Evaluación de la producción de celulosa por Acetobacter xylinum ifo en presencia de melaza de caña bajo condiciones estáticas y/o de flujo de aire intermitente

97 páginasLa producción de Celulosa Bacteriana en un cultivo con melaza (Max MZA) y aireación intermitente representa un importante avance para la comunidad científica. El cultivo se llevó a cabo a un pH 5,6 y a 30ºC. La incubación se realizó durante 1.5, 3, 7, 14, 21 y 28 días. Se determinaron la producción de celulosa, grosor, comprensibilidad, ufc/mL y concentración de glucosa, fructosa, y sacarosa en los medios de cultivo a diferentes tiempos. La producción de celulosa hasta los 28 días en el medio Max MZA con aireación se incrementó en un rango del 20% en relación a las obtenidas en Estático; asimismo el consumo de sustrato incidió directamente en la producción de celulosa durante el tiempo de cultivo

Efecto de la melaza de caña tratada con ácido sulfúrico en la produccion de celulosa por Gluconacetobacter xylinus IFO 13693

En este estudio se evaluó el efecto de la melazatratada con ácido sulfúrico (MZA-TR) y delas condiciones del cultivo (estático) sobrela síntesis de celulosa por Gluconacetobacterxylinus IFO 13693, para ello, se uso unreactor con 0,2 litros de medio de cultivo, conconcentraciones iniciales de 13,3 % y 26,6% de MZA-TR en el medio de cultivo a pH5,6. El volumen del inóculo fue del 10 % delvolumen total del medio; el proceso se realizóa temperatura ambiente (30 °C), con tiemposde incubación de 3, 7, 14, 21 y 28 días.Además, se evaluaron distintos parámetrosfisicoquímicos y mecánicos de la celulosa.El grosor de la película de celulosa presentóun máximo de 2,5 cm, siendo el mejorresultado obtenido, en comparación conanteriores reportes en la literatura. Tambiénse encontró que al usar MZA-TR en el mediode cultivo hay un incremento considerablede la producción de celulosa en estático a los28 días de incubación. Finalmente se observóque el consumo de glucosa y de fructosadisminuye durante la síntesis de celulosabacteriana (CB); durante los 3 primeros díasde incubación se observó el máximo descenso,lo que permite correlacionar la producciónde CB con el consumo de medio. Laconcentración de 13,3 %, presenta los mejoresresultados en los parámetros de velocidad decrecimiento microbiano, cantidad y calidad dela celulosa producida

Small leucine rich proteoglycans are differently distributed in normal and pathological endometrium

BACKGROUND: During the woman's fertile period, the non-pregnant uterus is subject to constant cyclic changes. The complex mechanisms that control the balance among proliferation, differentiation, cell death and the structural remodeling of the extracellular matrix can contribute to the benign or malignant endometrial pathological state. The small leucine-rich proteoglycans (SLRPs) are important components of cell surface and extracellular matrices. MATERIALS AND METHODS: Using immunohistochemistry, we showed that the distribution patterns of SLRPs were completely modified in the pathological compared to normal endometrium. RESULTS: The expression of SLRPs was low/absent in all endometrial pathologies examined compared to normal endometrium. We observed an increase of lumican from proliferative to secretory phase of the endometrium and a decrease of fibromodulin, biglycan and decorin. In menopause endometrial tissue, the level of expression of fibromodulin, biglycan, decorin and lumican dramatically decreased. CONCLUSION: The results revealed the prominence and importance of proteoglycans in the tissue architecture and extracellular matrix organization

Efecto De Diferentes Concentraciones De Fructosa Sobre La Producción De Celulosa Bacteriana En Cultivo Estático

In the synthesis of bacterial cellulose have used various carbon sources, various configurations and strategies of bioreactor cultivation. In this study we compared the production of bacterial cellulose evaluating the effect of different concentrations of fructose in the production of bacterial cellulose (BC) by Gluconacetobacter xylinus IFO static culture. The study was carried out in bioreactors of 750ml cylinder, 200 ml of medium containing initial concentrations of 1, 5, 10, 15 % p/v of fructose at pH 5.6. The inoculum volume was 10% v / v of culture medium volume. Cellulose synthesis was performed at room temperature and at different incubation times ranging from 1.5 to 28 days, which time is determined on the physicochemical and mechanical properties of bacterial cellulose, as well as fructose consumption versus time for different initial concentrations of fructose. The results indicate that 10% w/v fructose highest value obtained for the synthesis of BC in grams per liter of moist cellulose culture medium and the maximum thickness was obtained with a volume decrease of remnant; furthermore, fructose consumption observed until 90% of the initial concentration. The compressibility was less than a greater thickness of the cellulose film. The medium pH was kept in a region for optimal synthesis of BC. En la síntesis de celulosa bacteriana se han usado diversas fuentes de carbono, distintas configuraciones de biorreactores y estrategias de cultivo. En este estudio se compara la producción de celulosa bacteriana evaluando el efecto de diferentes concentraciones de fructosa en la producción de celulosa bacteriana (CB) por Gluconacetobacter xylinus IFO en un cultivo estático. El estudio se llevó a cabo en biorreactores cilíndricos de 750 ml, con 200 ml de medio que contenían concentraciones iniciales de 1, 5, 10, 15 % p/v de fructosa a pH 5,6. El volumen del inoculo fue el 10% v/v del volumen de medio de cultivo. La síntesis de celulosa se realizó a temperatura ambiente y a distintos tiempos de incubación que iban de 1,5 hasta 28 días, tiempo en el que se determinaron propiedades fisicoquímicas y mecánicas de la celulosa bacteriana, así como también el consumo de fructosa en función del tiempo para las diferentes concentraciones iniciales de fructosa. Los resultados indican que al 10% p/v de fructosa se obtiene el valor mas alto para la síntesis de CB en gramos de celulosa húmeda por litro de medio de cultivo y se obtuvo el máximo grosor con una disminución del volumen remanente de cultivo; además, se observó un consumo de fructosa hasta de un 90% de la concentración inicial. La comprensibilidad fue menor a un mayor grosor de la película de celulosa. El pH del medio se mantuvo en una región óptima para la síntesis de la CB

Effect of aliskiren on post-discharge outcomes among diabetic and non-diabetic patients hospitalized for heart failure: insights from the ASTRONAUT trial

Aims The objective of the Aliskiren Trial on Acute Heart Failure Outcomes (ASTRONAUT) was to determine whether aliskiren, a direct renin inhibitor, would improve post-discharge outcomes in patients with hospitalization for heart failure (HHF) with reduced ejection fraction. Pre-specified subgroup analyses suggested potential heterogeneity in post-discharge outcomes with aliskiren in patients with and without baseline diabetes mellitus (DM). Methods and results ASTRONAUT included 953 patients without DM (aliskiren 489; placebo 464) and 662 patients with DM (aliskiren 319; placebo 343) (as reported by study investigators). Study endpoints included the first occurrence of cardiovascular death or HHF within 6 and 12 months, all-cause death within 6 and 12 months, and change from baseline in N-terminal pro-B-type natriuretic peptide (NT-proBNP) at 1, 6, and 12 months. Data regarding risk of hyperkalaemia, renal impairment, and hypotension, and changes in additional serum biomarkers were collected. The effect of aliskiren on cardiovascular death or HHF within 6 months (primary endpoint) did not significantly differ by baseline DM status (P = 0.08 for interaction), but reached statistical significance at 12 months (non-DM: HR: 0.80, 95% CI: 0.64-0.99; DM: HR: 1.16, 95% CI: 0.91-1.47; P = 0.03 for interaction). Risk of 12-month all-cause death with aliskiren significantly differed by the presence of baseline DM (non-DM: HR: 0.69, 95% CI: 0.50-0.94; DM: HR: 1.64, 95% CI: 1.15-2.33; P < 0.01 for interaction). Among non-diabetics, aliskiren significantly reduced NT-proBNP through 6 months and plasma troponin I and aldosterone through 12 months, as compared to placebo. Among diabetic patients, aliskiren reduced plasma troponin I and aldosterone relative to placebo through 1 month only. There was a trend towards differing risk of post-baseline potassium ≥6 mmol/L with aliskiren by underlying DM status (non-DM: HR: 1.17, 95% CI: 0.71-1.93; DM: HR: 2.39, 95% CI: 1.30-4.42; P = 0.07 for interaction). Conclusion This pre-specified subgroup analysis from the ASTRONAUT trial generates the hypothesis that the addition of aliskiren to standard HHF therapy in non-diabetic patients is generally well-tolerated and improves post-discharge outcomes and biomarker profiles. In contrast, diabetic patients receiving aliskiren appear to have worse post-discharge outcomes. Future prospective investigations are needed to confirm potential benefits of renin inhibition in a large cohort of HHF patients without D

Cabbage and fermented vegetables : From death rate heterogeneity in countries to candidates for mitigation strategies of severe COVID-19

Large differences in COVID-19 death rates exist between countries and between regions of the same country. Some very low death rate countries such as Eastern Asia, Central Europe, or the Balkans have a common feature of eating large quantities of fermented foods. Although biases exist when examining ecological studies, fermented vegetables or cabbage have been associated with low death rates in European countries. SARS-CoV-2 binds to its receptor, the angiotensin-converting enzyme 2 (ACE2). As a result of SARS-CoV-2 binding, ACE2 downregulation enhances the angiotensin II receptor type 1 (AT(1)R) axis associated with oxidative stress. This leads to insulin resistance as well as lung and endothelial damage, two severe outcomes of COVID-19. The nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is the most potent antioxidant in humans and can block in particular the AT(1)R axis. Cabbage contains precursors of sulforaphane, the most active natural activator of Nrf2. Fermented vegetables contain many lactobacilli, which are also potent Nrf2 activators. Three examples are: kimchi in Korea, westernized foods, and the slum paradox. It is proposed that fermented cabbage is a proof-of-concept of dietary manipulations that may enhance Nrf2-associated antioxidant effects, helpful in mitigating COVID-19 severity.Peer reviewe

Nrf2-interacting nutrients and COVID-19 : time for research to develop adaptation strategies

There are large between- and within-country variations in COVID-19 death rates. Some very low death rate settings such as Eastern Asia, Central Europe, the Balkans and Africa have a common feature of eating large quantities of fermented foods whose intake is associated with the activation of the Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) anti-oxidant transcription factor. There are many Nrf2-interacting nutrients (berberine, curcumin, epigallocatechin gallate, genistein, quercetin, resveratrol, sulforaphane) that all act similarly to reduce insulin resistance, endothelial damage, lung injury and cytokine storm. They also act on the same mechanisms (mTOR: Mammalian target of rapamycin, PPAR gamma:Peroxisome proliferator-activated receptor, NF kappa B: Nuclear factor kappa B, ERK: Extracellular signal-regulated kinases and eIF2 alpha:Elongation initiation factor 2 alpha). They may as a result be important in mitigating the severity of COVID-19, acting through the endoplasmic reticulum stress or ACE-Angiotensin-II-AT(1)R axis (AT(1)R) pathway. Many Nrf2-interacting nutrients are also interacting with TRPA1 and/or TRPV1. Interestingly, geographical areas with very low COVID-19 mortality are those with the lowest prevalence of obesity (Sub-Saharan Africa and Asia). It is tempting to propose that Nrf2-interacting foods and nutrients can re-balance insulin resistance and have a significant effect on COVID-19 severity. It is therefore possible that the intake of these foods may restore an optimal natural balance for the Nrf2 pathway and may be of interest in the mitigation of COVID-19 severity

Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure &lt; 100 mmHg (n = 1127), estimated glomerular filtration rate &lt; 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival