-
Pharmaceutics Oct 2021Three-dimensional (3D) printing technology, specifically stereolithography (SLA) technology, has recently created exciting possibilities for the design and fabrication...
Three-dimensional (3D) printing technology, specifically stereolithography (SLA) technology, has recently created exciting possibilities for the design and fabrication of sophisticated dosages for oral administration, paving a practical way to precisely manufacture customized pharmaceutical dosages with both personalized properties and sustained drug release behavior. However, the sustained drug release achieved in prior studies largely relies on the presence of hydrophilic excipients in the printing formulation, which unfortunately impedes the printability and formability of the corresponding printing formulations. The current study developed and prepared mini-sized oral pellets using the SLA technique and successfully accomplished a hydrophilic excipient-independent drug release behavior. With ibuprofen as the model drug, the customized photopolymerizable printing formulation included polyethylene glycol diacrylate (PEGDA) as a monomer and diphenyl (2,4,6-trimethylbenzoyl) phosphine oxide (TPO) as a photoinitiator. The produced mini-sized pellets were thoroughly investigated for various factors, including their printability, physical properties, microscopic features, drug content, and drug-release profiles. The drug release profiles from the printed pellets that were larger size (3 mm and 6 mm) followed the Ritger-Peppas model, demonstrating that the release was influenced by both the diffusion of the dissolved drug and by the erosion of the hydrophilic excipients (PEG400). The profiles from the smaller printed pellets (1 mm and 2 mm) followed first release kinetics, not only illustrating that the release was impacted only by drug diffusion, but also indicating that there is a size boundary between the dependent and independent hydrophilic excipients. These results could create practical benefits to the pharmaceutical industry in terms of the design and development personalized dosages using the SLA printing technique with controllable drug release by manipulating size alone.
PubMed: 34684010
DOI: 10.3390/pharmaceutics13101717 -
Environmental Health Insights 2022Consumption of polluted surface waters are leading to waterborne diseases, especially in developing countries, which results in the deaths of millions of people annually...
BACKGROUND
Consumption of polluted surface waters are leading to waterborne diseases, especially in developing countries, which results in the deaths of millions of people annually around the world. Ethiopia, like the rest of developing countries, suffers a lot of water-associated health problems. Chemical disinfectants are in use to disinfect water with some drawbacks like expensiveness, unavailability, and detrimental effect on human health. Researchers are on the search for non-expensive and locally available methods, and natural plants are the ones in the study. Thus, this study is designed to test removal efficiency of () and () from surface water.
METHODS
A cross-sectional study was conducted from June to July 2021. A 14 L water sample was collected from Lake Hawassa. A 30, 60, and 100 mg weights of the leaf and seed powder dosages of and at contaminant settling times of 30, 60, and 90 minutes were used. Each 1-L water sample was treated with each of the dosages. count, temperature, pH and turbidity were measured using standard methods for water and wastewater analysis. Statistical package for social sciences (SPSS) version.23 was used for analysis. Treatment differences between plant parts and association between variables were also tested.
RESULT
The result indicated that raw water samples having 18 initial colonies per 100 mL of water showed zero colonies per 100 mL of water after treatment with 30 mg dosage of seed, 30 mg dosage of seed, and 60 mg dosage of leaf after 90 minutes of settling time, but leaf was unable to reduce colonies to 0 per 100 mL of water. leaf showed the highest turbidity reduction of 83.3% at 60 mg dosage. A pH of 7.30 and 8.50 and a temperature of 20°C to 23.5°C were recorded. There was a significant difference in removal between seed and leaf. Turbidity was identified as a factor that positively affects removal during seed and leaf. Dosage and settling time were also identified as predictors of removal.
CONCLUSION
and have antimicrobial properties against , but only showed , turbidity, and pH values within the recommended World Health Organization standards. So, we suggest as a promising natural disinfectant that needs attention from organizations working on the water.
PubMed: 35846165
DOI: 10.1177/11786302221111842 -
Molecular Cancer Sep 2022G-quadruplex (G4) binders have been investigated to discover new anticancer drugs worldwide in past decades. As these ligands are generally not highly cytotoxic, the... (Review)
Review
G-quadruplex (G4) binders have been investigated to discover new anticancer drugs worldwide in past decades. As these ligands are generally not highly cytotoxic, the discovery rational was mainly based on increasing the cell-killing potency. Nevertheless, no G4 binder has been shown yet to be effective in cancer patients. Here, G4 binder activity at low dosages will be discussed as a critical feature to discover ligands with therapeutic effects in cancer patients. Specific effects of G4 binders al low doses have been reported to occur in cancer and normal cells. Among them, genome instability and the stimulation of cytoplasmic processes related to autophagy and innate immune response open to the use of G4 binders as immune-stimulating agents. Thus, we propose a new rational of drug discovery, which is not based on cytotoxic potency but rather on immune gene activation at non-cytotoxic dosage.
Topics: Antineoplastic Agents; G-Quadruplexes; Genomic Instability; Humans; Ligands; Neoplasms
PubMed: 36114513
DOI: 10.1186/s12943-022-01649-y -
Animals : An Open Access Journal From... Nov 2021Antibiotics are major disruptors of the gastrointestinal microbiota, depleting bacterial species beneficial for the host health and favoring the emergence of potential... (Review)
Review
Antibiotics are major disruptors of the gastrointestinal microbiota, depleting bacterial species beneficial for the host health and favoring the emergence of potential pathogens. Furthermore, the intestine is a reactor of antibiotic resistance emergence, and the presence of antibiotics exacerbates the selection of resistant bacteria that can disseminate in the environment and propagate to further hosts. We reviewed studies analyzing the effect of antibiotics on the intestinal microbiota and antibiotic resistance conducted on animals, focusing on the main food-producing and companion animals. Irrespective of antibiotic classes and animal hosts, therapeutic dosage decreased species diversity and richness favoring the bloom of potential enteropathogens and the selection of antibiotic resistance. These negative effects of antibiotic therapies seem ineluctable but often were mitigated when an antibiotic was administered by parenteral route. Sub-therapeutic dosages caused the augmentation of taxa involved in sugar metabolism, suggesting a link with weight gain. This result should not be interpreted positively, considering that parallel information on antibiotic resistance selection was rarely reported and selection of antibiotic resistance is known to occur also at low antibiotic concentration. However, studies on the effect of antibiotics as growth promoters put the basis for understanding the gut microbiota composition and function in this situation. This knowledge could inspire alternative strategies to antibiotics, such as probiotics, for improving animal performance. This review encompasses the analysis of the main animal hosts and all antibiotic classes, and highlights the future challenges and gaps of knowledge that should be filled. Further studies are necessary for elucidating pharmacodynamics in animals in order to improve therapy duration, antibiotic dosages, and administration routes for mitigating negative effects of antibiotic therapies. Furthermore, this review highlights that studies on aminoglycosides are almost inexistent, and they should be increased, considering that aminoglycosides are the first most commonly used antibiotic family in companion animals. Harmonization of experimental procedures is necessary in this research field. In fact, current studies are based on different experimental set-up varying for antibiotic dosage, regimen, administration, and downstream microbiota analysis. In the future, shotgun metagenomics coupled with long-reads sequencing should become a standard experimental approach enabling to gather comprehensive knowledge on GIM in terms of composition and taxonomic functions, and of s. Decorticating GIM in animals will unveil revolutionary strategies for medication and improvement of animals' health status, with positive consequences on global health.
PubMed: 34828011
DOI: 10.3390/ani11113280 -
Frontiers in Nutrition 2023There is growing concern regarding elevated levels of circulating unmetabolized folic acid (UMFA) due to excessive intake of folic acid (FA). However, no randomized...
Association of folic acid dosage with circulating unmetabolized folic acid in Chinese adults with H-type hypertension: a multicenter, double-blind, randomized controlled trial.
BACKGROUND
There is growing concern regarding elevated levels of circulating unmetabolized folic acid (UMFA) due to excessive intake of folic acid (FA). However, no randomized clinical trial has been conducted to examine the FA-UMFA dose-response relationship.
OBJECTIVE
This study aimed to investigate the FA-UMFA dose-response relationship in Chinese adults with hypertension and elevated homocysteine (H-type hypertension), a population with clear clinical indication for FA treatment.
METHODS
The data for this study were derived from a randomized, double-blind, multicenter clinical trial of 8 FA dosages on efficacy of homocysteine (Hcy) lowering. The parent trial had three 3 stages: screening period (2-10 days), run-in period (0-2 weeks, baseline visit), and double-blind treatment period (8 weeks) with follow-up visits at the end of the 2nd, 4th, 6th, and 8th weeks of treatment. Participants were randomly assigned to 8 treatment groups corresponding to FA dosages of 0, 0.4, 0.6, 0.8, 1.2, 1.6, 2.0 mg to 2.4 mg.
RESULTS
This study included 1,567 Chinese adults aged ≥45 years with H-type hypertension. There was a positive but non-linear association between FA supplementation and UMFA levels in the dosage range of 0 mg to 2.4 mg. In the regression analysis, the coefficients for the linear and quadratic terms of FA dosage were both statistically significant ( < 0.001). Notably, the slope for UMFA was greater for FA dosages >0.8 mg (ß = 11.21, 95% CI: 8.97, 13.45) compared to FA dosages ≤0.8 mg (ß = 2.94, 95% CI: 2.59, 3.29). Furthermore, FA dosages higher than 0.8 mg did not confer additional benefits in terms of increasing 5-methyl tetrahydrofolic acid (5-MTHF, active form of folate) or reducing homocysteine (Hcy).
CONCLUSION
In Chinese adults with H-type hypertension, this study showed a positive, non-linear, dosage-response relationship between FA supplementation ranging from 0 to 2.4 mg and circulating UMFA levels. It revealed that 0.8 mg FA is an optimal dosage in terms of balancing efficacy (increasing 5-MTHF and lowering Hcy) while minimizing undesirable elevation of UMFA.
CLINICAL TRIAL REGISTRATION
https://clinicaltrials.gov/ct2/show/NCT03472508?term=NCT03472508&draw=2&rank=1, identifier NCT03472508.
PubMed: 37781132
DOI: 10.3389/fnut.2023.1191610 -
Ecotoxicology and Environmental Safety Dec 2023Allelopathy has been demonstrated to be an environmentally friendly way to control harmful algal blooms. Allelochemicals of submerged plants have attracted extensive...
Allelopathy has been demonstrated to be an environmentally friendly way to control harmful algal blooms. Allelochemicals of submerged plants have attracted extensive research due to their bioavailability. The dose-response of submerged plant extracts on algae growth is worth further study to improve the efficiency of bioremediation. In this study, the ultrasonic-enzymatic assistance method was utilized to extract allelochemicals from Ceratophyllum, Myriophyllum spicatum, and Vallisneria. The effects of low-dosage and high-dosage extracts on the growth of Microcystis aeruginosa were compared based on cell biomass and morphology, photosynthetic parameters, reactive oxygen species (ROS), superoxide dismutase (SOD), catalase (CAT), and malondialdehyde (MDA) levels. The results showed that the three submerged plant extracts exhibited hormetic effects at low dosages and inhibitory effects at high dosages on algal growth. Within 48 h of cultivation, the enzymatic activities of Microcystis aeruginosa fluctuated, suggesting that the extracts of the three submerged plants induced different oxidative reactions. After 120 h of cultivation with high-dosage extracts, the physiological and biochemical reactions of Microcystis aeruginosa significantly decreased, indicating the effectiveness of the allelopathy of Ceratophyllum, Myriophyllum spicatum, and Vallisneria extracts in controlling algal blooms. The phenomenon of hormesis and inhibition effect confirmed a significant dose-response relationship between the allelochemicals of submerged plant extracts and Microcystis aeruginosa, which could be attributed to the composition and content of allelochemicals. These findings highlight the importance of the relative concentration of the biological algaecide and will benefit other researchers in determining the safe dosage of plant allelochemicals when used in water.
Topics: Microcystis; Hormesis; Plants; Plant Extracts; Harmful Algal Bloom; Pheromones
PubMed: 37979364
DOI: 10.1016/j.ecoenv.2023.115703 -
International Journal of Molecular... Oct 2021Sublethal dosages of imidacloprid cause long-term destructive effects on honey bees at the individual and colony levels. In this review, the molecular effects of... (Review)
Review
Sublethal dosages of imidacloprid cause long-term destructive effects on honey bees at the individual and colony levels. In this review, the molecular effects of sublethal imidacloprid were integrated and reported. Several general effects have been observed among different reports using different approaches. Quantitative PCR approaches revealed that imidacloprid treatments during the adult stage are expressed as changes in immuneresponse, detoxification, and oxidation-reduction response in both workers and queens. In addition, transcriptomic approaches suggested that phototransduction, behavior, and somatic muscle development also were affected. Although worker larvae show a higher tolerance to imidacloprid than adults, molecular evidence reveals its potential impacts. Sublethal imidacloprid treatment during the larval stage causes gene expression changes in larvae, pupae, and adults. Transcriptome profiles suggest that the population and functions of affected differentially expressed genes, DEGs, vary among different worker ages. Furthermore, an early transcriptomic switch from nurse bees to foragers was observed, suggesting that precocious foraging activity may occur. This report comprehensively describes the molecular effects of sublethal dosages of imidacloprid on the honey bee . The corresponding molecular pathways for physiological and neurological responses in imidacloprid-exposed honey bees were validated. Transcriptomic evidence suggests a global and sustained sublethal impact of imidacloprid on honey bee development.
Topics: Animals; Bees; Larva; Neonicotinoids; Nitro Compounds; Transcriptome
PubMed: 34769266
DOI: 10.3390/ijms222111835 -
Journal of the American Heart... May 2024Hypertension and hypercholesterolemia are important risk factors for cardiovascular disease, and treatment with fixed-dose combination (FDC) regimens is recommended by...
BACKGROUND
Hypertension and hypercholesterolemia are important risk factors for cardiovascular disease, and treatment with fixed-dose combination (FDC) regimens is recommended by current guidelines. However, the clinical outcomes of different FDC dosages remain unknown. This study aimed to examine the clinical outcomes of FDC regimens and the free combination of amlodipine and atorvastatin at different dosages.
METHODS AND RESULTS
Patients with concurrent hypertension and hypercholesterolemia treated daily with an FDC of 5 mg amlodipine and 10 mg atorvastatin (5/10 fixed group), and FDC of 5 mg amlodipine and 20 mg atorvastatin (5/20 fixed group), or free combination of 5 mg amlodipine and 20 mg atorvastatin (5/20 free group) were identified from the National Health Insurance Research Database of Taiwan. The primary outcome was the composite cardiovascular outcomes, including cardiovascular death, acute myocardial infarction, stroke, and coronary intervention. A total of 9095 patients were eligible for inclusion. The incidence of primary outcome per 1000 person-years was 16.6 in the 5/10 fixed group, 12.6 in the 5/20 fixed group, and 16.5 in the 5/20 free group (5/20 fixed versus 5/20 free: hazard ratio [HR], 0.76 [95% CI, 0.64-0.91]; 5/20 fixed versus 5/10 fixed: HR, 0.76 [95% CI, 0.63-0.90]).
CONCLUSIONS
Among patients with concomitant hypertension and hypercholesterolemia, treatment with an FDC of amlodipine and high-dose atorvastatin led to a lower risk of a composite of cardiovascular outcomes than treatment with the free combination or a similar FDC with a lower dose of atorvastatin.
Topics: Humans; Amlodipine; Male; Hypercholesterolemia; Hypertension; Female; Middle Aged; Atorvastatin; Aged; Taiwan; Drug Combinations; Treatment Outcome; Antihypertensive Agents; Retrospective Studies; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Anticholesteremic Agents; Calcium Channel Blockers; Blood Pressure; Heptanoic Acids; Pyrroles
PubMed: 38686894
DOI: 10.1161/JAHA.123.033780 -
Briefings in Bioinformatics Nov 2023Large-scale imputation reference panels are currently available and have contributed to efficient genome-wide association studies through genotype imputation. However,...
Large-scale imputation reference panels are currently available and have contributed to efficient genome-wide association studies through genotype imputation. However, whether large-size multi-ancestry or small-size population-specific reference panels are the optimal choices for under-represented populations continues to be debated. We imputed genotypes of East Asian (180k Japanese) subjects using the Trans-Omics for Precision Medicine reference panel and found that the standard imputation quality metric (Rsq) overestimated dosage r2 (squared correlation between imputed dosage and true genotype) particularly in marginal-quality bins. Variance component analysis of Rsq revealed that the increased imputed-genotype certainty (dosages closer to 0, 1 or 2) caused upward bias, indicating some systemic bias in the imputation. Through systematic simulations using different template switching rates (θ value) in the hidden Markov model, we revealed that the lower θ value increased the imputed-genotype certainty and Rsq; however, dosage r2 was insensitive to the θ value, thereby causing a deviation. In simulated reference panels with different sizes and ancestral diversities, the θ value estimates from Minimac decreased with the size of a single ancestry and increased with the ancestral diversity. Thus, Rsq could be deviated from dosage r2 for a subpopulation in the multi-ancestry panel, and the deviation represents different imputed-dosage distributions. Finally, despite the impact of the θ value, distant ancestries in the reference panel contributed only a few additional variants passing a predefined Rsq threshold. We conclude that the θ value substantially impacts the imputed dosage and the imputation quality metric value.
Topics: Humans; Genome-Wide Association Study; Gene Frequency; Polymorphism, Single Nucleotide; Genotype
PubMed: 38221906
DOI: 10.1093/bib/bbad509 -
The American Journal of Clinical... Jan 2022There remains a lack of evidence demonstrating a potential relationship between vitamin D and cardiometabolic risk among children. (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
There remains a lack of evidence demonstrating a potential relationship between vitamin D and cardiometabolic risk among children.
OBJECTIVES
We examined the effect of 3 different dosages of vitamin D on cardiometabolic risk factors among children at risk of deficiency.
METHODS
Racially diverse schoolchildren aged 8-15 y were randomly assigned in a double-blind fashion to supplementation with 600, 1000, or 2000 IU vitamin D3/d for 6 mo. Changes in HDL cholesterol, triglycerides, LDL cholesterol, total cholesterol, and blood glucose over 6 mo and at 12 mo (6 mo post-supplementation) were assessed. Subgroup analyses were also performed by weight status and race.
RESULTS
Among 604 children, 40.9% were vitamin D-inadequate at baseline (<20 ng/mL; mean ± SD: 22.0 ± 6.8 ng/mL), 46.4% were overweight/obese, and 60.9% had ≥1 suboptimal blood lipids or glucose. Over 6 mo, serum 25-hydroxyvitamin D increased in all 3 dosage groups from baseline (mean ± SE change: 4.4 ± 0.6 ng/mL, 5.7 ± 0.7 ng/mL, and 10.7 ± 0.6 ng/mL for 600, 1000, and 2000 IU/d, respectively; P < 0.001). Whereas HDL cholesterol and triglycerides increased in the 600 IU group (P = 0.002 and P = 0.02, respectively), LDL cholesterol and total cholesterol decreased across dosage groups. At 6 mo post-supplementation, HDL cholesterol remained elevated in the 600 and 1000 IU groups ( P < 0.001 and P = 0.02, respectively) whereas triglycerides remained elevated in the 1000 and 2000 IU groups (P = 0.04 and P = 0.006, respectively). The suppression of LDL cholesterol and total cholesterol persisted in the 2000 IU group only (P = 0.04 and P < 0.001, respectively). There were no significant changes in blood glucose and similar responses were observed overall by weight status and racial groups across dosages.
CONCLUSIONS
Vitamin D supplementation demonstrated generally positive effects on HDL cholesterol, LDL cholesterol, and total cholesterol, especially at the lower dosage of 600 IU/d, with several significant changes persisting during the post-supplementation period. Increases in triglycerides across dosage groups may be due to natural changes during adolescence warranting further study.This trial was registered at clinicaltrials.gov as NCT01537809.
Topics: Adolescent; Blood Glucose; Cardiometabolic Risk Factors; Child; Child Nutritional Physiological Phenomena; Cholecalciferol; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Dietary Supplements; Double-Blind Method; Female; Humans; Male; Pediatric Obesity; Triglycerides; Vitamin D; Vitamin D Deficiency
PubMed: 34550329
DOI: 10.1093/ajcn/nqab319