RESUMEN

Natural products offer promising potential for the development of new therapies for Alzheimer's disease (AD). Blackberry fruits are rich in phytochemical compounds capable of modulating pathways involved in neuroprotection. Additionally, drug repurposing and repositioning could also accelerate the development of news treatments for AD. In light of the reduced brain glucose metabolism in AD, an alternative approach has been the use of the drug metformin. Thus, the aim of this study was to evaluate the effect of treatment with blackberry extract in a model of AD induced by streptozotocin (STZ) and compare it with metformin treatment. Male rats were divided into groups: I - Control; II - STZ; III - STZ + blackberry extract (100 mg/kg); IV - STZ + blackberry extract (200 mg/kg) and V - STZ + metformin (150 mg/kg). The animals received intracerebroventricular injection of STZ or buffer. Seven days after the surgical procedure, the animals were treated orally with blackberry extract or metformin for 21 days. Blackberry extract and metformin prevented the memory impairment induced by STZ. In animals of group II, an increase in acetylcholinesterase activity, phosphorylated tau protein, IL-6, oxidative damage, and gene expression of GSK-3ß and Nrf2 was observed in the hippocampus. STZ induced a decrease in IL-10 levels and down-regulated the gene expression of Akt1, IRS-1 and FOXO3a. Blackberry extract and metformin prevented the alterations in acetylcholinesterase activity, IL-6, GSK3ß, Nrf2, and oxidative damage. In conclusion, blackberry extract exhibits multi-target actions in a model of AD, suggesting new therapeutic potentials for this neurodegenerative disease.

RESUMEN

This research was carried out with the objective of evaluating the effects of using a chilling water sprinkler system during the cooling process of swine carcasses on the quantitative and qualitative parameters of carcass and meat. A total of 220 swine carcasses were divided in a completely randomized experiment and two treatments: (1) CONTROL, no water spraying; (2) SPRAY, with water spraying during cooling. Surface and internal temperature of carcasses throughout the cooling process, initial and final pH, and microbiological analyses of carcass surface were evaluated. Samples of the Longissimus lumborum (LL) were collected for analysis of color, cooking loss (CL), shear force (SF), and drip loss (DL). Data were submitted to analysis of variance through the SAS MIXED procedure adopting the most adequate model with treatments as fixed effects and pertinent random effects for each data set. The use of spray-chilling in the initial cooling process accelerates the surface and internal temperature decrease of swine carcasses, which may be a viable technological resource in swine industry.

Asunto(s)

RESUMEN

The blackberry (Rubus sp.) is a popular fruit that has a high concentration of phenolic compounds. Pharmacological investigations have demonstrated the important biological activities of the blackberry extract, such as neuroprotective actions. This study aimed to evaluate the effects of blackberry extract on memory and neurochemical parameters in rats subjected to scopolamine (SCO)-induced amnesia. Male rats were divided into five groups: I, control (saline); II, SCO; III, SCO + Rubus sp. (100 mg/kg); IV, SCO + Rubus sp. (200 mg/kg); and V, SCO + donepezil (5 mg/kg). Blackberry extract and donepezil were orally administered for 10 days. On day 11, group I received saline, and groups II, III, IV, and V received SCO (1 mg/kg) intraperitoneally after object recognition behavioral training. Twenty-four hours after the training session, animals were subjected to an object recognition test. Finally, the animals were euthanized, and the cerebral cortex, hippocampus, and cerebellum were collected to evaluate the oxidative stress and acetylcholinesterase (AChE) activity. Rubus sp. extract prevented memory impairment induced by SCO in a manner similar to that of donepezil. Additionally, Rubus sp. extract and donepezil prevented the increase in AChE activity induced by SCO in all the evaluated brain structures. SCO induced oxidative damage in the cerebral cortex, hippocampus, and cerebellum, which was prevented by Rubus sp. and donepezil. Our results suggest that the antioxidant and anticholinesterase activities of Rubus sp. are associated with memory improvement; hence, it can potentially be used for the treatment of neurodegenerative diseases.

Asunto(s)

RESUMEN

Metal alloys are widely used in the aerospace, biological, civil and automotive industries, thus being very important to develop techniques to identify these alloys. Nuclear technique based on gamma densitometry is a non-invasive technique that is able to identify metal alloys using a radiation source and a scintillator detector. The measurement geometry and the dataset for training an artificial neural network were developed using the MCNP6 code. Therefore, this study proposes the thickness prediction of five aluminum alloys (2024-O, 2090-T83, 3003, 5086-O and 7075-O), a titanium alloy, and two steel carbon alloys (stainless 302 and stainless 316) ranging from 2 to 50 mm for four different gamma-ray radiation energies using gamma transmission and artificial neural network. A study to evaluate the reliability of the results was performed by analyzing the uncertainties in the data from the simulation with the MCNP6 code and the data predicted by ANN. The results indicate that it was possible to predict all the alloys thicknesses using the energy of 137Cs radiation source, in which more than 96% of the cases with 5% of relative error, even for a group of alloys with very close densities values as aluminum alloys.

Asunto(s)

RESUMEN

Alzheimer's disease (AD) is characterized mostly by memory decline. The current therapeutic arsenal for treating AD is limited, and the available drugs only produce symptomatic benefits, but do not stop disease progression. The search for effective therapeutic alternatives with multitarget actions is therefore imperative. One such a potential alternative is thiazolidin-4-one, a compound that exhibits anti-amnesic, anticholinesterase, and antioxidant activities. The aim of this study was evaluated the effects of 2-(4-(methylthio)phenyl)- 3-(3-(piperidin-1-yl)propyl) thiazolidin-4-one (DS12) on memory and neurochemical parameters in a model of AD induced by an intracerebroventricular injection of streptozotocin (STZ). Adult male rats were divided into five groups: I, control (saline); II, DS12 (10 mg/kg); III, STZ; IV, STZ + DS12 (10 mg/kg); V, STZ + donepezil (5 mg/kg). The rats were orally treated with DS12 and donepezil for a period of 20 days. Memory, acetylcholinesterase (AChE) activity, phosphorylated tau protein levels and oxidative stress were analyzed in the cerebral cortex, hippocampus, and cerebellum. Biochemical and hematological parameters were evaluated in the blood and serum. Memory impairment and the increase in AChE activity and phosphorylated tau protein level induced by STZ were prevented by DS12 and donepezil treatment. Streptozotocin induces an increase in reactive oxygen species levels and a decrease in catalase activity in the hippocampus, cerebral cortex, and cerebellum. DS12 treatment conferred protection from oxidative alterations in all brain structures. No changes were observed in serum biochemical parameters (glucose, triglycerides, cholesterol, uric acid, and urea) or hematological parameters, such as platelets, lymphocytes, hemoglobin, hematocrit, and total plasma protein. DS12 improved memory and neurochemical changes in an AD model and did not show toxic effects, suggesting the promising therapeutic potential of this compound.

Asunto(s)

RESUMEN

Purpose: The purpose of this study was to compare volume measurements obtained using 2 image software packages on Digital Imaging and Communications in Medicine (DICOM) images acquired from 1 multidetector computed tomography and 5 cone-beam computed tomography devices, using different protocols for physical volume measurements. Materials and Methods: Four pieces of bovine leg were prepared. Marrow was removed from 3 pieces, leaving cortical bone exposed. The resulting space of 1 piece was filled with water, another was filled with propylene glycol, and the third was left unfilled. The marrow in the fourth sample was left fully intact. Volume measurements were obtained after importing DICOM images into the Dolphin Imaging 11.95 and ITK-SNAP software programs. Data were analyzed using 3-way analysis of variance with a generalized linear model to determine the effects of voxel size, software, and content on percentage mean volume differences between tomographic protocols. A significance level of 0.05 was used. Results: The intraclass correlation coefficients for intraobserver and interobserver reliability were, respectively, 0.915 and 0.764 for the Dolphin software and 0.894 and 0.766 for the ITK-SNAP software. Three sources of statistically significant variation were identified: the interaction between software and content (P=0.001), the main effect of content (P=0.014), and the main effect of software (P=0.001). Voxel size was not associated with statistically significant differences in volume measurements. Conclusion: Both content and software influenced the accuracy of volume measurements, especially when the content had gray values similar to those of the adjacent tissues.

RESUMEN

After the sudden death of captive marmosets in São Paulo, Brazil, we conducted a histologic and microbiologic study. We found hyperacute septicemia caused by hypermucoviscous sequence type 86 K2 Klebsiella pneumoniae. We implemented prophylactic antimicrobial therapy, selected dedicated staff for marmoset interactions, and sanitized the animals' fruit to successfully control this outbreak.

Asunto(s)

RESUMEN

Oxidative stress and inflammatory cytokines affect the human brain, increasing the risk for mood and cognitive disorders. Such risk might be selective to brain-specific regions. Here, we determined whether BXD recombinant inbred (RI) mice strains are more suitable than C57BL/6J mice for the understanding of the relationship between antioxidant response and inflammatory responses. We hypothesized that inflammatory responses could be independent of antioxidant response and be inherent to brain-specific regions. This hypothesis will be addressed by the analyses of mRNA expression. We explored, at 7-months-of-age, the innate activation of proinflammatory cytokines (tumor necrosis factor alpha (TNFα) and interleukin 6 (IL-6), as well as Kelch-like ECH-associating protein 1 (Keap1), nuclear factor erythroid 2 related factor 2 (Nrf2) and glutathione peroxidase 1 (Gpx1) mRNA in both male and female BXD84/RwwJ RI, BXD21/TyJ RI and control strain (C57BL/6J mice). We report that: (1) The cerebellum is more sensitive to antioxidant response in the BXD21/TyJ RI strain; (2) The cerebellum, hippocampus and striatum show increased levels of cytokines in the BXD21/TyJ RI strain; (3) The BXD RI strain has lower brain weight relative to control strain (C57BL/6 mice). In conclusion, our novel data show the utility of the BXD21/TyJ RI strain mice in offering mechanistic insight into Nrf2's role in the inflammatory system.

Asunto(s)

RESUMEN

In this work, we evaluated the ovicidal activity and the deleterious effects of cashew (Anacardium occidentale) nut shell oil and its fractions on the development of Musca domestica and Chrysomya megacephala, important vectors of several diseases. The insecticidal effects of this plant were also measured on the first and second instar larvae of Anticarsia gemmatalis and Spodoptera frugiperda, soy and maize pests, respectively. The fly eggs and the crop pest insect larvae were exposed to the cashew (Anacardium occidentale) nut shell liquid (CNSL) and its fractions: technical CNSL, anacardic acid, cardanol and cardol. The results show that the cardol fraction, for both species of flies, presented the lowest lethal concentration with LC50 of 80.4 mg/L for M. domestica and 90.2 mg/L for C. megacephala. For the mortality of the larvae of A. gemmatalis and S. frugiperda, the most effective fraction was anacardic acid with LC50 of 295.1 mg/L and 318.4 mg/L, respectively. In all species, the mortality rate of the commercial compounds (cypermethrin 600 mg/L and temephos 2 mg/L) was higher than that of the evaluated compounds. Despite this, the results obtained suggest their potential in field trials, once the fractions of A. occidentale presented high mortality at low lethal concentrations in laboratory conditions, with the possibility of integrated use in the control of disease vectors and agricultural pests, employing ecofriendly compounds.

Asunto(s)

RESUMEN

Mercury (Hg) exposure remains a major public health concern due to its widespread distribution in the environment. Organic mercurials, such as MeHg, have been extensively investigated especially because of their congenital effects. In this context, studies on the molecular mechanism of MeHg-induced neurotoxicity are pivotal to the understanding of its toxic effects and the development of preventive measures. Post-translational modifications (PTMs) of proteins, such as phosphorylation, ubiquitination, and acetylation are essential for the proper function of proteins and play important roles in the regulation of cellular homeostasis. The rapid and transient nature of many PTMs allows efficient signal transduction in response to stress. This review summarizes the current knowledge of PTMs in MeHg-induced neurotoxicity, including the most commonly PTMs, as well as PTMs induced by oxidative stress and PTMs of antioxidant proteins. Though PTMs represent an important molecular mechanism for maintaining cellular homeostasis and are involved in the neurotoxic effects of MeHg, we are far from understanding the complete picture on their role, and further research is warranted to increase our knowledge of PTMs in MeHg-induced neurotoxicity.

Asunto(s)

RESUMEN

Evidences show that purinergic signaling is involved in processes associated with health and disease, including noncommunicable, neurological, and degenerative diseases. These diseases strike from children to elderly and are generally characterized by progressive deterioration of cells, eventually leading to tissue or organ degeneration. These pathological conditions can be associated with disturbance in the signaling mediated by nucleotides and nucleosides of adenine, in expression or activity of extracellular ectonucleotidases and in activation of P2X and P2Y receptors. Among the best known of these diseases are atherosclerosis, hypertension, cancer, epilepsy, Alzheimer's disease (AD), Parkinson's disease (PD), and multiple sclerosis (MS). The currently available treatments present limited effectiveness and are mostly palliative. This review aims to present the role of purinergic signaling highlighting the ectonucleotidases E-NTPDase, E-NPP, E-5'-nucleotidase, and adenosine deaminase in noncommunicable, neurological, and degenerative diseases associated with the cardiovascular and central nervous systems and cancer. In conclusion, changes in the activity of ectonucleotidases were verified in all reviewed diseases. Although the role of ectonucleotidases still remains to be further investigated, evidences reviewed here can contribute to a better understanding of the molecular mechanisms of highly complex diseases, which majorly impact on patients' quality of life.

Asunto(s)

RESUMEN

Methylmercury (MeHg) is a hazardous environmental pollutant, which elicits significant toxicity in humans. The accumulation of MeHg through the daily consumption of large predatory fish poses potential health risks, and the central nervous system (CNS) is the primary target of toxicity. Despite well-described neurobehavioral effects (i.e., motor impairment), the mechanisms of MeHg-induced toxicity are not completely understood. However, several lines of evidence point out the oxidative stress as an important molecular mechanism in MeHg-induced intoxication. Indeed, MeHg is a soft electrophile that preferentially interacts with nucleophilic groups (mainly thiols and selenols) from proteins and low-molecular-weight molecules. Such interaction contributes to the occurrence of oxidative stress, which can produce damage by several interacting mechanisms, impairing the function of various molecules (i.e., proteins, lipids, and nucleic acids), potentially resulting in modulation of different cellular signal transduction pathways. This review summarizes the general aspects regarding the interaction between MeHg with regulators of the antioxidant response system that are rich in thiol and selenol groups such as glutathione (GSH), and the selenoenzymes thioredoxin reductase (TrxR) and glutathione peroxidase (Gpx). A particular attention is directed towards the role of the PI3K/Akt signaling pathway and the nuclear transcription factor NF-E2-related factor 2 (Nrf2) in MeHg-induced redox imbalance.

RESUMEN

Methylmercury (MeHg) is an environmental pollutant that affects primarily the central nervous system (CNS), causing neurological alterations. An early symptom of MeHg poisoning is the loss of body weight and appetite. Moreover, the CNS has an important role in controlling energy homeostasis. It is known that in the hypothalamus nutrient and hormonal signals converge to orchestrate control of body weight and food intake. In this study, we investigated if MeHg is able to induce changes in the expression of key hypothalamic neuropeptides that regulate energy homeostasis. Thus, hypothalamic neuronal mouse cell line GT 1-7 was treated with MeHg at different concentrations (0, 0.5, 1, and 5 µM). MeHg induced the expression of the anorexigenic neuropeptide pro-omiomelanocortin (Pomc) and the orexigenic peptide Agouti-related peptide (Agrp) in a concentration-dependent manner, suggesting deregulation of mechanisms that control body weight. To confirm these in vitro observations, 8-week-old C57BL/6J mice (males and females) were exposed to MeHg in drinking water, modeling the most prevalent exposure route to this metal. After 30-day exposure, no changes in body weight were detected. However, MeHg treated males showed a significant decrease in fat depots. Moreover, MeHg affected the expression of hypothalamic neuropeptides that control food intake and body weight in a gender- and dose-dependent manner. Thus, MeHg increases Pomc mRNA only in males in a dose-dependent way, and it does not have effects on the expression of Agrp mRNA. The present study shows, for first time, that MeHg is able to induce changes in hypothalamic neuropeptides that regulate energy homeostasis, favoring an anorexigenic/catabolic profile.

Asunto(s)

RESUMEN

Methylmercury is a toxic environmental contaminant that elicits significant toxicity in humans. The central nervous system is the primary target of toxicity, and is particularly vulnerable during development. Rho-associated protein kinase 1 (ROCK-1) is a major downstream effector of the small GTPase RhoA and a direct substrate of caspase-3. The activation of ROCK-1 is necessary for membrane blebbing during apoptosis. In this work, we examined whether MeHg could affect the RhoA/ROCK-1 signaling pathway in primary cultures of mouse astrocytes. Exposure of cells with 10 µM MeHg decreased cellular viability after 24 h of incubation. This reduction in viability was preceded by a significant increase in intracellular and mitochondrial reactive oxygen species levels, as well as a reduced NAD+/NADH ratio. MeHg also induced an increase in mitochondrial-dependent caspase-9 and caspase-3, while the levels of RhoA protein expression were reduced or unchanged. We further found that MeHg induced ROCK-1 cleavage/activation and promoted LIMK1 and MYPT1 phosphorylation, both of which are the best characterized ROCK-1 downstream targets. Inhibiting ROCK-1 and caspases activation attenuated the MeHg-induced cell death. Collectively, these findings are the first to show that astrocytes exposed to MeHg showed increased cleavage/activation of ROCK-1, which was independent of the small GTPase RhoA.

Asunto(s)

Asunto(s)

RESUMEN

Depression and anxiety are the most common psychiatric disorders, representing a major public health concern. Dysregulation of oxidative and inflammatory systems may be associated with psychiatric disorders, such as depression and anxiety. Due to the need to find appropriate animal models to the understanding of such disorders, we queried whether 2 BXD recombinant inbred (RI) mice strains (BXD21/TyJ RI and BXD84/RwwJ RI mice) and C57BL/6 wild-type mice show differential performance in depression and anxiety related behaviors and biomarkers. Specifically, we assessed social preference, elevated plus maze, forced swim, and Von Frey tests at 3-4 months-of-age, as well as activation of cytokines and antioxidant mRNA levels in the cortex at 7 months-of-age. We report that (1) the BXD84/RwwJ RI strain exhibits anxiety disorder and social avoidance-like behavior (2) BXD21/TyJ RI strain shows a resistance to depression illness, and (3) sex-dependent cytokine profiles and allodynia with elevated inflammatory activity were inherent to male BXD21/TyJ RI mice. In conclusion, we provide novel data in favor of the use of BXD recombinant inbred mice to further understand anxiety and depression disorders.

Asunto(s)

RESUMEN

Methylmercury (MeHg) is a potent environmental pollutant, which elicits significant toxicity in humans. The central nervous system (CNS) is the primary target of toxicity, and is particularly vulnerable during development. Maternal exposure to MeHg via consumption of fish and seafood can have irreversible effects on the neurobehavioral development of children, even in the absence of symptoms in the mother. It is well documented that developmental MeHg exposure may lead to neurological alterations, including cognitive and motor dysfunction. The neurotoxic effects of MeHg on the developing brain have been extensively studied. The mechanism of toxicity, however, is not fully understood. No single process can explain the multitude of effects observed in MeHg-induced neurotoxicity. This review summarizes the most current knowledge on the effects of MeHg during nervous system development considering both, in vitro and in vivo experimental models. Considerable attention was directed towards the role of glutamate and calcium dyshomeostasis, mitochondrial dysfunction, as well as the effects of MeHg on cytoskeletal components/regulators.

Asunto(s)

RESUMEN

The organophosphorus (OP) pesticide malathion is a neurotoxic compound whose acute toxicity is primarily caused by the inhibition of acetylcholinesterase (AChE), leading to cholinergic syndrome-related symptoms. Some lines of evidence indicate that long-term exposure to low levels of OP may produce neuropsychiatric and/or neurobehavioral signs that do not necessarily involve the AChE inhibition. This study evaluated the effects of a repeated (15-day period) and low-dose malathion exposure on spatial memory and discrimination (object location task), as well as on biochemical parameters in the hippocampus of mice [AChE and mitochondrial chain complexes activities; levels of proapoptotic proteins (Bax and Bak) and cholinergic neuronal and astroglial markers (ChAT and GFAP, respectively)]. Malathion treatments (30 and 100 mg/kg, s.c.) did not affect the body weight of animals and caused no evident signs of cholinergic toxicity throughout the treatment, although the highest dose (100 mg/kg) was associated with inhibition of AChE activity. Malathion-exposed animals showed a significant impairment on spatial memory and discrimination, which was correlated with a decrease in the mitochondrial complex I activity in the hippocampus. Moreover, malathion increased the levels of proapoptotic proteins and induced astroglial activation. The results show that long-term malathion exposure, at a dose that does not affect hippocampal AChE activity (30 mg/kg), caused impaired spatial memory and discrimination in mice that was related to hippocampal mitochondrial dysfunctional, astrogliosis and apoptosis. When extrapolated to humans, such results shed light on noncholinergic mechanisms likely related to the neurobehavioral and cognitive deficits observed in individuals chronically exposed to this pesticide.

Asunto(s)

RESUMEN

CONTEXT: Obesity in midlife is a risk factor for dementia, but it is unknown if caloric restriction-induced weight loss could prevent cognitive decline and therefore dementia in elderly patients with cognitive impairment. OBJECTIVE: To evaluate the cognitive effect of intentional weight loss in obese elderly patients with mild cognitive impairment (MCI), considering the influence of age, apolipoprotein E (APOE) genotype, physical activity, biochemical markers, and diet. DESIGN: Single-center, prospective controlled trial. SETTING: Academic medical center. PARTICIPANTS: Eighty obese patients with MCI, aged 60 or older (68.1 ± 4.9 y, body mass index [BMI] 35.5 ± 4.4 kg/m(2), 83.7% women, 26.3% APOE allele ϵ4 carriers). INTERVENTION: Random allocation to conventional medical care alone (n = 40) or together with nutritional counselling (n = 40) in group meetings aiming to promote weight loss through caloric restriction for 12 months. OUTCOME MEASUREMENTS: clinical data, body composition, neuropsychological tests (main outcome), serum biomarkers, APOE genotype, physical performance, dietary recalls. RESULTS: Seventy-five patients completed the follow-up. BMI, on average, decreased 1.7 ± 1.8 kg/m(2) (P = .021), and most of the cognitive tests improved, without difference between the groups. In analysis with linear generalized models, the BMI decrease was associated with improvements in verbal memory, verbal fluency, executive function, and global cognition, after adjustment for education, gender, physical activity, and baseline tests. This association was strongest in younger seniors (for memory and fluency) and in APOE allele ϵ4 carriers (for executive function). Changes in homeostasis model assessment-estimated insulin resistance, C-reactive protein, leptin and intake of energy, carbohydrates, and fats were associated with improvement in cognitive tests. CONCLUSIONS: Intentional weight loss through diet was associated with cognitive improvement in patients with MCI.

Asunto(s)

RESUMEN

Deposition of amyloid-ß (Aß) peptides into specific encephalic structures has been pointed as an important event related to Alzheimer's disease pathogenesis and associated with activation of glial cells, neuroinflammation, oxidative responses, and cognitive deficits. Aß-induced pro-oxidative damage may regulate the activity of glutamate transporters, leading to reduced glutamate uptake and, as a consequence, excitotoxic events. Herein, we evaluated the effects of the pretreatment of atorvastatin, a HMG-CoA reductase inhibitor, on behavioral and biochemical alterations induced by a single intracerebroventricular (i.c.v.) injection of aggregated Aß1-40 in mice. Atorvastatin (10 mg/kg/day, p.o.) was administered through seven consecutive days before Aß1-40 administration. Aß1-40 caused significant cognitive impairment in the object-place recognition task (2 weeks after the i.c.v. injection) and this phenomenon was abolished by atorvastatin pretreatment. Ex vivo evaluation of glutamate uptake into hippocampal and cerebral cortices slices showed atorvastatin, and Aß1-40 decreased hippocampal and cortical Na(+)-dependent glutamate uptake. However, Aß1-40 increased Na(+)-independent glutamate uptake and it was prevented by atorvastatin in prefrontal cortex slices. Moreover, Aß1-40 treatment significantly increased the cerebrocortical activities of glutathione reductase and glutathione peroxidase and these events were blunted by atorvastatin pretreatment. Reduced or oxidized glutathione levels were not altered by Aß1-40 and/or atorvastatin treatment. These results extend the notion of the protective action of atorvastatin against neuronal toxicity induced by Aß1-40 demonstrating that a pretreatment with atorvastatin prevents the spatial learning and memory deficits induced by Aß in rodents and promotes changes in glutamatergic and antioxidant systems mainly in prefrontal cortex.

Asunto(s)