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Children (Basel, Switzerland) Apr 2024Fever is one of the most frequent symptoms highlighted during medical assistance. Due to this great impact, our study has the purpose of analyzing the demographic and...
BACKGROUND
Fever is one of the most frequent symptoms highlighted during medical assistance. Due to this great impact, our study has the purpose of analyzing the demographic and laboratory characteristics of patients hospitalized in our center and identifying predictive markers to make the differential diagnosis between infectious and non-infectious fever.
METHODS
Our population included 220 children, collected from January 2017 to August 2022, hospitalized for continuous fever (4 days or more in duration with at least one temperature peak ≥37.5 °C) and excluded cases of discharge against medical advice and/or transfer to other operating units. Demographic (mean age at the time of admission, frequency of hospitalization, and mean days of hospitalization), laboratory, and instrumental variables were analyzed in order to find correlation with fever etiology.
RESULTS
Older age at the time of hospitalization, family history of periodic fever, fever lasting more than 8 days, and longer hospitalization are strongly associated with non-infectious fever, together with anemia, high platelet count, high CRP and ferritin, and hyponatremia at the time of admission. Paracetamol is the preferred antipyretic treatment. Echocardiogram has shown anomalies in patients with infectious fever, while ECG anomalies were detected in non-infectious fever.
CONCLUSIONS
Our data underline the importance of predictive markers, such as clinical and laboratory parameters, to differentiate infectious from non-infectious fevers, but further studies are necessary.
PubMed: 38790534
DOI: 10.3390/children11050539 -
Immunobiology May 2024Kangfuxin has been widely recognized for its use in treating ulcerative conditions and mucositis, primarily due to its anti-inflammatory properties, which promote cell...
Kangfuxin has been widely recognized for its use in treating ulcerative conditions and mucositis, primarily due to its anti-inflammatory properties, which promote cell proliferation, granulation tissue growth, and angiogenesis. However, the exact mechanisms underlying these effects remain poorly understood. In this study, we employed high-throughput mass spectrometry to identify 11 compounds in Kangfuxin, including uracil, hypoxanthine, xanthine, inosine, glutamic acid, glycine, alanine, valine, isoleucine, leucine, and lysine. Notably, the antipyretic and anti-inflammatory properties of inosine, one of these compounds, have not been well characterized. To address this gap, we induced fever in vivo using lipopolysaccharide (LPS) and conducted various experiments, including the analysis of endogenous mediators, inflammatory factors, quantitative polymerase chain reaction (QPCR), Western blotting, and hematoxylin and eosin (HE) staining. Our findings indicate that inosine significantly reduces LPS-induced fever, inhibits the expression of inflammatory factors, and alleviates the inflammatory response. These results suggest that inosine may serve as a potential therapeutic target for inflammatory diseases.
Topics: Inosine; Animals; Mice; Lipopolysaccharides; Anti-Inflammatory Agents; Antipyretics; Male; Inflammation; Fever; Disease Models, Animal; Inflammation Mediators; Cytokines; Drugs, Chinese Herbal
PubMed: 38781756
DOI: 10.1016/j.imbio.2024.152812 -
PloS One 2024The main goal of the study was to improve the compliance and convenience of patients by designing and development of an immediate release (IR) fixed-dose combination...
The main goal of the study was to improve the compliance and convenience of patients by designing and development of an immediate release (IR) fixed-dose combination (Clopidogrel bisulphate and Aspirin) tablets. The proposed combination product utilizes Clopidogrel to protect the moisture-sensitive aspirin component, enhancing its stability against atmospheric conditions. Response-surface approach (Design Expert vs. 13) was used to generate this IR tablet by calculating the right composition of independent variables such as Microcrystalline cellulose 102, pregelatinized starch and Hydroxypropyl cellulose. 32 factorial design was used to estimate the effects of these independent variables on the responses of dependent variables (disintegration & friability) and constructed a total of nine (9) formulations. Pre and Post formulation, quality control parameters were investigated as per pharmacopeia. A systematic approach was used for the optimization process and a prototype checkpoint batch (CPB) based on the better contrast of independent variables was prepared. In vitro analysis of formulations was carried out to estimate the responses. Friability was found in the range of 0.088-1.076%w/w, except F1 = 1.076 all are within limits (NMT 1.0%). Disintegration time was recorded 7.3 ± 1.20 as lower and 24.5 ± 1.63 min was the highest. The release of drugs from their dosage form was fast and rapid, for clopidogrel after 15min was 70.42-96.82% with SD ± 8.71 and aspirin was 69.88-91.49% in 15 min with SD ± 6.41, all the tablets were released more than 80% in 20 min. The stability outcomes of CPB tablets after 15 days of stress study (60 ± 2°C and 75 ± 5%) indicated good compatibility and stability of APIs with excipients. It was concluded that the direct compression method can be preferred to prepare a combination product with cost-effectiveness. It was also concluded that the proposed methodology could increase Aspirin's stability and allow for an aqueous coating system to finish the product with a film coating. By using Design Expert software, the best composition of the formulation can be selected and optimized in a short period of time with minimum trial and errors. The results also demonstrated that the use of a fixed-dose combination tablet instead of the individual is expected to be more convenient to patients and thus improves patient compliance and decreases the occurrence of adverse effects and side effects.
Topics: Clopidogrel; Aspirin; Tablets; Ticlopidine; Drug Combinations; Humans; Platelet Aggregation Inhibitors; Drug Compounding; Chemistry, Pharmaceutical
PubMed: 38781151
DOI: 10.1371/journal.pone.0303705 -
International Journal of Pharmaceutics Jun 2024Wet granulation, a particle size enlargement process, can significantly enhance the critical quality attributes of powders and improve the ability to form tablets in...
Wet granulation, a particle size enlargement process, can significantly enhance the critical quality attributes of powders and improve the ability to form tablets in pharmaceutical manufacturing. In this study, a mechanistic-based population balance model is applied to twin screw wet granulation. This model incorporated a recently developed breakage kernel specifically designed for twin screw granulation, along with nucleation, layering, and consolidation. Calibration and validation were performed on Hydrochlorothiazide and Acetaminophen formulations, which exhibit different particle size and wettability characteristics. Utilizing a compartmental experimental dataset, a comprehensive global sensitivity analysis identified critical inputs impacting quality attributes. The study revealed that the nucleation rate process model, effectively represented particle size distributions for both formulations. Adjustments to nucleation and breakage rate parameters, influenced by material properties and screw configuration, improved the model's accuracy. A model-driven workflow was proposed, offering step-by-step guidelines and facilitating PBM model usage, providing essential details for future active pharmaceutical ingredient (API) formulations.
Topics: Acetaminophen; Drug Compounding; Calibration; Hydrochlorothiazide; Particle Size; Workflow; Powders; Wettability; Chemistry, Pharmaceutical; Tablets; Models, Theoretical
PubMed: 38777305
DOI: 10.1016/j.ijpharm.2024.124246 -
Poultry Science Jul 2024This study was designed to examine the impact of aspirin eugenol ester (AEE) on the growth performance, serum antioxidant capacity, jejunal barrier function, and cecal...
Effect of dietary aspirin eugenol ester on the growth performance, antioxidant capacity, intestinal inflammation, and cecal microbiota of broilers under high stocking density.
This study was designed to examine the impact of aspirin eugenol ester (AEE) on the growth performance, serum antioxidant capacity, jejunal barrier function, and cecal microbiota of broilers raised under stressful high density (HD) stocking conditions compared with normal density broilers (ND). A total of 432 one-day-old AA+ male broilers were randomly divided into 4 groups: normal density (ND, 14 broilers /m), high density (HD, 22 broilers /m), ND + AEE, and HD + AEE. The results of the study revealed a significant decrease in the growth performance of broiler chickens as a result of HD stress (P < 0.05). The total antioxidant capacity (T-AOC) in serum demonstrated a significant decrease (P < 0.05) at both 28 and 35 d. Conversely, the serum level of malondialdehyde (MDA) exhibited a significant increase (P < 0.05). Dietary supplementation of AEE resulted in a significant elevation (P < 0.05) of serum GSH-PX, SOD and T-AOC activity at both 28 and 35 d. Moreover, exposure to HD stress resulted in a considerable reduction in the height of intestinal villi and mRNA expression of tight junction proteins in the jejunum, along with, a significant elevation in the mRNA expression of inflammatory cytokines (P < 0.05). However, the administration of AEE reversed the adverse effects of HD-induced stress on villus height and suppressed the mRNA expression of the pro-inflammatory genes, COX-2 and mPGES-1. Additionally, the exposure to HD stress resulted in a substantial reduction in the α-diversity of cecal microbiota and disruption in the equilibrium of intestinal microbial composition, with a notable decrease in the relative abundance of Bacteroides and Faecalibacterium (P < 0.05). In contrast, the addition of AEE to the feed resulted in a notable increase in the relative abundance of Phascolarctobacterium and enhanced microbial diversity (P < 0.05). The inclusion of AEE in the diet has been demonstrated to enhance intestinal integrity and growth performance of broilers by effectively mitigating disruptions in gut microbiota induced by HD stress.
Topics: Animals; Chickens; Male; Gastrointestinal Microbiome; Antioxidants; Diet; Cecum; Aspirin; Animal Feed; Dietary Supplements; Eugenol; Random Allocation; Animal Husbandry; Inflammation
PubMed: 38772090
DOI: 10.1016/j.psj.2024.103825 -
Journal of Ethnopharmacology Oct 2024Scutellaria baicalensis Georgi (SBG), a widely used traditional Chinese medicine, exhibits anti-inflammatory and antioxidant properties. Wogonin is one of the primary...
ETHNOPHARMACOLOGICAL RELEVANCE
Scutellaria baicalensis Georgi (SBG), a widely used traditional Chinese medicine, exhibits anti-inflammatory and antioxidant properties. Wogonin is one of the primary bioactive components of SBG. Acetaminophen (APAP)-induced liver injury (AILI) represents a prevalent form of drug-induced liver damage and is primarily driven by inflammatory responses and oxidative stress.
AIM OF STUDY
To investigate the therapeutic effects of Wogonin on AILI and the underlying mechanisms.
MATERIALS AND METHODS
C57BL/6 J mice were pre-treated with Wogonin (1, 2.5, and 5 mg/kg bodyweight) for 3 days, followed by treatment with APAP (300 mg/kg bodyweight). The serum and liver tissue samples were collected at 24 h post-APAP treatment. Bone marrow-derived macrophages and RAW264.7 cells were cultured and pre-treated with Wogonin (5, 10, and 20 μM) for 30 min, followed by stimulation with lipopolysaccharide (LPS; 100 ng/mL) for 3 h. To examine the role of the PI3K/AKT signaling pathway in the therapeutic effect of Wogonin on AILI, mice and cells were treated with LY294002 (a PI3K inhibitor) and MK2206 (an AKT inhibitor).
RESULTS
Wogonin pre-treatment dose-dependently alleviated AILI in mice. Additionally, Wogonin suppressed oxidative stress and inflammatory responses. Liver transcriptome analysis indicated that Wogonin primarily regulates immune function and cytokines in AILI. Wogonin suppressed inflammatory responses of macrophages by inhibiting the PI3K/AKT signaling pathway. Consistently, Wogonin exerted therapeutic effects on AILI in mice through the PI3K/AKT signaling pathway.
CONCLUSIONS
Wogonin alleviated AILI and APAP-induced hepatotoxicity in mice through the PI3K/AKT signaling pathway.
Topics: Animals; Flavanones; Acetaminophen; Mice, Inbred C57BL; Mice; Chemical and Drug Induced Liver Injury; Proto-Oncogene Proteins c-akt; Signal Transduction; Male; RAW 264.7 Cells; Phosphatidylinositol 3-Kinases; Liver; Oxidative Stress; Anti-Inflammatory Agents; Macrophages; Scutellaria baicalensis
PubMed: 38763368
DOI: 10.1016/j.jep.2024.118364 -
Journal of the American Heart... May 2024Recent clinical trials established the benefit of dual antiplatelet therapy with aspirin and clopidogrel (DAPT-AC) in early-presenting patients with minor ischemic...
BACKGROUND
Recent clinical trials established the benefit of dual antiplatelet therapy with aspirin and clopidogrel (DAPT-AC) in early-presenting patients with minor ischemic stroke. However, the impact of these trials over time on the use and outcomes of DAPT-AC among the patients with nonminor or late-presenting stroke who do not meet the eligibility criteria of these trials has not been delineated.
METHODS AND RESULTS
In a multicenter stroke registry, this study examined yearly changes from April 2008 to August 2022 in DAPT-AC use for stroke patients ineligible for CHANCE/POINT (Clopidogrel in High-Risk Patients with Acute Nondisabling Cerebrovascular Events/Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke) clinical trials due to National Institutes of Health Stroke Scale >4 or late arrival beyond 24 hours of onset. A total of 32 118 patients (age, 68.1±13.1 years; male, 58.5%) with National Institutes of Health Stroke Scale of 4 (interquartile range, 1-7) were analyzed. In 2008, DAPT-AC was used in 33.0%, other antiplatelets in 62.7%, and no antiplatelet in 4.3%. The frequency of DAPT-AC was relatively unchanged through 2013, when the CHANCE trial was published, and then increased steadily, reaching 78% in 2022, while other antiplatelets decreased to 17.8% in 2022 (<0.001). From 2011 to 2022, clinical outcomes nonsignificantly improved, with an average relative risk reduction of 2%/y for the composite of stroke, myocardial infarction, and all-cause mortality, both among patients treated with DAPT-AC and patients treated with other antiplatelets.
CONCLUSIONS
Use of DAPT-AC in stroke patients with stroke ineligible for recent DAPT clinical trials increased markedly and steadily after CHANCE publication in 2013, reaching deployment in nearly 4 of every 5 patients by 2022. The secondary prevention in patients with ischemic stroke seems to be gradually improving, possibly due to the enhancement of risk factor control.
Topics: Humans; Clopidogrel; Aspirin; Male; Aged; Female; Ischemic Stroke; Dual Anti-Platelet Therapy; Platelet Aggregation Inhibitors; Registries; Middle Aged; Treatment Outcome; Aged, 80 and over; Time Factors; Japan; Secondary Prevention; Drug Therapy, Combination; Risk Factors
PubMed: 38761083
DOI: 10.1161/JAHA.123.033611 -
Environmental Science and Pollution... May 2024Water pollution due to emerging contaminants, e.g., pharmaceuticals, is one of the most frequently discussed issues. Among them, paracetamol received great attention due...
Water pollution due to emerging contaminants, e.g., pharmaceuticals, is one of the most frequently discussed issues. Among them, paracetamol received great attention due to its physico-chemical properties, persistence, and adverse environmental effects. Different techniques were employed for its degradation and, among them, photodegradation is considered one of the most suitable to pursue the aim. This work aimed to synthesize mesoporous TiO, even with the presence of iron, through a one-pot method, with an enhanced ability to abate paracetamol. Precisely, pure and iron-containing (3.5 wt%) TiO were successfully obtained employing an uncommon procedure for this kind of material, mainly solution combustion synthesis (SCS). Moreover, a traditional hydrothermal method and a commercial Degussa P25 were also investigated for comparison purposes. The samples were characterized through N-physisorption at - 196 °C, XRD, XPS, EDX, DR UV-Vis, and FESEM analysis. The catalytic activity was investigated for the abatement of 10 ppm of paracetamol, under UV irradiation in acidic conditions (pH = 3) and in the presence of HO. As a whole, the best-performing catalysts were those obtained through the SCS procedure, highlighting a complete removal of the organic pollutant after 1 h in the case of Fe/TiO_SCS, thanks to its highly defective structure and the presence of metal Fe. To better investigate the performance of both pure and Fe-containing SCS samples, further oxidation tests were performed at pH = 7 and in the absence of HO. Noteworthy, in these conditions, the two samples exhibited different behaviors, highlighting different mechanisms depending on the presence or absence of iron in the structure. Finally, a kinetic study was conducted, demonstrating that a first order is suitable for its abatement.
Topics: Titanium; Acetaminophen; Catalysis; Photolysis; Iron; Water Pollutants, Chemical; Hydrogen Peroxide
PubMed: 38758438
DOI: 10.1007/s11356-024-33575-5 -
The Journal of Clinical Pediatric... May 2024Postoperative pain is generally a novel experience among paediatric patients. Topical anaesthetics, distraction procedures, and buffering of anaesthetic solutions have...
Postoperative pain is generally a novel experience among paediatric patients. Topical anaesthetics, distraction procedures, and buffering of anaesthetic solutions have been used in reducing the postoperative pain. In this review, the authors assessed various modalities used to alleviate postoperative pain in children's dental treatment under general anaesthesia. Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) protocol were strictly adhered to in this systematic review. Specific keywords including postoperative pain, general anaesthesia, children, and dental extraction were used in the search for relevant randomized control trial studies in Web of Science, Scopus and PubMed, and included articles published until June 2021. From a total of 191 abstracts, 21 were reviewed. From the six studies with the usage of non-steroidal anti-inflammatory drugs (NSAIDs) alone or in combination with paracetamol, four observed that the preoperative use of NSAIDs alone or in combination was better than paracetamol alone, one discovered preoperative intravenous paracetamol was better than postoperative intravenous paracetamol, and the remaining study found no difference among various groups. Of two studies comparing the usage of non-steroidal anti-inflammatory drugs with opioid analgesics, one stated intravenous fentanyl in combination was better, while the other study found no difference among groups. The results obtained in this review can be utilized by physicians to control postoperative pain in children undergoing dental treatment under general anaesthesia.
Topics: Humans; Pain, Postoperative; Anesthesia, General; Child; Anti-Inflammatory Agents, Non-Steroidal; Dental Care for Children; Acetaminophen; Analgesics, Opioid; Anesthesia, Dental; Tooth Extraction
PubMed: 38755977
DOI: 10.22514/jocpd.2024.054