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BACKGROUND: Incontinence-associated dermatitis (IAD) is a tough problem in clinical settings, not only increasing the risk of complications like catheter-related urinary tract infections and pressure ulcers in elderly and critically ill patients, but also prolonging hospital stays, raising hospital costs, and possibly leading to medical disputes. This study is aimed to evaluate the therapeutic effect of silicone dressing combined with topical oxygen therapy on IAD in a rat model. METHODS: An IAD rat model induced by synthetic urine with trypsin was established. Hematoxylin & eosin staining was carried out to examine skin histology. Using immunofluorescence, the microvessel density in the affected skin tissues was determined. ELISA was performed to measure the concentrations of inflammatory cytokines and angiogenic factors in serum. The mRNA expression of EGF, PDGF, and VEGF was detected via qRT-PCR. Western blotting was employed to determine NF-κB p65/STAT1 pathway-related protein levels. RESULTS: Compared to single therapy, silicone dressing combined with topical oxygen therapy could significantly reduce the severity of IAD, improve skin histology, inhibit inflammation, and promote angiogenesis in IAD rat models. Additionally, the results showed that relatively speaking, the combined therapy suppressed the NF-κB p65/STAT1 signaling pathway more effectively. CONCLUSION: These findings indicated that silicone dressing combined with topical oxygen therapy can alleviate IAD through promoting wound healing and inhibiting inflammation via NF-κB p65/STAT1 signaling pathway in a rat model, which provided a theoretical basis for the prevention and treatment of IAD in clinic.
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Bandagens , Dermatite , Modelos Animais de Doenças , Oxigênio , Ratos Sprague-Dawley , Fator de Transcrição STAT1 , Transdução de Sinais , Silicones , Fator de Transcrição RelA , Incontinência Urinária , Animais , Ratos , Transdução de Sinais/efeitos dos fármacos , Oxigênio/administração & dosagem , Fator de Transcrição STAT1/metabolismo , Dermatite/terapia , Dermatite/etiologia , Fator de Transcrição RelA/metabolismo , Incontinência Urinária/terapia , Incontinência Urinária/etiologia , MasculinoRESUMO
Aims: This paper was to scrutinize the toxicity mechanism of anti-programmed death 1 (anti-PD-1) therapy-caused spinal cord injury (SCI). Methods: Bone marrow transplant Rag1-/- mice were used to establish SCI model. Results: Anti-PD-1 results in SCI via CD8+ T-cells activation, while excessive activation of CD8+ T-cells further aggravated SCI. Both anti-PD-1 and the activation of CD8+ T-cells induced the expression of apoptosis-related perforin, GrB and FasL, but suppressed PI-9 level. The opposite results were observed in the effects of neuroserpin on these factors. CD8+ T-cells activation induced neurotoxicity via upregulation perforin, GrB and FasL and inhibiting PI-9. Additionally, neuroserpin suppressed CD8+ T-cells activation via perforin/GrB/PI-9/FasL pathways. Conclusion: These results may provide theoretical foundation for the clinical treatment of SCI caused by anti-PD-1.
What is this article about? In the process of treating cancer, immune checkpoint inhibitors such as anti-programmed death 1 (anti-PD-1) therapy, as a form of immunotherapy, have developed rapidly and changed the way to manage cancers significantly. However, some cancer patients who receive immune checkpoint blockade treatment suffer from severe adverse effects including spinal cord injury (SCI). This article for the first time constructed a bone marrow transplant mouse model to explore the toxicity mechanism of anti-PD-1 therapy-caused SCI.What were the results? We found that anti-PD-1 therapy can induce the activation of immune cells, while immune cell activation further promotes self-destruction of nerve cells by regulating cell death pathways.What do the results of the study mean? The mechanism of anti-PD-1 therapy-caused SCI is to activate of immune cells through regulating cell death pathways, thereby inducing self-destruction of nerve cells. These findings provide theoretical foundation for the clinical treatment of SCI caused by anti-PD-1 therapy.
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BACKGROUND: Existing remedial approaches for relieving neuropathic pain (NPP) are challenging and open the way for alternative therapeutic measures such as electroacupuncture (EA). The mechanism underlying the antinociceptive effects of repeated EA sessions, particularly concerning the regulation of the Adora3 receptor and its associated enzymes, has remained elusive. METHODS: This study used a mouse model of spared nerve injury (SNI) to explore the cumulative analgesic effects of repeated EA at ST36 (Zusanli) and its impact on Adora3 regulation in the spinal cord dorsal horn (SCDH). Forty-eight male mice underwent SNI surgery for induction of neuropathic pain and were randomly assigned to the SNI, SNI + 2EA, SNI + 4EA, and SNI + 7EA groups. Spinal cord (L4-L6) was sampled for immunofluorescence, adenosine (ADO) detection and for molecular investigations following repeated EA treatment. RESULTS: Following spared nerve injury (SNI), there was a significant decrease in mechanical withdrawal thresholds (PWTs) and thermal nociceptive withdrawal latency (TWL) in the ipsilateral hind paw on the third day post-surgery, while the contralateral hind paw PWTs showed no significant changes. On subsequent EA treatments, the SNI + EA groups led to a significant increase in pain thresholds (p < 0.05). Repeated EA sessions in SNI mice upregulated Adenosine A3 (Adora3) and cluster of differentiation-73 (CD73) expression while downregulating adenosine deaminase (ADA) and enhancing neuronal instigation in the SCDH. Colocalization analysis of Neun-treated cells revealed increased Adora3 expression, particularly in the SNI + 7EA group. CONCLUSIONS: In conclusion, cumulative electroacupuncture treatment reduced neuropathic pain by regulating Adora3 and CD73 expression, inhibiting ADA and most likely increasing neuronal activation in the SCDH. This study offers a promising therapeutic option for managing neuropathic pain, paving the way for further research.
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Atherosclerosis is essentially the leading factor behind occurrences of cardiovascular diseases (CVDs)-associated incidents, while mitochondrial dysfunction is also the main cause of atherosclerosis. The present study conducted a comparative analysis of mitochondrial function-related indicators in cholesterol-induced vascular endothelial cells (VECs) from Mongolian gerbils, Sprague-Dawley (SD) rats and humans. It reported that the inhibitory effect of cholesterol treatment on the viability of Mongolian gerbil VECs was markedly lower than the other two types of VECs at the same concentration. Following cholesterol treatment, mitochondrial DNA copy numbers, reactive oxygen species level, calcium concentration and mitochondrial membrane potential of Mongolian gerbil VECs did not change markedly. These results suggested that the function of mitochondria in the VECs of Mongolian gerbil is normal. Additionally, cholesterol treatment also did not alter the levels of superoxide dismutase, glutathione peroxidase, ATP, NADH-CoQ reductase and cytochrome c oxidase in Mongolian gerbil VECs. It was hypothesized that the VECs of Mongolian gerbils have certain resistance to oxidative damage induced by cholesterol. In brief, the present study demonstrated that VECs of Mongolian gerbils are resistant to cholesterol-induced mitochondrial dysfunction and oxidative damage. The aforementioned findings establish a theoretical foundation for the advancement of innovative strategies in the prevention and treatment of atherosclerosis.
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Background: Perivascular adipose tissue (PVAT) dysfunction impairs vascular homeostasis. Impaired inflammation and bone morphogenetic protein-4 (BMP4) signaling are involved in thoracic PVAT dysfunction by regulating adipokine secretion and adipocyte phenotype transformation. We investigated whether aerobic exercise training could ameliorate high-fat diet (HFD)-induced PVAT dysfunction via improved inflammatory response and BMP4-mediated signaling pathways. Methods: Sprague-Dawley rats (n = 24) were divided into three groups, namely control, high-fat diet (HFD), and HFD plus exercise (HEx). After a 6-week intervention, PVAT functional efficiency and changes in inflammatory biomarkers (circulating concentrations in blood and mRNA expressions in thoracic PVAT) were assessed. Results: Chronic HFD feeding caused obesity and dyslipidemia in rats. HFD decreased the relaxation response of PVAT-containing vascular rings and impaired PVAT-regulated vasodilatation. However, exercise training effectively reversed these diet-induced pathological changes to PVAT. This was accompanied by significantly (p < 0.05) restoring the morphological structure and the decreased lipid droplet size in PVAT. Furthermore, HFD-induced impaired inflammatory response (both in circulation and PVAT) was notably ameliorated by exercise training (p < 0.05). Specifically, exercise training substantially reversed HFD-induced WAT-like characteristics to BAT-like characteristics as evidenced by increased UCP1 and decreased FABP4 protein levels in PVAT against HFD. Exercise training promoted transcriptional activation of BMP4 and associated signaling molecules (p38/MAPK, ATF2, PGC1α, and Smad5) that are involved in browning of adipose tissue. In conjunction with gene expressions, exercise training increased BMP4 protein content and activated downstream cascades, represented by upregulated p38/MAPK and PGC1α proteins in PVAT. Conclusion: Regular exercise training can reverse HFD-induced obesity, dyslipidemia, and thoracic PVAT dysfunction in rats. The browning of adipose tissue through exercise appears to be modulated through improved inflammatory response and/or BMP4-mediated signaling cascades in obese rats.
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Electroacupuncture (EA) is an efficient treatment for visceral hypersensitivity (VH). However, the mechanism underlying VH remains obscure. This study aimed to examine the effect of EA at Housanli acupoint on PAR2 and PAR4 expression in the periaqueductal gray (PAG), rostral ventromedial medulla (RVM), and spinal cord dorsal horn (SCDH) axes, as well as on expression of the proinflammatory cytokines IL-1ß and TNF-α, COX-2 enzyme, c-Fos, and the neuropeptides CGRP and SP in the same areas of the descending pain modulatory system. To induce VH in male goats, a 2,4,6-trinitrobenzene-sulfonic acid (TNBS)-ethanol solution was administered to the ileal wall. The visceromotor response (VMR) and nociceptive response at different colorectal distension pressures were measured to evaluate VH. Goats in the TNBS group displayed significantly increased VMR and nociceptive response scores, and elevated protein and mRNA levels of PAR2 and PAR4 in the descending pain modulatory system compared to those in the control group. EA alleviated VMR and nociceptive responses, decreased the protein and mRNA expression levels of PAR2, and elevated those of PAR4 in the descending pain modulatory system. EA may relieve VH by reducing PAR2 expression and increasing PAR4 expression in the descending pain modulatory system.
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BACKGROUND: The purpose of our study was to study the composition and content of the feline plasma metabolome revealing the critical metabolites and metabolic pathways associated with age during growth and development. METHODS: Blood samples were collected from juvenile and adult groups for blood routine tests and serum biochemistry tests. Non-targeted metabolomics analyses of plasma were also performed to investigate changes in metabolites and metabolic pathways. RESULTS: In this study, we found that the red blood cell counts, liver function indexes (albumin and gamma-glutamyl transpeptidase), and the concentration of triglyceride and glucose changed significant with growth and development. The metabolomics results revealed that 1427 metabolites were identified in the plasma of young and adult cats. Most of these metabolites belong to major classes of lipids and lipid-like molecules. The most obvious age-related metabolites include reduced levels of chenodeoxycholate, taurocholate, cholate, and taurochenodeoxycholate but increased levels of L-cysteine and taurocyamine in the adult cat's serum. These metabolites are mainly involved in the primary bile acid biosynthesis pathway, the bile secretion pathway, and the taurine and hypotaurine metabolism pathway. CONCLUSION: This study revealed many age-related metabolite alterations in the feline plasma. These age-varying metabolites, especially in the bile acid biosynthesis and secretion metabolism pathways, indicate that the regulation of these pathways is involved in the growth and development of cats. This study promotes our understanding of the mechanism of feline growth and provides new insights into nutrition and medicine for cats of different ages.
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Metaboloma , Metabolômica , Gatos , Animais , Plasma , Ácidos e Sais Biliares , Crescimento e DesenvolvimentoRESUMO
BACKGROUND: Electroacupuncture (EA) can effectively relieve visceral hypersensitivity (VH). However, its mechanisms are still unclear. OBJECTIVE: To investigate the impact of EA on VH caused by ileitis, and whether EA relieves VH by modulating the endogenous cannabinoid system (ECS). METHODS: Thirty male native goats were randomly divided into a saline-treated control group (Saline, n = 9) and three 2,4,6-trinitro-benzenesulfonic acid (TNBS)-treated VH model groups that underwent injection of TNBS into the ileal wall to induce VH and remained untreated (TNBS, n = 9) or received six sessions of EA (for 30 min every 3 days) (TNBS + EA, n = 6) or sham acupuncture (TNBS + Sham, n = 6). The visceromotor response (VMR) to colorectal distention (CRD) was measured after each EA treatment. Three goats in the Saline/TNBS groups were euthanized after 7 days for histopathological examination; the remaining 24 (n = 6/group) underwent sampling of the ileal wall, T11 spinal cord and brain nuclei/areas related to visceral regulation and ascending pain modulation system on day 22. Expression of cannabinoid receptor 1 (CB1R), fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) was detected by immunohistochemistry. RESULTS: VMR to CRD was greater in TNBS-treated goats than in saline-treated goats (p < 0.01) from day 7 to 22. After day 7, EA-treated goats showed a decreased (p < 0.05) VMR compared with untreated TNBS-exposed goats. TNBS treatment decreased CB1R and increased FAAH and MAGL expression in the ileum and related nuclei/areas; this was reversed by EA. CONCLUSION: EA ameliorates VH, probably by regulating the ECS in the intestine and nuclei/areas related to visceral regulation and descending pain modulation systems.
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Canabinoides , Eletroacupuntura , Dor Visceral , Ratos , Animais , Masculino , Ratos Sprague-Dawley , Dor Visceral/terapia , Dor Visceral/metabolismo , CabrasRESUMO
Background and aims: Overweight or obesity is one of the most prevalent health burdens in companion pets and predisposes subjects to multiple comorbidities and reduced longevity. Dietary management and sufficient exercise are effective options for weight loss but challenged by modern lifestyle and calorie control-triggered malnutrition. Therefore, this study aimed to develop a formulated obesity control diet characterized by protein- and fiber-rich diet and supplemented with astaxanthin. We systemically evaluated global influences of the designed weight-loss diet on metabolic homeostasis in an obese beagle model. Materials and methods: Beagles were induced for obesity by a 24-week HFD treatment and then included into weight-loss programs. Briefly, obese beagles were randomly assigned to two groups that were fed with a formulated weight-loss diet or control diet, respectively. Body weight and body condition scoring (BCS) were analyzed biweekly. Computed tomography (CT), nuclear magnetic resonance imaging (MRI) measurements, and blood and adipose tissue biopsies were collected at 0 and 8 weeks. Plasma lipids and adipocyte size were also measured after 8 weeks of weight-loss diet feeding. The global influence of the formulated diet on the whole spectrum of gene panels were examined by adipose RNA assays. Results: Twenty-four weeks of continuous HFD feeding significantly induced obesity in beagles, as evidenced by increased body weight, BCS, abdominal fat mass, and serum lipid levels. The obese and metabolic condition of the modeled canine were effectively improved by an 8-week weight-loss diet administration. Importantly, we did not observe any side effects during the weight loss duration. Transcriptional analysis of adipose tissues further supported that a weight-loss diet significantly increased energy metabolism-related pathways and decreased lipid synthesis-related pathways. Conclusion: The prescribed weight-loss diet exhibited profound benefits in canine weight management with well safety and palatability. These findings support effective strategies of nutritional management and supplementation approaches for weight control in companion animals.
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Inflammatory lung injury is a common respiratory disease with limited therapeutic effects. Increasing opinions approved that prevention is more important than drug treatment for inflammatory lung injury. Astragalus polysaccharides (APS) has multiple bioactivities including anti-inflammation and immunoregulation. However, its preventive effects on inflammatory lung injury remain unclear. In this study, mice were pretreated with APS via intragastric gavage and then were intratracheally instilled with lipopolysaccharides (LPS) to determine the role of APS in preventing lung injury. The results showed that APS pre-treatment improved the pathological changes of lung tissues, reduced the neutrophils infiltration, and inhibited the LPS-induced inflammation. Increasing evidence confirmed the close relationship between intestinal microbiota and lung inflammatory response. 16S rRNA analysis showed that APS treatment changed the microbiota composition in colon, increased the abundance of short-chain fatty acids (SCFAs)-producing genus such as Oscillospira, Akkermansia, and Coprococcus. Also, APS treatment significantly increased the serum concentrations of SCFAs including butyrate and propionate, and their anti-inflammation effects were demonstrated on mice primary alveolar macrophages. Our data confirmed the preventive effects of APS on LPS-induced lung injury, which were partly contributed by the alteration of intestinal microbiota composition and the resulting increase of serum SCFAs.
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In this study, we investigated the effects of intestinal alkaline phosphatase (IAP) in controlled intestinal inflammation and alleviated associated insulin resistance (IR). We also explored the possible underlying molecular mechanisms, showed the preventive effect of IAP on IR in vivo, and verified the dephosphorylation of IAP for the inhibition of intestinal inflammation in vitro. Furthermore, we examined the preventive role of IAP in IR induced by a high-fat diet in mice. We found that an IAP + IAP enhancer significantly ameliorated blood glucose, insulin, low-density lipoprotein, gut barrier function, inflammatory markers, and lipopolysaccharide (LPS) in serum. IAP could dephosphorylate LPS and nucleoside triphosphate in a pH-dependent manner in vitro. Firstly, LPS is inactivated by IAP and IAP reduces LPS-induced inflammation. Secondly, adenosine, a dephosphorylated product of adenosine triphosphate, elicited anti-inflammatory effects by binding to the A2A receptor, which inhibits NF-κB, TNF, and PI3K-Akt signalling pathways. Hence, IAP can be used as a natural anti-inflammatory agent to reduce intestinal inflammation-induced IR.
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Fosfatase Alcalina , Resistência à Insulina , Fosfatase Alcalina/metabolismo , Animais , Inflamação/metabolismo , Lipopolissacarídeos/farmacologia , Camundongos , Fosfatidilinositol 3-QuinasesRESUMO
The adverse effects of plastic on adult animal and human health have been receiving increasing attention. However, its potential toxicity to fetuses has not been fully elucidated. Herein, biodistribution of polystyrene (PS) particles was determined after the maternal mice were orally given PS micro- and/or nano-particles with and without surface modifications during gestational days 1 to 17. The results showed that PS microplastics (MPs) and nanoparticles (NPs) mainly emerged in the alimentary tract, brain, uterus, and placenta in maternal mice, and only the latter infiltrated into the fetal thalamus. PS NPs and carboxyl-modified NPs induced differentially expressed genes mainly enriched in oxidative phosphorylation and GABAergic synapse. Maternal administration of PS particles during gestation led to anxiety-like behavior of the progenies and their γ-aminobutyric acid (GABA) reduction in the prefrontal cortex and amygdala at Week 8. N-Acetylcysteine (NAC), an antioxidant, alleviated PS particles-induced oxidative injury in the fetal brain and rescued the anxiety-like behavior of the progenies. Additionally, PS nanoparticles caused excessive ROS and apoptosis in neuronal cell lines, which were prevented by glutathione supplementation. These results suggested that PS particles produced a negative effect on fetuses by inducing oxidative injury and suppressing GABA synthesis in their brain. The findings contribute to estimating the risk for PS particles to human and animal health.
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Nanopartículas , Poluentes Químicos da Água , Gravidez , Feminino , Humanos , Animais , Camundongos , Poliestirenos/toxicidade , Poliestirenos/metabolismo , Plásticos/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Distribuição Tecidual , Feto/metabolismo , Apoptose , Ácido gama-Aminobutírico/metabolismo , Nanopartículas/toxicidade , Poluentes Químicos da Água/toxicidadeRESUMO
Endometritis is the foremost reason for reduced reproductive performance, which impedes the establishment of pregnancy in ruminants. Baicalin is extensively acknowledged as a tocolytic drug. However, the preventive effect of baicalin on endometrial inflammatory injury remains unclear. The present study aimed to determine the potential benefits of baicalin on endometrial inflammatory injury in animal and cellular models. The results showed that baicalin alleviated the impairment of tight junctions (TJs) and inflammation in the endometrium induced by LPS treatment. Baicalin increased claudin 3 (CLDN3) and tight junction protein 1 (TJP1) levels in a dose-dependent manner in endometrial epithelial cells (EECs) accompanied by autophagy activation with or without LPS treatment. Immunofluorescence staining revealed that baicalin pretreatment prompted MAP1LC3B-positive structures to surround TJ proteins in the cytoplasm and decreased the abnormal aggregation of CLDN3 and TJP1 in the cytosol of EECs. Activation or blockage of autophagy using pharmacologic methods affected the redistribution of TJ proteins by baicalin pretreatment with LPS treatment. The role of autophagy in the modulation of TJ proteins was also confirmed by ATG7 and TFEB overexpression, as evidenced by accelerated redistribution of CLDN3 and TJP1 from the EEC cytosol to the membrane and a loss of membranous CLDN2 in EECs. These data demonstrate that baicalin influences the redistribution of TJ proteins to maintain the barrier function during LPS-induced endometrial inflammatory injury by regulating autophagy and provides a new therapeutic to potentially prevent embryo loss and endometritis.
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Endometrite , Proteínas de Junções Íntimas , Animais , Claudina-3/metabolismo , Endometrite/tratamento farmacológico , Feminino , Flavonoides , Humanos , Lipopolissacarídeos/farmacologia , Gravidez , Proteínas de Junções Íntimas/genética , Proteínas de Junções Íntimas/metabolismo , Junções ÍntimasRESUMO
BACKGROUND: The role of adenosine (AD) in neuromodulation of nociceptive signaling at the level of the spinal cord has been established in both preclinical and clinical models. Recently, the signaling pathway that involves adenosine 5-monophosphate activated protein kinase has been reported to mediate the antinociceptive effects of xylazine (XYL). The objective of this study was to investigate the antinociceptive, cardiorespiratory and hematological effects of intrathecal administration of combined XYL-AD in goats as compared to XYL alone. Six clinically healthy adult goats weighing 25 ± 2 kg were randomly assigned to one of three groups in a cross-over design. Goats were sedated with XYL (0.05 mg/kg, IM) in all groups. Ten min later, 0.9% saline solution [SAL group], XYL (0.05 mg/kg) [XYL group] or a combination of XYL (0.05 mg/kg) and AD (2000 µg) [XYL-AD group] was injected intrathecally. Antinociception scores and both cardiorespiratory and hematological parameters were measured before XYL sedation and intrathecal injection (baseline), and at 5, 10, 15, 30, 60, 90, 120 and 150 min thereafter. RESULTS: The XYL-AD group showed significantly earlier onset of antinociception [5 (5-7) min] than XYL [13 (12-14.25] min (P = 0.031). The duration of complete antinociception in goats that received XYL-AD was significantly longer (P = 0.031) than that received XYL alone [65 (58.75-66.25) and 47.5 (43.75-51.25) min, respectively]. In both XYL and XYL-AD groups, heart rate (HR), arterial blood pressure (SAP, MAP and DAP) were significantly decreased (P < 0.05) compared to the baseline. Compared to the SAL group, a statistically significant reduction in HR from 10 to 150 min (P < 0.05) was detected in the XYL group contrary to the XYL-AD group. Differences in the hematological parameters among different groups were insignificant. CONCLUSIONS: AD injected intrathecally interacts synergistically with XYL to promote antinociception in goats. This discovery supports the use of AD in combination with XYL in clinical trials.
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Cabras , Xilazina , Adenosina/farmacologia , Animais , Estudos Cross-Over , Frequência Cardíaca , Xilazina/farmacologiaRESUMO
α2-Adrenegic receptors (α2Rs) are important presynaptic modulators of central noradrenergic function (auto receptors) and postsynaptic mediators of many of the widespread effects of catecholamines and related drugs. Studies have shown that ruminants (such as goats and cattle) express special α2DR subtypes in addition to α2BR and α2CR. Real-time quantitative PCR and Western blotting were used to investigate the distribution and density of α2R in different nuclei of the goat central nervous system, selected regions of the spinal cord (L4-L6), and in various peripheral tissues. α2-AR subtype-specific antibodies were injected intrathecally and intracerebroventricularly into the tested goats to block the corresponding subtype of receptors. Pain threshold and physiological parameters were evaluated to explore the functional characteristics of α2BR, α2CR and α2DR in goats. Our results suggest that the expression of the mRNAs and proteins of all three α2R subtypes are widely but unevenly distributed in the goat CNS and peripheral tissues. Furthermore, α2DR plays a more important role in α2R-mediated analgesia in goats than α2BR and α2CR, whereas α2CR activation exerts a greater effect on body temperature than α2BR and α2DR.
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Goats have been used as animal models in research, and the need for achieving safer anesthesia for research or surgical intervention is gaining much attention. The objective of this study was to evaluate intraoperative effects and the immediate postoperative analgesia of nalbuphine-ketamine regimen in goats. Twenty clinically healthy adult female crossbred goats weighing 14 ± 2 kg were allocated randomly into each of two equally sized groups. All animals were sedated with intramuscular (IM) xylazine (0.07 mg/kg), then anesthesia was intravenously (IV) induced with ketamine alone (10 mg/kg) (XK group), or a combination of nalbuphine (0.5 mg/kg) and ketamine (5 mg/kg) (XNK group). Following induction, left flank laparotomy was performed and then sutured. The quality of anesthesia and immediate postoperative analgesia was evaluated. Immediate postoperative analgesia was assessed up to 5 h after standing, using a modified Unesp-Botucatu acute composite pain scale (USAPS). Serum cortisol, glucose, insulin, and C-reactive protein (CRP) were measured at ½, 1, 2, 4, 6, 12, and 24 h, postoperatively (PO). The USAPS pain scores were significantly lower in the XNK compared to the XK group (p < 0.05). The XNK group exhibited a statistically significant difference in the level of serum cortisol at ½ and 1 h PO (p = 0.018 and 0.045, respectively) compared to the XK group. At 2, 4, 6 h PO, CRP significantly decreased (p = 0.023, 0.040 and 0.005, respectively) in the XNK compared to the XK group. Nalbuphine-ketamine produced an acceptable induction of anesthesia and recovery compared to ketamine. Recovery with nalbuphine-ketamine was faster and better quality. The USAPS pain scores were lower in nalbuphine-ketamine, indicating that this novel combination produces better postoperative pain control than ketamine alone.
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Background and aims: The metabolomic profile of a biofluid can be affected by age, and thus provides detailed information about the metabolic alterations in biological processes and reflects the in trinsic rule regulating the growth and developmental processes. Methods: To systemically investigate the characteristics of multiple metabolic profiles associated with canine growth, we analyzed the metabolomics in the plasma and urine samples from 15 young and 15 adult beagle dogs via UHPLC-Q-TOFMS-based metabolomics. Blood routine and serum biochemical analyses were also performed on fasting blood samples. Results: The metabolomics results showed remarkable differences in metabolite fingerprints both in plasma and urine between the young and adult groups. The most obvious age-related metabolite alterations include decreased serumlevels of oxoglutaric acid and essential amino acids and derivatives but increased levels of urine levels of O-acetylserine. These changes primarily involved in amino acid metabolism and bile secretion pathways. We also found that the levels of glutamine were consistently higher in both serum and urine of adults, while N-acetylhistamine and uracil concentrations were much lower in the adult group compared to younger ones. Conclusion: Our study provides a whole metabolic profile of serum and urine characteristics of young and adult canines, identifying several metabolites that were significantly associated with age change, which provides theoretical support for the nutrition-related research and age-related homeostasis maintenance in dogs.
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Introduction: The primo vascular system (PVS), an intensive network structure, has been claimed to be representative of the acupuncture meridian. Here, we explored the role of the PVS in local enteritis and its modification by acupuncture. Methods: Chronic cecitis in rabbits was induced by 2,4,6-trinitro-benzene-sulfonic acid (TNBS). The PVS on the cecum was visualized with trypan blue staining, and collected with the help of microsurgical forceps under an optical stereomicroscope. Results: The increased primo vessels (PVs) and primo nodes (PNs) of the PVS on the surface of the cecum were induced by local inflammation, which was positively correlated with the inflammatory cells in the cecal mucosa. Tandem mass tag (TMT) based proteomic analysis revealed that 110 differentiated proteins of the PVS existed between TNBS-treated and control rabbits; 65 proteins were upregulated, while 45 proteins were downregulated. These proteins were mainly enriched in inflammation- and immunity-related processes, such as inflammatory cell proliferation, antigen presentation, and cell adhesion in the proliferated PVS (data are available via ProteomeXchange with the identifiers PXD034280). Importantly, TNBS-induced cecitis, the proliferated PVS and inflammation response-related proteins (CD40, CD45, HLA-DRA1, LAMP1, JAGN1 and FGL1) in the PVS were alleviated or reversed by repetitive electroacupuncture (EA) stimulations. Conclusion: These results suggest that the proliferated PVS and its active inclusions were related to the inflammatory process, which was modified by EA. Our study provides a new avenue for further exploration of the mechanism by which EA exerts anti-inflammatory effects.
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Eletroacupuntura , Enterite , Tiflite , Animais , Coelhos , Proteômica , Inflamação , Enterite/induzido quimicamente , Enterite/terapiaRESUMO
BACKGROUND Over-exposure to visible white light can cause retinal damage. Lotus seedpod proanthocyanidins (LSPCs) possess a variety of biological activities, including potent antioxidant and protective effects. Herein, this study observed whether LSPCs can protect against light exposure-induced retinal damage. MATERIAL AND METHODS We randomly separated 40 Prague-Dawley rats into a control group, a light exposure-induced retinal injury model group, and low-dose (50 mg/kg), medium-dose (100 mg/kg), and high-dose (100 mg/kg) LSPCs groups. Light-induced retinal damage models were established by 5000±200 Lx light treatment for 6 h. Five days and 0.5 h before the light treatment, rats in the LSPCs groups were separately administered 50, 100, and 200 mg/kg LSPCs by gavage. After 7 days, H&E staining of retinal sections was performed and the thickness of the ONL was measured. Oxidative stress-related markers and antioxidant enzymes were measured in serum by biochemical testing. TUNEL staining of retinal sections was also performed. Apoptosis-relevant proteins were examined by RT-qPCR and western blotting. GFAP expression was examined with immunohistochemistry. RESULTS Our H&E staining showed that LSPCs can prevent retinal degeneration following light exposure. Histological analysis showed a significant reduction in the ONL thickness of light exposure-induced retinal injury rats, but LSPCs substantially improved the ONL thickness. LSPCs markedly ameliorated the light-induced increase in levels of MDA, NO, and NOS, and decrease in activity of GSH-Px and SOD. Moreover, LSPCs treatment alleviated light-induced retinal apoptosis and limited the light-induced increase in GFAP expression. CONCLUSIONS LSPCs effectively attenuated light-induced retinal damage through antioxidative stress, anti-apoptosis, and neuroprotective effects.
Assuntos
Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Lotus/química , Fármacos Neuroprotetores/farmacologia , Proantocianidinas/farmacologia , Retina/efeitos dos fármacos , Animais , Apoptose/efeitos da radiação , Western Blotting , Relação Dose-Resposta à Radiação , Feminino , Marcação In Situ das Extremidades Cortadas , Luz/efeitos adversos , Masculino , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/efeitos da radiação , Componentes Aéreos da Planta/química , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase em Tempo Real , Retina/efeitos da radiaçãoRESUMO
Total intravenous anesthesia (TIVA) is increasingly used in companion animals. The effect of electroacupuncture (EA) on alfaxalone-based TIVA has not been previously reported in goats. Therefore, the objective of this study was to determine the minimum infusion rate (MIR) of alfaxalone required to prevent purposeful movement of the extremities in response to standardized noxious stimulation during its combination with EA in goats. Twelve clinically healthy goats weighing 18.5 ± 2 kg were randomly assigned to two groups (six goats/group). Alfaxalone alone (ALF group) and alfaxalone combined with EA (EA-ALF group). In the EA-ALF, alfaxalone was administered 30 min after EA stimulation. For induction of anesthesia, a bolus of alfaxalone was given at 3 mg/kg IV, and an infusion dose of 9.6 mg/kg/h was initially set for maintenance. The MIR of alfaxalone in both groups was determined by testing for responses to stimulation (clamping on a digit with Vulsellum forceps) at 10-min intervals after induction of anesthesia till the entire period of the experiment. Cardiopulmonary parameters and nociceptive threshold were measured throughout anesthesia. The median alfaxalone MIR was significantly lower in the EA-ALF group than the ALF group [9 (4.8-9.6) and 12 (11.4-18)], respectively; p = 0.0035). In the ALF group, goats anesthetized with MIR showed a significant increase in heart rate and cardiac output (p < 0.0001 and 0.0312, respectively), and decrease in respiratory rate (p < 0.0001), hemoglobin oxygen saturation (p = 0.0081), and rectal temperature (p = 0.0046) compared with those in the EA-ALF. Additionally, goats in the EA-ALF showed a higher nociceptive threshold than those in the ALF group (p < 0.0001). EA provided analgesia, reduced the MIR of alfaxalone-based IV anesthesia and thereby alleviated the adverse cardiorespiratory effects associated with alfaxalone anesthesia in goats.