Interleukin-21 expanded NKDC in vitro reduces the B16F10 tumor growth in vivo

AbstractInnate immunity to tumors is mediated mainly by natural killer cells (NKs) and dendritic cells (DCs). The function of these cells is coordinated by cytokines produced during the inflammatory process. NK cells are highly active against tumors, being an important source of IFN-γ. Natural killer dendritic cells (NKDCs) were recently identified as a group of hybrid cells; some studies claim that they have lytic activity, produce IFN-γ and can also stimulate antigen-specific T cells. Interleukin 21 (IL-21) regulates the proliferation capacity and cytotoxicity of NK and T cells. The main objective of this study was to investigate if IL-21 influences the frequency of NKDCs in vitro as well as IFN-γ production and also to verify if these cells could enhance the antitumor activity against B16F10 tumor model in vivo. Splenocytes from C57BL/6 mice were isolated and the DC were enriched by immunomagnetic beads and cultured for four days with recombinant IL-21 (10, 20, 40 or 100ng/ml). NKDC population was characterized as CD11clow/medB220+NK1.1+. Expanded cells were used to treat B16F10 tumor bearing mice and tumor growth was compared between the doses of IL-21 10ng/ml and 20ng/ml. The results indicate that IL-21 increases the expansion of splenic NKDCs in vitro in doses of 10ng/ml and 20ng/ml and these cells produce IFN-γ. In vivo, cells expanded with IL-21 and injected directly into the growing tumor efficiently reduced the tumor size. Together, these results showed for the first time that IL-21 influences the biology and the effector activity of NKDCs

Ruminal Degradability Of Agro-industrial Fruit Residues

The aim of this study was to evaluate the chemical composition and ruminal degradability of the dry matter (DM), crude protein (CP) and neutral detergent fiber (NDF) of fruit residues. Three fistulated sheep were held collectively in a pen, and fed daily with the studied residues in a diet consisting of canarana grass (Echinochloa pyramidalis) and a concentrate of corn and soybeans. The animals were allowed an adjustment period of seven days. The residues were dried in the sun, crushed in a forage machine, sorted using a 4.0-mm sieve, and incubated for 3, 6, 12, 24, 48, 72, and 96 h using nonwoven bags (weight 60g/m2, 14 ×12 cm2). Chemical analyses of the residues were performed using a randomized block experimental design with split plots. The cherimoya and tamarind residues showed the highest concentrations of CP (12.66% and 11.79%) the ether extract of cherimoya residue was the highest at 22.30%stands out the sour soup residue. The cashew and guava residues showed the highest levels of lignin (22.13 and 18.34%). The effective degradability of DM for the pineapple and tamarind residues to a passage rate of 5%/h were 53.04% and 42.61%, respectively. The guava, cherimoya, and cashew residues showed lower values at 19.16%, 26.86%, and 29.21%, respectively. The cherimoya, guava and pineapple residues showed the highest values of potential degradability for CP at 87%, 81%, 86.02% and 90.94%, respectively, with an average effective degradability of 50.0% at the rate of 5%/h. The pineapple (35.38%) and tamarind residues (34.49%) showed higher values of the effective degradability of NDF at a passage rate of 5%/h. Among the studied residues, the pineapple residue showed the greatest potential for use in animal feed based on chemical composition and rates of degradability.37127929

Incorporating oldman saltbush hay and prickly pear in diets for red Sindhi calves

This study was designed to evaluate the nutrient intake, digestibility, degradability, and ruminal characteristics of Sindhi heifers fed diets that contained a combined total of 75% oldman saltbush hay (hereafter saltbush hay) and prickly pear cactus. Eight 12-month old intact male red Sindhi calves (four fistulated and four non-fistulated) with an initial mean weight of 170 ± 5 kg were assigned to 4 × 4 Latin squares, where factors consisted of four diets, namely 15% hay and 60% cactus; 30% hay and 45% cactus; 45% hay and 30% cactus; and 60% hay and 15% cactus, and four times at which rumen fluid was collected. Neutral detergent fibre (NDF) and acid detergent fibre (ADF) intakes in kg/day and NDF in percentage live weight (LW), water intake, salinity, and conductivity increased with hay level. Intake and digestibility of non-fibrous carbohydrates were curvilinear with higher values in diets containing 30% saltbush hay. The apparent digestibility of dry matter (DM) and organic matter decreased linearly as the concentration of saltbush hay increased in the diet. The pH of the rumen fluid was within the acceptable range for favourable microbial growth. The low temperature and high salinity and conductivity indices in the diets should be viewed with caution at higher concentrations of saltbush hay, because of a possible decrease in nutrient absorption and the development of health problems in the animals. Apparent degradability coefficients of DM and NDF were affected significantly by inclusion of prickly pear and saltbush hay in the diets.Keywords: animal nutrition, apparent digestibility, Atriplex nummularia Lindl, Opuntia ficus, ruminal degradation, semi-arid environmen

Treatment of hemorrhagic shock with hypertonic saline solution modulates the inflammatory response to live bacteria in lungs

Shock and resuscitation render patients more susceptible to acute lung injury due to an exacerbated immune response to subsequent inflammatory stimuli. To study the role of innate immunity in this situation, we investigated acute lung injury in an experimental model of ischemia-reperfusion (I-R) followed by an early challenge with live bacteria. Conscious rats (N = 8 in each group) were submitted to controlled hemorrhage and resuscitated with isotonic saline (SS, 0.9% NaCl) or hypertonic saline (HS, 7.5% NaCl) solution, followed by intratracheal or intraperitoneal inoculation of Escherichia coli. After infection, toll-like receptor (TLR) 2 and 4 mRNA expression was monitored by RT-PCR in infected tissues. Plasma levels of tumor necrosis factor α and interleukins 6 and 10 were determined by ELISA. All animals showed similar hemodynamic variables, with mean arterial pressure decreasing to nearly 40 mmHg after bleeding. HS or SS used as resuscitation fluid yielded equal hemodynamic results. Intratracheal E. coli inoculation per se induced a marked neutrophil infiltration in septa and inside the alveoli, while intraperitoneal inoculation-associated neutrophils and edema were restricted to the interseptal space. Previous I-R enhanced lung neutrophil infiltration upon bacterial challenge when SS was used as reperfusion fluid, whereas neutrophil influx was unchanged in HS-treated animals. No difference in TLR expression or cytokine secretion was detected between groups receiving HS or SS. We conclude that HS is effective in reducing the early inflammatory response to infection after I-R, and that this phenomenon is achieved by modulation of factors other than expression of innate immunity components.FAPESPFundação Faculdade de MedicinaCoordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES

Comparison of the timed inspiratory effort index with the T-piece trial as a decision-making tool for extubation: a randomized controlled non-inferiority trial

The “timed inspiratory effort” (TIE) index, a new predictor of weaning outcome, normalizes the maximal inspiratory pressure with the time required to reach this value up to 60 s, incorporating the time domain into the assessment of inspiratory muscle function. The objective of this study was to determine whether the TIE predicts successful extubation at a similar rate as the T-piece trial with less time required. A non-inferiority randomized controlled trial was performed with ICU subjects eligible for weaning. The participants were allocated to the TIE or the T-piece groups. The primary outcome was successful weaning, and the main secondary outcome was ICU mortality. Eighty participants of each group were included in the final analysis. Time from the start of a successful test to effective extubation was significantly lower in the TIE group than in the T-piece group, 15 (10 to 24) vs 55 (40 to 75) min, P<0.001. In the Kaplan-Meier analysis, no significant differences were found in successful weaning (79.5 vs 82.5%, P=0.268) or survival rate (62.9 vs 53.8%, P=0.210) between the TIE and T-piece groups at the 30th day. In this preliminary study, the TIE index was not inferior to the T-piece trial as a decision-making tool for extubation and allowed a reduction in the decision time

Beneficial effects of the activation of the Angiotensin-(1-7) MAS receptor in a murine model of adriamycin-induced nephropathy

Angiotensin-(1-7) [Ang-(1-7)] is a biologically active heptapeptide that may counterbalance the physiological actions of angiotensin II (Ang II) within the renin-angiotensin system (RAS). Here, we evaluated whether activation of the Mas receptor with the oral agonist, AVE 0991, would have renoprotective effects in a model of adriamycin (ADR)-induced nephropathy. We also evaluated whether the Mas receptor contributed for the protective effects of treatment with AT1 receptor blockers. ADR (10 mg/kg) induced significant renal injury and dysfunction that was maximal at day 14 after injection. Treatment with the Mas receptor agonist AVE 0991 improved renal function parameters, reduced urinary protein loss and attenuated histological changes. Renoprotection was associated with reduction in urinary levels of TGF-{beta}. Similar renoprotection was observed after treatment with the AT1 receptor antagonist, Losartan. AT1 and Mas receptor mRNA levels dropped after ADR administration and treatment with losartan reestablished the expression of Mas receptor and increased the expression of ACE2. ADR-induced nephropathy was similar in wild type (Mas(+/+)) and Mas knockout (Mas (-/-)) mice, suggesting there was no endogenous role for Mas receptor activation. However, treatment with Losartan was able to reduce renal injury only in Mas(+/+) , but not in Mas (-/-) mice. Therefore, these findings suggest that exogenous activation of the Mas receptor protects from ADR-induced nephropathy and contributes to the beneficial effects of AT1 receptor blockade. Medications which target specifically the ACE2/Ang-(1-7)/Mas axis may offer new therapeutic opportunities to treat human nephropathies

Acute complications of chronic liver diseases

As doenças hepáticas crônicas, em fases avançadas, cursam com graves complicações, responsáveis pela maioria das indicações de internações hospitalares e causas de morte dos pacientes. Neste capítulo, são discutidas as principais complicações das doenças hepáticas crônicas, que são a encefalopatia hepática, a peritonite bacteriana espontânea e a síndrome hepatorrenal. São apresentados os aspectos importantes, na prática médica, dessas três condições clínicas, com ênfase na abordagem diagnóstica e terapêutica.Advanced chronic liver diseases lead to severe complications that are responsible for the majority of indications of hospitalization and patients’ death. In this article the main complications of chronic liver diseases such as hepatic encephalopathy, spontaneous bacterial peritonitis and hepatorenal syndrome are discussed. The main aspects in practical clinic of these three clinical conditions with emphasis in the diagnostic and therapeutic approach are shown

Sub- and above barrier fusion of loosely bound 6^6Li with 28^{28}Si

Fusion excitation functions are measured for the system $^6$Li+$^{28}$Si using the characteristic $\gamma$-ray method, encompassing both the sub-barrier and above barrier regions, viz., $E_{lab}$= 7-24 MeV. Two separate experiments were performed, one for the above barrier region ($E_{lab}$= 11-24 MeV) and another for the below barrier region ($E_{lab}$= 7-10 MeV). The results were compared with our previously measured fusion cross section for the $^7$Li+$^{28}$Si system. We observed enhancement of fusion cross section at sub-barrier regions for both $^6$Li and $^7$Li, but yield was substantially larger for $^6$Li. However, for well above barrier regions, similar type of suppression was identified for both the systems.Comment: 8 pages, 6 figures, as accepted for publication in Eur.Phys.J.

Resting spontaneous baroreflex sensitivity and cardiac autonomic control in anabolic androgenic steroid users

OBJECTIVES: Misuse of anabolic androgenic steroids in athletes is a strategy used to enhance strength and skeletal muscle hypertrophy. However, its abuse leads to an imbalance in muscle sympathetic nerve activity, increased vascular resistance, and increased blood pressure. However, the mechanisms underlying these alterations are still unknown. Therefore, we tested whether anabolic androgenic steroids could impair resting baroreflex sensitivity and cardiac sympathovagal control. In addition, we evaluate pulse wave velocity to ascertain the arterial stiffness of large vessels. METHODS: Fourteen male anabolic androgenic steroid users and 12 nonusers were studied. Heart rate, blood pressure, and respiratory rate were recorded. Baroreflex sensitivity was estimated by the sequence method, and cardiac autonomic control by analysis of the R-R interval. Pulse wave velocity was measured using a noninvasive automatic device. RESULTS: Mean spontaneous baroreflex sensitivity, baroreflex sensitivity to activation of the baroreceptors, and baroreflex sensitivity to deactivation of the baroreceptors were significantly lower in users than in nonusers. In the spectral analysis of heart rate variability, high frequency activity was lower, while low frequency activity was higher in users than in nonusers. Moreover, the sympathovagal balance was higher in users. Users showed higher pulse wave velocity than nonusers showing arterial stiffness of large vessels. Single linear regression analysis showed significant correlations between mean blood pressure and baroreflex sensitivity and pulse wave velocity. CONCLUSIONS: Our results provide evidence for lower baroreflex sensitivity and sympathovagal imbalance in anabolic androgenic steroid users. Moreover, anabolic androgenic steroid users showed arterial stiffness. Together, these alterations might be the mechanisms triggering the increased blood pressure in this population

Impact of adding different concentrations of IGF-I and insulin to the semen extender on bull sperm quality post-cryopreservation

ABSTRACT This study aimed to evaluate the addition of different concentrations of IGF-I and insulin to egg yolk-based extender to improve bovine semen cryopreservation. Two experiments were developed to evaluate the effects of the additives in two commercial extenders, Botubov® (Experiment 1) and Triladyl® (Experiment 2), both with the same design. Three ejaculates from four bulls (n = 12) were used. Each ejaculate was divided into seven equal fractions for dilution (60x106 spermatozoa/mL) in the following treatments: CON: extender only; IGF100: IGF-I 100ng/mL; IGF200: IGF-I 200ng/mL; INS150: insulin 150µUI/mL; INS200: insulin 200µUI/mL; ASS1: IGF-I 100ng/mL + insulin 150µUI/mL; ASS2: IGF-I 200ng/mL + insulin 200µUI/mL. Semen was cryopreserved by an automated system. Post-thawed sperm were evaluated regarding motility by CASA (Computer-assisted sperm analysis), and membranes by fluorescent probes (H342, PI, FITC-PSA and JC-1). For Botubov® extender, INS150 was more efficient in preserving total and progressive motility, VCL, BCF, plasma and mitochondrial membranes. A similar response was seen when insulin was added to the Triladyl® extender, INS150 was more efficient in preserving sperm motility, plasma membrane integrity and mitochondrial potential. Thus, the addition of insulin 150µUI/mL, regardless of the composition of the extender, contributes to better preserving bovine sperm from the cryopreservation effects