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The study examined the antihypertensive effect of peptides derived from pepsin-hydrolyzed corn gluten meal, namely KQLLGY and PPYPW, and their in silico gastrointestinal tract digested fragments, KQL and PPY, respectively. KQLLGY and PPYPW showed higher angiotensin I-converting enzyme (ACE)-inhibitory activity and lower ACE inhibition constant (Ki) values when compared to KQL and PPY. Only KQL showed a mild antihypertensive effect in spontaneously hypertensive rats with -7.83 and - 5.71 mmHg systolic and diastolic blood pressure values, respectively, after 8 h oral administration. During passage through Caco-2 cells, KQL was further degraded to QL, which had reduced ACE inhibitory activity. In addition, molecular dynamics revealed that the QL-ACE complex was less stable compared to the KQL-ACE. This study reveals that structural transformation during peptide permeation plays a vital role in attenuating antihypertensive effect of the ACE inhibitor peptide.
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Inibidores da Enzima Conversora de Angiotensina , Anti-Hipertensivos , Peptidil Dipeptidase A , Zea mays , Animais , Humanos , Masculino , Ratos , Inibidores da Enzima Conversora de Angiotensina/química , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Inibidores da Enzima Conversora de Angiotensina/metabolismo , Anti-Hipertensivos/química , Anti-Hipertensivos/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Células CACO-2 , Digestão/efeitos dos fármacos , Trato Gastrointestinal/metabolismo , Glutens/química , Glutens/metabolismo , Hidrólise , Hipertensão/metabolismo , Hipertensão/tratamento farmacológico , Hipertensão/fisiopatologia , Peptídeos/química , Peptídeos/farmacologia , Peptidil Dipeptidase A/química , Peptidil Dipeptidase A/metabolismo , Hidrolisados de Proteína/química , Hidrolisados de Proteína/farmacologia , Ratos Endogâmicos SHR , Zea mays/química , Zea mays/metabolismoRESUMO
Schizophrenia is a psychiatric disorder characterized by cognitive dysfunctions. These dysfunctions significantly impact the daily lives of schizophrenic patients, yet effective interventions remain scarce. In this study, we explored the effects of two enriched housing types-cognitive and physical-on cognitive dysfunctions in a rat model of schizophrenia. Male neonatal Wistar-Imamichi rats were administered MK-801, a noncompetitive NMDAR antagonist, twice daily from postnatal day (PND) 7 to PND 20. Physical enrichment ameliorated memory deficits in both object and place recognition tests, while cognitive enrichment primarily improved object recognition performance. Our findings suggest that exercise therapy could be a potential approach to address cognitive dysfunctions in schizophrenia patients.
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Modelos Animais de Doenças , Maleato de Dizocilpina , Ratos Wistar , Reconhecimento Psicológico , Esquizofrenia , Animais , Esquizofrenia/tratamento farmacológico , Esquizofrenia/fisiopatologia , Masculino , Reconhecimento Psicológico/efeitos dos fármacos , Reconhecimento Psicológico/fisiologia , Maleato de Dizocilpina/farmacologia , Ratos , Abrigo para Animais , Antagonistas de Aminoácidos Excitatórios/farmacologia , Antagonistas de Aminoácidos Excitatórios/administração & dosagem , Psicologia do Esquizofrênico , Animais Recém-Nascidos , Transtornos da Memória/etiologia , Transtornos da Memória/tratamento farmacológicoRESUMO
Experimental elevation of intraocular pressure (IOP), a major glaucoma risk factor, has been a mainstay of research into mechanisms of glaucomatous optic nerve damage for decades. Methods that produce sustained IOP elevation can mimic the chronic nature of glaucoma and produce optic nerve damage. However, the pressure course for individual animals can be variable, unpredictably high at times, and difficult to monitor with current tonometry methods. All of this can complicate correlations of pressure history with axonal injury. An alternative is to control the extent and duration of IOP elevation over a period of several hour-long enough to produce axonal injury and gene expression changes within the optic nerve head that may indicate cellular mechanisms of glaucomatous optic nerve damage. The prolonged general anesthesia that this requires does have the potential to reduce systemic blood pressure, which may contribute to axonal injury in the face of elevated IOP. This chapter will describe our Controlled Elevation of IOP (CEI) model in laboratory rats. We will include methods for applying this to several animals at a time, as well as how to maintain blood pressure, oxygenation, and body temperature to ensure that the resulting injury and tissue events reflect the effects of elevated IOP on optic nerve tissues and not simply reduced ocular perfusion and ischemia.
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Modelos Animais de Doenças , Glaucoma , Pressão Intraocular , Animais , Pressão Intraocular/fisiologia , Glaucoma/fisiopatologia , Glaucoma/patologia , Ratos , Nervo Óptico/patologia , Nervo Óptico/metabolismo , Tonometria Ocular/métodos , Pressão SanguíneaRESUMO
Abstract Introduction: Adverse or favourable rearing conditions early in life affect emotional response during adolescence. To study the effect of early rearing on emotional response, animal models such as maternal separation (MS) and social enrichment (SE) by community nesting have been useful. However, the comparison of the effect of MS and SE on anxiety-related behaviours in adolescent rats is unknown. Objective: This study aimed to assess the effects of MS and SE on the emotional response of adolescent rats exposed to the elevated plus-maze test (EPM). Method: Pregnant Wistar rats were randomly distributed into three groups according to the rearing condition. In the MS group, pups were separated daily from their dams for 180 minutes, from postnatal day (P) 2 to 14. In the SE group, two females that gave birth synchronously were housed in a cage with a litter of eight pups. Females from control standard housing (SH) were individually housed and kept with their offspring until weaning (P23). On P32, anxiety-related measures were evaluated using an EPM. Results: MS and SE increase anxiety-related behaviours and locomotion in rats exposed to the EPM. SE had sex-dependent effects on anxiety-related measures, increasing vertical activity in females and horizontal activity in males. MS but not SE increased body weight gain in female rats. Conclusion: Adverse or favourable rearing conditions early in life may result in an increased anxiety phenotype in the EPM during adolescence. It is likely that the favourable effect of SE depends on the number of dams per communal nest.
Resumen Introducción: Las condiciones de crianza adversas o favorables en etapas tempranas de la vida afectan la respuesta emocional durante la adolescencia. Para estudiar el efecto de la crianza temprana sobre la respuesta emocional, han sido útiles modelos animales como la separación materna (SM) y el enriquecimiento social (ES) mediante anidamiento comunitario. Sin embargo, se desconoce la comparación del efecto de la SM y el ES sobre las conductas relacionadas con la ansiedad en ratas adolescentes. Objetivo: Este estudio pretende evaluar los efectos de la SM y el ES sobre la respuesta emocional de ratas adolescentes expuestas al test del laberinto en cruz elevado (EPM). Método: Las ratas Wistar preñadas se distribuyeron aleatoriamente en tres grupos según la condición de crianza. En el grupo SM, las crías fueron separadas diariamente de sus madres durante 180 minutos, desde el día postnatal (P) 2 hasta el 14. En el grupo ES, dos hembras que parieron de forma sincronizada se alojaron en una caja con una camada de ocho crías. Las hembras del alojamiento estándar de control (SH) se alojaron individualmente y se mantuvieron con sus crías hasta el destete (P23). En P32, se evaluaron las medidas relacionadas con la ansiedad mediante un EPM. Resultados: La SM y el ES aumentan las conductas relacionadas con la ansiedad y la locomoción en las ratas expuestas al EPM. El ES tuvo efectos dependientes del sexo en las medidas relacionadas con ansiedad, aumentando la actividad vertical en las hembras y la actividad horizontal en los machos. La SM, pero no el ES, incrementó la ganancia de peso corporal en las ratas hembra. Conclusiones: Condiciones de crianza adversas o favorables en etapas tempranas de la vida pueden dar lugar a un fenotipo de ansiedad aumentado en el EPM durante la adolescencia. Es probable que el efecto favorable del ES dependa del número de hembras por nido comunitario.
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PURPOSE: Bufalin (BU) is a bioactive ingredient extracted from the skin and parotid venom glands of Bufo raddei, which can effectively inhibit angiogenesis. The aim of this study was to investigate whether BU could affect corneal neovascularization (CoNV). METHODS: A rat CoNV model (right eye) was constructed by administration of NaOH, and the left eye served as a control. Corneal damage scores of rats were detected. Hematoxylin & eosin, TUNEL, and Masson staining examined pathological changes, apoptosis, and fibrosis of corneal tissues. Immunohistochemistry and western blotting assessed the expression of proteins. RESULTS: BU intervention resulted in a significant reduction in corneal inflammatory cells, repair of corneal epithelial hyperplasia, significant reduction in stromal edema, and reduction in vascular proliferation. BU can inhibit corneal neovascularization. CONCLUSION: This study demonstrated that BU inhibits CoNV, fibrosis, and inflammation by modulating the STAT3 signaling pathway, elucidating the intrinsic mechanism of its protective effect. BU has great potential in the treatment of CoNV caused by corneal alkali burns.
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Introduction Type 2 diabetes mellitus (T2DM) is characterized by insulin resistance, impaired insulin secretion, and beta cell dysfunction, often leading to chronic hyperglycemia and associated complications. Berberis asiatica (BA) and Withania somnifera (WS) are ancient medicinal plants with a reputation for having potential therapeutic effects in diabetes management. The purpose of this study was to look into how body weight (BW) was affected in streptozotocin-nicotinamide (STZ-NIC) induced T2DM in Wistar rats by BA, WS, and their polyherbal combination (PHC). Materials and methods Seventy-eight Wistar rats of both sexes were divided into 13 groups, with six rats in each group, including normal and diabetic controls, and treated with varying doses of BA, WS, and PHC. The rats were under observation over the course of 35 days for any change in BW. The Organization for Economic Co-operation and Development (OECD) rules and guidelines were followed in the conduct of acute toxicity tests. One-way analysis of variance (ANOVA), followed by Tukey-Kramer post hoc tests, was used for statistical analysis. Results The findings indicated that the highest dose of BA (1000 mg/kg) significantly improved BW in diabetic rats, approaching that of the normal control group. The combination of BA and WS also demonstrated significant improvements in BW, suggesting a synergistic effect. The standard antidiabetic drugs, metformin and glimepiride, were effective in increasing BW in diabetic rats. Conclusion The study concludes that BA, WS, and their combination have a positive impact on BW management in T2DM rats, with the combination therapy showing enhanced effects. These findings support the potential utilization of these herbs in managing BW and other T2DM-associated metabolic disturbances and abnormalities.
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Polycystic ovary syndrome (PCOS) is a complex endocrine and metabolic disorder characterized by hyperandrogenism, prolonged anovulation and polycystic ovaries. However, there are no effective interventions to treat this disorder. As previously shown, mangiferin modulated the AMPK and NLRP3 signal pathways to alleviate nonalcoholic fatty liver disease (NAFLD). In recent years, mangiferin has emerged as a promising drug candidate for treating metabolic diseases. In this study, we evaluated the effects of mangiferin on a letrozole (LET) combined with high-fat diet (HFD)-induced PCOS rat model through estrous cycle detection, serum/tissue biochemical analysis, and hematoxylin and eosin (HE) staining of ovarian tissue. The mechanisms of mangiferin's effects on PCOS rats were analyzed using 16S rRNA sequencing, RNA-seq, western blotting (WB), and immunohistochemical (IHC) staining. Our results displayed that mangiferin showed a promising effect in PCOS rats. It improved lipid metabolism, glucose tolerance, insulin resistance, hormonal imbalance, ovarian dysfunction, and adipocyte abnormalities. RNA-seq analysis indicated that mangiferin may be involved in several signal pathways, including apoptosis, necrosis, and inflammation. Furthermore, western blot and immunohistochemical staining demonstrated that mangiferin regulates Caspase-3 and Cytc, exhibiting anti-apoptotic activity in the ovaries. Additionally, mangiferin significantly altered the gut microbiota community of PCOS rats, changing the abundance of firmicutes, bacteroidota, proteobacteria, and actinobacteria at the phylum level and the abundance of Blautia, Coprococcus, Roseburia, and Pseudomonas at the genus level. In conclusion, mangiferin is a promising and novel therapeutic agent for PCOS as it ameliorates insulin resistance, gut microbiota and ovarian cell apoptosis.
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Traumatic brain injury (TBI) remains a significant global public health epidemic with adverse health and cost implications. Due to its complex, heterogeneous nature and wide-ranging impacts, definitive TBI treatments remain elusive. As such, continued laboratory research using animal models is warranted. In accordance with guidelines set forth for the humane treatment of research animals, TBI animal models are often administered analgesics for pain management. The choice of drug, timing, dose, and formulation of analgesic can vary depending on the study's unique needs and can potentially and unintentionally influence experimental results. In TBI studies utilizing rats as animal models, buprenorphine is a common analgesic administered. In addition to pain management in such studies, investigators must also monitor the research animals post-operatively and make the decision for humane euthanasia before intended experimental survival timepoint if the animals are assessed to be excessively suffering. This study investigated the differences in adult, male Sprague Dawley rats used for various TBI studies that reached weight-loss-induced humane endpoints following a single administration of buprenorphine slow-release LAB (bup-SR-LAB) or buprenorphine slow-release HCl (bup-SR-HCl). Our findings indicate that TBI-induced rats receiving bup-SR-LAB in conjunction with a secondary surgical insult such as artificial intracranial pressure elevation and/or osmotic pump implantation reach a weight-loss-induced humane euthanasia endpoint more often compared to sham-injured rats. When stratifying into the same groups, we did not find this pattern to hold true for rats administered bup-SR-HCl. Overall, this study contributes to the limited body of literature addressing different analgesic formulations' effects on laboratory animals.
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Studies on the pathophysiology of shoulder contracture and development of interventions have greatly benefited from the use of animal models. This narrative review comprehensively analyzes research on established rat model of shoulder contracture and new treatment approaches. This review evaluated existing literature on the available techniques for inducing contracture models, assessed these models, conducted pathological analyses, and explored their application in developing new treatment interventions. Our review highlights the usefulness of different rat shoulder contracture models, including external immobilization, internal immobilization, and intra-articular injection models, each with varying levels of success. Pathological analyses have demonstrated similarities to the human condition. The effective models have been instrumental in developing new treatment interventions, including recombinant human relaxin-2, platelet-rich plasma, collagenase clostridium histolyticum, and peroxisome proliferator-activated receptor-γ agonists. Therefore, rat shoulder contracture models serve as valuable tools for researchers to establish an effective animal model foundation for investigating the etiology and potential treatment.
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The present study examined the effect of two dietary regimens with elevated salt concentrations (4% and 8% salt) on hemorheological functions of SD rats, and explored the underlying mechanisms mainly through microbiome-metabolome analysis. An 8% HSD substantially altered the hemorheological parameters, and compromised intestinal barrier integrity and reduced the short-chain fatty acid levels. The microbiome-metabolome analysis revealed that 49 genus-specific microorganisms and 156 metabolites showed a consistent trend after exposure to both 4% and 8% HSDs. Pathway analysis identified significant alterations in key metabolites within bile acid and arachidonic acid metabolism pathways. A two-sample Mendelian randomization (MR) analysis verified the link between high dietary salt intake and hemorheology. It also suggested that some key microbes and metabolites (such as Ruminococcaceae_UCG-005, Lachnospiraceae_NK4A136, Ruminiclostridium_6, and Ruminococcaceae_UCG-010, TXB-2, 11,12-diHETrE, glycochenodeoxycholate) may involve in abnormalities in blood rheology caused by high salt intake. Collectively, our findings underscored the adverse effects of high dietary salt on hemorheological functions and provide new insight into the underlying mechanism based on microbiome-metabolome analysis.
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BACKGROUND: Chronic constipation is a gastrointestinal functional disorder which affects patient quality of life. Therefore, many studies were oriented to search herbal laxative agents. In this study, we investigated the phytochemical composition of beetroot juice (BJ) and its laxative potential in an experimental model of constipation and colonic dysmotility induced by loperamide (LOP) in Wistar rats. METHODS: Animals were concurrently pretreated with LOP (3 mg/kg, b.w., i.p.) and BJ (5 and 10 mL/kg, b.w., p.o.), or yohimbine (2 mg/kg, b.w., i.p.), during 1 week. The laxative activity was determined based on the weight, frequency, and water content of the feces matter. The gastric-emptying test and intestinal transit were determined. Colon histology was examined, and oxidative status was evaluated using biochemical-colorimetric methods. KEY RESULTS: The in vivo study revealed that LOP induced a significant inhibition of gastrointestinal motility, negative consequences on defecation parameters, oxidative stress, and colonic mucosa lesions. Conversely, administration of BJ reestablished these parameters and restored colonic oxidative balance. Importantly, BJ treatment protected against LOP-induced inflammatory markers (pro-inflammatory cytokines and WBC) and the increase in intracellular mediators such as hydrogen peroxide, free iron, and calcium levels. CONCLUSIONS & INFERENCES: This study demonstrated that the bioactive compounds in BJ provided an anti-constipation effect by modulating intestinal motility and regulating oxidative stress and inflammation induced by LOP intoxication.
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In this work, an optimal air supply mode was selected to create a model of cerebral arterial air embolism (CAAE) on conscious male Sprague-Dawley rats (n=49). The efficacy of the selected model (administration of 100 µl/kg of air at a rate of 10 µl/min with an infusion pump) was determined by changes in serum biochemical parameters (cholesterol, alkaline phosphatase, inorganic phosphates, AST, and triglycerides), impaired motor functions in the Rotarod test, and visual assessment of the ischemic foci (staining of frontal sections with 1% triphenyltetrazolium chloride solution) at different terms after AAE. The model of AAE created by us confirmed impairment of coordination and motor function in conscious animals and reproduced the lethal consequences of this condition. The obtained results can serve as the basis for drug testing and the development of new approaches to the treatment of ischemic stroke.
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Modelos Animais de Doenças , Embolia Aérea , Ratos Sprague-Dawley , Animais , Masculino , Ratos , Estado de Consciência/fisiologia , Fosfatase Alcalina/sangue , Colesterol/sangue , Triglicerídeos/sangueRESUMO
The age-related loss of muscle mass is partly accounted for by the loss of sarcomeres in series, contributing to declines in muscle mechanical performance. Resistance training biased to eccentric contractions increases serial sarcomere number (SSN) in young muscle, however, maximal eccentric training in old rats previously did not alter SSN and worsened performance. A submaximal eccentric training stimulus may be more conducive to adaptation for aged muscle. The purpose of this study was to assess whether submaximal eccentric training can increase SSN and improve mechanical function in old rats. Twelve 32-month-old male F344/BN rats completed 4 weeks of submaximal (60% maximum) eccentric plantar-flexion training 3 days/week. Pre- and post-training, we assessed in-vivo maximum isometric torque at a stretched and neutral ankle angle, the passive torque-angle relationship, and the isotonic torque-velocity-power relationship. The soleus and medial gastrocnemius (MG) were harvested for SSN measurements via laser diffraction, with the untrained leg as a control. SSN increased 11% and 8% in the soleus and MG, respectively. Training also shifted optimal torque production towards longer muscle lengths, reduced passive torque 42%, and increased peak isotonic power 23%. Submaximal eccentric training was beneficial for aged muscle adaptations, increasing SSN, reducing muscle passive tension, and improving dynamic contractile performance.
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Músculo Esquelético , Condicionamento Físico Animal , Ratos Endogâmicos F344 , Treinamento Resistido , Sarcômeros , Animais , Masculino , Músculo Esquelético/fisiologia , Sarcômeros/fisiologia , Ratos , Condicionamento Físico Animal/fisiologia , Condicionamento Físico Animal/métodos , Treinamento Resistido/métodos , Envelhecimento/fisiologia , Torque , Contração Muscular/fisiologia , Ratos Endogâmicos BN , Contração Isométrica/fisiologia , Força Muscular/fisiologiaRESUMO
Neurotrophic growth factor (GF) loaded hydrogels have shown promise as a treatment approach for spinal cord injury (SCI). However, SCI presents complex challenges for the direct administration of treatment due to the spinal cord's intricate anatomy and highly sensitive environment. Many current hydrogel administration approaches overlook this complexity, limiting their translational potential. To address this, we propose a novel intrathecal administration method using an in situ gelling, hyaluronic acid-modified heparin-poloxamer hydrogel loaded with neurotrophin-3 (NT-3) for the direct delivery of NT-3 to the spinal cord. We injected a NT-3 loaded hydrogel into the intrathecal space immediately after contusion SCI in Sprague Dawley (SpD) rats. Our results indicate that injecting the NT-3 loaded hydrogel into the intrathecal space was safe and that the gel was retained alongside the cord for at least one week. Additionally, no adverse effects were observed on rat behaviour. While functional improvement trends were noted, statistical significance was not reached, and immunohistochemistry results showed no significant difference between treatment groups. Overall, our findings suggest the feasibility, safety, and potential of the developed intrathecal administration technique for delivering diverse therapeutic molecules for SCI recovery.
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Modelos Animais de Doenças , Hidrogéis , Injeções Espinhais , Neurotrofina 3 , Ratos Sprague-Dawley , Traumatismos da Medula Espinal , Animais , Traumatismos da Medula Espinal/tratamento farmacológico , Neurotrofina 3/administração & dosagem , Hidrogéis/química , Hidrogéis/administração & dosagem , Ratos , Medula Espinal/metabolismo , Medula Espinal/efeitos dos fármacos , Ácido Hialurônico/administração & dosagem , Ácido Hialurônico/química , Poloxâmero/química , Poloxâmero/administração & dosagemRESUMO
There is a gap in existing knowledge of stress-triggered neurochemical and behavioral adaptations in females. This study was designed to explore the short-term consequences of a single social defeat (SD) on accumbal dopamine (DA) dynamics and related behaviors in female Wistar rats. During the SD procedure, rats demonstrated different stress-handling strategies, which were defined as active and passive coping. The "active" subjects expressed a significantly higher level of activity directed toward handling stress experience, while the "passive" ones showed an escalated freezing pattern. Remarkably, these opposite behavioral manifestations were negatively correlated. Twenty-four hours following the SD exposure, decreased immobility latency in the Porsolt test and cognitive augmentation in the new object recognition evaluation were evident, along with an increase in electrically evoked mesolimbic DA release in passive coping rats. Rats exhibiting an active pattern of responses showed insignificant changes in immobility and cognitive performance as well as in evoked mesolimbic DA response. Furthermore, the dynamics of the decline and recovery of DA efflux under the depletion protocol were significantly altered in the passive but not active female rats. Taken together, these data suggest that female rats with a passive coping strategy are more susceptible to developing behavioral and neurochemical alterations within 24 h after stress exposure. This observation may represent both maladaptive and protective responses of an organism on a short timescale.
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Adaptação Psicológica , Dopamina , Ratos Wistar , Estresse Psicológico , Animais , Feminino , Dopamina/metabolismo , Ratos , Estresse Psicológico/metabolismo , Núcleo Accumbens/metabolismo , Comportamento Animal , Capacidades de EnfrentamentoRESUMO
Several reports, including our previous studies, indicate that hyperglycemia and diabetes mellitus exert differential effects on vascular function in males and females. This study examines sex differences in the vascular effects of type 2 diabetes (T2D) in an established monogenic model of obesity-induced T2D, Zucker Diabetic Fatty (ZDF) rats. Acetylcholine (ACh) responses were assessed in phenylephrine pre-contracted rings before and after apocynin, a NADPH oxidase (NOX) inhibitor. The mRNA expressions of aortic endothelial NOS (eNOS), and key NOX isoforms were also measured. We demonstrated the following: (1) diabetes had contrasting effects on aortic vasorelaxation in ZDF rats, impairing relaxation to ACh in females while enhancing it in male ZDF rats; (2) inhibition of NOX, a major source of superoxide in vasculature, restored aortic vasorelaxation in female ZDF rats; and (3) eNOS and NOX4 mRNA expressions were elevated in female (but not male) ZDF rat aortas compared to their respective leans. This study highlights sexual dimorphism in ACh-mediated vasorelaxation in the aorta of ZDF rats, suggesting that superoxide may play a role in the impaired vasorelaxation observed in female ZDF rats.
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Acetilcolina , Aorta , Diabetes Mellitus Tipo 2 , Óxido Nítrico Sintase Tipo III , Obesidade , Ratos Zucker , Caracteres Sexuais , Vasodilatação , Animais , Acetilcolina/farmacologia , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/fisiopatologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/genética , Masculino , Feminino , Obesidade/metabolismo , Obesidade/fisiopatologia , Ratos , Vasodilatação/efeitos dos fármacos , Óxido Nítrico Sintase Tipo III/metabolismo , Óxido Nítrico Sintase Tipo III/genética , Aorta/metabolismo , Aorta/fisiopatologia , Aorta/efeitos dos fármacos , NADPH Oxidase 4/metabolismo , NADPH Oxidase 4/genética , Modelos Animais de Doenças , NADPH Oxidases/metabolismo , NADPH Oxidases/genética , Superóxidos/metabolismoRESUMO
OBJECTIVES: Minimally invasive anatomic segmentectomy for the resection of pulmonary nodules has significantly increased in the last years. Nevertheless, there is limited evidence on the safety and feasibility of robotic segmentectomy compared to video-assisted thoracic surgery. This study aimed to compare the real-world early outcomes of robotic and video-thoracoscopic in anatomic segmentectomy. METHODS: Single centre cohort study including all consecutive patients undergoing segmentectomy by either robotic or video-thoracoscopic from June 2018 to November 2023. Propensity score case matching analysis generated two matched groups undergoing robotic or video-thoracoscopic segmentectomy. Short-term outcomes were analysed and compared between groups. RESULTS: 204 patients (75 robotic and 129 video-thoracoscopic patients) were included. After matching, 146 patients (73 cases in each group) were compared. One 30-day death was observed in the robotic group (P = 1). Two conversions to thoracotomy occurred in the robotic, and none in the video-thoracoscopic group (P = 0.5). Surgical time was longer in the robotic group (P = 0.091). There were no significant differences between robotic and video-thoracoscopic groups in postoperative complications (13.7% vs 15.1%, P = 1), cardiopulmonary complications (6.8% vs 6.8%, P = 1), major complications (4.1% vs 4.1%, P = 1), prolonged air leak (4.1% vs 5.5%, P = 1), arrythmia (1.4% vs 0%, P = 1) and reoperation (2.7% vs 2.7%, P = 1). Median length of stay was 3 days (IQR, 2-3 days) in the robotic group vs 3 days (IQR, 2.5-4 days) in the video-thoracoscopic group (P = 0.212). CONCLUSIONS: Robotic segmentectomy is a safe and feasible alternative to video-thoracoscopy, as no significant differences in early postoperative outcomes were found between the two techniques.
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Measures of individual behavioural differences (personality) are highly valuable in many areas of ethology, particularly studies of animal emotion and welfare. However, there are limitations to current behavioural tests of personality. Caregiver questionnaires may provide a complementary approach to overcome some of these limitations and provide a richer insight into personality. Drawing on previous studies, we developed a questionnaire in which caregivers were asked to rate the extent to which a given adjective/term described a rat under their care. We then used factor analysis to identify personality dimensions and assess whether those dimensions mapped to rat sex, rat age, number of companions, predator exposure, or owner experience. We obtained usable data from 296 rat caregivers and identified six personality dimensions: tameness, shyness, liveliness, interspecific sociability, inquisitiveness, aggressiveness. These dimensions are, with the exception of 'inquisitiveness', in line with previous studies and the broader literature on personality in non-human animals. With the exception of shyness, which was significantly associated with sex and owner experience, we found no strong evidence for a relationship between the personality dimensions and age, sex, number of companions, predator exposure, or owner experience. Although there remain important issues to be answered by future research, such as whether there is interobserver agreement in personality ratings and the extent to which the personality ratings are repeatable over time, the present study indicates that questionnaires of caregivers could in future provide a valuable tool to assess personality in rats.
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Chlorine dioxide (CD) is a broad-spectrum disinfectant agent used to disinfect food products and, more recently, to treat diseases such as avian influenza and COVID-19 due to its potent antimicrobial properties. However, excessive use of chlorine dioxide can cause adverse health effects. While numerous in vivo studies have evaluated its toxicity CD's toxicity, few have investigated its impact on the intestinal microbiota. This study assesses the effects of oral administration of CD on hematological and physiological parameters, and the intestinal microbiota in a murine model. CD was produced at a concentration of 16578.62 mg/L after 7 days of reaction. Results showed a significant antimicrobial effect on dietary yeasts compared to probiotics. There were significant changes in the percentages of Firmicutes (CD 81.9-87.1%, control 63.05%) and Bacteroidetes (DC 3.4-4.5%, control 22.5%) in the CD administered groups compared to the control group. CD exposure showed toxicity in hematological parameters. Additionally, consuming CD for 90 days at 10 mg/kg body weight caused colon and cecum damage and decreased the rats' weight. These findings indicate than even low doses of CD can negative effect on the microbiota, the morphology of the cecum and colon, and body weight, suggesting that prolonged consumption should be avoided.
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Preclinical and clinical studies have shown a wide-range of individual differences in response to stressors or novel environments which can affect the susceptibility to develop abnormal behaviors and neuropsychiatric disorders. Both vulnerability and resiliency have been observed in animals and humans experiencing stressful events. Chronic unpredictable mild stress (CUMS) is a rodent depression model consisting of various stressors. This protocol leads to depressive- and anhedonic-like behaviors in rodents. The present study aimed to evaluate potential individual differences in response to CUMS in rats, with respect to the expression level of brain-derived neurotrophic factor (BDNF) and glycogen synthase kinases 3-beta (GSK3-ß) (proteins involved in the modulation of mood, neuroplasticity, and cognition) in the hippocampus. CUMS was performed for four consecutive weeks. Depressive-like behavior, locomotor activity, anxiety-like behavior, and pain threshold were also evaluated using forced swim test (FST), open field test (OFT), and the hot plate (HP), respectively. Real-time PCR was used to evaluate BDNF and GSK3-ß expression levels. The results showed that CUMS rats can be classified as two clusters: affected and non-affected (depressed and non-depressed). Affected rats showed depressive- and anxiety-like behaviors, decreased locomotor activity, and increased pain threshold. However, non-affected rats were similar to controls. In addition, there was a downregulation of BDNF and upregulation of GSK3-ß in affected rats. Spearman correlation analysis also showed a relationship between BDNF and GSK3-ß expression levels with individual differences. In conclusion, the present study showed that BDNF and GSK3-ß may be involved in individual differences in CUMS rats.