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Scientific Reports Jun 2024Naringenin (NAR) has various biological activities but low bioavailability. The current study examines the effect of Naringenin-loaded hybridized nanoparticles...
Naringenin (NAR) has various biological activities but low bioavailability. The current study examines the effect of Naringenin-loaded hybridized nanoparticles (NAR-HNPs) and NAR on depression induced by streptozotocin (STZ) in rats. NAR-HNPs formula with the highest in vitro NAR released profile, lowest polydispersity index value (0.21 ± 0.02), highest entrapment efficiency (98.7 ± 2.01%), as well as an acceptable particle size and zeta potential of 415.2 ± 9.54 nm and 52.8 ± 1.04 mV, respectively, was considered the optimum formulation. It was characterized by differential scanning calorimetry, examined using a transmission electron microscope, and a stability study was conducted at different temperatures to monitor its stability efficiency showing that NAR-HNP formulation maintains stability at 4 °C. The selected formulation was subjected to an acute toxicological test, a pharmacokinetic analysis, and a Diabetes mellitus (DM) experimental model. STZ (50 mg/kg) given as a single i.p. rendered rats diabetic. Diabetic rat groups were allocated into 4 groups: one group received no treatment, while the remaining three received oral doses of unloaded HNPs, NAR (50 mg/kg), NAR-HNPs (50 mg/kg) and NAR (50 mg/kg) + peroxisome proliferator-activated receptor-γ (PPAR-γ) antagonist, GW9662 (1mg/kg, i.p.) for three weeks. Additional four non-diabetic rat groups received: distilled water (normal), free NAR, and NAR-HNPs, respectively for three weeks. NAR and NAR-HNPs reduced immobility time in forced swimming test and serum blood glucose while increasing serum insulin level. They also reduced cortical and hippocampal 5-hydroxyindoeacetic acid, 3,4-Dihydroxy-phenylacetic acid, malondialdehyde, NLR family pyrin domain containing-3 (NLRP3) and interleukin-1beta content while raised serotonin, nor-epinephrine, dopamine and glutathione level. PPAR-γ gene expression was elevated too. So, NAR and NAR-HNPs reduced DM-induced depression by influencing brain neurotransmitters and exhibiting anti-oxidant and anti-inflammatory effects through the activation PPAR-γ/ NLRP3 pathway. NAR-HNPs showed the best pharmacokinetic and therapeutic results.
Topics: Animals; Flavanones; PPAR gamma; Diabetes Mellitus, Experimental; Nanoparticles; Rats; Male; NLR Family, Pyrin Domain-Containing 3 Protein; Antidepressive Agents; Depression; Signal Transduction; Streptozocin; Rats, Wistar; Anilides
PubMed: 38866877
DOI: 10.1038/s41598-024-62676-x -
PloS One 2024Abomasal ulcers are recognized in sheep of all ages, but research regarding therapeutic interventions is limited. Proton Pump Inhibitors (PPIs) such as pantoprazole, are...
Abomasal ulcers are recognized in sheep of all ages, but research regarding therapeutic interventions is limited. Proton Pump Inhibitors (PPIs) such as pantoprazole, are clinically used with a paucity of evidence regarding efficacy in mature sheep. Intravenous and subcutaneously administered pantoprazole dosed at 1.0 mg/kg in adult sheep will increase the pH of abomasal fluid compared to pre-administration baseline. The objectives were to assess the effect of pantoprazole, after single and multiple administration, on abomasal fluid pH in adult sheep. A third objective was to describe the pharmacokinetic parameters of IV and SC pantoprazole. Four clinically healthy adult Southdown ewes previously fitted with a gastrostomy tube in the abomasum were utilized in this randomized, 2-way cross-over trial. Ewes received pantoprazole (1.0 mg/kg) as a single and 3-dose regimen (every 24 hours). After a 10 day washout period the reverse treatment was applied. Blood for analysis of pantoprazole concentration was collected intermittently for 24 hours, and abomasal fluid pH was measured at intervals for a 96-hour period. The pH of the abomasal fluid was higher in pantoprazole treatments for up to 24 hours after dosing. Following intravenous administration of pantoprazole to study ewes, elimination half-life, volume of distribution, and clearance of pantoprazole was estimated as 3.29 hours, 0.35 L/kg, and 65.26 mL/hr/kg respectively. After subcutaneous dosing, maximum concentration, time to maximum concentration, half-life of elimination, and volume of distribution, were estimated as 2604 ng/mL, 0.55 hours, 2.48 hours, and 0.37 L/kg. Additionally, the bioavailability was estimated as 83.33%. Pantoprazole administered IV or SC may be useful for treatment or prevention of abomasal ulcers in adult sheep.
Topics: Animals; Pantoprazole; Sheep; Female; Injections, Subcutaneous; Hydrogen-Ion Concentration; Proton Pump Inhibitors; Abomasum; Administration, Intravenous; Cross-Over Studies; Injections, Intravenous
PubMed: 38865425
DOI: 10.1371/journal.pone.0304533 -
PloS One 2024Rebamipide has been widely co-prescribed with non-steroidal anti-inflammatory drugs (NSAIDs) in Japan for decades. This study aimed to evaluate the effectiveness of...
Continuous co-prescription of rebamipide prevents upper gastrointestinal bleeding in NSAID use for orthopaedic conditions: A nested case-control study using the LIFE Study database.
BACKGROUND
Rebamipide has been widely co-prescribed with non-steroidal anti-inflammatory drugs (NSAIDs) in Japan for decades. This study aimed to evaluate the effectiveness of rebamipide in preventing upper gastrointestinal bleeding in new users of NSAIDs without risk factors of NSAID-induced ulcers other than age.
METHODS
A nested case-control study was conducted using medical claims data of 1.66 million inhabitants of 17 municipalities participating in Japan's Longevity Improvement & Fair Evidence study. The cohort entry (t0) corresponded to a new user of NSAIDs for osteoarthritis or low back pain. Patients with risk factors of NSAID-induced ulcers other than age were excluded. Cases were defined as patients who underwent gastroscopy for upper gastrointestinal bleeding (occurrence date was defined as index date). A maximum of 10 controls were selected from non-cases at the index date of each case by matching sex, age, follow-up time, and type and dosage of NSAIDs. Exposure to rebamipide was defined as prescription status from t0 to index date: Non-user (rebamipide was not co-prescribed during the follow-up period), Continuous-user (rebamipide was co-prescribed from t0 with the same number of tablets as NSAIDs), and Irregular-user (neither Non-user nor Continuous-user). Conditional logistic regression analysis was conducted to estimate each category's odds ratio compared to non-users.
FINDINGS
Of 67,561 individuals who met the inclusion criteria, 215 cases and 1,516 controls were selected. Compared with that of Non-users, the odds ratios and 95% confidence interval were 0.65 (0.44-0.96) for Continuous-users and 2.57 (1.73-3.81) for Irregular-users.
CONCLUSIONS
Continuous co-prescription of rebamipide significantly reduced the risk of upper gastrointestinal bleeding in an Asian cohort of new users of NSAIDs with osteoarthritis or low back pain without risk factors other than age.
Topics: Humans; Alanine; Anti-Inflammatory Agents, Non-Steroidal; Male; Quinolones; Female; Case-Control Studies; Aged; Gastrointestinal Hemorrhage; Middle Aged; Anti-Ulcer Agents; Aged, 80 and over; Databases, Factual; Osteoarthritis; Japan; Risk Factors
PubMed: 38861561
DOI: 10.1371/journal.pone.0305320 -
BMC Pregnancy and Childbirth Jun 2024However, misoprostol is often used to terminate a pregnancy, but it can also cause side effects. Isosorbide mononitrate (ISMN) can help the cervix mature by increasing... (Meta-Analysis)
Meta-Analysis Comparative Study
Efficacy and safety of isosorbide mononitrate plus misoprostol compared to misoprostol alone in the management of the first and second trimester abortion: a systematic review and meta-analysis.
BACKGROUND
However, misoprostol is often used to terminate a pregnancy, but it can also cause side effects. Isosorbide mononitrate (ISMN) can help the cervix mature by increasing the production of prostaglandin E2 and vasodilation. Considering that the results of studies in this field are contradictory, it is the purpose of this study to evaluate the efficacy and safety of vaginal ISMN plus misoprostol compared to misoprostol alone in the management of first- and second-trimester abortions.
METHOD
The search process was conducted for MEDLINE through the PubMed interface, Scopus, Web-of-Science, Science Direct, the Cochrane Central Register of Controlled Trials (CENTRAL), Google Scholar, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform until November 10, 2023. Our assessment of bias was based on version 2 of the risk-of-bias tool (RoB2) for randomized trials and our level of evidence quality was determined by GRADE. Meta-analysis of all data was carried out using Review Manager (RevMan) version 5.1.
RESULT
Seven randomized clinical trials were included in the systematic review and three in the meta-analysis, with mixed quality. The results of the meta-analysis revealed that in the second-trimester abortion, the inclusion of ISMN in conjunction with vaginal misoprostol results in a noteworthy reduction in the induction abortion interval, specifically by 4.21 h (95% CI: -7.45 to -0.97, P = 0.01). The addition of vaginal ISMN to misoprostol, compared to vaginal misoprostol alone, increased the odds of a completed abortion by 3.76 times. (95% CI: 1.08 to 13.15, P = 0.04).
CONCLUSION
The findings of this study can offer valuable insights aimed at enhancing counseling and support for non-surgical methods of medication abortion within professional settings. Moreover, it improves the effectiveness of clinical treatment and reduces the occurrence of unnecessary surgical interventions in the abortion management protocol.
Topics: Humans; Misoprostol; Female; Pregnancy; Pregnancy Trimester, Second; Isosorbide Dinitrate; Abortion, Induced; Abortifacient Agents, Nonsteroidal; Pregnancy Trimester, First; Drug Therapy, Combination; Administration, Intravaginal; Treatment Outcome
PubMed: 38858628
DOI: 10.1186/s12884-024-06614-9 -
Scientific Reports Jun 2024This study aimed to compare the clinical efficacy and investigate patients' preferences for two mucin secretagogues in the treatment of dry eye disease (DED). Thirty... (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study
This study aimed to compare the clinical efficacy and investigate patients' preferences for two mucin secretagogues in the treatment of dry eye disease (DED). Thirty patients with DED were randomly treated with either 3% diquafosol or 2% rebamipide ophthalmic solution for 4 weeks, followed by an additional 4-week treatment using the other eye drop after a 2-week washout period. Objective and subjective assessments, including the corneal and conjunctival staining score, tear breakup time (TBUT), Schirmer 1 test, tear osmolarity, tear matrix metalloproteinase-9 (MMP-9), lipid layer thickness (LLT) and ocular surface disease index (OSDI), were performed at baseline, 4 weeks, 6 weeks, and 10 weeks. Patient preferences were assessed based on four categories (comfort, efficacy, convenience, willingness to continue) using a questionnaire and the overall subjective satisfaction score for each drug was obtained at the end of the trial. In total, 28 eyes from 28 patients were included in the analysis. Both diquafosol and rebamipide significantly improved the OSDI (p = 0.033 and 0.034, respectively), TBUT (p < 0.001 and 0.026, respectively), and corneal (p < 0.001 and 0.001, respectively) and conjunctival (p = 0.017 and 0.042, respectively) staining after 4 weeks of treatment. An increase in Schirmer test scores was observed only after rebamipide treatment (p = 0.007). No significant changes were detected in tear osmolarity, MMP-9, and LLT following both treatments. The patients' preference was slightly greater for diquafosol (46.4%) than rebamipide (36.7%), presumably due to rebamipide's bitter taste. The self-efficacy of both drugs and overall satisfaction scores were comparable. These findings indicate that two mucin secretagogues showed comparable effects in ameliorating symptoms and improving signs (TBUT, corneal and conjunctival staining) in patients with DED.
Topics: Humans; Dry Eye Syndromes; Female; Male; Middle Aged; Quinolones; Prospective Studies; Mucins; Uracil Nucleotides; Alanine; Aged; Tears; Cross-Over Studies; Ophthalmic Solutions; Polyphosphates; Treatment Outcome; Adult; Matrix Metalloproteinase 9
PubMed: 38858411
DOI: 10.1038/s41598-024-63784-4 -
Carbohydrate Polymers Sep 2024Brown macroalgae synthesize large amounts of fucoidans, sulfated fucose-containing polysaccharides, in the ocean. Fucoidans are of importance for their recently...
Brown macroalgae synthesize large amounts of fucoidans, sulfated fucose-containing polysaccharides, in the ocean. Fucoidans are of importance for their recently discovered contribution to marine carbon dioxide sequestration and due to their potential applications in biotechnology and biomedicine. However, fucoidans have high intra- and intermolecular diversity that challenges assignment of structure to biological function and the development of applications. Fucoidan-active enzymes may be used to simplify this diversity by producing defined oligosaccharides more applicable for structural refinement, characterization, and structure to function assignment for example via bioassays. In this study, we combined MALDI mass spectrometry with biocatalysis to show that the endo-fucoidanases P5AFcnA and Wv323 can produce defined oligosaccharide structures directly from unrefined macroalgal biomass. P5AFcnA released oligosaccharides from seven commercial fucoidan extracts in addition to unrefined biomass of three macroalgae species indicating a broadly applicable approach reproducible across 10 species. Both MALDI-TOF/TOF and AP-MALDI-Orbitrap systems were used, demonstrating that the approach is not instrument-specific and exploiting their combined high-throughput and high-resolution capabilities. Overall, the combination of MALDI-MS and endo-fucoidanase assays offers high-throughput evaluation of fucoidan samples and also enables extraction of defined oligosaccharides of known structure from unrefined seaweed biomass.
Topics: Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Polysaccharides; Glycoside Hydrolases; Hydrolysis; Seaweed; Phaeophyceae; Oligosaccharides; Biomass
PubMed: 38858030
DOI: 10.1016/j.carbpol.2024.122317 -
BMJ Open Gastroenterology Jun 2024The management of non-alcoholic steatohepatitis (NASH) is an unmet clinical need. Misoprostol, a structural analogue of naturally occurring prostaglandin E1, has been... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
The management of non-alcoholic steatohepatitis (NASH) is an unmet clinical need. Misoprostol, a structural analogue of naturally occurring prostaglandin E1, has been reported to decrease proinflammatory cytokine production and may have a potential role in treating NASH. We aimed to evaluate the efficacy and safety of misoprostol in treating patients with NASH.
METHODS
In this phase 2, double-blind, randomised, placebo-controlled trial, patients with NASH were randomly assigned in a 1:1 ratio to receive 200 µg of misoprostol or placebo thrice daily for 2 months. The primary endpoint was an improvement in liver function tests (LFTs), interleukin-6 (IL-6) and endotoxin levels. The secondary endpoint was improvement in insulin resistance, dyslipidaemia, hepatic fibrosis and hepatic steatosis.
RESULTS
A total of 50 patients underwent randomisation, of whom 44 (88%) were males. The age range was 25-64 years (mean±SE of mean (SEM) 38.1±1.4). 19 (38%) patients had concomitant type 2 diabetes mellitus. 32 (64%) patients were either overweight or obese. At the end of 2 months' treatment, a reduction in total leucocyte count (TLC) (p=0.005), alanine aminotransferase (ALT) (p<0.001), aspartate aminotransferase (AST) (p=0.002) and controlled attenuation parameter (CAP) (p=0.003) was observed in the misoprostol group, whereas placebo ensued a decline in ALT (p<0.001), AST (p=0.018), gamma-glutamyl transferase (GGT) (p=0.003), CAP (p=0.010) and triglycerides (p=0.048). There was no diminution in insulin resistance, hepatic fibrosis (elastography) and dyslipidaemia in both groups. However, misoprostol resulted in a significant reduction in CAP as compared with the placebo group (p=0.039). Moreover, in the misoprostol group, pretreatment and post-treatment IL-6 and endotoxin levels remained stable, while in the placebo group, an increase in the IL-6 levels was noted (p=0.049). Six (12%) patients had at least one adverse event in the misoprostol group, as did five (10%) in the placebo group. The most common adverse event in the misoprostol group was diarrhoea. No life-threatening events or treatment-related deaths occurred in each group.
CONCLUSION
Improvement in the biochemical profile was seen in both misoprostol and placebo groups without any statistically significant difference. However, there was more improvement in steatosis, as depicted by CAP, in the misoprostol group and worsening of IL-6 levels in the placebo group.
TRIAL REGISTRATION NUMBER
NCT05804305.
Topics: Humans; Male; Female; Non-alcoholic Fatty Liver Disease; Middle Aged; Double-Blind Method; Adult; Misoprostol; Interleukin-6; Treatment Outcome; Insulin Resistance; Liver Cirrhosis; Liver Function Tests; Liver
PubMed: 38844374
DOI: 10.1136/bmjgast-2023-001342 -
Reproductive Health Jun 2024Medical abortion with mifepristone and misoprostol can be provided up to 63 days' gestation in India. This accounts for 67.5 percent of all abortions in the country. We...
BACKGROUND
Medical abortion with mifepristone and misoprostol can be provided up to 63 days' gestation in India. This accounts for 67.5 percent of all abortions in the country. We conducted an assessment to determine the availability of medical abortion medicines, specifically the combi-pack, in India.
METHODS
We applied the World Health Organization landscape assessment protocol at the national level. The assessment protocol included a five-step adaptation of an existing availability framework, including online data collection, desk review, country-level key informant interviews, and an analysis to identify barriers and opportunities to improve medical abortion availability. The assessment was conducted between August and March 2021.
RESULTS
Medicines for medical abortion are included in the national essential drug list and available with prescription in India. The assessment identified 42 combi-pack products developed by 35 manufacturers. The quality of medical abortion medicines is regulated by national authorities; but as health is devolved to states, there are significant inter-state variations. This is seen across financing, procurement, manufacturing, and monitoring mechanisms for quality assurance of medical abortion medicines prior to distribution. There is a need to strengthen supply chain systems, ensure consistent availability of trained providers and build community awareness on use of medical abortion medicines for early abortions, at the time of the assessment.
CONCLUSION
Opportunities to improve availability and quality of medical abortion medicines exist. For example, uniform implementation of regulatory standards, greater emphasis on quality-assurance during manufacturing, and standardizing of procurement and supply chain systems across states. Regular in-service training of providers on medical abortion is required. Finally, innovations in evidence dissemination and community engagement about the recently amended abortion law are needed.
Topics: Humans; India; Abortion, Induced; Female; Pregnancy; Health Services Accessibility; Abortifacient Agents; Misoprostol; Mifepristone; Drugs, Essential
PubMed: 38840263
DOI: 10.1186/s12978-024-01774-5 -
Reproductive Health Jun 2024Despite their importance in reducing maternal mortality, information on access to Mifepristone, Misoprostol, and contraceptive medicines in the Eastern Mediterranean...
Access to mifepristone, misoprostol, and contraceptive medicines in eight countries in the Eastern Mediterranean Region: descriptive analyses of country-level assessments.
BACKGROUND
Despite their importance in reducing maternal mortality, information on access to Mifepristone, Misoprostol, and contraceptive medicines in the Eastern Mediterranean Region is limited.
METHODS
A standardized assessment tool measuring access to Mifepristone, Misoprostol, and contraceptive medicines included in the WHO essential medicines list (EML) was implemented in eight countries in the Eastern Mediterranean Region (Afghanistan, Iraq, Lebanon, Libya, Morocco, Palestine, Pakistan, and Somalia) between 2020-2021. The assessment focused on five access measures: 1) the inclusion of medicines in national family planning guidelines; 2) inclusion of medicines in comprehensive abortion care guidelines; 3) inclusion of medicines on national essential medicines lists; 4) medicines registration; and 5) procurement and forecasting of Mifepristone, Misoprostol, and contraceptive medicines. A descriptive analysis of findings from these eight national assessments was conducted.
RESULTS
Only Lebanon and Pakistan included all 12 contraceptives that are enlisted in the WHO-EML within their national family planning guidelines. Only Afghanistan and Lebanon included mifepristone and mifepristone-misoprostol combination in post-abortion care guidelines, but these medicines were not included in their national EMLs. Libya and Somalia lacked a national regulatory authority for medicines registration. Most contraceptives included on the national EMLs for Lebanon, Morocco and Pakistan were registered. Misoprostol was included on the EMLs-and registered-in six countries (Afghanistan, Iraq, Lebanon, Morocco, Palestine, and Pakistan). However, only three countries procured misoprostol (Iraq, Morocco, and Somalia).
CONCLUSION
These findings can guide efforts aimed at improving the availability of Mifepristone, Misoprostol, and contraceptive medicines in the Eastern Mediterranean Region. Opportunities include expanding national EMLs to include more options for Mifepristone, Misoprostol, and contraceptive medicines and strengthening the registration and procurement systems to ensure these medicines' availability were permitted under national law and where culturally acceptable.
Topics: Misoprostol; Humans; Health Services Accessibility; Female; Mifepristone; Mediterranean Region; Contraceptive Agents; Middle East; Abortion, Induced; Pregnancy; Family Planning Services
PubMed: 38835050
DOI: 10.1186/s12978-024-01805-1 -
International Journal of Biological... Jun 2024Brown seaweed-derived polysaccharides, notably fucoidan and laminarin, are known for their extensive array of bioactivities and physicochemical properties. However, the...
Physiochemical changes, metabolite discrepancies of brown seaweed-derived sulphated polysaccharides in the upper gastrointestinal tract and their effects on bioactive expression.
Brown seaweed-derived polysaccharides, notably fucoidan and laminarin, are known for their extensive array of bioactivities and physicochemical properties. However, the effects of upper digestive tract modification on the bioactive performance of fucoidan and laminarin fractions (FLFs) sourced from Australian native species are largely unknown. Here, the digestibility and bioaccessibility of FLFs were evaluated by tracking the dynamic changes in reducing sugar content (C), profiling the free monosaccharide composition using LC-MS, and comparing high-performance gel permeation chromatography profile variation via LC-SEC-RI. The effects of digestive progression on bioactive performance were assessed by comparing the antioxidant and antidiabetic potential of FLFs and FLF digesta. We observed that molecular weight (M) decreased during gastric digestion indicating that FLF aggregates were disrupted in the stomach. During intestinal digestion, M gradually decreased and C increased indicating cleavage of glycosidic bonds releasing free sugars. Although the antioxidant and antidiabetic capacities were not eliminated by the digestion progression, the bioactive performance of FLFs under a digestive environment was reduced contrasting with the same concentration level of the undigested FLFs. These data provide comprehensive information on the digestibility and bioaccessibility of FLFs, and shed light on the effects of digestive progression on bioactive expression.
Topics: Polysaccharides; Seaweed; Antioxidants; Upper Gastrointestinal Tract; Molecular Weight; Hypoglycemic Agents; Digestion; Sulfates; Glucans; Phaeophyceae; Humans
PubMed: 38830495
DOI: 10.1016/j.ijbiomac.2024.132845