Background: Multiple Sclerosis (MS) is a chronic autoimmune, inflammatory neurological disease of the CNS. Riluzole and dimethyl fumarate (DMF) are two FDA-approved drugs to treat amyotrophic lateral sclerosis (ALS) and MS. Riluzole (a benzothiazole derivative) inhibits glutamate release from nerve terminals by antagonizing the N-Methyl-D-Aspartate (NMDA) receptor, and DMF upregulates anti-oxidative pathways.
Objectives: Herein, using molecular hybridization strategy, we synthesized some new hybrid structures of Riluzole and DMF through some common successive synthetic pathways for evaluating their potential activity for remyelination in MS treatment.
Methods: Molecular docking experiments assessed the binding affinity of proposed structures to the NMDA active site. The designed structures were synthesized and purified based on well-known chemical synthesis procedures. Afterward, in vivo evaluation for their activity was done in the C57Bl/6 Cuprizone-induced demyelination MS model.
Results and conclusion: The proposed derivatives were recognized to be potent enough based on docking studies (ΔGbind of all derivatives were -7.2 to -7.52 compare to the Ifenprodil (-6.98) and Riluzole (-4.42)). The correct structures of desired derivatives were confirmed using spectroscopic methods. Based on in vivo studies, D4 and D6 derivatives exhibited the best pharmacological results, although only D6 showed a statistically significant difference compared to the control. Also, for D4 and D6 derivatives, myelin staining confirmed reduced degeneration in the corpus callosum. Consequently, D4 and D6 derivatives are promising candidates for developing new NMDA antagonists with therapeutic value against MS disorders.
Background: Treatment management for opioid poisoning is critical and, at the same time, requires specialized knowledge and skills. This study was designed to develop and evaluate machine learning algorithms for predicting the maintenance dose and duration of hospital stay in opioid poisoning, in order to facilitate appropriate clinical decision-making.
Method and results: This study used artificial intelligence technology to predict the maintenance dose and duration of administration by selecting clinical and paraclinical features that were selected by Pearson correlation (filter method) (Stage 1) and then the (wrapper method) Recursive Feature Elimination Cross-Validated (RFECV) (Stage2). The duration of administration was divided into two categories: A (which includes a duration of less than or equal to 24 h of infusion) and B (more than 24 h of naloxone infusion). XGBoost algorithm model with an accuracy rate of 91.04%, a prediction rate of 91.34%, and a sensitivity rate of 91.04% and area under the Curve (AUC) 0.97 was best model for classification patients. Also, the best maintenance dose of naloxone was obtained with XGBoost algorithm with R2 = 0.678. Based on the selected algorithm, the most important features for classifying patients for the duration of treatment were bicarbonate, respiration rate, physical sign, The partial pressure of carbon dioxide (PCO2), diastolic blood pressure, pulse rate, naloxone bolus dose, Blood Creatinine(Cr), Body temperature (T). The most important characteristics for determining the maintenance dose of naloxone were physical signs, bolus dose of 4.5 mg/kg, Glasgow Coma Scale (GCS), Creatine Phosphokinase (CPK) and intensive care unit (ICU) add.
Conclusion: A predictive model can significantly enhance the decision-making and clinical care provided by emergency physicians in hospitals and medical settings. XGBoost was found to be the superior model.
Background: It has been reported that High-Fructose (HF) consumption, considered one of the etiological factors of Metabolic Syndrome (MetS), causes changes in the gut microbiota and metabolic disorders. There is limited knowledge on the effects of metformin in HF-induced intestinal irregularities in male and female rats with MetS.
Objectives: In this study, we investigated the sex-dependent effects of metformin treatment on the gut microbiota, intestinal Tight Junction (TJ) proteins, and inflammation parameters in HF-induced MetS.
Methods: Fructose was given to the male and female rats as a 20% solution in drinking water for 15 weeks. Metformin (200 mg/kg) was administered by gastric tube once a day during the final seven weeks. Biochemical, histopathological, immunohistochemical, and bioinformatics analyses were performed. Differences were considered statistically significant at p < 0.05.
Results: The metformin treatment in fructose-fed rats promoted glucose, insulin, Homeostasis Model Assessment of Insulin Resistance Index (HOMA-IR), and Triglyceride (TG) values in both sexes. The inflammation score was significantly decreased with metformin treatment in fructose-fed male and female rats (p < 0.05). Moreover, metformin treatment significantly decreased Interleukin-1 Beta (IL-1β) and Tumor Necrosis Factor-Alpha (TNF-α) in ileum tissue from fructose-fed males (p < 0.05). Intestinal immunoreactivity of Occludin and Claudin-1 was increased with metformin treatment in fructose-fed female rats. HF and metformin treatment changed the gut microbial composition. Firmicutes/Bacteroidetes (F/B) ratio increased with HF in females. In the disease group, Bifidobacterium pseudolongum; in the treatment group, Lactobacillus helveticus and Lactobacillus reuteri are the prominent species in both sexes. When the male and female groups were compared, Akkermansia muciniphila was prominent in the male treatment group.
Conclusion: In conclusion, metformin treatment promoted biochemical parameters in both sexes of fructose-fed rats. Metformin showed a sex-dependent effect on inflammation parameters, permeability factors, and gut microbiota. Metformin has partly modulatory effects on fructose-induced intestinal changes.
Objectives: The efficient delivery of drugs from dry powder inhaler (DPI) formulations is associated with the complex interaction between the device design, drug formulations, and patient's inspiratory forces. Several challenges such as limited emitted dose of drugs from the formulation, low and variable deposition of drugs into the deep lungs, are to be resolved for obtaining the efficiency in drug delivery from DPI formulations. The objective of this study is to review the current challenges of inhaled drug delivery technology and find a way to enhance the efficiency of drug delivery from DPIs.
Methods/evidence acquisition: Using appropriate keywords and phrases as search terms, evidence was collected from the published articles following SciFinder, Web of Science, PubMed and Google Scholar databases.
Results: Successful lung drug delivery from DPIs is very challenging due to the complex anatomy of the lungs and requires an integrated strategy for particle technology, formulation design, device design, and patient inhalation force. New DPIs are still being developed with limited performance and future device design employs computer simulation and engineering technology to overcome the ongoing challenges. Many issues of drug formulation challenges and particle technology are concerning factors associated with drug dispersion from the DPIs into deep lungs.
Conclusion: This review article addressed the appropriate design of DPI devices and drug formulations aligned with the patient's inhalation maneuver for efficient delivery of drugs from DPI formulations.
Background: Diabetes mellitus (DM) increases the risk of cardiovascular diseases (CVD) significantly. Statins are recommended for all diabetic patients aged ≥ 40 years to alleviate this risk.
Objectives: This study aimed to determine the status of the implementation of the recommendations of lipid management strategies for diabetic patients.
Methods: In this cross-sectional study, 500 patients with DM, aged ≥ 40 referring to a public pharmacy with at least one diabetic medication in their prescription, were enrolled. Patients' demographics, lipid panel data, medications, personal and family history of atherosclerotic cardiovascular disease (ASCVD), and risk factors for ASCVD were documented. The appropriateness of stain dosing intensity was judged based on the American Diabetes Association (ADA) guideline.
Results: The mean ± SD of the age of patients was 61.39 ± 10.49 years. Among patients, 238 (47.6) were men. More than half of the patients were subject to receiving primary prevention (59.8%, n = 299). For 80.8% (n = 404) of patients, a statin, most frequently atorvastatin (61.8%), was prescribed. The appropriate statin dose based on the guideline for 470 patients (94%), was high-intensity statin. In 70.6% (n = 353) of patients, lipid management was not in accordance with the guideline. Patients with ASCVD were more likely to receive the statins and the appropriate doses compared to patients without ASCVD (p-value < 0.001).
Conclusion: Despite a relatively high percentage of patients who received statins, the lipid management in most patients was not in accordance with the guideline. The profound problem was the suboptimal dosage of statins. Investigating the reasons and barriers of the appropriate management can be helpful. Additionally, since patients without ASCVD who should receive statins for primary prevention were significantly less likely to receive statins and evidence-based doses, more attention is needed for this population.
Background: Amorphous hydrogel is a strategic wound healing dressings that comprised of water, polymers and excipients with no shape. The dense cross-linked network of polymer is interspersed by the immobilized water component could rehydrate and promote healing in wound tissue.
Objective: In this work, various polysaccharide/gelatin amorphous hydrogels with the impregnation of oil palm leaf derived total flavonoid enriched extract (OPL-TFEE) were fabricated via one-pot synthesis method to provide multiple crosslinking networks.
Method: The bioflavonoids (OPL-TFEE) were derived from Elaeis guineensis leaf using an integrated green extraction and enrichment process. Amorphous hydrogels with good wound healing properties were developed by incorporating 0.3% antioxidant agent into the hybrid polymeric gelling system.
Result: The formulations appeared as a semi-solid dark yellow translucent hydrogel with good spreading and consistency characteristics and satisfying aesthetic properties. The FTIR analysis indicated that the bioflavonoid was compatible with the matrix, and the hydrogels showed porous morphological structures when observed under SEM. Furthermore, the hydrogels possessed shear thinning, pseudoplastic, and elastic properties. Bioflavonoids-impregnated polysaccharide/gelatin hydrogel release 95-98% bioflavonoids within 24 h, while the drug release profile followed the Korsmeyer-Peppas kinetic model. The hydrogels showed antioxidant and wound healing properties with no sign of cytotoxicity.
Conclusion: Overall, the results revealed bioflavonoid-loaded hydrogels exhibited good physicochemical and biological properties, thus could serve as new innovative formulation in the sustainable advancement of wound care product for promoting wound healing.
Background: A persistent difficult-to-treat cough can be exhausting. Iron is an essential element that plays an important role in regulating the production of pro-inflammatory cytokines, and its deficiency may potentiate airway inflammation and dysfunction. There is a paucity of data regarding a link between iron deficiency (ID) and idiopathic cough.
Objectives: In this study, a case of persistent non-productive cough, which was unresponsive to targeted treatment approaches but responsive to iron therapy, is reported.
Methods: A 53-year-old woman came to a medical clinic with complaints of a chronic and progressive non-productive cough. She underwent a complete clinical and paraclinical evaluation.
Results: Her vital signs were stable and no abnormalities were found on the physical examination. The results of the spirometry and chest radiography were unremarkable. The laboratory test indicated hypochromic microcytic anemia, with a hemoglobin value of 9.6 g/dL. Her cough was resolved after treatment of iron-deficiency anemia with an oral nutraceutical capsule containing 28 mg of elemental iron (as ferrous bis-glycinate) plus folic acid, vitamin B12, and vitamin C, once daily for six months.
Conclusion: In the case of unexplained chronic cough, resistant to targeted therapies, investigation and treatment of ID may contribute to the resolution of cough.
Background: Rhinovirus (RV) infection is a major cause of common colds and asthma exacerbations, with no antiviral drug available. Curcumin exhibits broad-spectrum antiviral activities, but its therapeutic effect is limited by a poor pharmacokinetics profile. Curcumin-like diarylpentanoid analogs, particularly 2-benzoyl-6-(3,4-dihydroxybenzylidene)cyclohexen-1-ol (BDHBC) and 5-(3,4-dihydroxyphenyl)-3-hydroxy-1-(2-hydroxyphenyl)penta-2,4-dien-1-one (DHHPD), have better solubility and stability compared to curcumin.
Objectives: Therefore, this study aims to evaluate and compare the antiviral effects of curcumin, BDHBC, and DHHPD in an in vitro model of RV infection.
Methods: The inhibitory effects on RV-16 infection in H1 HeLa cells were assessed using cytopathic effect (CPE) reduction assay, virus yield reduction assay, RT-qPCR, and Western blot. Antiviral effects in different modes of treatment (pre-, co-, and post-treatment) were also compared. Additionally, intercellular adhesion molecule 1 (ICAM-1) expression, RV binding, and infectivity were measured with Western blot, flow cytometry, and virucidal assay, respectively.
Results: When used as a post-treatment, BDHBC (EC50: 4.19 µM; SI: 8.32) demonstrated stronger antiviral potential on RV-16 compared to DHHPD (EC50: 18.24 µM; SI: 1.82) and curcumin (less than 50% inhibition). BDHBC also showed the strongest inhibitory effect on RV-induced CPE, virus yield, vRNA, and viral proteins (P1, VP0, and VP2). Furthermore, BDHBC pre-treatment has a prophylactic effect against RV infection, which was attributed to reduced basal expression of ICAM-1. However, it did not affect virus binding, but exerted virucidal activity on RV-16, contributing to its antiviral effect during co-treatment.
Conclusion: BDHBC exhibits multiple antiviral mechanisms against RV infection and thus could be a potential antiviral agent for RV.
Objectives: In the recent years, in-situ hydrogel based on gellan gum has been investigated for delivery of various drug molecules particularly to treat neurological disorders via intranasal route. The major objective of the present manuscript is to review the recent research studies exploring gellan gum as ionic triggered in-situ gel for intranasal administration to enhance absorption of drugs and to increase their therapeutic efficacy.
Methods: This review include literature from 1982 to 2023 and were collected from various scientific electronic databases like Scopus, PubMed and Google Scholar to review source, chemistry, ionotropic gelation mechanism, and recent research studies for gellan gum based in-situ hydrogel for intransasl administration.Keywords such as gellan gum, in-situ hydrogel, intranasal administration and brain targeting were used to search literature. The present review included the research studies which explored gellan gum based in-situ gel for intranasal drug delivery.
Results: The findings have shown enhanced biavailability of various drugs upon intranasal administration using gellan-gum based in-situ hydrogel.Moreover, the review indicated that intranasal administration of in-situ hydrogel facilitate to overcome blood brain barrier effectively. Hence, significantly higher drug concentration was found to be achieved in brain tissues upon intranasal administration than that of other routes like oral and intravenous.
Conclusion: The present work conducted a comprehensive review for gellan gum based in-situ hydrogel particularly for intransal administration to overcome BBB. The study concluded that gellan gum based in-situ hydrogel could be potential promising delivery system for intranasal administration to improve bioavailability and efficacy of drugs specifically to treat neurological disorders.
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