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International Journal of Colorectal... May 2024A high number of topical products are available for the treatment of hemorrhoidal symptoms. Sucralfate-based topical products constitute a new treatment alternative that... (Observational Study)
Observational Study
BACKGROUND AND AIMS
A high number of topical products are available for the treatment of hemorrhoidal symptoms. Sucralfate-based topical products constitute a new treatment alternative that act as a mechanical barrier to facilitate healing. The aim of this prospective, observational study was to determine patient- and physician-assessed effectiveness and tolerability of rectal ointment and suppositories containing sucralfate for the treatment of hemorrhoidal symptoms in routine clinical practice.
METHODS
Adult patients with diagnosed, mild-to-moderate, symptomatic non-bleeding hemorrhoids treated with rectal ointment or suppositories containing sucralfate were enrolled. Patients were administered treatment twice per day for at least 1 week until symptom resolution and/or for a maximum of 4 weeks. The primary endpoint was patient-assessed effectiveness on a modified Symptom Severity Score (mSSS, range 0 to 14). Physician-assessed effectiveness (9 symptoms, 0 to 5 Likert scale), hemorrhoid grade, and patient satisfaction were also determined.
RESULTS
Five investigators enrolled 60 patients; mean age was 48.4 ± 16.6 years and 72.4% were female. Pain or pressure sensitivity was reported as the most severe symptom by patients, and pressure sensitivity, discharge, soiling, and prolapse by physicians. Mean patient-assessed mSSS at baseline was 6.6 ± 1.9 and was significantly improved overall and in the ointment and suppository groups individually by -4.6 ± 2.0, -4.4 ± 1.8, and -4.8 ± 2.2, respectively (p < 0.0001). Investigator-assessed mean baseline symptom score was 18.1 ± 3.9 and improved by -7.1 ± 4.5, -6.9 ± 5.4, and -7.3 ± 3.5, respectively (p < 0.0001). Investigator-assessed symptoms of pressure sensitivity, swelling, and discharge were improved to the greatest extent. Hemorrhoid grade was improved in 38% of patients at the end of treatment. Compliance with treatment was 97.4% and patient satisfaction with application and onset of action was high (81.3% and 76.2%, respectively). Both the ointment and suppository were well tolerated.
CONCLUSIONS
The effectiveness of topical ointment or suppository containing sucralfate on patient- and investigator-assessed hemorrhoidal symptoms in real-life clinical practice was demonstrated. Patient satisfaction was high and treatments were well tolerated. Larger controlled trials are warranted to confirm the results.
Topics: Humans; Sucralfate; Hemorrhoids; Female; Suppositories; Male; Middle Aged; Ointments; Prospective Studies; Treatment Outcome; Patient Satisfaction; Adult; Aged; Administration, Rectal
PubMed: 38750150
DOI: 10.1007/s00384-024-04642-7 -
Chemical & Pharmaceutical Bulletin 2024The solid-state properties of drug candidates play a crucial role in their selection. Quality control of active pharmaceutical ingredients (APIs) based on their...
The solid-state properties of drug candidates play a crucial role in their selection. Quality control of active pharmaceutical ingredients (APIs) based on their structural information involves ensuring a consistent crystal form and controlling water and residual solvent contents. However, traditional crystallographic techniques have limitations and require high-quality single crystals for structural analysis. Microcrystal electron diffraction (microED) overcomes these challenges by analyzing difficult-to-crystallize or small-quantity samples, making it valuable for efficient drug development. In this study, microED analysis was able to rapidly determine the configuration of two crystal forms (Forms 1, 2) of the API ranitidine hydrochloride. The structures obtained with microED are consistent with previous structures determined by X-ray diffraction, indicating microED is a useful tool for rapidly analyzing molecular structures in drug development and materials science research.
Topics: Ranitidine; Crystallization; Molecular Structure; Electrons
PubMed: 38749738
DOI: 10.1248/cpb.c23-00745 -
Emerging Microbes & Infections Dec 2024The study investigates the potential of lansoprazole, a proton pump inhibitor, to interfere with fungal respiration and enhance the antifungal activity of amphotericin B...
The study investigates the potential of lansoprazole, a proton pump inhibitor, to interfere with fungal respiration and enhance the antifungal activity of amphotericin B against multidrug-resistant Candida auris. The authors administered lansoprazole at concentrations significantly higher than typical therapeutic doses, which demonstrated promising results but also raised concerns about potential toxicity. We suggest incorporating a control group, monitoring toxicity indicators, performing pathological examinations, and conducting cellular assays to improve the study's rigor and reliability. We also highlight the need for further research into the mechanisms of lansoprazole's antifungal activity, its long-term effects on amphotericin B resistance, and potential drug-drug interactions with amphotericin B. Addressing these concerns is crucial for the clinical translation of lansoprazole as an adjuvant to amphotericin B.
Topics: Lansoprazole; Amphotericin B; Antifungal Agents; Drug Resistance, Multiple, Fungal; Drug Synergism; Microbial Sensitivity Tests; Humans; Candida auris; Candidiasis; Proton Pump Inhibitors
PubMed: 38742537
DOI: 10.1080/22221751.2024.2356144 -
Experimental Gerontology Jul 2024Sorghum is a promising treatment for Alzheimer's disease (AD), due to its rich antioxidant and anti-inflammatory qualities. Fermentation may also affect nutritional...
Sorghum is a promising treatment for Alzheimer's disease (AD), due to its rich antioxidant and anti-inflammatory qualities. Fermentation may also affect nutritional values. Therefore, the purpose of this study was to discover the phenolic and flavonoid chemicals found in both fermented and non-fermented red sorghum, as well as their potential therapeutic uses for AD. L. fermentum, and L. reuteri, and/or L. plantarum and L. casei were used to ferment samples of sorghum. The rats were grouped into five groups, healthy animals, and rats with Alzheimer's receiving 200 mg/kg of saline, non-fermented sorghum, and fermented sorghum fermented with L. fermentum and L. reuteri, as well as L. plantarum and L. casei. Various assessments were conducted, including evaluations of behavioral responses, antioxidant responses, inflammatory responses, acetylcholine levels and acetylcholine esterase, and bacterial populations in stool. P-hydroxybenzoic acid, eriodictyo naringenin, and apigenin were significantly higher in fermented samples, while glycerols were higher in non-fermented samples. The induction of Alzheimer's led to decrease step-through latency, time in target zone, FRAP, acetylcholine levels, Bifidobacterium population and lactobacillus population, while increased escape latency, platform location latency, MDA levels, IL-6, TNF-α, acetylcholine esterase, and coliform population (P = 0.001). The administration of both non-fermented sorghum and fermented sorghum demonstrated the potential to reverse the effects of AD, with a notably higher efficacy observed in the fermented samples compared to the non-fermented ones. In conclusion, fermentation exerted significant effects on the bioactive compounds the administration of fermented sorghum resulted in improved behavioral responses, characterized by a reduction in oxidation, inflammation and microbial population.
Topics: Sorghum; Alzheimer Disease; Fermentation; Animals; Male; Antioxidants; Rats; Rats, Wistar; Flavanones; Gastrointestinal Microbiome; Disease Models, Animal; Flavonoids; Apigenin; Phenols; Acetylcholine; Acetylcholinesterase; Anti-Inflammatory Agents; Lactobacillus; Plant Extracts; Feces
PubMed: 38740315
DOI: 10.1016/j.exger.2024.112459 -
Chemosphere Jul 2024The effective removal of micropollutants by water treatment technologies remains a significant challenge. Herein, we develop a CoFe layered double hydroxide (CoFeLDH)...
The effective removal of micropollutants by water treatment technologies remains a significant challenge. Herein, we develop a CoFe layered double hydroxide (CoFeLDH) catalytic membrane for peroxymonosulfate (PMS) activation to achieve efficient micropollutant removal with improved mass transfer rate and reaction kinetics. This study found that the CoFeLDH membrane/PMS system achieved an impressive above 98% degradation of the probe chemical ranitidine at 0.1 mM of PMS including five more micropollutants (Sulfamethoxazole, Ciprofloxacin, Carbamazepine, Acetaminophen and Bisphenol A) at satisfactory level (above 80%). Moreover, significant improvements in water flux and antifouling properties were observed, marking the membrane as a specific advancement in the removal of membrane fouling in water purification technology. The membrane demonstrated consistent degradation efficiency for several micropollutants and across a range of pH (4-9) as well as different anionic environments, thereby showing it suitability for scale-up application. The key role of reactive species such as SO, and O - radicals in the degradation process was elucidated. This is followed by the confirmation of the occurrence of redox cycling between Co and Fe, and the presence of CoOH that promotes PMS activation. Over the ten cycles, the membrane could be operated with a flux recovery of up to 99.8% and maintained efficient performance over 24 h continuous operation. Finally, the efficiency in degrading micropollutants, coupled with reduced metal leaching, makes the CoFeLDH membrane as a promising technology for application in water treatment.
Topics: Water Purification; Water Pollutants, Chemical; Membranes, Artificial; Hydroxides; Phenols; Peroxides; Benzhydryl Compounds; Carbamazepine; Ranitidine; Acetaminophen; Sulfamethoxazole; Ciprofloxacin; Catalysis; Cobalt; Oxidation-Reduction
PubMed: 38735495
DOI: 10.1016/j.chemosphere.2024.142318 -
International Journal of Molecular... Apr 2024Favipiravir (FP) and ebselen (EB) belong to a diverse class of antiviral drugs known for their significant efficacy in treating various viral infections. Utilizing...
Favipiravir (FP) and ebselen (EB) belong to a diverse class of antiviral drugs known for their significant efficacy in treating various viral infections. Utilizing molecular dynamics (MD) simulations, machine learning, and van der Waals density functional theory, we accurately elucidate the binding properties of these antiviral drugs on a phosphorene single-layer. To further investigate these characteristics, this study employs four distinct machine learning models-Random Forest, Gradient Boosting, XGBoost, and CatBoost. The Hamiltonian of antiviral molecules within a monolayer of phosphorene is appropriately trained. The key aspect of utilizing machine learning (ML) in drug design revolves around training models that are efficient and precise in approximating density functional theory (DFT). Furthermore, the study employs SHAP (SHapley Additive exPlanations) to elucidate model predictions, providing insights into the contribution of each feature. To explore the interaction characteristics and thermodynamic properties of the hybrid drug, we employ molecular dynamics and DFT calculations in a vacuum interface. Our findings suggest that this functionalized 2D complex exhibits robust thermostability, indicating its potential as an effective and enabled entity. The observed variations in free energy at different surface charges and temperatures suggest the adsorption potential of FP and EB molecules from the surrounding environment.
Topics: Machine Learning; Antiviral Agents; Molecular Dynamics Simulation; Density Functional Theory; Thermodynamics; Isoindoles; Organoselenium Compounds; Azoles
PubMed: 38732115
DOI: 10.3390/ijms25094897 -
BMJ Open Quality May 2024Stress ulcer prophylaxis is started in the critical care unit to decrease the risk of upper gastrointestinal ulcers in critically ill persons and to decrease mortality...
UNLABELLED
Stress ulcer prophylaxis is started in the critical care unit to decrease the risk of upper gastrointestinal ulcers in critically ill persons and to decrease mortality caused by stress ulcer complications. Unfortunately, the drugs are often continued after recovery through discharge, paving the way for unnecessary polypharmacy.
STUDY DESIGN
We conducted a retrospective cross-sectional study including patients admitted to the adult critical care unit and started on the stress ulcer prophylaxis with a proton pump inhibitor (PPI) or histamine receptor 2 blocker (H2 blocker) with an aim to determine the prevalence of inappropriate continuation at discharge and associated factors.
RESULT
3200 people were initiated on stress ulcer prophylaxis, and the medication was continued in 1666 patients upon discharge. Indication for long-term use was not found in 744 of 1666, with a 44% prevalence of inappropriate continuation. A statistically significant association was found with the following risk factors: discharge disposition (home vs other medical facilities, p=0.002), overall length of stay (more than 10 days vs less than or equal to 10 days, p<0.0001), mechanical ventilator use (p<0.001), number of days on a mechanical ventilator (more than 2 days vs less than or equal to 2 days, p<0.001) and class of stress ulcer prophylaxis drug used (H2 blocker vs PPI, p<0.001).
CONCLUSION
The prevalence of inappropriate continuation was found to be higher than prior studies. Given the risk of unnecessary medication intake and the associated healthcare cost, a web-based quality improvement initiative is being considered.
Topics: Humans; Male; Retrospective Studies; Female; Cross-Sectional Studies; Middle Aged; Prevalence; Peptic Ulcer; Patient Discharge; Proton Pump Inhibitors; Aged; Histamine H2 Antagonists; Adult; Risk Factors; Anti-Ulcer Agents; Intensive Care Units; Inappropriate Prescribing
PubMed: 38729753
DOI: 10.1136/bmjoq-2023-002678 -
PloS One 2024Nature has proven to be a treasure resource of bioactive metabolites. In this regard, Tamarix aphylla (F. Tamaricaceae) leaves crude extract was investigated for its...
Tamarix aphylla derived metabolites ameliorate indomethacin-induced gastric ulcers in rats by modulating the MAPK signaling pathway, alleviating oxidative stress and inflammation: In vivo study supported by pharmacological network analysis.
Nature has proven to be a treasure resource of bioactive metabolites. In this regard, Tamarix aphylla (F. Tamaricaceae) leaves crude extract was investigated for its gastroprotective effect against indomethacin-induced damage to the gastric mucosa. Additionally, phytochemical investigation of the methanolic extract afforded eight flavonoids' derivatives (1-8). On pharmacology networking study, the isolated compounds identified 123 unique targets where only 45 targets were related to peptic ulcer conditions, these 45 targets include 11 targets specifically correlate to gastric ulcer. The protein-protein interaction defined the PTGS2 gene as one of the highly interacted genes and the complete pharmacology network defined the PTGS2 gene as the most represented gene. The top KEGG signaling pathways according to fold enrichment analysis was the EGFR tyrosine kinase inhibitor resistance pathway. As a result, these findings highlighted the significance of using T. aphylla leaves crude extract as an anti-gastric ulcer candidate, which provides a safer option to chemical antisecretory medicines, which are infamous for their negative side effects. Our findings have illuminated the potent anti-inflammatory and antioxidant effects of T. aphylla, which are likely mediated by suppressing IL-1β, IL-6, TNF-α, and MAPK signaling pathways, without compromising gastric acidity.
Topics: Animals; Male; Rats; Anti-Ulcer Agents; Flavonoids; Gastric Mucosa; Indomethacin; Inflammation; MAP Kinase Signaling System; Network Pharmacology; Oxidative Stress; Plant Extracts; Plant Leaves; Rats, Sprague-Dawley; Stomach Ulcer; Tamaricaceae
PubMed: 38728332
DOI: 10.1371/journal.pone.0302015 -
International Journal of... 2024This study investigated the raft-forming suspension of famotidine as an anti-reflux formulation to improve the oral bioavailability of narrow absorption window drugs by...
OBJECTIVE
This study investigated the raft-forming suspension of famotidine as an anti-reflux formulation to improve the oral bioavailability of narrow absorption window drugs by enhancing gastric residence time (GRT) and preventing gastro-esophageal reflux disease (GERD).
METHOD
Various combinations of raft-forming agents, such as Tragacanth gum (TG), guar gum (GG), and xanthan gum (XG), were evaluated alongside sodium alginate (SA) to develop an effective raft. Preformulation studies and preliminary screening were conducted to identify the most suitable raft-forming agent, and GG was chosen due to its mucilaginous properties. The formulation was optimized using a 32 full factorial design, with the quantities of GG and SA as independent factors and apparent viscosity and in-vitro drug release (%) as dependent factors. The in vivo floating behavior study was performed for optimized and stabilized formulation.
RESULTS
Among the tested batches, F6 was selected as the optimized formulation. It exhibited desirable characteristics such as adequate raft weight for extended floating in gastric fluid, improved apparent viscosity, and a significant percentage of drug release at 12 h. A mathematical model was applied to the in-vitro data to gain insights into the drug release mechanism of the formulation. The stability of the suspension was assessed under accelerated conditions, and it demonstrated satisfactory stability. The formulation remains floating in the Rabbit stomach for more than 12 h.
CONCLUSION
It concludes that the developed formulation has enhanced bioavailability in the combination of GG and SA. The floating layer of the raft prevents acid reflux, and the famotidine is retained for an extended period of time in the gastric region, preventing excess acid secretion. The developed formulations are effective for stomach ulcers and GERD, with the effect of reducing acid secretion by H2 receptor antagonists.
Topics: Famotidine; Animals; Drug Delivery Systems; Galactans; Drug Liberation; Alginates; Gastroesophageal Reflux; Biological Availability; Mannans; Plant Gums; Viscosity; Male; Rabbits; Gastric Mucosa; Polysaccharides, Bacterial; Drug Stability; Administration, Oral
PubMed: 38721971
DOI: 10.1177/03946320241249429 -
Translational Psychiatry May 2024Lithium is an effective augmenting agent for depressed patients with inadequate response to standard antidepressant therapy, but numerous adverse effects limit its use.... (Randomized Controlled Trial)
Randomized Controlled Trial
Lithium is an effective augmenting agent for depressed patients with inadequate response to standard antidepressant therapy, but numerous adverse effects limit its use. We previously reported that a lithium-mimetic agent, ebselen, promoted a positive emotional bias-an indicator of potential antidepressant activity in healthy participants. We therefore aimed to investigate the effects of short-term ebselen treatment on emotional processing and brain neurochemistry in depressed patients with inadequate response to standard antidepressants. We conducted a double-blind, placebo-controlled 7-day experimental medicine study in 51 patients with major depressive disorder who were currently taking antidepressants but had an inadequate response to treatment. Participants received either ebselen 600 mg twice daily for seven days or identical matching placebo. An emotional testing battery, magnetic resonance spectroscopy and depression and anxiety rating scales were conducted at baseline and after seven days of treatment. Ebselen did not increase the recognition of positive facial expressions in the depressed patient group. However, ebselen increased the response bias towards fear emotion in the signal detection measurement. In the anterior cingulate cortex, ebselen significantly reduced the concentrations of inositol and Glx (glutamate+glutamine). We found no significant differences in depression and anxiety rating scales between visits. Our study did not find any positive shift in emotional bias in depressed patients with an inadequate response to antidepressant medication. We confirmed the ability of ebselen to lower inositol and Glx in the anterior cingulate cortex. These latter effects are probably mediated through inhibition of inositol monophosphatase and glutaminase respectively.
Topics: Humans; Isoindoles; Female; Male; Organoselenium Compounds; Double-Blind Method; Adult; Depressive Disorder, Major; Antidepressive Agents; Middle Aged; Emotions; Azoles; Magnetic Resonance Spectroscopy; Depressive Disorder, Treatment-Resistant; Gyrus Cinguli; Brain
PubMed: 38714646
DOI: 10.1038/s41398-024-02899-8