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International Journal of Pharmaceutics Apr 2024The current investigation emphasizes the use of fucoidan and sericin as dual-role biomaterials for obtaining novel nanohybrid systems for the delivery of diclofenac...
The current investigation emphasizes the use of fucoidan and sericin as dual-role biomaterials for obtaining novel nanohybrid systems for the delivery of diclofenac sodium (DS) and the potential treatment of chronic inflammatory diseases. The innovative formulations containing 4 mg/ml of fucoidan and 3 mg/ml of sericin showed an average diameter of about 200 nm, a low polydispersity index (0.17) and a negative surface charge. The hybrid nanosystems demonstrated high stability at various pHs and temperatures, as well as in both saline and glucose solutions. The Rose Bengal assay evidenced that fucoidan is the primary modulator of relative surface hydrophobicity with a two-fold increase of this parameter when compared to sericin nanoparticles. The interaction between the drug and the nanohybrids was confirmed through FT-IR analysis. Moreover, the release profile of DS from the colloidal systems showed a prolonged and constant drug leakage over time both at pH 5 and 7. The DS-loaded nanohybrids (DIFUCOSIN) induced a significant decrease of IL-6 and IL-1β with respect to the active compound in human chondrocytes evidencing a synergistic action of the individual components of nanosystems and the drug and demonstrating the potential application of the proposed nanomedicine for the treatment of inflammation.
Topics: Humans; Diclofenac; Sericins; Spectroscopy, Fourier Transform Infrared; Nanoparticles; Pharmaceutical Preparations; Sodium Chloride; Polysaccharides
PubMed: 38531433
DOI: 10.1016/j.ijpharm.2024.124034 -
Physiology & Behavior May 2024The utilization of methylphenidate (MPH) is experiencing a notable surge within the adult population. This growth can be attributed to two key factors: its recreational...
BACKGROUND
The utilization of methylphenidate (MPH) is experiencing a notable surge within the adult population. This growth can be attributed to two key factors: its recreational and cognitive enhancement purposes, as well as the rising prevalence of ADHD diagnoses within this population. This study examined acute and chronic oral MPH effects on attention in male and female Wistar rats. To this end, we used a prepulse inhibition (PPI) task, which is widely used to assess psychoactive drug effects in both humans and rodents. This task allowed us to evaluate changes in attention by analyzing sensorimotor gating associated with stimulus selection process.
METHODS
Animals were administered a clinically relevant dose of MPH (5 mg/kg) daily for seven days. The estrous cycle phases of the female rats were measured during behavioral sessions. The PPI task was conducted 20 min after drug administration on day 1 (acute), day 7 (chronic), and 48 h post-treatment.
RESULTS
Results indicated that both acute and chronic MPH treatment impaired PPI expression in male rats, but not in female rats, regardless of their estrous cycle phase. Furthermore, a differential effect of chronic MPH treatment on the PPI task was found in male rats. Specifically, on the seventh treatment day, the PPI effect was observed when animals undertook the PPI task for the first time but was impaired in those animals in which the initial PPI session occurred under the acute influence of the drug (day 1).
CONCLUSIONS
These findings suggest that the impact of MPH on sensorimotor gating responses may vary based on sex and task experience, possibly leading to state-dependent effects in healthy individuals.
Topics: Humans; Female; Male; Rats; Animals; Methylphenidate; Rats, Wistar; Central Nervous System Stimulants; Prepulse Inhibition; Sex Characteristics
PubMed: 38531426
DOI: 10.1016/j.physbeh.2024.114526 -
International Ophthalmology Mar 2024Rhegmatogenous retinal detachment is a severe vision-threatening complication that can result into proliferative vitreoretinopathy (PVR) and re-detachment of the retina...
Anti-inflammatory potential of simvastatin and amfenac in ARPE-19 cells; insights in preventing re-detachment and proliferative vitreoretinopathy after rhegmatogenous retinal detachment surgery.
PURPOSE
Rhegmatogenous retinal detachment is a severe vision-threatening complication that can result into proliferative vitreoretinopathy (PVR) and re-detachment of the retina if recovery from surgery fails. Inflammation and changes in retinal pigment epithelial (RPE) cells are important contributors to the disease. Here, we studied the effects of simvastatin and amfenac on ARPE-19 cells under inflammatory conditions.
METHODS
ARPE-19 cells were pre-treated with simvastatin and/or amfenac for 24 h after which interleukin (IL)-1α or IL-1β was added for another 24 h. After treatments, lactate dehydrogenase release, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) processing, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activity, prostaglandin E2 (PGE2) level, and extracellular levels of IL-6, IL-8, monocytic chemoattractant protein (MCP-1), vascular endothelial growth factor (VEGF), and pigment epithelium-derived factor, as well as the production of reactive oxygen species (ROS) were determined.
RESULTS
Pre-treatment of human ARPE-19 cells with simvastatin reduced the production of IL-6, IL-8, and MCP-1 cytokines, PGE2 levels, as well as NF-κB activity upon inflammation, whereas amfenac reduced IL-8 and MCP-1 release but increased ROS production. Together, simvastatin and amfenac reduced the release of IL-6, IL-8, and MCP-1 cytokines as well as NF-κB activity but increased the VEGF release upon inflammation in ARPE-19 cells.
CONCLUSION
Our present study supports the anti-inflammatory capacity of simvastatin as pre-treatment against inflammation in human RPE cells, and the addition of amfenac complements the effect. The early modulation of local conditions in the retina can prevent inflammation induced PVR formation and subsequent retinal re-detachment.
Topics: Humans; Vitreoretinopathy, Proliferative; Retinal Detachment; NF-kappa B; Vascular Endothelial Growth Factor A; Retinal Pigment Epithelium; Simvastatin; Reactive Oxygen Species; Dinoprostone; Interleukin-6; Interleukin-8; Cytokines; Anti-Inflammatory Agents; Inflammation; Phenylacetates
PubMed: 38530532
DOI: 10.1007/s10792-024-03067-z -
Plant Signaling & Behavior Dec 2024Tobacco black shank (TBS), caused by , is a severe disease. Plant root exudates play a crucial role in mediating plant-pathogen interactions in the rhizosphere. However,...
Tobacco black shank (TBS), caused by , is a severe disease. Plant root exudates play a crucial role in mediating plant-pathogen interactions in the rhizosphere. However, the specific interaction between key secondary metabolites present in root exudates and the mechanisms of disease resistance remains poorly understood. This study conducted a comprehensive comparison via quasi-targeted metabolomic analysis on the root exudate metabolites from the tobacco cultivar Yunyan87 and K326, both before and after inoculation with . The results showed that the root exudate metabolites changed after inoculation, and the root exudate metabolites of different tobacco cultivar was significantly different. Furthermore, homovanillic acid, lauric acid, and isoliquiritigenin were identified as potential key compounds for TBS resistance based on their impact on the mycelium growth of the pathogens. The pot experiment showed that isoliquiritigenin reduced the incidence by 55.2%, while lauric acid reduced it by 45.8%. This suggests that isoliquiritigenin and lauric acid have potential applications in the management of TBS. In summary, this study revealed the possible resistance mechanisms of differential metabolites in resistance of commercial tobacco cultivar, and for the first time discovered the inhibitory effects of isoliquiritigenin and homovanillic acid on , and attempt to use plants secondary metabolites of for plant protection.
Topics: Homovanillic Acid; Lauric Acids; Chalcones; Nicotiana
PubMed: 38527068
DOI: 10.1080/15592324.2024.2332019 -
World Journal of Gastroenterology Feb 2024Endoscopic ultrasound (EUS) with fine needle aspiration or fine needle biopsy is the gold standard for sampling tissue to diagnose pancreatic cancer and autoimmune... (Review)
Review
Endoscopic ultrasound (EUS) with fine needle aspiration or fine needle biopsy is the gold standard for sampling tissue to diagnose pancreatic cancer and autoimmune pancreatitis or to analyze cyst fluid. The most common reported adverse event of fine needle aspiration and/or fine needle biopsy is acute pancreatitis, which is likely induced by the same pathophysiological mechanisms as after endoscopic retrograde cholangiopancreatography (ERCP). According to the current European Society of Gastrointestinal Endoscopy guideline, nonsteroidal anti-inflammatory drugs are administered prior to ERCP as a scientifically proven treatment to reduce post-ERCP pancreatitis incidence rate. A single suppository of diclofenac or indomethacin prior to EUS guided tissue acquisition (TA) is harmless in healthy adults. Since it is associated with low costs and, most important, may prevent a dreadsome complication, we strongly recommend the administration of 100 mg diclofenac rectally prior to EUS-TA. We will explain this recommendation in more detail in this review as well as the risk and pathophysiology of post-EUS TA pancreatitis.
Topics: Adult; Humans; Pancreatitis; Incidence; Diclofenac; Acute Disease; Anti-Inflammatory Agents, Non-Steroidal; Cholangiopancreatography, Endoscopic Retrograde; Ultrasonography, Interventional; Endoscopic Ultrasound-Guided Fine Needle Aspiration
PubMed: 38516233
DOI: 10.3748/wjg.v30.i8.811 -
Journal of Feline Medicine and Surgery Mar 2024The main objective of this study was to compare the postoperative analgesic effects of grapiprant with those of robenacoxib in cats undergoing ovariohysterectomy (OVH).
Evaluation of the analgesic efficacy of grapiprant compared with robenacoxib in cats undergoing elective ovariohysterectomy in a prospective, randomized, masked, non-inferiority clinical trial.
OBJECTIVES
The main objective of this study was to compare the postoperative analgesic effects of grapiprant with those of robenacoxib in cats undergoing ovariohysterectomy (OVH).
METHODS
In total, 37 female cats (age range 4 months-10 years, weighing ⩾2.5 kg) were enrolled in a prospective, randomized, masked, non-inferiority (NI) clinical trial. Cats received oral robenacoxib (1 mg/kg) or grapiprant (2 mg/kg) 2 h before OVH. Analgesia was assessed via the Feline Grimace Scale (FGS), the Glasgow Composite Measure Pain Scale-Feline (CMPS-F), von Frey monofilaments (vFFs) and pressure algometry (ALG) 2 h before treatment administration, at extubation, and 2, 4, 6, 8, 18 and 24 hours after extubation. Hydromorphone (<8 h postoperatively) or buprenorphine (>18 h postoperatively) were administered to cats with scores of ⩾5/20 on CMPS-F and/or ⩾4/10 on FGS. NI margins for CMPS-F and vFFs were set at 3 and -0.2, respectively. A mixed-effect ANOVA was used for FGS scores ( <0.05). Data are reported as mean ± SEM.
RESULTS
The data from 33 cats were analyzed. The upper limit of the 95% confidence interval (CI) (0.35) was less than the NI margin of 3 for CMPS-F, and the lower limit of the 95% CI (0.055) was greater than the NI margin of -0.2 for vFFs, indicating NI of grapiprant. The FGS scores were greater than baseline at extubation for both treatments (1.65 ± 0.63; = 0.001); however, there was no difference between treatments. There was no difference between treatments, nor treatment by time interaction, for vFFs ( <0.001). The CMPS-F scores for both treatments were higher at extubation but returned to baseline after 4 h ( <0.001). For ALG, there was no difference in treatment or treatment by time interaction. The robenacoxib group had lower pressure readings at extubation and 6 h compared with baseline.
CONCLUSIONS AND RELEVANCE
These results indicate that grapiprant was non-inferior to robenacoxib for mitigating postsurgical pain in cats after OVH performed via ventral celiotomy. The impact of grapiprant for analgesia in OVH via the flank is unknown.
Topics: Cats; Animals; Female; Ovariectomy; Prospective Studies; Analgesics; Hysterectomy; Pain, Postoperative; Cat Diseases; Benzenesulfonamides; Pyridines; Diphenylamine; Phenylacetates; Sulfonylurea Compounds; Imidazoles
PubMed: 38511293
DOI: 10.1177/1098612X241230941 -
Attention-Deficit/Hyperactivity Disorder Medications and Work Disability and Mental Health Outcomes.JAMA Network Open Mar 2024Individuals with attention-deficit/hyperactivity disorder (ADHD) often have comorbid psychiatric conditions. Relatively little is known about how specific ADHD...
IMPORTANCE
Individuals with attention-deficit/hyperactivity disorder (ADHD) often have comorbid psychiatric conditions. Relatively little is known about how specific ADHD medications are associated with overall treatment outcomes among these patients.
OBJECTIVE
To investigate the association of the use of specific ADHD medications with hospitalization outcomes and work disability among adolescents and adults with ADHD.
DESIGN, SETTING, AND PARTICIPANTS
This nationwide register-based cohort study identified individuals (aged 16-65 years) with ADHD from Swedish nationwide registers of inpatient health care, specialized outpatient health care, sickness absence, and disability pension during the years 2006 to 2021. Data analysis was performed from November 2022 to August 2023.
EXPOSURE
Use of specific ADHD medications.
MAIN OUTCOMES AND MEASURES
The main outcome measure was psychiatric hospitalization, and secondary outcomes were suicide attempt and/or death by suicide, nonpsychiatric hospitalization, and work disability (ie, sickness absence or disability pension). The risk of outcomes between use vs nonuse periods of ADHD medications was compared in a within-individual design, where a person acts as their own control, and was analyzed with stratified Cox models.
RESULTS
A total of 221 714 persons with ADHD were included in the study cohort (mean [SD] age, 25.0 [11.2] years; 120 968 male individuals [54.6%]). Methylphenidate was the most commonly used ADHD medication (151 837 individuals [68.5%]), followed by lisdexamphetamine (78 106 individuals [35.2%]) during the follow-up (mean [SD], 7.0 [4.7] years). The following medications were associated with a decreased risk of psychiatric hospitalization: amphetamine (adjusted hazard ratio [aHR], 0.74; 95% CI, 0.61-0.90), lisdexamphetamine (aHR, 0.80; 95% CI, 0.78-0.82), ADHD drug polytherapy (aHR, 0.85; 95% CI, 0.82-0.88), dexamphetamine (aHR, 0.88; 95% CI, 0.83-0.94), and methylphenidate (aHR, 0.93; 95% CI, 0.92-0.95). No associations were found for modafinil, atomoxetine, clonidine, and guanfacine. Decreased risk of suicidal behavior was associated with the use of dexamphetamine (aHR, 0.69; 95% CI, 0.53-0.89), lisdexamphetamine (aHR, 0.76; 95% CI, 0.68-0.84), and methylphenidate (aHR, 0.92; 95% CI, 0.86-0.98). None of the medications was associated with increased risk of nonpsychiatric hospitalization; instead, use of amphetamine, lisdexamphetamine, polytherapy, dexamphetamine, methylphenidate, and atomoxetine were associated with decreased risk of nonpsychiatric hospitalization. The results regarding work disability were significant only for the use of atomoxetine (aHR, 0.89; 95% CI, 0.82-0.97), especially among adolescents and young adults aged 16 to 29 years, (aHR, 0.82; 95% CI, 0.73-0.92).
CONCLUSIONS AND RELEVANCE
In this nationwide cohort study of adolescents and adults with ADHD, the use of ADHD medication was associated with fewer hospitalizations for both psychiatric and nonpsychiatric morbidity and lower suicidal behavior.
Topics: Adolescent; Young Adult; Humans; Male; Adult; Attention Deficit Disorder with Hyperactivity; Atomoxetine Hydrochloride; Cohort Studies; Lisdexamfetamine Dimesylate; Methylphenidate; Amphetamine
PubMed: 38506810
DOI: 10.1001/jamanetworkopen.2024.2859 -
CNS Drugs Apr 2024An increasing number of women of reproductive age are treated with attention-deficit hyperactivity disorder (ADHD) medication; however, patterns of ADHD medication use...
BACKGROUND
An increasing number of women of reproductive age are treated with attention-deficit hyperactivity disorder (ADHD) medication; however, patterns of ADHD medication use for women in the perinatal period have not been well described.
OBJECTIVE
This study aimed to describe ADHD medication use patterns from 1 year before pregnancy to 1 year after delivery, and to describe sociodemographic characteristics and clinical features by medication trajectories.
METHODS
The population-based cohort study included pregnancies in Denmark between 1997 and 2020, from the Medical Birth Register, by women who filled at least one prescription for ADHD medication from 12 months before pregnancy until 12 months after delivery. We applied group-based trajectory modeling to classify women into subgroups based on the identification of heterogeneous ADHD medication treatment patterns, and described the characteristics associated with these groups.
RESULTS
Overall, we included 4717 pregnancies leading to liveborn singletons by 4052 mothers with a mean (standard deviation) age of 27.5 (5.6) years. We identified four treatment trajectories across pregnancy and the postpartum period: continuers (23.3%), discontinuers (41.8%), interrupters who ceased filling prescriptions during pregnancy but resumed postpartum (17.2%), and postpartum initiators (17.7%). Continuers were older at the time of conception, gave birth in more recent years, were more likely to smoke during pregnancy, and used other psychotropic medications during pregnancy. A large proportion of continuers used methylphenidate (89.1%) compared with the other groups (75.9-84.1%) and had switched ADHD medication type during the whole period (16.4% vs. 7.4-14.8%).
CONCLUSION
We found that approximately 60% of women discontinued or interrupted their ADHD medication around pregnancy, and those who continued differed in sociodemographic and clinical factors that may reflect more severe ADHD.
Topics: Pregnancy; Humans; Female; Adult; Attention Deficit Disorder with Hyperactivity; Cohort Studies; Methylphenidate; Registries; Central Nervous System Stimulants
PubMed: 38489019
DOI: 10.1007/s40263-024-01076-1 -
International Journal of Nanomedicine 2024Rheumatoid arthritis (RA) is a common acute inflammatory autoimmune connective tissue arthropathy. The genetic studies, tissue analyses, experimental animal models, and...
BACKGROUND
Rheumatoid arthritis (RA) is a common acute inflammatory autoimmune connective tissue arthropathy. The genetic studies, tissue analyses, experimental animal models, and clinical investigations have confirmed that stromal tissue damage and pathology driven by RA mounts the chronic inflammation and dysregulated immune events.
METHODS
We developed methotrexate (MTX)-loaded lipid-polymer hybrid nanoparticles (MTX-LPHNPs) and aceclofenac (ACE)-loaded nanostructured lipid carriers (ACE-NLCs) for the efficient co-delivery of MTX and ACE via intravenous and transdermal routes, respectively. Bio-assays were performed using ex-vivo skin permeation and transport, macrophage model of inflammation (MMI) (LPS-stimulated THP-1 macrophages), Wistar rats with experimental RA (induction of arthritis with Complete Freund's adjuvant; CFA and BCG), and programmed death of RA affected cells. In addition, gene transcription profiling and serum estimation of inflammatory, signaling, and cell death markers were performed on the blood samples collected from patients with RA.
RESULTS
Higher permeation of ACE-NLCs/CE across skin layers confirming the greater "therapeutic index" of ACE. The systemic delivery of MTX-loaded LPHNPs via the parenteral (intravenous) route is shown to modulate the RA-induced inflammation and other immune events. The regulated immunological and signaling pathway(s) influence the immunological axis to program the death of inflamed cells in the MMI and the animals with the experimental RA. Our data suggested the CD40-mediated and Akt1 controlled cell death along with the inhibited autophagy in vitro. Moreover, the ex vivo gene transcription profiling in drug-treated PBMCs and serum analysis of immune/signalling markers confirmed the therapeutic role co-delivery of drug nanoparticles to treat RA. The animals with experimental RA receiving drug treatment were shown to regain the structure of paw bones and joints similar to the control and were comparable with the market formulations.
CONCLUSION
Our findings confirmed the use of co-delivery of drug nanoformulations as the "combination drug regimen" to treat RA.
Topics: Humans; Rats; Animals; Methotrexate; Rats, Wistar; Arthritis, Rheumatoid; Nanoparticles; Inflammation; Arthritis, Experimental; Lipids; Diclofenac
PubMed: 38482519
DOI: 10.2147/IJN.S439359 -
Talanta Jun 2024Primary Open-Angle Glaucoma (POAG) is the most prevalent glaucoma type, and the leading cause of irreversible visual impairment and blindness worldwide. Identification...
Primary Open-Angle Glaucoma (POAG) is the most prevalent glaucoma type, and the leading cause of irreversible visual impairment and blindness worldwide. Identification of early POAG biomarkers is of enormous value, as there is not an effective treatment for the glaucomatous optic nerve degeneration (OND). In this pilot study, a metabolomic analysis, by using proton (H) nuclear magnetic resonance (NMR) spectroscopy was conducted in tears, in order to determine the changes of specific metabolites in the initial glaucoma eyes and to discover potential diagnostic biomarkers. A classification model, based on the metabolomic fingerprint in tears was generated as a non-invasive tool to support the preclinical and clinical POAG diagnosis. H NMR spectra were acquired from 30 tear samples corresponding to the POAG group (n = 11) and the control group (n = 19). Data were analysed by multivariate statistics (partial least squares-discriminant analysis: PLS-DA) to determine a model capable of differentiating between groups. The whole data set was split into calibration (65%)/validation (35%), to test the performance and the ability for glaucoma discrimination. The calculated PLS-DA model showed an area under the curve (AUC) of 1, as well as a sensitivity of 100% and a specificity of 83.3% to distinguish POAG group versus control group tear data. This model included 11 metabolites, potential biomarkers of the disease. When comparing the study groups, a decrease in the tear concentration of phenylalanine, phenylacetate, leucine, n-acetylated compounds, formic acid, and uridine, was found in the POAG group. Moreover, an increase in the tear concentration of taurine, glycine, urea, glucose, and unsaturated fatty acids was observed in the POAG group. These results highlight the potential of tear metabolomics by H NMR spectroscopy as a non-invasive approach to support early POAG diagnosis and in order to prevent visual loss.
Topics: Humans; Glaucoma, Open-Angle; Pilot Projects; Metabolomics; Biomarkers; Taurine
PubMed: 38479028
DOI: 10.1016/j.talanta.2024.125826