Subacute Models Research Articles

Angiographic and Histopathological Characteristics of a Novel Polyacrylate Liquid Embolic Agent Compared with Ethylene Vinyl Alcohol Copolymer in a Large Animal Model

PurposeTo study the in vivo safety and effectiveness of a novel radiopaque nonadhesive polyacrylate (PA) peripheral liquid embolic system (AMBER SEL-P) relative to ethylene vinyl alcohol copolymer (EVOH, Onyx) in a healthy swine endovascular model. Materials and MethodsTwenty-five swine underwent rete mirabile and bilateral kidney embolization with PA or EVOH and were followed up for 24 hours (n = 5) and 30 days (n = 10), and 3 (n = 10) months. Angiographic features (penetrability, radiopacity, catheter entrapment, fragmentation, occlusion, and vasospasm) were evaluated. Necropsy and histology were used to evaluate the nontarget embolization, safety, and target embolization effectiveness by recanalization and analyze the vascular response. ResultsNo adverse events occurred during the embolization process or study period. The angiographic performance confirmed a significant positive effect of PA compared with that of EVOH in terms of penetrability (P = .007), catheter entrapment (P = .007), fragmentation (P = .007), vascular occlusion (P = .038), vasospasm (P = .038), and follow-up vascular occlusion (P = .038). Prenecropsy angiography found no vascular recanalization in the organs treated with PA, whereas it was detected at 3 months in 2 samples treated with EVOH. Histologically, PA was classified as nonirritant compared with EVOH under the study conditions according to ISO 10993-6:2016 as modified. No systemic effects during necropsy were detected in the animals treated with these agents. ConclusionsThis in vivo study concludes that the angiographic behavior of PA has advantages compared with EVOH. The embolization and biocompatibility of PA are similar to those of EVOH. PA is safe and effective for transarterial embolization in an acute, subacute, and chronic endovascular embolization models.

Preclinical safety evaluation of the ethanolic extract from campomanesia guazumifolia (cambess.) O. Berg fruits peels in rats

The toxicological potential of the ethanolic extract from Campomanesia guazumifolia (EECG), a species traditionally recognised for its antidiabetic, anti-inflammatory and hypercholesterolemic properties, was investigated in acute and subacute toxicity models in rats. In the acute toxicity test, 2000 mg/kg of EECG was administered orally in female rats, while male and female rats received 250, 500 or 750 mg/kg of EECG for the subacute toxicity test. No evidence of toxicity was observed in the animals acutely exposed, indicating that the LD50 is above 2000 mg/kg. However, repeated exposure to this extract resulted in alterations in important biochemical parameters indicative of hepatic and renal toxicity, including AST, ALT, creatinine, urea, and cholesterol. Additionally, some hematological parameters were also changed by the treatment. EECG demonstrated low toxicological potential. Nevertheless, given the observed changes in liver and kidney enzymes, further investigations into the protective effects of this extract following repeated administration are warranted.

Acute and subacute toxicological evaluation of the ethanol leaf extract of Morus mesozygia stapf. (Moraceae) in rodents

Ethnopharmacological relevanceTraditionally, the Morus mesozygia tree leaf has been used to manage maladies such as peptic ulcer, hyperglycemia, dermatitis, rheumatism, stomach-ache, arthritis, cough, malignancies, and malaria in parts of Africa. Aim of the studyThe study aimed to evaluate the potential of ethanol leaf extract of Morus mesozygia (EEMm) to induce toxicity by employing both acute and sub-acute oral toxicity experimental models. Material and methodsThe extract's cytotoxicity was studied using brine shrimps (Artemia salina) lethality assay (BSLA), while in the acute toxicity test, male and female mice were administered a single oral dose of EEMm (2000 mg/kg). Male and female Wistar rats received repeated doses of 100 or 500 mg/kg EEMm orally for 28 days in the sub-acute toxicity experiment. The phytochemical analysis of EEMm was done using the HPLC. ResultsThe BSLA revealed a moderate cytotoxic potential of the extract, with an LC50 of 567.13 ± 0.27 μg/mL. All the animals survived the acute toxicity test, with no significant changes in the relative organ weights, suggesting that LD50 is greater than 2000 mg/kg. The animal weights did not vary significantly in the sub-acute toxicity test neither were the alterations in biochemical and hematological tests pronounced, although the histoarchitectures of the kidney, liver and spleen indicated slight anomalies in the evaluated animals. The HPLC analysis revealed the presence of quercetin, ferulic acid, rutin, caffeic acid, morin and gallic acid. ConclusionsEthanol leaf extract of Morus mesozygia demonstrated a safe toxicity profile in rodents, supporting its broad folkloric use in African ethnomedicine.

Evaluation of Anti-Inflammatory Activity of the Methanol Extracts of Premna schimperi Engl (Lamiaceae) Leaves in Rats.

Even though it is a protective reaction, inflammation continues to be one of the most challenging medical disorders. The current conventional anti-inflammatory drugs have many undesirable health effects and are in need of newer drugs. The purpose of this study was to evaluate the anti-inflammatory effects of an aqueous methanol crude extract of Premna schimperi leaves. Premna schimperi leaf was extracted with 80% methanol and concentrated; the concentrated extract was used to evaluate the acute toxicity and anti-inflammatory effects. For the acute toxicity study, a single dose of Premna schimperi extract at a dose of 2000 mg/kg was administered and observed for 14 days. Acute, sub-acute, and chronic anti-inflammatory models were employed to evaluate the anti-inflammatory effect of the extract compared to the standard drug. Data were analyzed with SPSS V. 27, and the significance was established with a one-way ANOVA followed by a post hoc Tukey's test. Acute oral toxicity testing at a dose of 2000 mg/kg did not show any sign of toxicity. According to the phytochemical study, the plants contained flavonoids, terpenoids, tannins, cardiac glycosides, steroids, phenolics, and anthraquinones. The extract doses of 200 mg/kg, 400 mg/kg, and 800 mg/kg of extracts effectively (p<0.001) reduced paw edema in the acute and sub-acute models of inflammation. When compared to the negative control group, all tested doses in the chronic model significantly (p<0.05) decreased the production of exudates and the amount of granuloma tissue. Premna schimperi displayed significant anti-inflammatory activity. The tested doses inhibit the formation of edema, granulomas, and exudates.

Microalgae-based natural oral hydrogel system for synergistic treatment of lead poisoning-related diseases

Lead (Pb) is highly toxic to human body and can induce oxidative stress, causing irreversible hepato-renal and intestinal injury. Once accumulated, it is difficult to fully eliminate it from the body. However, the chelation therapy most widely used in the clinical against lead poisoning has severe side effects, such as oral dimethylaminosulfanilid will cause gastrointestinal symptoms, rash, and excessive deficiency of essential trace elements in the human body and prolonged treatment with it even has the disadvantage of causing kidney failure. Here we developed a multifunctional oral hydrogel system, BBR-CV@ALG, which composed of biocompatible carrier, Chlorella vulgaris (CV), anti-inflammation drug molecules, berberine (BBR), and stabilizer, carboxymethyl chitosan/sodium alginate complex, to adsorb and remove Pb in the living body, and alleviate lead poisoning-related diseases. In acute, subacute, and chronic models of lead poisoning, our microalgal gel has contributed to longer retention in the gastrointestinal tract to function the use of microalga in biosorption, effectively removing lead in the liver, kidney, and bone. Also, the BBR can be released to further reduce tissue damage caused by oxidative stress under lead exposure. Meanwhile, BBR-CV@ALG can also repair the intestinal barrier, significantly increase the abundance of Akkermansia muciniphila and Lactobacillus taiwanensis, and maintain intestinal homeostasis. In addition, this system exhibits many advantages such as biodegradability, low cost, and high biosafety, demonstrating a potential for clinical application.

Efficacy of a Novel Electroconductive Matrix To Treat Muscle Atrophy and Fat Accumulation in Chronic Massive Rotator Cuff Tears of the Shoulder.

The high retear rate after a successful repair of the rotator cuff (RC) is a major clinical challenge. Muscle atrophy and fat accumulation of RC muscles over time adversely affect the rate of retear. Since current surgical techniques do not improve muscle degenerative conditions, new treatments are being developed to reduce muscle atrophy and fat accumulation. In the previous study, we have shown the efficacy of aligned electroconductive nanofibrous fabricated by coating poly(3,4-ethylene dioxythiophene): poly(styrenesulfonate) (PEDOT:PSS) nanoparticles onto aligned poly(ε-caprolactone) (PCL) electrospun nanofibers (PEDOT:PSS matrix) to reduce muscle atrophy in acute and subacute models of RC tears (RCTs). In this study, we further evaluated the efficacy of the PEDOT:PSS matrix to reduce muscle atrophy and fat accumulation in a rat model of chronic massive full-thickness RCTs (MRCTs). The matrices were transplanted on the myotendinous junction to the belly of the supraspinatus and infraspinatus muscles at 16 weeks after MRCTs. The biomechanics and histological assessments showed the potential of the PEDOT:PSS matrix to suppress the progression of muscle atrophy, fat accumulation, and fibrosis in both supraspinatus and infraspinatus muscles at 24 and 32 weeks after MRCTs. We also demonstrated that the PEDOT:PSS matrix implantation significantly improved the tendon morphology and tensile properties compared with current surgical techniques.

Identification of RNA-binding Proteins in Spinal Cord Injury: An In-silico Approach

Introduction: Gene expression is regulated by trans-acting factors such as microRNA, and RNA-binding proteins (RBPs). Dysregulation of RNA-binding proteins (RBPs) are found in neurological diseases. However, the role RBPs in spinal cord injury (SCI) have not been identified. The objective of this study was to identify RBPs by re-analyzing RNA-sequencing data from SCI mice model using the latest version of Tuxedo pipeline. Methods: Reads from transcriptomic sequence of acute, subacute, and control mice models, from the Sequence Read Archive (SRA) website, were uploaded to a scientific workflow system called usegalaxy.org. The reads were assessed for their quality using FastQC, before they were mapped to the mouse mm10 reference genome using HISAT2. The fragments were then aligned to full-length transcripts using Stringtie, followed by DESeq2 to find differentially expressed genes (false discovery rate of 0.05 and fold change of -1&lt; x &gt;1). Finally, to find functional annotations, the Protein Analysis through Evolutionary Relationship (PANTHER) and g:Profiler were used. Results: There were 24 RBP-coding genes identified in the acute injury, and 27 in the subacute injury. Four RBPs that were commonly expressed at high levels in both acute and subacute injury; Hnrnpm, Ptbp3, Rbfox3 and Znf385a. These proteins regulate alternative splicing, and RNA transport. Other RBP-coding genes with a role in inflammatory response and apoptosis were also discovered. Conclusion: Novel RBP-coding genes differentially expressed in SCI were discovered, suggesting their role in the pathophysiology of SCI. These findings contribute to a better understanding of the regulatory mechanisms employed by RBPs in SCI.

Ex Vivo and In Silico Approaches of Tracheal Relaxation through Calcium Channel Blockade of 6-Aminoflavone and Its Toxicological Studies in Murine Models.

Asthma is a condition in which a person's airways become inflamed, narrowed, and produce greater amounts of mucus than normal. It can cause shortness of breath, chest pain, coughing, or wheezing. In some cases, symptoms may be exacerbated. Thus, the current study was designed to determine the mechanism of action of 6-aminoflavone (6-NH2F) in ex vivo experiments, as well as to determine its toxicity in acute and sub-chronic murine models. Tissues were pre-incubated with 6-NH2F, and concentration-response curves to carbachol-induced contraction were constructed. Therefore, tracheal rings pre-treated with glibenclamide, 2-aminopyridine, or isoproterenol were contracted with carbachol (1 µM), then 6-NH2F relaxation curves were obtained. In other sets of experiments, to explore the calcium channel role in the 6-NH2F relaxant action, tissues were contracted with KCl (80 mM), and 6-NH2F was cumulatively added to induce relaxation. On the other hand, tissues were pre-incubated with the test sample, and after that, CaCl2 concentration-response curves were developed. In this context, 6-NH2F induced significant relaxation in ex vivo assays, and the effect showed a non-competitive antagonism pattern. In addition, 6-NH2F significantly relaxed the contraction induced by KCl and CaCl2, suggesting a potential calcium channel blockade, which was corroborated by in silico molecular docking that was used to approximate the mode of interaction with the L-type Ca2+ channel, where 6-NH2F showed lower affinity energy when compared with nifedipine. Finally, toxicological studies revealed that 6-NH2F possesses pharmacological safety, since it did not produce any toxic effect in both acute and sub-acute murine models. In conclusion, 6-aminoflavone exerted significant relaxation through calcium channel blockade, and the compound seems to be safe.

Injectable hypoxia-preconditioned cartilage progenitor cells-laden GelMA microspheres system for enhanced osteoarthritis treatment.

Osteoarthritis (OA) is the most common age-related degenerative joint disease mainly characterized by the destruction of articular cartilage. Owing to its native avascular property, intrinsic repair of articular cartilage is very limited. Thus, a chondrogenic microenvironment in the joint is essential to the preservation of healthy chondrocytes and OA treatment. Recently, cartilage progenitor cells (CPCs)-based therapy is emerging as a promising strategy to repair degenerated and damaged articular cartilage. In this study, injectable hypoxia-preconditioned three-dimensional (3D) cultured CPCs-laden gelatin methacryloyl (GelMA) microspheres (CGMs) were constructed and characterized. Compared to normoxia-pretreated 3D CPCs and two-dimensional (2D) cultured CPCs, hypoxia-preconditioned 3D cultured CPCs exhibited enhanced cartilage extracellular matrix (ECM) secretion and greater chondrogenic ability. In addition, hypoxia-preconditioned 3D cultured CPCs more effectively maintained cartilage matrix metabolism balance and attenuated articular cartilage degeneration in subacute and chronic rat OA models. Mechanistically, our results demonstrated hypoxia-preconditioned 3D cultured CPCs exerted chondro-protective effects by inhibiting inflammation and oxidative stress via NRF2/HO-1 pathway in vitro and in vivo. Together, through the 3D culture of CPCs using GelMA microspheres (GMs) under hypoxia environment, our results proposed an efficient articular cartilage regeneration strategy for OA treatment and could provide inspiration for other stem cells-based therapies.

IRAK-M deficiency exacerbates dopaminergic neuronal damage in a mouse model of sub-acute Parkinson's disease.

Emerging evidence has proved that inflammatory responses aggravate the pathological progression of Parkinson's disease. This study aimed to identify the role of Interleukin-1 receptor-associated kinase-M (IRAK-M) as an important negative regulator of innate immunity, in the pathological progression of Parkinson's disease. In the present study, a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) injection was administered to prepare the acute and sub-acute Parkinson's disease mouse models. Western blot analysis was utilized to examine the protein expressions of tyrosine hydroxylase and IRAK-M. The mRNA expression levels of IRAK-M, interleukin (IL)-6, IL-β, and cyclooxygenase-2 were evaluated via using reverse transcription quantitative PCR (RT-qPCR). The expression of tyrosine hydroxylase-positive neurons in corpus striatum and substantia nigra pars compacta (SNc) tissues was detected using immunohistochemistry. The results showed that the protein and mRNA levels of IRAK-M were considerably upregulated in corpus striatum and SNc tissues in the sub-acute Parkinson's disease model. Furthermore, IRAK-M knockout significantly enhanced the MPTP-induced loss of tyrosine hydroxylase-positive fibers in corpus striatum and tyrosine hydroxylase-positive neurons in SNc, and intensified the effect of MPTP on the activation of microglial cells and the expression of inflammatory cytokines. In addition, sub-acute Parkinson's disease mice with IRAK-M deletion exhibited worse motor abilities than those of wild-type littermates. Overall, the present study suggested that IRAK-M reduces dopaminergic neuron damage in sub-acute Parkinson's disease by suppressing inflammation, which may provide a new therapeutic target for Parkinson's disease treatment.

Cell-Specific Expression of Human SIRT1 by Gene Therapy Reduces Retinal Ganglion Cell Loss Induced by Elevated Intraocular Pressure.

SIRT1 prevents retinal ganglion cell (RGC) loss in several acute and subacute optic neuropathy models following pharmacologic activation or genetic overexpression. We hypothesized that adeno-associated virus (AAV)-mediated overexpression of SIRT1 in RGCs in a chronic ocular hypertension model can reduce RGC loss, thereby preserving visual function by sustained therapeutic effect. A control vector AAV-eGFP and therapeutic vector AAV-SIRT1 were constructed and optimized for transduction efficiency. A magnetic microbead mouse model of ocular hypertension was optimized to induce a time-dependent and chronic loss of visual function and RGC degeneration. Mice received intravitreal injection of control or therapeutic AAV in which a codon-optimized human SIRT1 expression is driven by a RGC selective promoter. Intraocular pressure (IOP) was measured, and visual function was examined by optokinetic response (OKR) weekly for 49days following microbead injection. Visual function, RGC survival, and axon numbers were compared among control and therapeutic AAV-treated animals. AAV-eGFP and AAV-SIRT1 showed transduction efficiency of ~ 40%. AAV-SIRT1 maintains the transduction of SIRT1 over time and is selectively expressed in RGCs. Intravitreal injections of AAV-SIRT1 in a glaucoma model preserved visual function, increased RGC survival, and reduced axonal degeneration compared with the control construct. Over-expression of SIRT1 through AAV-mediated gene transduction indicates a RGC-selective component of neuroprotection in multiple models of acute optic nerve degeneration. Results here show a neuroprotective effect of RGC-selective gene therapy in a chronic glaucoma model characterized by sustained elevation of IOP and subsequent RGC loss. Results suggest that this strategy may be an effective therapeutic approach for treating glaucoma, and warrants evaluation for the treatment of other chronic neurodegenerative diseases.

Whether the Subacute MPTP-Treated Mouse is as Suitable as a Classic Model of Parkinsonism.

1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mice model is one of the most common animal models for Parkinson's disease (PD). It is classified into three types: acute, subacute, and chronic intoxication models. The subacute model has attracted much attention for its short period and similarity to PD. However, whether subacute MPTP intoxication in mouse mimics the movement and cognitive disorders of PD still remains highly controversial. Therefore, the present study reassessed the behavioral performances of subacute MPTP intoxication in mice using open field, rotarod, Y maze, and gait analysis at different time points (1, 7, 14, and 21days) after modeling. Results of the current study showed that although MPTP-treated mice using subacute regimen showed severe dopaminergic neuronal loss and evident astrogliosis, they failed to display significant motor and cognitive deficits. Besides, expression of mixed lineage kinase domain-like (MLKL), a marker of necroptosis, was also significantly increased in the ventral midbrain and striatum of MPTP-intoxicated mice. This evidently implies that necroptosis may play an important role in MPTP-induced neurodegeneration. In conclusion, the findings of the present study suggest that subacute MPTP-intoxicated mice may not be a suitable model for studying parkinsonism. However, it can help in revealing the early pathophysiology of PD and studying the compensatory mechanisms which occur in early PD that prevent the emergence of behavioral deficits.

Allogenic bone marrow-derived mesenchymal stem cells and its conditioned media for repairing acute and sub-acute peripheral nerve injuries in a rabbit model

The present study evaluated healing potential of bone marrow-derived mesenchymal stem cells (BM-MSCs) and BM-MSCs-conditioned medium (BM-MSCs-CM) for acute and subacute injuries in the rabbit peripheral nerve injury model. The regenerative capacity of MSCs was evaluated in 40 rabbits divided into eight groups, four groups each for acute and subacute injury models. BM-MSCs and BM-MSCS-CM were prepared by isolating allogenic bone marrow from the iliac crest. After inducing sciatic nerve crush injury, different treatments consisting of PBS, Laminin, BM-MSCs + laminin, and BM-MSCS-CM + laminin were used on the day of injury in the acute injury model and after ten days of crush injury in the subacute groups. The parameters studied included: pain, total neurological score, gastrocnemius muscle weight and volume ratio, histopathology of the sciatic nerve and gastrocnemius muscle, and scanning electron microscopy (SEM). Findings indicate that BM-MSCs and BM-MSCS-CM have augmented the regenerative capacity in acute and subacute injury groups with a slightly better improvement in the subacute groups than the animals in acute injury groups. Histopathology data revealed different levels of regenerative process undergoing in the nerve. Neurological observations, gastrocnemius muscle evaluation, muscle histopathology, and the SEM results depicted better healing in animals treated with BM-MSCs and BM-MSCS-CM. With this data, it could be concluded that BM-MSCs support the healing of injured peripheral nerves, and the BM-MSCS-CM does accelerate the healing of acute and subacute peripheral nerve injuries in rabbits. However, stem cell therapy may be indicated during the subacute phase for better results.

Effect of Bezafibrate, a PPARα Activator, on Acute and Subacute Inflammation in Male Wistar Rats

Aim To investigate the anti-inflammatory effect of bezafibrate on acute and subacute inflammation in adult male Wistar rats. Methods The study was carried out in adult male Wistar rats and they were allocated into three groups, that is, control, aspirin and bezafibrate, after obtaining clearance from Institutional Animal Ethics Committee. Acute inflammation was studied using carrageenan-induced rat paw oedema, and the volume displacement due to paw oedema using the plethysmograph. Subacute inflammation was studied using foreign body induced granuloma models. Analysis was performed using one-way ANOVA followed by post hoc tests of Dunnett’s. The value p &lt; 0.05 was considered statistically significant. Results Bezafibrate showed a significant anti-inflammatory effect in acute as well as subacute models of inflammation when compared to control in the present study. Conclusions In patients receiving bezafibrate for hyperlipidemia, its anti-inflammatory potential may have an additional benefit in preventing complication of atherosclerosis.

Identification of mouse metabolic variations related to patulin-induced acute and subacute hepatotoxicity by ultra-high-performance liquid chromatography high-resolution mass spectrometry

Patulin (PAT), a toxin produced by molds in fruits and related products, has caused frequent food poisoning incidents worldwide. However, its potential mechanism of hepatotoxicity remains presently unclear. Herein, we intragastrically administered the C57BL/6J mice with 0, 1, 4, and 16 mg/kg b.wt of PAT on a single occasion (acute model), and 0, 50, 200, and 800 μg/kg b.wt of PAT daily over two weeks (subacute model). Assessments of histopathology and aminotransferase activities confirmed that significant hepatic damages were induced. Metabolic profiling on the liver using ultra-high-performance liquid chromatography high-resolution mass spectrometry discovered 43 and 61 differential metabolites in two models, respectively. Notably, acute and subacute models shared the common 18 differential metabolites, among which N-acetyl-leucine, inosine, 2-O-methyladenosine, PC 40:7, PC 38:6, and PC 34:2 could be regarded as the biomarkers indicative of PAT exposure. Moreover, analysis of metabolic pathways demonstrated that pentose phosphate pathway and purine metabolism were the main altered pathways in the acute model. Nevertheless, more pathways related to amino acids were affected in the subacute model. These results reveal the comprehensive influence of PAT on hepatic metabolism and provide a deeper understanding of the hepatotoxicity mechanism of PAT.

Potential Antifibrotic Effect of Blueberry and Grape Polyphenol Extracts in Acute and Subacute Bleomycin-Induced Lung Tissue Injury Models in Mice

An experimental morphological and morphometric study of the antifibrotic function of blueberry and grape extracts was carried out on a model of lung injury in mice induced by intraperitoneal administration of bleomycin. During intraperitoneal administration of bleomycin to mice, acute and subacute damage to the pulmonary system was noted. Both patterns had the same prevalence and severity. The administration of polyphenolic extracts of blueberry and grape to mice showed a significant reduction in the severity of the acute and subacute pattern of lung injury. Blueberry and grape extracts reduce the acute phase of damage to the microvasculature, enhance phagocytic function, have an anti-inflammatory effect, reducing the degree of lymphohistiocytic infiltration and locoregional foci of residual inflammatory effects.

Conductive Metal-Organic Framework Microelectrodes Regulated by Conjugated Molecular Wires for Monitoring of Dopamine in the Mouse Brain.

Herein, we demonstrated a strategy to regulate the conductive metal-organic framework (MOF) surface, by the conjugated molecule wires for selective and sensitive determination of dopamine (DA) in the live brain. The MOFs were decorated at the carbon fiber electrode deposited by Au nanoleaves as the upper electric transducer to provide rich electrocatalytic sites for electron transfer of neurochemicals at the electrode surface, leading to greatly enhanced sensitivity for detection of neurochemicals. On the other hand, the conjugated molecular wire, 4-(thiophen-3-ylethynyl)-benzaldehyde (RP1), was synthesized and assembled as an underlying bridge to regulate the electrochemical processes at the MOF-based electrode, specifically decreasing the reaction Gibbs free energy of DA oxidation, thus selectively promoting the heterogeneous electron transfer of DA from the MOF layer to the electrode surface. Owing to the electrocatalytic activity for DA oxidation, the present microsensor exhibited high selectivity for real-time tracking of DA in a good linear relationship in the range of 0.004-0.4 μM with a detection limit of 1 nM. Eventually, this functionalized electrode was successfully applied for in vivo monitoring of DA in mouse brains with Parkinson's disease (PD) model. The results indicated that the levels of DA were obviously decreased in both acute and subacute PD models. Moreover, the level of DA strongly depended on the amount of uric acid (UA), a physiological antioxidant, which rose as the UA amount was lower than 200 mg kg-1 but was downregulated again after treatment by a higher amount of UA.

Validation of a classification to identify emergency department visits suitable for subacute and virtual care models: a randomised single-blinded agreement study protocol

IntroductionRedirecting suitable patients from the emergency department (ED) to alternative subacute settings may assist in reducing ED overcrowding while delivering equivalent care. The Emergency Department Avoidance Classification (EDAC) was constructed...

Quercetin Protected from Aluminum Phosphide-induced Acute and Subacute Cardio- and Hepatotoxicity in Rats.

Aluminum phosphide (ALP) intoxication either accidentally or intentionally, is one of the major health concerns in developing countries. Its poisoning causes severe damage to organs including the heart and liver. This study aimed to investigate the hepato- and cardioprotective effects of quercetin (QCN) on the acute/subacute toxicity of ALP in rodent models. Acute (single dose, 12.5 mg/kg, orally) and subacute (2 mg/kg, orally and 7 days) intoxication of ALP were induced in rats and the protective effects of QCN on altered hepatic/cardiac functional enzyme concentrations, myeloperoxidase activity, oxidative stress biomarkers, and histopathological changes were studied at three doses of 10, 50 and 100 mg/kg BW. To record any heart abnormality, an electrocardiogram (ECG) was recorded 3 h after the last treatment. Quercetin reduced the ALP-increased hepatic and cardiac functional enzyme concentrations and myeloperoxidase activity. Moreover, QCN improved remarkably the ALP-induced ECG abnormalities (T inversion, bigeminy in R waves) and arrhythmias. QCN attenuated significantly (p < 0.05) the ALP-induced oxidative/ nitrosative stress and histopathological injuries in the liver and heart. Our results suggest that QCN is able to protect the ALP-induced cardiac and hepatic injuries in both acute and subacute models and its effects attribute to its antioxidant and anti-inflammatory properties.

Phytochemical Screening, Anti-Inflammatory, and Antidiabetic Activities of Different Extracts from Caralluma edulis Plant.

The plant Caralluma edulis is traditionally used against diabetes and inflammatory conditions in Pakistan. This study was designed to provide scientific validation of the traditional use of Caralluma edulis. Phytochemicals were extracted from the plant by different solvents (distilled water, methanol, ethanol, and acetone) using the Soxhlet’s extraction method. Bioactive compounds were detected by gas chromatography–mass spectrometry (GC-MS). The in vitro anti-inflammatory activities (albumin denaturation, membrane stabilization, and proteinase inhibition) and antioxidant capacity (DPPH scavenging activity, FRAP reducing activity) of different extracts from Caralluma edulis were assessed. The antidiabetic potential of Caralluma edulis plant extracts was determined in acute and subacute diabetic rabbit models. Oxidative stress and enzymatic antioxidant status were also estimated in MDA, CAT, and SOD levels. Results showed that the methanol extract yielded the highest contents of phenolics, flavonoids, alkaloids, and terpenoids. The in vitro anti-inflammatory activity and antioxidant potential of the methanol extract were the highest among the tested solvents. The tested extracts did not show any remarkable antidiabetic activity in the acute diabetic model. However, all tested extracts demonstrated antidiabetic potential in the subacute diabetic model. No adverse effect was observed at the tested dose (200 mg/kg) of Caralluma edulis extracts in experimental animals. It is concluded that methanol is the key solvent for extracting bioactive compounds from Caralluma edulis. The plant can be used against inflammatory disorders and may prove a potential candidate for drug development. Long-term use of Caralluma edulis at the tested dose (200 mg/kg) showed antidiabetic properties in the animal model.