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Acta Pharmaceutica (Zagreb, Croatia) Jun 2024Oral solid dosage forms are most frequently administered with a glass of water which empties from the stomach relatively fast, but with a certain variability in its...
Oral solid dosage forms are most frequently administered with a glass of water which empties from the stomach relatively fast, but with a certain variability in its emptying kinetics. The purpose of this study was thus to simulate different individual water gastric emptying (GE) patterns in an glass-bead flow-through dissolution system. Further, the effect of GE on the dissolution of model drugs from immediate-release tablets was assessed by determining the amount of dissolved drug in the samples pumped out of the stomach compartment. Additionally, different HCl solutions were used as dissolution media to assess the effect of the variability of pH of the gastric fluid on the dissolution of three model drugs: paracetamol, diclofenac sodium, and dipyridamole. The difference in fast and slow GE kinetics resulted in different dissolution profiles of paracetamol in all studied media. For diclofenac sodium and dipyridamole tablets, the effect of GE kinetics was well observed only in media, where the solubility was not a limiting factor. Therefore, GE kinetics of co-ingested water influences the drug release from immediate-release tablets, however, in certain cases, other parameters influencing drug dissolution can partly or fully hinder the expression of this effect.
Topics: Gastric Emptying; Drug Liberation; Diclofenac; Water; Solubility; Tablets; Dipyridamole; Acetaminophen; Hydrogen-Ion Concentration; Kinetics; Administration, Oral; Glass
PubMed: 38815199
DOI: 10.2478/acph-2024-0016 -
PloS One 2024The skin microbiome maintains healthy human skin, and disruption of the microbiome balance leads to inflammatory skin diseases such as folliculitis and atopic...
The skin microbiome maintains healthy human skin, and disruption of the microbiome balance leads to inflammatory skin diseases such as folliculitis and atopic dermatitis. Staphylococcus aureus and Cutibacterium acnes are pathogenic bacteria that simultaneously inhabit the skin and cause inflammatory diseases of the skin through the activation of innate immune responses. Silkworms are useful invertebrate animal models for evaluating innate immune responses. In silkworms, phenoloxidase generates melanin as an indicator of innate immune activation upon the recognition of bacterial or fungal components. We hypothesized that S. aureus and C. acnes interact to increase the innate immunity-activating properties of S. aureus. In the present study, we showed that acidification is involved in the activation of silkworm hemolymph melanization by S. aureus. Autoclaved-killed S. aureus (S. aureus [AC]) alone does not greatly activate silkworm hemolymph melanization. On the other hand, applying S. aureus [AC] treated with C. acnes culture supernatant increased the silkworm hemolymph melanization. Adding C. acnes culture supernatant to the medium decreased the pH. S. aureus [AC] treated with propionic acid, acetic acid, or lactic acid induced higher silkworm hemolymph melanization activity than untreated S. aureus [AC]. S. aureus [AC] treated with hydrochloric acid also induced silkworm hemolymph melanization. The silkworm hemolymph melanization activity of S. aureus [AC] treated with hydrochloric acid was inhibited by protease treatment of S. aureus [AC]. These results suggest that acid treatment of S. aureus induces innate immune activation in silkworms and that S. aureus proteins are involved in the induction of innate immunity in silkworms.
Topics: Animals; Hemolymph; Bombyx; Staphylococcus aureus; Melanins; Immunity, Innate; Hydrogen-Ion Concentration; Monophenol Monooxygenase
PubMed: 38814922
DOI: 10.1371/journal.pone.0298502 -
Trials May 2024Paediatric convulsive status epilepticus is the most common neurological emergency presenting to emergency departments. Risks of resultant neurological morbidity and...
Seizure control via pH manipulation: a phase II double-blind randomised controlled trial of inhaled carbogen as adjunctive treatment of paediatric convulsive status epilepticus (Carbogen for Status Epilepticus in Children Trial (CRESCENT)).
BACKGROUND
Paediatric convulsive status epilepticus is the most common neurological emergency presenting to emergency departments. Risks of resultant neurological morbidity and mortality increase with seizure duration. If the seizure fails to stop within defined time-windows, standard care follows an algorithm of stepwise escalation to more intensive treatments, ultimately resorting to induction of general anaesthesia and ventilation. Additionally, ventilatory support may also be required to treat respiratory depression, a common unwanted effect of treatment. There is strong pre-clinical evidence that pH (acid-base balance) is an important determinant of seizure commencement and cessation, with seizures tending to start under alkaline conditions and terminate under acidic conditions. These mechanisms may be particularly important in febrile status epilepticus: prolonged fever-related seizures which predominantly affect very young children. This trial will assess whether imposition of mild respiratory acidosis by manipulation of inhaled medical gas improves response rates to first-line medical treatment.
METHODS
A double-blind, placebo-controlled trial of pH manipulation as an adjunct to standard medical treatment of convulsive status epilepticus in children. The control arm receives standard medical management whilst inhaling 100% oxygen; the active arm receives standard medical management whilst inhaling a commercially available mixture of 95% oxygen, 5% carbon dioxide known as 'carbogen'. Due to the urgent need to treat the seizure, deferred consent is used. The primary outcome is success of first-line treatment in seizure cessation. Planned subgroup analyses will be undertaken for febrile and non-febrile seizures. Secondary outcomes include rates of induction of general anaesthesia, admission to intensive care, adverse events, and 30-day mortality.
DISCUSSION
If safe and effective 95% oxygen, 5% carbon dioxide may be an important adjunct in the management of convulsive status epilepticus with potential for pre-hospital use by paramedics, families, and school staff.
TRIAL REGISTRATION
EudraCT: 2021-005367-49. CTA: 17136/0300/001.
ISRCTN
52731862. Registered on July 2022.
Topics: Humans; Status Epilepticus; Double-Blind Method; Hydrogen-Ion Concentration; Randomized Controlled Trials as Topic; Administration, Inhalation; Child; Carbon Dioxide; Child, Preschool; Treatment Outcome; Clinical Trials, Phase II as Topic; Acidosis, Respiratory; Infant; Seizures, Febrile; Acid-Base Equilibrium; Female; Male; Oxygen
PubMed: 38812049
DOI: 10.1186/s13063-024-08188-5 -
Scientific Reports May 2024The correlation between altered extracellular pH and various pathological conditions, including cancer, inflammation and metabolic disorders, is well known. Bulk pH...
The correlation between altered extracellular pH and various pathological conditions, including cancer, inflammation and metabolic disorders, is well known. Bulk pH measurements cannot report the extracellular pH value at the cell surface. However, there is a limited number of suitable tools for measuring the extracellular pH of cells with high spatial resolution, and none of them are commonly used in laboratories around the world. In this study, a versatile ratiometric nanosensor for the measurement of extracellular pH was developed. The nanosensor consists of biocompatible polystyrene nanoparticles loaded with the pH-inert reference dye Nile red and is surface functionalized with a pH-responsive fluorescein dye. Equipped with a targeting moiety, the nanosensor can adhere to cell membranes, allowing direct measurement of extracellular pH at the cell surface. The nanosensor exhibits a sensitive ratiometric pH response within the range of 5.5-9.0, with a calculated pKa of 7.47. This range optimally covers the extracellular pH (pH) of most healthy cells and cells in which the pH is abnormal, such as cancer cells. In combination with the nanosensors ability to target cell membranes, its high robustness, reversibility and its biocompatibility, the pH nanosensor proves to be well suited for in-situ measurement of extracellular pH, even over extended time periods. This pH nanosensor has the potential to advance biomedical research by improving our understanding of cellular microenvironments, where extracellular pH plays an important role.
Topics: Hydrogen-Ion Concentration; Humans; Fluorescent Dyes; Nanoparticles; Cell Membrane; Biosensing Techniques; Oxazines; Polystyrenes
PubMed: 38811698
DOI: 10.1038/s41598-024-62976-2 -
Scientific Reports May 2024Salmonella is a primary enteric pathogen related to the contamination of poultry and other food products in numerous foodborne outbreaks. The continuous emergence of...
Salmonella is a primary enteric pathogen related to the contamination of poultry and other food products in numerous foodborne outbreaks. The continuous emergence of multidrug-resistant bacteria has become a serious issue due to the overuse of antibiotics. Hence, lytic phages are considered alternative biocontrol agents against these bacterial superbugs. Here, two Salmonella phages-S4lw and D5lw-were subjected to genomic and biological characterization and further encapsulated to improve the stability under acidic conditions mimicking gastrointestinal conditions. The two lytic phages, S4lw and D5lw, taxonomically belong to new species under the Guernseyvirinae and Ackermannviridae families, respectively. Each phage showed antimicrobial activities against diverse Salmonella spp., such as S. Enteritidis and S. Typhimurium, achieving 1.7-3.4 log reduction after 2-6 h of treatment. The phage cocktail at a multiplicity of infection (MOI) of 100 or 1000 completely inhibited these Salmonella strains for at least 14 h at 25 °C. Additionally, the bead-encapsulated phage cocktail could withstand low pH and different simulated gut environments for at least 1 h. Overall, the newly isolated phages can potentially mitigate Salmonella spp. under the gastrointestinal environments through encapsulation and may be further applied via oral administration to resolve common antimicrobial resistance issues in the poultry production chain.
Topics: Salmonella Phages; Salmonella; Animals; Genome, Viral; Gastrointestinal Tract; Biological Control Agents; Hydrogen-Ion Concentration
PubMed: 38811648
DOI: 10.1038/s41598-024-59502-9 -
Anais Da Academia Brasileira de Ciencias 2024In the present study, the effect of xanthan gum was evaluated on the metabolic activity and survival of two probiotic strains, namely B. lactis and L. casei using in...
In the present study, the effect of xanthan gum was evaluated on the metabolic activity and survival of two probiotic strains, namely B. lactis and L. casei using in vitro assay and skim milk model system. In vitro assay was carried out identifying by pH, optical cell density (OD), and formation of postbiotics (lactic, acetic, propionic, and butyric acids) in different basal media including glucose, inulin, and xanthan gum as carbon source. The highest pH values were recorded for control (without carbon source) and media with xanthan gum, whereas the media with glucose and xanthan gum had the highest OD values. In comparison to strains, B. lactis had higher pH and lower OD values than L. casei. It was found that xanthan gum supported the formation of postbiotics as a result of bacterial fermentation. In the skim milk model system, xanthan gum did not negatively affect probiotic viability, and the counts of both strains were above the required level for health benefits (8 log cfu g-1) after 28-day storage. The use of xanthan gum in skim milk matrix positively affected techno-functional properties such as syneresis, color, and textural parameters of samples.
Topics: Polysaccharides, Bacterial; Probiotics; Animals; Milk; Lacticaseibacillus casei; Bifidobacterium animalis; Hydrogen-Ion Concentration; Fermentation
PubMed: 38808815
DOI: 10.1590/0001-3765202420230658 -
Brazilian Journal of Biology = Revista... 2024This study compares the physicochemical characteristics of breast meat (Pectoralis major) from conventional chicken and free-range chicken production systems. Analyses... (Comparative Study)
Comparative Study
This study compares the physicochemical characteristics of breast meat (Pectoralis major) from conventional chicken and free-range chicken production systems. Analyses of pH, instrumental color measurement, weight loss from cooking (WLC), and water retention capacity (WRC) were carried out. Average pH values were slightly higher for conventional chicken samples. WLC did not show a significant difference between conventional and free-range chicken samples. The WRC was better and higher for the free-range chicken samples than the conventional ones. The mean values for luminosity (L*) were within the normal range, with slightly higher values for conventional chicken. In chromatids a* and b*, there was a tendency towards a more reddish color for free-range chicken samples. The differences found for types of production can be explained mainly by the difference in age at slaughter, the degree of physical activity, animal feeding, among other characteristics that differentiate an animal raised by the extensive system from the intensive system.
Topics: Animals; Chickens; Meat; Pectoralis Muscles; Animal Husbandry; Hydrogen-Ion Concentration; Food Quality; Cooking
PubMed: 38808782
DOI: 10.1590/1519-6984.276805 -
Microbial Cell Factories May 2024This study aimed to investigate the operation of three parallel biotrickling filters (BTFs) in removing HS at different pH conditions (haloalkaliphilic, neutrophilic,...
This study aimed to investigate the operation of three parallel biotrickling filters (BTFs) in removing HS at different pH conditions (haloalkaliphilic, neutrophilic, and acidophilic) and their associated microbial population in the biodesulfurization process. BTF columns were inoculated with enriched inoculum and experiments were performed by gradually reducing Empty Bed Retention Time (EBRT) and increasing inlet concentration in which the maximum removal efficiency and maximum elimination capacity in EBRT 60 s reached their maximum level in haloalkaline condition (91% and 179.5 g S-HS m h). For visualizing the attached microbial biofilms on pall rings, Scanning Electron Microscopy (SEM) was used and microbial community structure analysis by NGS showed that the most abundant phyla in haBTF, nBTF, and aBTF belong to Gammaproteobacteria, Betaproteobacteria, and Acidithiobacillia, respectively. Shannon and Simpson indexes evaluation showed a lower diversity of bacteria in the aBTF reactor than that of nBTF and haBTF and beta analysis indicated a different composition of bacteria in haBTF compared to the other two filters. These results indicated that the proper performance of BTF under haloalkaliphilic conditions is the most effective way for HS removal from air pollutants of different industries.
Topics: Hydrogen-Ion Concentration; Hydrogen Sulfide; Biofilms; Bioreactors; Filtration; Bacteria; Air Pollutants; Biodegradation, Environmental; Betaproteobacteria
PubMed: 38807121
DOI: 10.1186/s12934-024-02427-9 -
BMC Plant Biology May 2024Davidia involucrata is a woody perennial and the only living species in the Genus Davidia. It is native to southern China where it holds cultural and scientific...
Davidia involucrata is a woody perennial and the only living species in the Genus Davidia. It is native to southern China where it holds cultural and scientific importance. However, D. involucrata is now an endangered species and its natural range includes low pH soils which are increasingly impacted by acid rain, nitrogen deposition and imbalanced nutrient cycling. The combination of these stresses also poses the additional risk of aluminum (Al) toxicity. Since the responses of D. involucrata to low pH and aluminum toxicity have not been investigated previously, a hydroponic experiment was conducted to examine the growth of one year old D. involucrata saplings after 50 d growth in a range of pH and Al conditions. Plant biomass, morphology, antioxidant enzyme activity, mineral concentrations and plant ecological strategy were compared at pH 5.8 and pH 4.0 without added Al (AlCl) and in 0.1, 0.2 and 0.5 mM Al at pH 4.0. Our results showed that compared with pH 5.8, pH 4.0 (without added Al) not only inhibited root and shoot growth but also limited accumulation of nitrogen (N) and phosphorus (P) in leaves of D. involucrate. However, low Al concentrations (0.1 and 0.2 mM Al) at pH 4.0 partially restored the aboveground growth and leaf N concentrations, suggesting an alleviation of H toxicity by low Al concentrations. Compared with low Al concentrations, 0.5 mM Al treatment decreased plant growth and concentrations of N, P, and magnesium (Mg) in the leaves, which demonstrated the toxicity of high Al concentration. The results based on plant ecological strategy showed that D. involucrate decreased the competitiveness and favored its stress tolerance as pH changed from 5.8 to 4.0. Meanwhile, the competitiveness and stress tolerance of D. involucrata increased and decreased at low Al concentrations, respectively, and decreased and increased at high Al concentration, respectively. These trade-offs in ecological strategy were consistent with the responses of growth and antioxidant enzyme activity, reflecting a sensitive adaptation of D. involucrata to acid and Al stresses, which may aid in sustaining population dynamics. These findings are meaningful for understanding the population dynamics of D. involucrata in response to aluminum toxicity in acid soils.
Topics: Aluminum; Hydrogen-Ion Concentration; Plant Leaves; Plant Roots; Phosphorus; Soil; Nitrogen; Biomass
PubMed: 38807074
DOI: 10.1186/s12870-024-05173-7 -
Scientific Reports May 2024The human microbiome contains genetic information that regulates metabolic processes in response to host health and disease. While acidic vaginal pH is maintained in...
The human microbiome contains genetic information that regulates metabolic processes in response to host health and disease. While acidic vaginal pH is maintained in normal conditions, the pH level increases in infectious vaginitis. We propose that this change in the vaginal environment triggers the biosynthesis of anti-vaginitis metabolites. Gene expression levels of Chryseobacterium gleum, a vaginal symbiotic bacterium, were found to be affected by pH changes. The distinctive difference in the metabolic profiles between two C. gleum cultures incubated under acidic and neutral pH conditions was suggested to be an anti-vaginitis molecule, which was identified as phenylacetic acid (PAA) by spectroscopic data analysis. The antimicrobial activity of PAA was evaluated in vitro, showing greater toxicity toward Gardnerella vaginalis and Candida albicans, two major vaginal pathogens, relative to commensal Lactobacillus spp. The activation of myeloperoxidase, prostaglandin E, and nuclear factor-κB, and the expression of cyclooxygenase-2 were reduced by an intravaginal administration of PAA in the vaginitis mouse model. In addition, PAA displayed the downregulation of mast cell activation. Therefore, PAA was suggested to be a messenger molecule that mediates interactions between the human microbiome and vaginal health.
Topics: Female; Animals; Phenylacetates; Vagina; Mice; Humans; Chryseobacterium; Candida albicans; Symbiosis; Hydrogen-Ion Concentration; Gardnerella vaginalis; Disease Models, Animal; Vaginitis
PubMed: 38806600
DOI: 10.1038/s41598-024-62947-7