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The objective of the present study was to evaluate the effects of a novel Inhibin (INH) DNA vaccine (C500/pVAX-asd-IS) on the immune response, reproductive hormone levels, and spermatogenesis of rats. Forty healthy male rats were divided into four groups, and respectively immunized (thrice, 14 d apart) with 1×108, 1×109, and 1×1010 CFU of the recombinant inhibin vaccine (group C500/pVAX-asd-IS-L, C500/pVAX-asd-IS-M, and C500/pVAX-asd-IS-H) or 1×1010 CFU C500. P/N values increased after vaccination and differed (p <0.05) at 7 d, and sharply increased at 14 d following the booster vaccination (p <0.01); The weight and volume of testes in C500/pVAX-asd-IS groups were increased (p < 0.05) at decapitation, respectively; Histological evaluation showed that the number of spermatogenic cells in the lumen was increased, and the cytoplasmic remnants of sperms were allergy increased significantly compared with the control group. Oral vaccination with INH DNA reduced (P < 0.05) serum concentrations of INH B, enhanced serum concentrations of testosterone (T) and FSH. Furthermore, mRNA expressions of VIM and SMAD4 in the testes were increased in C500/pVAX-asd-IS-M and C500/pVAX-asd-IS-H groups (p < 0.05 or p < 0.01). The mRNA amount of INHß-B in C500/pVAX-asd-IS-M group was greater than control group (p < 0.05).These results suggested that neutralization of endogenous INH through oral vaccination with INH DNA delivered by C500 strain successfully elicited a humoral immune response. INH gene immunization may have a positive effect on spermatogenesis and reproductive efficiency in male rats.
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Rats are major reservoirs for pathogenic Leptospira, the bacteria causing leptospirosis, particularly in urban informal settlements. However, the impact of variation in rat abundance and pathogen shedding rates on spillover transmission to humans remains unclear. This study aimed to investigate how spatial variation in reservoir abundance and pathogen pressure affect Leptospira spillover transmission to humans in a Brazilian urban informal settlement. A longitudinal eco-epidemiological study was conducted from 2013 to 2014 to characterize the spatial distribution of rat abundance and Leptospira shedding rates in rats and determine the association with human infection risk in a cohort of 2,206 community residents. Tracking plates and live-trapping were used to measure rat abundance and quantify rat shedding status and load. In parallel, four sequential biannual serosurveys were used to identify human Leptospira infections. To evaluate the role of shedding on human risk, we built three statistical models for: (1) the relative abundance of rats, (2) the shedding rate by individual rats, and (3) human Leptospira infection, in which "total shedding", obtained by multiplying the predictions from those two models, was used as a risk factor. We found that Leptospira shedding was associated with older and sexually mature rats and varied spatially and temporally-higher at valley bottoms and with seasonal rainfall (December to March). The point estimate for "total shedding" by rat populations was positive, i.e., Leptospira infection risk increased with total shedding, but the association was not significant [odds ratio (OR) = 1.1; 95% confidence interval (CI): 0.9, 1.4]. This positive trend was mainly driven by rat abundance, rather than individual rat shedding (OR = 1.8; 95% CI: 0.6, 5.4 vs. OR = 1.0; 95% CI: 0.7, 1.4]. Infection risk was higher in areas with more vegetative land cover (OR = 2.4; 95% CI: 1.2, 4.8), and when floodwater entered the house (OR = 2.4; 95% CI: 1.6, 3.4). Our findings indicate that environmental and hydrological factors play a more significant role in Leptospira spillover than rat associated factors. Furthermore, we developed a novel approach combining several models to elucidate complex links between animal reservoir abundance, pathogen shedding and environmental factors on zoonotic spillover in humans that can be extended to other environmentally transmitted diseases.
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Reservatórios de Doenças , Leptospira , Leptospirose , Zoonoses , Animais , Humanos , Leptospirose/epidemiologia , Leptospirose/microbiologia , Leptospirose/transmissão , Leptospira/isolamento & purificação , Reservatórios de Doenças/microbiologia , Brasil/epidemiologia , Ratos , Zoonoses/microbiologia , Masculino , Feminino , Adulto , Derrame de Bactérias , Estudos Longitudinais , Pessoa de Meia-Idade , Fatores de Risco , População Urbana/estatística & dados numéricos , Adolescente , Adulto JovemRESUMO
Rodents are commonly used as animal models in studies investigating various experimental conditions, often requiring gene expression analysis. Quantitative real-time reverse transcription PCR (RT-qPCR) is the most widely used tool to quantify target gene expression levels under different experimental conditions in various biological samples. Relative normalization with reference genes is a crucial step in RT-qPCR to obtain reliable quantification results. In this work, the main reference genes used in gene expression studies among the three rodents commonly employed in scientific research-hamster, rat, and mouse-are analyzed and described. An individual literature search for each rodent was conducted using specific search terms in three databases: PubMed, Scopus, and Web of Science. A total of 157 articles were selected (rats = 73, mice = 79, and hamsters = 5), identifying various reference genes. The most commonly used reference genes were analyzed according to each rodent, sample type, and experimental condition evaluated, revealing a great variability in the stability of each gene across different samples and conditions. Classic genes, which are expected to be stably expressed in both samples and conditions analyzed, demonstrated greater variability, corroborating existing concerns about the use of these genes. Therefore, this review provides important insights for researchers seeking to identify suitable reference genes for their validation studies in rodents.
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Perfilação da Expressão Gênica , Padrões de Referência , Roedores , Animais , Camundongos , Ratos , Expressão Gênica/genética , Perfilação da Expressão Gênica/métodos , Perfilação da Expressão Gênica/normas , Reação em Cadeia da Polimerase em Tempo Real/normas , Reação em Cadeia da Polimerase em Tempo Real/métodos , Roedores/genéticaRESUMO
This review provides a comprehensive analysis of the pelvic plexus and its regulation across various mammalian species, including rats, cats, dogs, and pigs. The pelvic and hypogastric nerves play crucial roles in regulating pelvic functions such as micturition, defecation, and erection. The anatomical organization of these nerves varies, forming either well-defined ganglia or complex plexuses. Despite these variations, the neurons within these structures are consistently regulated by key neurotransmitters, norepinephrine and acetylcholine. These neurons also possess receptors for testosterone and prolactin, particularly in rats, indicating the significant role of these hormones in neuronal function and development. Moreover, neuropeptides such as vasoactive intestinal peptide (VIP), substance P, neuropeptide Y (NPY), somatostatin (SOM), galanin (GAL), and calcitonin gene-related peptide (CGRP) are co-released with neurotransmitters to modulate pelvic functions. This review highlights the complex interplay between neurotransmitters, neuropeptides, and hormones in regulating pelvic physiology and emphasizes the importance of hormonal regulation in maintaining the functionality and health of the pelvic plexus across different species.
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Glaucoma is the second leading cause of blindness worldwide and is, in most cases, a consequence of elevated intraocular pressure (IOP), ultimately resulting in the death of retinal ganglion cells (RGCs). Current treatments are mostly focused on normalizing IOP, but we propose the additional use of neuroprotective agents, including methylene blue (MB), to block the loss of RGCs. Wistar rats were subjected to episcleral vein cauterization (EVC) in the left eye while the right eye was sham-operated. One week later, they were divided into two groups, which were injected with either 2.0 mg/kg MB or phosphate-buffered saline (PBS), twice a day, for 7 days. Fifteen days after surgery, rats were tested with scotopic electroretinography (ERG) or pattern electroretinography (PERG). After sacrifice, the number of RGCs and the thickness of the inner retina (IR) were evaluated both in the peripheral and central areas of the retina. Scotopic ERG showed a marked reduction (p < 0.0001) on the a- and b-wave amplitude and oscillatory potential (OP) complexity of the eyes subjected to EVC. These parameters were significantly (p < 0.01) restored by the application of MB. PERG indicated that EVC was responsible for a very significant decrease in N2 amplitude (p < 0.0001) and prolongation of N2 implicit time (p < 0.0001). Treatment with MB significantly restored N2 amplitude (p < 0.0001). In parallel with the ERG results, morphological analysis showed a significant loss of RGCs (p < 0.0001) and IR thickness (p < 0.0001) in both the peripheral and central retinas subjected to EVC, which was significantly prevented (p < 0.0001) by MB treatment. We have shown that MB treatment can be effective in preventing physiological and morphological hallmarks of optic neuropathy in a model of ocular hypertension, which faithfully recapitulates human open-angle glaucoma. Due to its high safety profile, this drug could therefore represent a new pharmacologic strategy to prevent vision loss in glaucoma patients.
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This study aimed to investigate the toxicity of the fungicide ipconazole on oxidative status, cell death and inflammasome complex activation in the hypothalamus, cerebral cortex, striatum and hippocampus of rats. Female albino rats were randomly divided into a control group and four groups treated with ipconazole at doses of 1, 5, 10 and 20 mg/kg b.w., administered for six days. Ipconazole significantly increased MDA and ROS levels in all brain regions studied, while reducing catalase enzyme activity. The molecular expression of cell death-related genes (AKT1, APAF1, BNIP3, CASP3 and BAX) and the inflammasome complex (CASP1, IL1ß, IL6, NLRP3, NFĸB and TNFα) was also assessed, showing increased expression in at least one brain region. The findings demonstrate that ipconazole induces central nervous system toxicity in mammals, highlighting its potential role as a risk factor in the development of neurodegenerative disorders in individuals exposed to this contaminant.
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Body temperature is primarily regulated by the hypothalamus, ensuring proper metabolic function. Envenomation by Phoneutria nigriventer can cause symptoms such as hypothermia, hyperthermia, sweating, and shivering, all related to thermoregulation. This study aims to analyze and identify components of the venom that affect thermoregulation and to evaluate possible mechanisms. Rats were used for thermoregulation analysis, venom fractionation by gel filtration and reverse-phase chromatography (C18), and sequencing by Edman degradation. The venom exhibited hypothermic effects in rats, while its fractions demonstrated both hypothermic (pool II) and hyperthermic (pool III) effects. Further separations of the pools with C18 identified specific peaks responsible for these effects. However, as the peaks were further purified, their effects became less significant. Tests on U87 human glioblastoma cells showed no toxicity. Sequencing of the most active peaks revealed masses similar to those of the Tachykinin and Ctenotoxin families, both known to act on the nervous system. The study concludes that molecules derived from venom can act synergistically or antagonistically. Additionally, toxins that affect thermoregulation are poorly studied and require further characterization. These toxins could potentially serve as sources for the development of new thermoregulatory drugs.
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Regulação da Temperatura Corporal , Animais , Regulação da Temperatura Corporal/efeitos dos fármacos , Linhagem Celular Tumoral , Humanos , Masculino , Ratos Wistar , Ratos , Venenos de Escorpião/toxicidade , Venenos de Escorpião/química , Animais Peçonhentos , AranhasRESUMO
Introduction: Corneal ulcers are common lesions in both human and veterinary medicine. However, only a few studies have evaluated the efficacy of cross-linked hyaluronic acid (X-HA) eye drops on corneal wound healing. To our knowledge, this is the first study to demonstrate and compare the efficacy of amniotic membrane extract eye drops (AMEED) and X-HA for corneal wound healing in rats. Material and methods: A total of 15 male Wistar rats (30 eyes) were used in this study. Then, 10 eyes were treated with X-HA, AMEED, or 0.9% saline. After general and topical anesthesia, a superficial corneal ulcer was created using a corneal trephine. The defect was further polished with a diamond burr. Three groups of 10 eyes each were treated with either one drop of 0.75% X-HA or AMEED or 0.9% saline (control), administered every 12 h for a duration of 72 h. The median epithelial defect area (MEDA), expressed as a percentage of the total corneal surface, was measured at 0, 12, 24, 36, 48, and 72 h. Re-epithelization time scores were also evaluated. The Kruskal-Wallis test was used to compare median times for re-epithelization and histopathologic scores between groups, while the Friedman test (for paired data) was employed to compare results from the serial analysis of MEDA and vascularization scores between groups. Results: MEDA was not significantly different between X-HA and AMEED. However, MEDA was significantly smaller in the X-HA group compared to the control group at 36 h (2.73 interquartile range (IQR) 5.52% x 9.95 IQR 9.10%, P=0.024) and 48 h (0.00 IQR 0.26% x 6.30 IQR 8.54%, P=0.030). The overall time for re-epithelization was significantly lower in the X-HA group (3.00 IQR 3.00) compared to the AMEED (6.5 IQR 3.00) and control (7.00 IQR 1.00) groups (P=0.035). Vascularization, hydropic degeneration, and epithelial-stromal separation were significantly less observed in samples in the X-HA-treated compared to samples in the AMEED- and saline-treated groups. Significantly more corneal epithelium cells were labeled for caspase3 in samples from the AMEED- and saline-treated groups compared to those from the X-HA-treated group. Discussion: Topical X-HA has been shown to accelerate corneal epithelial healing. AMEED did not decrease corneal re-epithelialization time. X-HA may also potentially be used as an adjunct therapy for treating corneal ulcers in clinical situations.
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The rat is one of the most employed animal models in biomedicine. Traditionally, weight gain has been utilized to gauge development and compare across species. Numerous studies have conducted longitudinal analyses of rat development, with emphasis on weight gain analysis. Given the high variability in these patterns, experimental data from a single laboratory may not be reliable for generalized estimation. This study aimed to analyze the effect of different factors on the pattern of weight gain during rat development. A literature survey was conducted to compile a database comprising nearly 300 data points of age and weight from 15 longitudinal studies. The database comprised both pre- and postnatal data. Utilizing the Gompertz equation, the data was analyzed to formulate a comprehensive model describing rat development. Differences in growth patterns became increasingly evident at later developmental stages, when significant differences in the maximum asymptote between sexes and strains were reached.
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Revealing unknown cues that regulate oligodendrocyte progenitor cell (OPC) function in remyelination is important to optimise the development of regenerative therapies for multiple sclerosis (MS). Platelets are present in chronic non-remyelinated lesions of MS and an increase in circulating platelets has been described in experimental autoimmune encephalomyelitis (EAE) mice, an animal model for MS. However, the contribution of platelets to remyelination remains unexplored. Here we show platelet aggregation in proximity to OPCs in areas of experimental demyelination. Partial depletion of circulating platelets impaired OPC differentiation and remyelination, without altering blood-brain barrier stability and neuroinflammation. Transient exposure to platelets enhanced OPC differentiation in vitro, whereas sustained exposure suppressed this effect. In a mouse model of thrombocytosis (Calr+/-), there was a sustained increase in platelet aggregation together with a reduction of newly-generated oligodendrocytes following toxin-induced demyelination. These findings reveal a complex bimodal contribution of platelet to remyelination and provide insights into remyelination failure in MS.
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Plaquetas , Diferenciação Celular , Células Precursoras de Oligodendrócitos , Remielinização , Animais , Células Precursoras de Oligodendrócitos/fisiologia , Remielinização/fisiologia , Camundongos , Plaquetas/fisiologia , Encefalomielite Autoimune Experimental/patologia , Camundongos Endogâmicos C57BL , Esclerose Múltipla/patologia , Modelos Animais de Doenças , Oligodendroglia/fisiologia , FemininoRESUMO
(-)-Carvone, a ketone monoterpene, is the main component of essential oils from several medicinal plants and has been reported to have anti-arthriric, anticonvulsive, antidiabetic, anti-inflammatory, anticancer, and immunomodulatory effects. Therefore, this study aimed to investigate the spasmolytic activity of (-)-carvone in rodent models. The isolated virgin rat uterus was mounted in an organ bath apparatus, and the relaxing effect of ( -)-carvone and its mechanism of action were evaluated in tonic contractions induced by carbachol, KCl, PGF2α, or oxytocin. The animal model of primary dysmenorrhea was replicated with the injection of estradiol benzoate in female mice for three consecutive days, followed by intraperitoneal administration of oxytocin. Non-clinical acute toxicity evaluation was also performed. (-)-Carvone potency and effectiveness were larger in carbachol (pEC50 = 5.41 ± 0.14 and Emax = 92.63 ± 1.90% at 10-3 M) or oxytocin (pEC50 = 4.29 ± 0.17 and Emax = 86.69 ± 1.56% at 10-3 M) contractions. The effect of ( -)-carvone was altered in the presence of 4-aminopyridine, glibenclamide, L-NAME, or methylene blue. Mice pre-treated with (-)-carvone at a dose of 100 mg/kg showed a significant reduction in the number of writhing after oxytocin administration. No toxicity was observed after oral administration of 1 g/kg ( -)-carvone. Taken together, we showed that (-)-carvone reduced writhing by a spasmolytic effect, probably through the participation of KV and KATP channels and the nitric oxide pathway.
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Monoterpenos Cicloexânicos , Monoterpenos , Ocitocina , Útero , Animais , Ocitocina/farmacologia , Feminino , Monoterpenos Cicloexânicos/farmacologia , Camundongos , Útero/efeitos dos fármacos , Monoterpenos/farmacologia , Contração Uterina/efeitos dos fármacos , Ratos , Ratos Wistar , Parassimpatolíticos/farmacologia , Relaxamento Muscular/efeitos dos fármacos , Carbacol/farmacologiaRESUMO
Glioblastoma (GBM) is an aggressive form of cancer affecting the Central Nervous System (CNS) of thousands of people every year. Redox alterations have been shown to play a key role in the development and progression of these tumors as Reactive Oxygen Species (ROS) formation is involved in the modulation of several signaling pathways, transcription factors, and cytokine formation. The second-generation oral alkylating agent temozolomide (TMZ) is the first-line chemotherapeutic drug used to treat of GBM, though patients often develop primary and secondary resistance, reducing its efficacy. Antioxidants represent promising and potential coadjutant agents as they can reduce excessive ROS formation derived from chemo- and radiotherapy, while decreasing pharmacological resistance. S-allyl-cysteine (SAC) has been shown to inhibit the proliferation of several types of cancer cells, though its precise antiproliferative mechanisms remain poorly investigated. To date, SAC effects have been poorly explored in GBM cells. Here, we investigated the effects of SAC in vitro, either alone or in combination with TMZ, on several toxic and modulatory endpoints-including oxidative stress markers and transcriptional regulation-in two glioblastoma cell lines from rats, RG2 and C6, to elucidate some of the biochemical and cellular mechanisms underlying its antiproliferative properties. SAC (1-750 µM) decreased cell viability in both cell lines in a concentration-dependent manner, although C6 cells were more resistant to SAC at several of the tested concentrations. TMZ also produced a concentration-dependent effect, decreasing cell viability of both cell lines. In combination, SAC (1 µM or 100 µM) and TMZ (500 µM) enhanced the effects of each other. SAC also augmented the lipoperoxidative effect of TMZ and reduced cell antioxidant resistance in both cell lines by decreasing the TMZ-induced increase in the GSH/GSSG ratio. In RG2 and C6 cells, SAC per se had no effect on Nrf2/ARE binding activity, while in RG2 cells TMZ and the combination of SAC + TMZ decreased this activity. Our results demonstrate that SAC, alone or in combination with TMZ, exerts antitumor effects mediated by regulatory mechanisms of redox activity responses. SAC is also a safe drug for testing in other models as it produces non-toxic effects in primary astrocytes. Combined, these effects suggest that SAC affords antioxidant properties and potential antitumor efficacy against GBM.
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Acanthamoeba genus can affect humans with diseases such as granulomatous amebic encephalitis (GAE), a highly lethal neuroinfection. Several aspects of the disease still need to be elucidated. Animal models of GAE have advanced our knowledge of the disease. This work tested Wistar rats (Rattus norvegicus albinus) as an animal model of GAE. For this, 32 animals were infected with 1 × 106A. castellanii trophozoites of the T4 genotype. Ameba recovery tests were carried out using agar plates, vascular extravasation assays, behavioral tests, and histopathological technique with H/E staining. Data were subjected to linear regression analysis, one-way ANOVA, and Tukey's test, performed in the GraphPad Prism® 8.0 program, with a significance level of p < 0.05. The results revealed the efficiency of the model. Amebae were recovered from the liver, lungs, and brain of infected animals, and there were significant encephalic vascular extravasations and behavioral changes in these animals, but not in the control animals. However, not all infected animals showed positive histopathology for the analyzed organs. Nervous tissues were the least affected, demonstrating the role of the BBB in the defense of the CNS. Supported by the demonstrated evidence, we confirm the difficulties and the feasibilities of using rats as an animal model of GAE.
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Early life stress (ELS) is a risk factor for the development of chronic diseases resulting from functional alterations of organs in the cardiorespiratory and renal systems. This work studied the changes in oxidative stress enzyme activities (EAs) of SOD, CAT, GPX, GR, GST, NOS, MDA, and FRAP in different organs (heart, liver, kidney, adrenal glands (AGs), and pancreas) of male and female Sprague-Dawley rat pups on postnatal day (PN) 15, immediately after basal and acute or chronic stress conditions were accomplished, as follows: basal control (BC; undisturbed maternal pups care), stress control (SC; 3 h maternal separation on PN15), basal maternal separation (BMS; daily 3 h maternal separation on PN 1-14), and stress maternal separation (SMS; daily 3 h maternal separation on PN 1-14 and 3 h maternal separation on PN15). Acute or long-term stress resulted in overall oxidative stress, increase in EA, and reduced antioxidant capacity in these organs. Some different response patterns, due to precedent SMS, were observed in specific organs, especially in the AGs. Acute stress exposure increases the EA, but chronic stress generates a response in the antioxidant system in some of the organs studied and is damped in response to a further challenge.
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Osteonecrosis of the jaw (ONJ) is a relatively rare side effect after prolonged use of bisphosphonates, which are drugs used to treat bone resorption in osteoporosis and certain cancers. This study introduces a novel ONJ model in rats by combining exposure to bisphosphonates, oral surgery, and bacterial inoculation. Potential ONJ preventive effects of polyguanidine (GuaDex) or antibiotics were evaluated. The study consisted of twenty-four male Wistar rats were divided into four groups. Groups 1 to 3 were given weekly doses of i.v. Zoledronic acid (ZA), four weeks before and two weeks after an osteotomy procedure on their left mandibular first molar. Group 4 was a negative control. Streptococcus gordonii bacteria were introduced into the osteotomy pulp chamber and via the food for seven days. On day eight, the rats were given different treatments. Group 1 was given a GuaDex injection into the osteotomy socket, Group 2 was given an intramuscular (i.m.) injection of clindamycin, Group 3 (positive control) was given an i.m. injection of saline, and Group 4 was given an i.m. injection of saline. Blood samples were taken two weeks after the osteotomy procedure, after which the rats were euthanized. Bone healing, bone mineral density, histology, and blood status were analyzed. The results showed that Group 1 (GuaDex) had no ONJ, extensive ongoing bone regeneration, active healing activity, vascularization, and no presence of bacteria. Group 2 (clindamycin) showed early stages of ONJ, avascular areas, and bacteria. Group 3 showed stages of ONJ, inflammatory infiltrates, defective healing, and bacterial presence, and Group 4 had normal healing activity and no bacterial presence. Conclusion: ZA treatment and bacterial inoculation after tooth extraction inhibited bone remodeling/healing and induced ONJ characteristic lesions in the rats. Only GuaDex apparently prevented ONJ development, stimulated bone remodeling, and provided an antimicrobial effect.
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Osteonecrose da Arcada Osseodentária Associada a Difosfonatos , Ratos Wistar , Animais , Masculino , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/prevenção & controle , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/patologia , Ratos , Difosfonatos/farmacologia , Difosfonatos/efeitos adversos , Guanidinas/farmacologia , Guanidinas/uso terapêuticoRESUMO
α-Bisabolol (α-BIS) is a sesquiterpene alcohol present in chamomile essential oil [Chamomilla recutita (L.) Rauschert]. Despite its numerous pharmacological effects, its pharmacokinetics remain understudied. An analytical method capable of quantifying α-BIS in plasma is crucial to enable pharmacokinetic analysis. Presently, only one study has quantified it using mass spectrometry. Administering α-BIS requires a nanoemulsion for intravenous injection. This study aimed to develop and validate a bioanalytical method using high-performance liquid chromatography with an ultraviolet detector to quantify α-BIS in rat plasma. The method employed acetonitrile and ultrapure water (80:20, v/v) as the mobile phase, with a flow rate of 1 ml/min and concentrations ranging from 465 to 29.625 µg/ml. All US Food and Drug Administration-designated assays were successful, indicating the method's precision, accuracy, sensitivity and linearity in determining α-BIS in rat plasma. The developed nanoemulsion, assessed through dynamic light scattering analysis, the ensemble collection of particles and polydispersity index evaluation, proved safe and effective for intravenous administration. The pharmacokinetic parameters such as volume of distribution, clearance and half-life indicated that α-BIS tends to persist in the body. This study provides a foundation for further research to explore α-BIS's potential pharmaceutical applications in the future.
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Emulsões , Sesquiterpenos Monocíclicos , Animais , Cromatografia Líquida de Alta Pressão/métodos , Ratos , Emulsões/química , Reprodutibilidade dos Testes , Sesquiterpenos Monocíclicos/farmacocinética , Sesquiterpenos Monocíclicos/sangue , Sesquiterpenos Monocíclicos/química , Masculino , Projetos Piloto , Modelos Lineares , Limite de Detecção , Sesquiterpenos/farmacocinética , Sesquiterpenos/sangue , Sesquiterpenos/química , Ratos Sprague-Dawley , Espectrofotometria Ultravioleta/métodosRESUMO
This study analyzes the extracellular matrix (ECM) signatures of the outer (OF = capsule + subcapsular + zona glomerulosa cells) and inner fractions (IF = zona fasciculata cells) of the rat adrenal cortex, which comprise two distinct microenvironment niches. Proteomic profiles of decellularized OF and IF samples, male and female rats, identified 252 proteins, with 32 classified as ECM-component and ECM-related. Among these, 25 proteins were differentially regulated: 17 more abundant in OF, including Col1a1, Col1a2, Col6a1, Col6a2, Col6a3, Col12a1, Col14a1, Lama5, Lamb2, Lamc1, Eln, Emilin, Fbln5, Fbn1, Fbn2, Nid1, and Ltbp4, and eight more abundant in IF, including Col4a1, Col4a2, Lama2, Lama4, Lamb1, Fn1, Hspg2, and Ecm1. Eln, Tnc, and Nid2 were abundant in the female OF, while Lama2, Lama5, Lamb2, and Lamc1 were more abundant in the male IF. The complex protein signature of the OF suggests areas of tissue stress, stiffness, and regulatory proteins for growth factor signaling. The higher concentrations of Col4a1 and Col4a2 and their role in steroidogenesis should be further investigated in IF. These findings could significantly enhance our understanding of adrenal cortex functionality and its implications for human health and disease. Key findings were validated, and data are available in ProteomeXchange (PXD046828).
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Córtex Suprarrenal , Proteínas da Matriz Extracelular , Animais , Feminino , Masculino , Ratos , Proteínas da Matriz Extracelular/metabolismo , Córtex Suprarrenal/metabolismo , Proteômica/métodos , Matriz Extracelular/metabolismo , Zona Glomerulosa/metabolismo , Zona Fasciculada/metabolismo , Proteoma/análise , Proteoma/metabolismoRESUMO
Oxidative stress (OS) and endoplasmic reticulum stress (ERS) are at the genesis of placental disorders observed in preeclampsia, intrauterine growth restriction, and maternal hypothyroidism. In this regard, cationic manganese porphyrins (MnPs) comprise potent redox-active therapeutics of high antioxidant and anti-inflammatory potential, which have not been evaluated in metabolic gestational diseases yet. This study evaluated the therapeutic potential of two MnPs, [MnTE-2-PyP]5+ (MnP I) and [MnT(5-Br-3-E-Py)P]5+ (MnP II), in the fetal-placental dysfunction of hypothyroid rats. Hypothyroidism was induced by administration of 6-Propyl-2-thiouracil (PTU) and treatment with MnPs I and II 0.1 mg/kg/day started on the 8th day of gestation (DG). The fetal and placental development, and protein and/or mRNA expression of antioxidant mediators (SOD1, CAT, GPx1), hypoxia (HIF1α), oxidative damage (8-OHdG, MDA), ERS (GRP78 and CHOP), immunological (TNFα, IL-6, IL-10, IL-1ß, IL-18, NLRP3, Caspase1, Gasdermin D) and angiogenic (VEGF) were evaluated in the placenta and decidua on the 18th DG using immunohistochemistry and qPCR. ROS and peroxynitrite (PRX) were quantified by fluorometric assay, while enzyme activities of SOD, GST, and catalase were evaluated by colorimetric assay. MnPs I and II increased fetal body mass in hypothyroid rats, and MnP I increased fetal organ mass. MnPs restored the junctional zone morphology in hypothyroid rats and increased placental vascularization. MnPs blocked the increase of OS and ERS mediators caused by hypothyroidism, showing similar levels of expression of HIFα, 8-OHdG, MDA, Gpx1, GRP78, and Chop to the control. Moreover, MnPs I and/or II increased the protein expression of SOD1, Cat, and GPx1 and restored the expression of IL10, Nlrp3, and Caspase1 in the decidua and/or placenta. However, MnPs did not restore the low placental enzyme activity of SOD, CAT, and GST caused by hypothyroidism, while increased the decidual and placental protein expression of TNFα. The results show that treatment with MnPs improves the fetal-placental development and the placental inflammatory state of hypothyroid rats and protects against oxidative stress and reticular stress caused by hypothyroidism at the maternal-fetal interface.
Assuntos
Hipotireoidismo , Inflamassomos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Estresse Oxidativo , Animais , Gravidez , Feminino , Ratos , Hipotireoidismo/tratamento farmacológico , Hipotireoidismo/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Inflamassomos/metabolismo , Modelos Animais de Doenças , Placenta/metabolismo , Placenta/efeitos dos fármacos , Placentação/efeitos dos fármacos , Antioxidantes/farmacologia , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Desenvolvimento Fetal/efeitos dos fármacos , Manganês , Metaloporfirinas/farmacologia , Chaperona BiP do Retículo EndoplasmáticoRESUMO
A rotor design of a Ram Air Turbine (RAT) for a commercial aircraft was created taking three sections with different airfoils along the blade; those sections were assessed to evaluate their performance at different critical velocities (41, 81 and 251 m/s) and choose the best profile configuration generating a new proposal to increase the glide ratio by reducing the drag, which is helpful in emergency cases. The Blade Element Momentum (BEM) theory and Computational Fluid Dynamics (CFD) were used to analyze an initial design, then validating these results with the open software QBlade. For the BEM theory a program was created for the design and performance of the RAT adding the Viterna methodology for airfoil analysis. 16 designs were proposed by strategically interchanging wing profiles in different blade sections. These designs were analyzed by CFD, using the complete rotor and the S S T k - ω turbulence model. An optimal geometry was found, presenting a significant drag reduction of 25% generating an increase in the glide ratio and improving aircraft control in addition to maintaining the power generation above the desired values; therefore, it recommends using different airfoils for each section of a RAT's rotor blade.
RESUMO
Obesity is a global health problem and is increasing in prevalence in most countries. Although obesity affects all age groups, children are the most vulnerable sector. Functional foods are novel formulated foods containing substances (i.e., nutrients, phytochemicals, probiotics, etc.) that have potential health-enhancing or disease-preventing value. The research objective was to study the possible beneficial effects of providing a functional food made with amaranth flour, chia seed, and curcumin extract on the metabolism and behavior of a rat model of childhood obesity. Male Wistar rat pups from two litters of different sizes, a normal litter (NL) (10 pups) and a small litter (SL) (4 pups), were used. After weaning, the rats were fed a hypercaloric diet (HD) or an HD supplemented with the functional food mixture. Body weight and energy intake were measured for seven weeks, and locomotor activity, learning, and memory tests were also performed. At the end of the experiment, glucose and lipid metabolism parameters were determined. The results showed that in this model of obesity produced by early overfeeding and the consumption of a hypercaloric diet, anxiety-like behaviors and metabolic alterations occurred in the rat offspring; however, the provision of the functional food failed to reduce or prevent these alterations, and an exacerbation was even observed in some metabolic indicators. Interestingly, in the NL rats, the provision of the functional food produced some of the expected improvements in health, such as significant decreases in body weight gain and liver cholesterol and non-significant decreases in adipose tissue and leptin and insulin serum levels.