The vitamin E derivative (+)α-tocopheryl succinate (α-TOS) exerts pro-apoptotic effects in a wide range of tumors and is well tolerated by normal tissues. Previous studies point to a mitochondrial ...involvement in the action mechanism; however, the early steps have not been fully elucidated. In a model of acute promyelocytic leukemia (APL) derived from hCG-PML-RARα transgenic mice, we demonstrated that α-TOS is as effective as arsenic trioxide or all-trans retinoic acid, the current gold standards of therapy. We also demonstrated that α-TOS induces an early dissipation of the mitochondrial membrane potential in APL cells and studies with isolated mitochondria revealed that this action may result from the inhibition of mitochondrial respiratory chain complex I. Moreover, α-TOS promoted accumulation of reactive oxygen species hours before mitochondrial cytochrome c release and caspases activation. Therefore, an in vivo antileukemic action and a novel mitochondrial target were revealed for α-TOS, as well as mitochondrial respiratory complex I was highlighted as potential target for anticancer therapy.
Aiming to increase damage tolerance of adhesively bonded joints, this work explores the influence of CFRP layup of the adherends on the crack onset and crack propagation of composite bonded joints ...under mode I loading. Quasi-static Double Cantilever Beam tests were performed using four different CFRP layups bonded with two adhesives. Parallel to the experimental program, finite element analyses were performed to aid in understanding and identifying the various damage mechanisms in each specimen type. The results show that the CFRP layup and adhesive fracture toughness significantly influence the joint fracture phenomena at crack onset and further crack propagation. An enhancement of the joint's mode I fracture toughness values at crack onset was observed in the specimens where a crack competition between the propagation within the bondline and the composite's layers was triggered. During crack propagation, the fracture toughness of the joint increases at crack deflections between the different plies of the CFRP layup until reaching the 0° ply, where sudden delamination occurs. It has been shown that CFRP layup tailoring is a promising toughening method that, when carefully designed, has the potential to increase the maximum effective fracture toughness up to 100% when compared to pure cohesive failure.
•CFRP layup tailoring is studied as a toughening mechanism of DCB adhesive joints.•The joints present complex damage mechanisms triggered by crack deflection and crack competition.•The 0-degree layup combined with an adhesive with an embedded carrier triggered cohesive failure with carrier bridging.•Fibre orientation of the plies in direct contact with the adhesive layer is crucial for the joint's damage evolution.•CFRP layup tailoring in adhesive joints has the potential to increase their maximum fracture toughness up to 100%.
Intestinal damage and severe diarrhea are serious side effects of cancer chemotherapy and constrain the usage of most such therapies. Here we show that interleukin-33 (IL-33) mediates the severe ...intestinal mucositis in mice treated with irinotecan (CPT-11), a commonly used cancer chemotherapeutic agent. Systemic CPT-11 administration led to severe mucosal damage, diarrhea, and body weight loss concomitant with the induction of IL-33 in the small intestine (SI). This mucositis was markedly reduced in mice deficient in the IL-33R (ST2(-/-)). Moreover, recombinant IL-33 exacerbated the CPT-11-induced mucositis, whereas IL-33 blockade with anti-IL-33 antibody or soluble ST2 markedly attenuated the disease. CPT-11 treatment increased neutrophil accumulation in the SI and adhesion to mesenteric veins. Supernatants from SI explants treated with CPT-11 enhanced transmigration of neutrophils in vitro in an IL-33-, CXCL1/2-, and CXCR2-dependent manner. Importantly, IL-33 blockade reduced mucositis and enabled prolonged CPT-11 treatment of ectopic CT26 colon carcinoma, leading to a beneficial outcome of the chemotherapy. These results suggest that inhibition of the IL-33/ST2 pathway may represent a novel approach to limit mucositis and thus improve the effectiveness of chemotherapy.
Neuroanatomy is often considered a difficult subject to teach, due to its broad scope, multitude of terms, and high degree of complexity. Thus, newer educational strategies that facilitate learning ...while also stimulating students by allowing increased student autonomy and group discussions should be carefully considered. This study aimed to evaluate the impact of introducing team‐based learning (TBL) in the traditional discipline of neuroanatomy and to measure student knowledge acquisition and perception relative to traditional lectures (TL). A quasi‐experimental, nonrandomized study was performed using two consecutive TBL classes (intervention group, n = 157 students, 25% content using TBL) with a TL class (control group, n = 76). Team‐based learning sessions included all stages according to the classic description of the method. Student knowledge acquisition was assessed in regularly scheduled tests during the discipline, and their perception regarding TBL was evaluated using a questionnaire (developed by the authors). The groups presented a similar sociodemographic profile (sex and age) and the same performance in another anatomy discipline before the study. Team‐based learning was significantly associated with greater acceptance, higher motivation, better student perception, and feelings that the methodology was able to integrate clinical and basic sciences. Nevertheless, according to tests, knowledge acquisition was similar between the TBL and lectures. In conclusion, since TBL is comparable to TL for knowledge acquisition, TBL seems to be a promising strategy to improve the teaching of neuroanatomy in medical schools. It fosters group discussions and increases satisfaction and the perception of integration between clinical and basic sciences.
Mercury is a toxic metal that can be found in the environment in three different forms - elemental, organic and inorganic. Inorganic mercury has a lower liposolubility, which results in a lower ...organism absorption and reduced passage through the blood-brain barrier. For this reason, exposure models that use inorganic mercury in rats in order to evaluate its effects on the central nervous system are rare, especially in adult subjects. This study investigated if a chronic exposure to low doses of mercury chloride (HgCl2), an inorganic form of mercury, is capable of promoting motor alterations and neurodegenerative in the motor cortex of adult rats. Forty animals were exposed to a dose of 0.375 mg/kg/day, for 45 days. They were then submitted to motor evaluation and euthanized to collect the motor cortex. Measurement of mercury deposited in the brain parenchyma, evaluation of oxidative balance, quantification of cellular cytotoxicity and apoptosis and density of mature neurons and astrocytes of the motor cortex were performed. It was observed that chronic exposure to inorganic mercury caused a decrease in balance and fine motor coordination, formation of mercury deposits and oxidative stress verified by the increase of lipoperoxidation and nitrite concentration and a decrease of the total antioxidant capacity. In addition, we found that this model of exposure to inorganic mercury caused cell death by cytotoxicity and induction of apoptosis with a decreased number of neurons and astrocytes in the motor cortex. Our results provide evidence that exposure to inorganic mercury in low doses, even in spite of its poor ability to cross biological barriers, is still capable of inducing motor deficits, cell death by cytotoxicity and apoptosis, and oxidative stress in the motor cortex of adult rats.
Scorpion envenomation represents an important health problem in many parts of the world, due to the high number and severity of accidents. Recent studies demonstrated that some species can produce ...venoms with genetic damage potential. Here, we evaluated whether Tityus stigmurus venom causes genetic damage in blood and testicular cells of Swiss mice. We also analyzed the effect of the venom on the number of spermatogenic lineage cells. Five groups of mice received 0.387 mg/kg of the venom, intraperitoneally; one group received saline solution (control group). Blood and testicular cells were collected for comet assay and histological analysis at different times after treatment (1, 2, 6, 12, and 48 h). Blood was also collected 48 h after treatment for the micronucleus test in erythrocytes. Histological analysis was performed by counting cells of the spermatogenic lineages; the nuclear area of elongated spermatocytes was also evaluated. Treatment with the venom induced DNA damage that endured from 1 h to 48 h, as confirmed by the comet assay. The micronucleus test demonstrated that the venom induced mutations in erythrocytes. The number of spermatogonia and rounded spermatids decreased in some groups; the number of elongated spermatids increased, and their nuclear size decreased 1 h after treatment. Genetic damage can be caused directly by the venom, but we suggested that reactive oxygen species that result from inflammatory process caused by the envenomation may have an important role in the DNA damage. Genetic damage and apoptosis may explain the changes in the number of spermatogenic cells. Furthermore, the decrease in nuclear area may result from chromatin loss. Genetic damage in testicular cells, associated with alterations in the number and morphology of spermatogenic cells, can result in reproduction disorders in animals, or humans, stung by T. stigmurus.
•Tityus stigmurus venom induces DNA damage in blood and testicular cells of mice.•The venom also induces mutations in blood of mice as seen by micronucleus test.•Number and nuclear morphology of spermatogenic lineage is altered by the venom.•Tityus stigmurus sting may result in reproductive disorders in animals and humans.
Aging increases the risk of chronic diseases, especially cardiovascular diseases, leading to changes in cardiovascular anatomy and physiology even in the absence of other comorbidities. Numerous ...cardiovascular risk factors (CVRFs), such as diabetes mellitus (DM) and systemic arterial hypertension (SAH), can modify the functional and structural properties of large vessels, increasing arterial stiffness.
To determine whether elderly patients with hypertension with DM have greater central arterial stiffness than elderly patients with SAH without DM.
The Study of Pulse Wave Velocity in the Elderly in an Urban Area in Brazil (EVOPIU) included 1,192 patients aged ≥ 60 years who underwent applanation tonometry (AT) to evaluate carotid-femoral pulse wave velocity (cfPWV). From this database, 1,133 patients were selected from 6 groups: NDN (nondiabetic normotensives; n: 127); DN (diabetic normotensives; n: 64); NDCH (nondiabetic controlled hypertensives; n: 168); DCH (diabetic controlled hypertensives; n: 275); NDH (nondiabetic hypertensives; n: 217) and DH (diabetic hypertensives; n: 282). All groups underwent AT to obtain cfPWV and central and peripheral arterial pressures.
The pulse wave velocities found were as follows: NDN vs DN (8.9 ± 0.2 m/s vs 9.4 ± 0.2; P = .103); NDCH vs DCH (9.0 ± 0.2 m/s vs. 9.6 ± 0.1 m/s; P= .04) and NDH vs DH (9.2 ± 0.1 m/s vs. 9.6 ± 0.1 m/s; P= .045). When the diabetic groups were compared, there were no differences in cfPWV values, and the same occurred when the nondiabetic groups were compared.
Elderly patients with diabetes and hypertension have greater central arterial stiffness than patients without diabetes and hypertension, regardless of systemic blood pressure control. The central arterial stiffness caused by vascular aging seems to be a common factor among all the studied groups.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Cyanobacteria blooms are a risk to environmental health and public safety due to the potent toxins certain cyanobacteria can produce. These nuisance organisms can be removed from water bodies by ...biomass flocculation and sedimentation. Here, we studied the efficacy of combinations of a low dose coagulant (poly-aluminium chloride-PAC-or chitosan) with different ballast compounds (red soil, bauxite, gravel, aluminium modified zeolite and lanthanum modified bentonite) to remove cyanobacterial biomass from water collected in Funil Reservoir (Brazil). We tested the effect of different cyanobacterial biomass concentrations on removal efficiency. We also examined if zeta potential was altered by treatments. Addition of low doses of PAC and chitosan (1-8 mg Al L-1) to the cyanobacterial suspensions caused flock formation, but did not settle the cyanobacteria. When those low dose coagulants were combined with ballast, effective settling in a dose-dependent way up to 99.7% removal of the flocks could be achieved without any effect on the zeta potential and thus without potential membrane damage. Removal efficacy was influenced by the cyanobacterial biomass and at higher biomass more ballast was needed to achieve good removal. The combined coagulant-ballast technique provides a promising alternative to algaecides in lakes, ponds and reservoirs.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Incidence of Yellow Fever (YF) has increased in Brazil, and cardiac findings such as bradyarrhythmias and conduction abnormalities have been described. We aimed to perform a comprehensive cardiac ...evaluation of patients with YF, and to assess the association between cardiac involvement and disease severity. Patients hospitalized with YF from February to March 2018 underwent clinical and laboratory evaluation, focused bedside echocardiography (GE Vivid IQ), electrocardiogram and, in case of alterations, 24-hours Holter. Patients were divided into 2 groups according to YF severity. Five patients underwent magnetic resonance imaging and 3 had necropsy. Seventy patients had confirmed YF, 69% with severe form. Mean age was 48 ± 14 years, 63 (90%) were males and 5 (7%) died. Significant electrocardiogram abnormalities were present in 52% of patients with mild/moderate form of YF (G1) and 77% of those with severe form (G2), p = 0.046. Sinus bradycardia was observed in 24% (N = 17): G1 23% versus G2 25%, p = 0.67. Among 32 patients who underwent Holter, 14 (44%) had mean HR <60 beats per minute, being 8 from G2. Echocardiogram revealed left ventricular dysfunction in 4 (6%) patients, from G2. Left ventricular wall thickening with a hyper-refringent myocardial texture suggesting infiltration was observed in 17 patients (G1 18% vs G2 27%, p = 0.55). One magnetic resonance (G2) was suggestive of myocarditis, and one necropsy revealed areas of myocardial necrosis and acute myocarditis. In conclusion, cardiac involvement was observed in patients with YF, most commonly bradycardia and myocardial hyper-refringent texture suggestive of infiltration.
Climate change is being intensified by anthropogenic emission of greenhouse gasses, highlighting the value of forests for carbon dioxide storing carbon in their biomass. Seasonally dry tropical ...forests are a neglected, threatened, but potentially critical biome for helping mitigate climate change. In South America, knowing the amount and distribution of carbon in Caatinga seasonally dry vegetation is essential to understand its contribution to the global carbon cycle and subsequently design a strategic plan for its conservation. The present study aimed to model and map the spatial distribution of the potential forest biomass stock across 32 forest fragments of Caatinga, in the state of Bahia, Brazil, using regression kriging and Inverse Square of Distance techniques, building from point measurements of vegetation biomass made on-the-ground in ecological plots. First, a model for estimating biomass was fitted as a function of environmental variables to apply regression kriging, and then applied to the maps of the selected components. Elevation, temperature, and precipitation explained 46% of the biomass variations in the Caatinga. The model residuals showed strong spatial dependence and were mapped based on geostatistical criteria, selecting the spherical semivariogram model for interpolation by ordinary kriging. Biomass was also mapped by the Inverse Square of Distance approach. The quality of the regression model suggests that there is good potential for estimating biomass here from environmental variables. The regression kriging showed greater detail in the spatial distribution and revealed a spatial trend of increasing biomass from the north to south of the domain. Additional studies with greater sampling intensity and the use of other explanatory variables are suggested to improve the model, as well as to maximize the technique’s ability to capture the actual biomass behavior in this newly studied seasonally dry ecosystem.
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