Formulation of Metoclopramide Hydrochloride-Loaded Lipid Carriers by QbD Approach for Combating Nausea: Safety and Bioavailability Evaluation in New Zealand Rabbit.

The focus of the research was to overcome the limitations of metoclopramide (MTC) when administered intranasally. The aim was to improve its bioavailability, increase patient compliance, and prolong its residence time in the nasal cavity. MTC-loaded liposomes were prepared by applying the film hydration method. A study was conducted to determine how formulation variables affected encapsulation efficiency (EE %), mean particle size (MPS), and zeta potential (ZP). The MTC-liposomes were further loaded into the in situ gel (gellan gum) for longer residence times following intranasal administration. pH, gelling time, and in vitro release tests were conducted on the formulations produced. In vivo performance of the MTC-loaded in situ gels was appraised based on disparate parameters such as plasma peak concentration, plasma peak time, and elimination coefficient compared to intravenous administration. When the optimal liposome formulation contained 1.98% of SPC, 0.081% of cholesterol, 97.84% of chloroform, and 0.1% of MTC, the EE of MTC was 83.21%, PS was 107.3 nm. After 5 h, more than 80% of the drug was released from MTC-loaded liposome incorporated into gellan gum in situ gel formulation (Lip-GG), which exhibited improved absorption and higher bioavailability compared to MTC loaded into gellan gum in situ gel (MTC-GG). Acceptable cell viability was also achieved. It was found out that MTC-loaded liposomal in situ gel formulations administered through the nasal route could be a better choice than other options due to its ease of administration, accurate dosing, and higher bioavailability in comparison with MTC-GG.

Green Biosynthesis of Silver Nanoparticles from Olive and Walnut-Related Bacteria, Synthesis, Characterization, and Antimicrobial Activity.

Many studies have demonstrated the effectiveness of various plant extracts in the synthesis of silver nanoparticles. The phytochemical components of plant extracts contain biodegradable agents necessary for the stabilization and synthesis of nanoparticles. However, extracellular components of microorganisms have been shown to have similar activity in recent years. This study expects nanoparticle synthesis using silver nitrate using bacteria from different plant and soil parts in the Proteobacteria and Actinomycetes families in the endophytic and free form obtained from various sources, determining their antimicrobial properties on other pathogenic microorganisms. Nanoparticules showed a positive effect on antibiotic-resistant human pathogenic bacteria (Staphylococcus, Escherichia, and Acinetobacter), two strains of the human pathogenic Candida, and six different plant pathogenic fungi (Aspergillus, Fusarium, Gaeumannomyces, and Penicillium) compared to the reference antibiotics and antifungals. The physical forms and dimensions of the nanoparticles were determined by XRD, FTIR, UV-vis, and scanning electron microscopy. We believe that our findings will be the basis for the bacterial nanoparticle production procedures. Supplementary Information: The online version contains supplementary material available at 10.1007/s12088-023-01127-z.

Phospholipase D inhibitors screening: Probing and evaluation of ancient and novel molecules.

Phospholipase D (PLD) is a ubiquitous enzyme that cleaves the distal phosphoester bond of phospholipids generating phosphatidic acid (PA). In plants, PA is involved in numerous cell responses triggered by stress. Similarly, in mammals, PA is also a second messenger involved in tumorigenesis. PLD is nowadays considered as a therapeutic target and blocking its activity with specific inhibitors constitutes a promising strategy to treat cancers. Starting from already described PLD inhibitors, this study aims to investigate the effect of their structural modifications on the enzyme's activity, as well as identifying new potent inhibitors of eukaryotic PLDs. Being able to purify the plant PLD from Vigna unguiculata (VuPLD), we obtained a SAXS model of its structure. We then used a fluorescence-based test suitable for high-throughput screening to review the effect of eukaryotic PLD inhibitors described in the literature. In this regard, we found that only few molecules were in fact able to inhibit VuPLD and we confirmed that vanadate is the most potent of all with an IC50 around 58 µM. Moreover, the small-scale screening of a chemical library of 3120 compounds allowed us to optimize the different screening's steps and paved the way towards the discovery of new potent inhibitors.

Identification of alternative oxidase encoding genes in Caulerpa cylindracea by de novo RNA-Seq assembly analysis.

Alternative oxidases (AOX) are defined in plants, fungi and algae. The main function of AOX proteins has been described for electron flow through electron transport chain and regulation of mitochondrial retrograde signaling pathway. The roles of AOX proteins have been characterized in reproduction and resistance against oxidative stress, cold stress, starvation, and biotic attacks. Caulerpa cylindracea is an invasive marine green alga. Although the natural habitats of the species are Australia coasts, the impact of the invasion has been monitored through the Mediterranean Sea and the Aegean Sea. C. cylindracea species have advantages against others by showing higher resistance to stress conditions such as cold, starvation, pathogen attacks and by their capability of sexual and vegetative reproduction. Comparing the advantages of C. cylindracea over the niche and defined functional roles of mitochondrial AOX proteins, it is evident that AOX proteins are likely involved in developing those advantageous skills in C. cylindracea. However, there is limited data about biochemical and molecular mechanisms that take part in stress resistance and invasion characteristics. We aimed to identify mitochondrial alternative oxidase encoding genes in C. cylindracea while annotating whole transcriptome data for the species. Samples were collected from Seferihisar/Izmir. Transcriptome analysis from pooled RNA samples revealed 47,400 assembled contigs represented by 33,340 unigenes. Using standalone Blast analysis, we were able to identify two alternative oxidase encoding genes.

The Effect of Oral Care with Chlorhexidine, Vitamin E and Honey on Mucositis in Pediatric Intensive Care Patients: A Randomized Controlled Trial.

PURPOSE: This study was performed to determine the effect of oral care using chlorhexidine, vitamin E and honey on oral mucositis (OM) management in children treated in a pediatric intensive care unit (PICU). DESIGN AND METHODS: The study was a randomized controlled trial with a parallel design. The study sample was composed of 150 children who were treated in the PICU of a university hospital in Turkey. Children enrolled in the study were randomly divided into six groups based on the oral care solutions used (n = 25 in each group). The Demographic Information Form and the World Health Organization Oral Mucositis Index were used for data collection. RESULTS: The mucositis indices of the children presenting with and without OM upon admission to the PICU were compared on days 1, 3, 6, 9, 12, 15, 18 and 21 and the study found that the mucositis index values of the children treated with vitamin E were significantly lower than in the other groups (p < 0.05 for each), while those of the children given chlorhexidine were significantly higher than in the other groups (p < 0.05 for each). CONCLUSIONS: At the end of the study, vitamin E was determined to be the most effective agent in OM management, followed by honey as the second most effective agent. Chlorhexidine was found to be less effective in OM management compared to the other two agents. Based on this, vitamin E is recommended for use in oral mucositis-preventive and therapeutic oral care practices. PRACTICE IMPLICATIONS: The results of the present study conducted with PICU patients will be useful in the administration of oral care. These findings are also important for nurses who have the responsibility of oral mucositis management.

Comparative effects of high-dose atorvastatin versus moderate-dose rosuvastatin on lipid parameters, oxidized-LDL and inflammatory markers in ST elevation myocardial infarction.

BACKGROUND: The important role of oxidized low density lipoprotein (oxidized-LDL) in preclinic atherosclerosis and pathophysiology of acute coronary syndromes studies have reported. Oxidation of LDL activates many inflammatory and atherogenic pathways and plays a pivotal role in atherosclerosis. Our aim in this study is to compare the effects of 80 mg daily dose of atorvastatin and 20 mg daily dose of rosuvastatin on lipid profiles and the levels of oxidized-LDL and inflammatory markers in ST elevation myocardial infarction (STEMI). METHODS: One hundred and twenty patients with STEMI were enrolled in this study. The patients were randomly assigned to receive atorvastatin (80 mg/day) or rosuvastatin (20 mg/day) by using a ratio of 1:1 after revascularization. The levels of total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C), LDL-C, apolipoprotein B and apolipoprotein A were compared between groups after 4-week therapy. The values of oxidized-LDL, tumor necrosis factor receptor 1 and 2, Interleukin-6 and hs-CRP were also compared between groups. The Student's t test was used to detect absolute and percent changes between groups, and p < 0.05 was considered as statistically significant for all tests. RESULTS: After treatment in both treatment groups LDL-C, oxidized-LDL, hs-CRP, tumor necrosis factor receptor 1 and 2, Interleukin-6 values significantly decreased according to baseline. The only difference was in HDL-C levels. HDL-C slightly decreased in atorvastatin group while it increased in the rosuvastatin group compared baseline (-1.4 ± 8.9 mg/dl vs 2.0 ± 9.4 mg/dl, p = 0.04). CONCLUSION: We reported that both statin treatment regiments have comparable effects on LDL-C, oxidized-LDL and inflammatory markers. Moreover, it was observed that rosuvastatin was more effective in terms of ability to increase HDL-C level. Based on these findings, 20 mg daily dose of rosuvastatin may be an alternative to 80 mg daily dose of atorvastatin in patients with acute coronary syndrome.

An unusual electrocardiographic presentation of acute obstruction of the left anterior descending coronary artery.

Acute obstruction of the left anterior descending coronary artery is generally presented electrocardiographically as isolated anterior or combined anterior and inferior ST-elevation myocardial infarction. We described an isolated inferolateral ST-elevation myocardial infarction due to acute occlusion of the distal left anterior descending coronary artery.

Combined anterior and inferior ST segment elevation during the exercise stress testing.

Exercise induced ST elevation, especially in anterior derivations, does localize the ischemic region. We describe a patient who presented with exercise induced ST elevation in both anterior and inferior leads without prior myocardial infarction. Coronary angiography showed a "wrap around LAD" with significant proximal lesion.