcescens has emerged as an important opportunistic pathogen responsible for nosocomial and severe infections. Here, we determined phenotypic and molecular characteristics of 54 S. marcescens isolates obtained from patient samples from intensive-care-unit (ICU) and neonatal intensive-care-unit (NIUC) of a Brazilian tertiary hospital. All isolates were resistant to beta-lactam group antibiotics, and 92.6% (50/54) were not susceptible to tigecycline. Furthermore, 96.3% showed intrinsic resistance to polymyxin E (colistin), a last-resort antibiotic for the treatment of infections caused by MDR (multidrug-resistant) Gram-negative bacteria. In contrast, high susceptibility to other antibiotics such as fluoroquinolones (81.5%), and to aminoglycosides (as gentamicin 81.5%, and amikacin 85.2%) was found. Of all isolates, 24.1% were classified as MDR. The presence of resistance and virulence genes were examined by PCR and sequencing. All isolates carried KPC-carbapenemase (bla KPC ) and extended spectrum beta-lactamase bla TEM genes, 14.8% carried bla OXA- 1, and 16.7% carried bla CTX-M- 1 group genes, suggesting that bacterial resistance to ß-lactam antibiotics found may be associated with these genes. The genes SdeB/HasF and SdeY/HasF that are associated with efflux pump mediated drug extrusion to fluoroquinolones and tigecycline, respectively, were found in 88.9%. The aac(6')-Ib-cr variant gene that can simultaneously induce resistance to aminoglycoside and fluoroquinolone was present in 24.1% of the isolates. Notably, the virulence genes to (i) pore-forming toxin (ShlA); (ii) phospholipase with hemolytic and cytolytic activities (PhlA); (iii) flagellar transcriptional regulator (FlhD); and (iv) positive regulator of prodigiosin and serratamolide production (PigP) were present in 98.2%. The genetic relationship among the isolates determined by ERIC-PCR demonstrated that the vast majority of isolates were grouped in a single cluster with 86.4% genetic similarity. In addition, many isolates showed 100% genetic similarity to each other, suggesting that the S. marcescens that circulate in this ICU are closely related. Our results suggest that the antimicrobial resistance to many drugs currently used to treat ICU and NIUC patients, associated with the high frequency of resistance and virulence genes is a worrisome phenomenon. Our findings emphasize the importance of active surveillance plans for infection control and to prevent dissemination of these strains.
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Overt stroke in adults with sickle cell anemia (SCA) continues to be a major cause of morbidity and mortality, while no evidence-based strategy for prevention has been reached so far. Although transcranial Doppler ultrasonography represents the most important tool for identifying young patients with SCA at risk of primary stroke, strategies for stroke prediction in adulthood remain challenging. Emerging data suggest that oxidative stress may exert a pivotal role in the pathogenesis of ischemic brain injury. Combining these pieces of evidences with the well-known genetic contribution to the development of stroke in SCA, we hypothesized that genetic variants related to the biology of oxidative stress could be used to identify adult patients at higher risk of stroke. Overall, 499 unrelated patients with SCA aged >18 years were genotyped for SOD2 Val16Ala (rs4880), GPX3 T-568C (rs8177404), GPX3 T-518C (rs8177406), GPX3 T-65C (rs8177412), and CAT01 C-262 T (rs1001179) polymorphisms, along with α-thalassemia status and ß-globin gene haplotypes. Of these, only the SOD2 Val16Ala polymorphism was associated with stroke. SOD2 Val16Ala polymorphism was independently associated with risk of stroke (odds ratio: 1.98; 95% confidence interval [CI]: 1.18-3.32; P = .009) and with the long-term cumulative incidence of stroke (hazard ratio: 2.24, 95% CI: 1.3-3.9; P = .004). In summary, we provide evidence that oxidative stress-related genetic variants, in particular, the SOD2 Val16Ala polymorphism, may represent a simple and inexpensive alternative for identifying patients at risk of stroke.
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Anemia de Células Falciformes , Accidente Cerebrovascular , Talasemia alfa , Adulto , Anciano , Anemia de Células Falciformes/complicaciones , Anemia de Células Falciformes/genética , Humanos , Estrés Oxidativo/genética , Accidente Cerebrovascular/diagnóstico por imagen , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/genética , Ultrasonografía Doppler TranscranealRESUMEN
OBJECTIVE: To compare results of a commercially available device for oscillometrically measured blood pressure (OBP) with invasively measured blood pressure (IBP) in awake and anesthetized dogs. ANIMALS: 19 adult dogs (mean ± SD body weight, 17.8 ± 7.5 kg). PROCEDURES: Blood pressures were measured in dogs while they were awake and anesthetized with isoflurane. The OBP was recorded on a thoracic limb, and IBP was simultaneously recorded from the median caudal artery. Agreement between OBP and IBP was evaluated with the Bland-Altman method. Guidelines of the American College of Veterinary Internal Medicine (ACVIM) were used for validation of the oscillometric device. RESULTS: In awake dogs, mean bias of the oscillometric device was -11.12 mm Hg (95% limits of agreement [LOA], -61.14 to 38.90 mm Hg) for systolic arterial blood pressure (SAP), 9.39 mm Hg (LOA, -28.26 to 47.04 mm Hg) for diastolic arterial blood pressure (DAP), and -0.85 mm Hg (LOA, -40.54 to 38.84 mm Hg) for mean arterial blood pressure (MAP). In anesthetized dogs, mean bias was -12.27 mm Hg (LOA, -47.36 to 22.82 mm Hg) for SAP, -3.92 mm Hg (LOA, -25.28 to 17.44 mm Hg) for DAP, and -7.89 mm Hg (LOA, -32.31 to 16.53 mm Hg) for MAP. The oscillometric device did not fulfill ACVIM guidelines for the validation of such devices. CONCLUSIONS AND CLINICAL RELEVANCE: Agreement between OBP and IBP results for awake and anesthetized dogs was poor. The oscillometric blood pressure device did not fulfill ACVIM guidelines for validation. Therefore, clinical use of this device cannot be recommended.
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Anestesia/veterinaria , Determinación de la Presión Sanguínea/instrumentación , Monitores de Presión Sanguínea/veterinaria , Oscilometría/veterinaria , Animales , Presión Sanguínea/fisiología , Determinación de la Presión Sanguínea/normas , Monitores de Presión Sanguínea/normas , Perros , Femenino , Miembro Anterior , Masculino , Oscilometría/instrumentación , Oscilometría/normas , VigiliaRESUMEN
Two performance studies were conducted to investigate the effects of 3 different sources of Cu on production parameters of piglets. A total of 256 piglets weaned at 24 ± 2 d were randomly allocated into 4 treatments with 10 or 8 replicates per treatment of 4 or 3 piglets per pen in Exp. 1 and 2, respectively. The experimental period was divided into 3 feeding phases: Phase 1 (24 to 35 d), Phase 2 (36 to 49 d), and Phase 3 (50 to 70 d). Treatments included a Control group (fed 10 mg/kg of Cu from CuSO4), a group fed 160 mg/kg of either CuSO4 (CuSO4-160) or tri-basic copper chloride (TBCC), and a group fed Cu methionine hydroxy analogue chelated (Cu-MHAC) at 150, 80, and 50 mg/kg in Phases 1, 2, and 3, respectively. The methionine value of Cu-MHAC was accounted during diet formulation to achieve the same levels of methionine across treatments. Phases 1 and 2 diets contained 2,200 and 1,500 ppm of ZnO, respectively; and antibiotics were used as growth promoters. Performance parameters were analyzed as completely randomized block design, in which each experiment was considered as a block. In trial 2, blood serum and mucosal samples, from the fundic region of the stomach, were collected from 1 piglet per replicate at day 70 and tested for serum growth hormone levels (GH) and ghrelin mRNA expression, respectively. The contrast between Cu-MHAC vs. CuSO4-160 + TBCC showed that piglets fed Cu-MHAC exhibited better feed conversion ratio (FCR) in all feeding phases compared with feeding inorganic Cu (P < 0.05). Overall, feeding Cu-MHAC improved body weight (BW), BW gain, feed intake (FI), and FCR vs. Control diet fed piglets; yet, it improved BW and FCR vs. TBCC fed piglets, and improved BW, BW gain, and FI vs. CuSO4-160 fed piglets (P < 0.05). Feeding TBCC promoted similar performance than feeding CuSO4-160, regardless of age (P > 0.05). Both ghrelin expression and growth hormone serum levels were significantly increased by feeding Cu-MHAC vs. Control diet fed animals (P < 0.01). Feeding CuSO4-160 upregulated ghrelin expression vs. Control (P < 0.01) while GH serum levels and ghrelin expression did no change by feeding TBCC compared with Control diet fed animals (P > 0.05). It was concluded that feeding Cu-MHAC at the levels tested herein can improve growth performance of piglets beyond feeding 160 ppm of either CuSO4 or TBCC, which may be partially explained by the increased expression of ghrelin and GH serum levels.
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Alimentación Animal/análisis , Cobre/administración & dosificación , Suplementos Dietéticos/análisis , Ghrelina/genética , Hormona del Crecimiento/sangre , Porcinos/fisiología , Animales , Peso Corporal/efectos de los fármacos , Dieta/veterinaria , Femenino , Masculino , Metionina/análogos & derivados , Metionina/química , ARN Mensajero/genética , Distribución Aleatoria , Estómago/fisiología , Porcinos/genética , Porcinos/crecimiento & desarrollo , Destete , Aumento de Peso/efectos de los fármacosRESUMEN
Beta-thalassaemia (BT) is classified according to blood transfusion requirement as minor (BTMi), intermedia (BTI) and major (BTM). BTM is the most severe form, requiring regular transfusions while transfusion need is only occasional in BTI. Differential gene expression between patients has not been assessed so far. Here, we evaluated the global gene expression profiles during differentiation of human erythroid cells of two patients carrying the same mutation [CD39, (C â T)], though displaying different phenotypes (BTI and BTM). Considering the role of reactive oxygen species (ROS) in the pathophysiology of thalassaemia, we focused on differentially expressed genes involved in metabolic pathways triggered by ROS, such as inflammation and apoptosis, and, from these, we selected the Apurinic/Apyrimidinic Endodeoxyribonuclease 1 (APEX1) and High Mobility Group Box1 (HMGB1) genes, whose role in BT is not well established. An in-depth expression analysis of transcriptional and protein levels in patients carrying a range of mutations associated with BT phenotypes indicated that APEX1 was increased in both BTI and BTM. Furthermore, higher amounts of HMGB1 was found in the plasma of BTI patients. Our findings suggest that these proteins have important roles in BT and could represent new targets for further studies aiming to improve the management of the disease.
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ADN-(Sitio Apurínico o Apirimidínico) Liasa/genética , Proteína HMGB1/genética , Estrés Oxidativo , Transducción de Señal , Transcriptoma , Talasemia beta/genética , Talasemia beta/metabolismo , Adulto , Apoptosis , Apirasa/metabolismo , Biomarcadores , Estudios de Casos y Controles , Diferenciación Celular/genética , Biología Computacional/métodos , ADN-(Sitio Apurínico o Apirimidínico) Liasa/metabolismo , Células Eritroides/citología , Células Eritroides/metabolismo , Femenino , Perfilación de la Expresión Génica , Regulación de la Expresión Génica , Redes Reguladoras de Genes , Proteína HMGB1/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Fenotipo , Especies Reactivas de Oxígeno/metabolismo , Talasemia beta/diagnósticoRESUMEN
Recently, the inflammation of the intestinal mucosa has been related to many diseases in humans and animals. The concept of Microscopic Enteritis (ME) used in human pathology through the Marsh classification system has no counter-part in veterinary medicine. In poultry science, the I See Inside (ISI) methodology, unlike the current linear measures of villi and crypts, generates possibilities to describe and understand the avian ME. Through specific parameters, graded from 0 to 3, the model links proliferative and/or inflammatory reactions in the intestinal layers to some loss in performance. Herein, two trials were conducted in order to describe the development of ME through the ISI methodology in chickens challenged or not with Eimeria spp. and Clostridium perfringens. In each trial, a total of 64 birds were divided in 2 treatments with 4 replicates containing 8 birds each: non-challenged (NCH) and challenged (CH) through gavage with an Eimeria spp. vaccine at 1 day of age and 108 CFU/mL of Clostridium perfringens administered at 10, 11, and 12 days of age. At 7, 14, 21, and 28 days of age birds were euthanized and samples of ileum and liver were collected for ISI evaluation, cytokines and presence of macrophages, CD4+ and CD8+ cell. The results allowed the description of the avian Microscopic Enteritis and of its two basic components: a basal enteritis (BE) in NCH broilers, over which the infectious enteritis is developed in CH birds. In addition, the chronology of ME translated by the ISI methodology parameters were associated to losses in zootechnical performance.
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ß-thalassemia is a worldwide distributed monogenic red cell disorder, characterized by an absent or reduced beta globin chain synthesis. The unbalance of alpha-gamma chain and the presence of pathological free iron promote severe oxidative damage, playing crucial a role in erythrocyte hemolysis, exacerbating ineffective erythropoiesis and decreasing the lifespan of red blood cells (RBC). Catalase, glutathione peroxidase and peroxiredoxins act together to protect RBCs from hydrogen peroxide insult. Among them, peroxiredoxins stand out for their overall abundance and reactivity. In RBCs, Prdx2 is the third most abundant protein, although Prdxs 1 and 6 isoforms are also found in lower amounts. Despite the importance of these enzymes, Prdx1 and Prdx2 may have their peroxidase activity inactivated by hyperoxidation at high hydroperoxide concentrations, which also promotes the molecular chaperone activity of these proteins. Some studies have demonstrated the importance of Prdx1 and Prdx2 for the development and maintenance of erythrocytes in hemolytic anemia. Now, we performed a global analysis comparatively evaluating the expression profile of several antioxidant enzymes and their physiological reducing agents in patients with beta thalassemia intermedia (BTI) and healthy individuals. Furthermore, increased levels of ROS were observed not only in RBC, but also in neutrophils and mononuclear cells of BTI patients. The level of transcripts and the protein content of Prx1 were increased in reticulocyte and RBCs of BTI patients and the protein content was also found to be higher when compared to beta thalassemia major (BTM), suggesting that this peroxidase could cooperate with Prx2 in the removal of H2O2. Furthermore, Prdx2 production is highly increased in RBCs of BTM patients that present high amounts of hyperoxidized species. A significant increase in the content of Trx1, Srx1 and Sod1 in RBCs of BTI patients suggested protective roles for these enzymes in BTI patients. Finally, the upregulation of Nrf2 and Keap1 transcription factors found in BTI patients may be involved in the regulation of the antioxidant enzymes analyzed in this work.
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Células Eritroides/metabolismo , Peroxirredoxinas/metabolismo , Talasemia beta/metabolismo , Talasemia beta/patología , Adolescente , Adulto , Western Blotting , Niño , Preescolar , Eritrocitos/citología , Eritrocitos/metabolismo , Femenino , Humanos , Leucocitos Mononucleares/citología , Leucocitos Mononucleares/metabolismo , Masculino , Persona de Mediana Edad , Neutrófilos/citología , Neutrófilos/metabolismo , Oxidación-Reducción , Peroxirredoxinas/genética , Especies Reactivas de Oxígeno/metabolismo , Reacción en Cadena en Tiempo Real de la Polimerasa , Adulto JovenRESUMEN
The topic of 'fungal stress' is central to many important disciplines, including medical mycology, chronobiology, plant and insect pathology, industrial microbiology, material sciences, and astrobiology. The International Symposium on Fungal Stress (ISFUS) brought together researchers, who study fungal stress in a variety of fields. The second ISFUS was held in May 8-11 2017 in Goiania, Goiás, Brazil and hosted by the Instituto de Patologia Tropical e Saúde Pública at the Universidade Federal de Goiás. It was supported by grants from CAPES and FAPEG. Twenty-seven speakers from 15 countries presented their research related to fungal stress biology. The Symposium was divided into seven topics: 1. Fungal biology in extreme environments; 2. Stress mechanisms and responses in fungi: molecular biology, biochemistry, biophysics, and cellular biology; 3. Fungal photobiology in the context of stress; 4. Role of stress in fungal pathogenesis; 5. Fungal stress and bioremediation; 6. Fungal stress in agriculture and forestry; and 7. Fungal stress in industrial applications. This article provides an overview of the science presented and discussed at ISFUS-2017.
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Hongos/fisiología , Hongos/patogenicidad , Estrés Fisiológico , Brasil , Microbiología Ambiental , Microbiología Industrial , MicologíaAsunto(s)
Mialgia , Gemelos Monocigóticos , Estudios de Casos y Controles , Humanos , Hipertrofia , Músculo EsqueléticoRESUMEN
Klebsiella pneumoniae is an important opportunistic pathogen that commonly causes nosocomial infections and contributes to substantial morbidity and mortality. We sought to investigate the antibiotic resistance profile, pathogenic potential and the clonal relationships between K. pneumoniae (n = 25) isolated from patients and sources at a tertiary care hospital's intensive care units (ICUs) in the northern region of Brazil. Most of K. pneumoniae isolates (n = 21, 84%) were classified as multidrug resistant (MDR) with high-level resistance to ß-lactams, aminoglycosides, quinolones, tigecycline, and colistin. All the 25 isolates presented extended-spectrum beta-lactamase-producing (ESBL), including carbapenemase producers, and carried the bla KPC (100%), bla TEM (100%), bla SHV variants (n = 24, 96%), bla OXA-1 group (n = 21, 84%) and bla CTX-M-1 group (n = 18, 72%) genes. The K2 serotype was found in 4% (n = 1) of the isolates, and the K1 was not detected. The virulence-associated genes found among the 25 isolates were mrkD (n = 24, 96%), fimH-1 (n = 22, 88%), entB (100%), iutA (n = 10, 40%), ybtS (n = 15, 60%). The genes related with efflux pumps and outer membrane porins found were AcrAB (100%), tolC (n = 24, 96%), mdtK (n = 22, 88%), OmpK35 (n = 15, 60%), and OmpK36 (n = 7, 28%). ERIC-PCR was employed to determine the clonal relationship between the different isolated strains. The obtained ERIC-PCR patterns revealed that the similarity between isolates was above 70%. To determine the sequence types (STs) a multilocus sequence typing (MLST) assay was used. The results indicated the presence of high-risk international clones among the isolates. In our study, the wide variety of MDR K. pneumoniae harboring ß-lactams and virulence genes strongly suggest a necessity for the implementation of effective strategies to prevent and control the spread of antibiotic resistant infections.
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OBJECTIVES: 1) To determine which peripheral artery commonly used for invasive arterial blood pressure (IBP) monitoring yields the least bias when compared with noninvasive blood pressure (NIBP) values obtained at the antebrachium of the dog, and 2) to identify and describe differences in systolic (SAP), mean (MAP) and diastolic arterial pressures (DAP) among different anatomical locations. STUDY DESIGN: Prospective experimental study. ANIMALS: Twenty adult hound dogs weighing 24.5 ± 1.1 kg (mean ± standard deviation). METHODS: Four peripheral arteries-dorsal pedal, median caudal, intermediate auricular and superficial palmar arteries-were catheterized with 20 gauge, 3.8 cm catheters. One NIBP cuff was placed in the middle third of the antebrachium. Four sets of IBP and NIBP measurements were simultaneously collected every 2 minutes. A linear mixed model was performed to analyze the collected data. RESULTS: IBP values varied depending on the arterial catheterization site. The difference was greater for SAP. NIBP measured at the antebrachium had the best agreement with IBP measured at the median caudal artery. CONCLUSION AND CLINICAL RELEVANCE: IBP varies among anatomical locations. The smallest bias and narrowest limits of agreement were obtained at the median caudal artery, providing the best overall agreement with the equipment studied. The median caudal artery may be the preferable anatomical location for clinical comparison studies between IBP and NIBP in dogs when the cuff is on the antebrachium.