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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 -
FASEB Journal : Official Publication of... May 2015Body surface area (BSA) scaling has been used for prescribing individualized dosages of various drugs and has also been recommended by the U.S. Food and Drug... (Review)
Review
Body surface area (BSA) scaling has been used for prescribing individualized dosages of various drugs and has also been recommended by the U.S. Food and Drug Administration as one method for using data from animal model species to establish safe starting dosages for first-in-human clinical trials. Although BSA conversion equations have been used in certain clinical applications for decades, recent recommendations to use BSA to derive interspecies equivalents for therapeutic dosages of drug and natural products are inappropriate. A thorough review of the literature reveals that BSA conversions are based on antiquated science and have little justification in current translational medicine compared to more advanced allometric and physiologically based pharmacokinetic modeling. Misunderstood and misinterpreted use of BSA conversions may have disastrous consequences, including underdosing leading to abandonment of potentially efficacious investigational drugs, and unexpected deadly adverse events. We aim to demonstrate that recent recommendations for BSA are not appropriate for animal-to-human dosage conversions and use pharmacokinetic data from resveratrol studies to demonstrate how confusion between the "human equivalent dose" and "pharmacologically active dose" can lead to inappropriate dose recommendations. To optimize drug development, future recommendations for interspecies scaling must be scientifically justified using physiologic, pharmacokinetic, and toxicology data rather than simple BSA conversion.
Topics: Animals; Body Surface Area; Clinical Trials as Topic; Dose-Response Relationship, Drug; Drugs, Investigational; Humans; Models, Animal; Species Specificity; Therapeutic Equivalency; Tissue Distribution
PubMed: 25657112
DOI: 10.1096/fj.14-269043 -
Drugs Mar 2015Fluticasone furoate/vilanterol (Relvar(®)) is a once-daily, fixed combination of an inhaled corticosteroid (ICS) and a long-acting β2-adrenoreceptor agonist (LABA),... (Review)
Review
Fluticasone furoate/vilanterol (Relvar(®)) is a once-daily, fixed combination of an inhaled corticosteroid (ICS) and a long-acting β2-adrenoreceptor agonist (LABA), delivered via a dry powder inhaler (Ellipta(®)). It is approved for the treatment of asthma in the EU and Japan, and is the first once-daily ICS/LABA to be available for this indication. Fluticasone furoate is an enhanced-affinity glucocorticoid receptor agonist, with potent anti-inflammatory activity. Vilanterol produces rapid and prolonged bronchodilation. In phase III trials in adolescents and adults with various levels of asthma uncontrolled on ICS and/or ICS/LABA, fluticasone furoate/vilanterol 100/25 or 200/25 µg once daily (approved dosages in the EU) significantly improved pulmonary function compared with placebo or equivalent dosages of fluticasone furoate alone (in some trials) or fluticasone propionate. In similar trials, fluticasone furoate/vilanterol 100/25 µg once daily was as effective as fluticasone propionate/salmeterol 250/50 µg twice daily in improving pulmonary function and significantly reduced the risk of severe asthma exacerbation relative to fluticasone furoate alone. In clinical trials, fluticasone furoate/vilanterol was generally well tolerated with fewer than 15 % of patients experiencing treatment-related adverse events, the most common of which were oral/oropharyngeal candidiasis, dysphonia, extrasystoles and cough. The tolerability profile of fluticasone furoate/vilanterol was generally similar to that of fluticasone propionate/salmeterol. Thus, fluticasone furoate/vilanterol is an effective and generally well tolerated ICS/LABA option for the treatment of uncontrolled asthma.
Topics: Administration, Inhalation; Androstadienes; Anti-Asthmatic Agents; Asthma; Benzyl Alcohols; Chlorobenzenes; Drug Therapy, Combination; Humans; Randomized Controlled Trials as Topic
PubMed: 25648266
DOI: 10.1007/s40265-015-0354-5 -
International Journal of General... 2021Droxidopa is approved for the treatment of neurogenic orthostatic hypotension (nOH) symptoms and requires patients to be titrated to individualized effective doses...
Droxidopa is approved for the treatment of neurogenic orthostatic hypotension (nOH) symptoms and requires patients to be titrated to individualized effective doses (100-600 mg, three times daily) based on symptomatic response. As per the product label, droxidopa should be titrated every 24-48 hours to an optimum maintenance dose (maximum daily dosage 1,800 mg). In an examination of patients with nOH treated in clinical practice settings (n=4,506) using data from the central Northera specialty-pharmacy hub, titration schedules, daily titration dosage (ie, dosage during first dispensation, the assumed titration period), and daily maintenance dosage (dosage during subsequent dispensations) were characterized. It was found that customized titration schedules (ie, different from the product-label recommendation) had been used in 53% of patients, and these patients had had an average daily titration dosage of 567 mg. In contrast, patients who were titrated as per the label schedule (48 hours, 37%; 24 hours, 10%) had daily titration dosages of 1,500-1,650 mg. A relationship between treatment persistence (measured by number of refills) and maintenance dosage was identified. Average daily maintenance doses in patients who received 2, 3-6, 7-24, and >25 dispensations were 938, 969, 1,069, and 1,167 mg, respectively (<0.0001). In summary, our data suggest that more than half the patients treated with droxidopa in clinical practice settings are not titrated using the schedule recommended on the product label (ie, not 24-48 hours), and as a result receive lower daily dosages of droxidopa than those treated using the recommended titration schedules. Lower daily maintenance dosages of droxidopa were associated with shorter treatment persistence (ie, fewer dispensations). Reasons for discontinuation could not be examined in this study, but further investigation of these persistence data is warranted.
PubMed: 34421309
DOI: 10.2147/IJGM.S304012 -
Water Research May 2021Anaerobic digestion (AD) of source-diverted blackwater (toilet flush) at ambient room temperature presents challenges for fast hydrolysis of particulate matters. This...
Anaerobic digestion (AD) of source-diverted blackwater (toilet flush) at ambient room temperature presents challenges for fast hydrolysis of particulate matters. This study investigated the effect of different micro-aeration dosages for blackwater AD. Sequencing batch reactors were operated at ambient room temperature (22 ± 1°C) with micro-aeration (0, 5, 10, 50, and 150 mg O g COD per cycle) and gradually reduced hydraulic retention times from 5 d to 2 d. The methanogenesis efficiencies were greater at low oxygen dosages (i.e., 0, 5, 10) while the volatile fatty acids (VFAs) accumulated more at high oxygen dosages (i.e., 50, 150). Microbial communities were significantly different under different oxygen dosages (p<0.05), with segregation of microbial ecological niches in low and high oxygen dosage communities. The low-oxygen-dosage niche (0, 5, and 10 mg g COD) was inhabited by fermenting and syntrophic bacteria (e.g., Cytophaga, Syntrophomonas) and methanogens (e.g., Methanobacterium, Methanolinea, Methanosaeta). The high-oxygen-dosage niche (50 and 150 mg g COD) had significantly (p<0.05) more facultative anaerobic bacteria (Ignavibacteriales and Cloacamonales), and aerobic bacteria (Rhodocyclales). Moreover, blackwater can be a source of antimicrobial resistance genes (ARGs), which are affected by different oxygen dosages. The ARG variation correlated with the microbial community composition (p<0.05). Low-oxygen-dosage communities contained a higher prevalence of mobile gene elements (intI1 and korB) and tetM, ermB, sul1, sul2, and blaCTX-M than the high-oxygen-dosage communities, indicating that oxygen dosage influenced the prevalence of populations carrying ARGs. These findings suggest that application of micro-aeration to AD can be used to control ARG profiles.
Topics: Anaerobiosis; Anti-Bacterial Agents; Bioreactors; Drug Resistance, Bacterial; Methane; Sewage
PubMed: 33751974
DOI: 10.1016/j.watres.2021.117035 -
The European Journal of Contraception &... Dec 2014To evaluate pain and other early adverse events associated with different regimens of medical abortion up to nine weeks of amenorrhoea. (Review)
Review
OBJECTIVES
To evaluate pain and other early adverse events associated with different regimens of medical abortion up to nine weeks of amenorrhoea.
METHODS
The literature was searched for comparative studies of medical abortion using mifepristone followed by the prostaglandin analogue misoprostol. Publications, which included pain assessment were further analysed.
RESULTS
Of the 1459 publications on medical abortion identified, only 23 comparative, prospective trials corresponded to the inclusion criteria. Patients in these studies received different dosages of mifepristone in combination with different dosages of misoprostol administered via diverse routes or at various intervals. Information on pain level was reported in 12/23 papers (52%), information regarding systematic administration of analgesics in 12/23 articles (52%) and information concerning analgesia used was available for only 10/23 studies (43%).
CONCLUSIONS
Neither pain nor its treatment are systematically reported in clinical trials of medical abortion; this shortcoming reflects a neglect of the individual pain perception. When data are mentioned, they are too inconsistent to allow for any comparison between different treatment protocols. Standardised evaluation of pain is needed and the correlation between the dosage of misoprostol and the intensity of pain must be assessed in future studies.
Topics: Abortion, Induced; Adult; Analgesics; Drug Therapy, Combination; Female; Humans; Mifepristone; Misoprostol; Pain; Pain Management; Pain Measurement; Pregnancy; Prospective Studies
PubMed: 25180961
DOI: 10.3109/13625187.2014.950730 -
Der Radiologe Aug 2015The Euratom directive 2013/59 ("EU directive for radiation protection") has to be implemented into national law by spring 2018 and requires a complete recording of... (Review)
Review
BACKGROUND
The Euratom directive 2013/59 ("EU directive for radiation protection") has to be implemented into national law by spring 2018 and requires a complete recording of patient dosages and relevant parameters. Additionally, a medical physics expert has to be consulted for each radiological examination above a defined threshold.
OBJECTIVES
A complete recording of the dosage administered from all modalities and optimization of the radiological procedures should result in a reduction of the total dosage.
MATERIAL AND METHODS
This can be achieved by automated systems that incorporate not only the detection of the dose parameters but also the evaluation and analysis of these data. When provided with warning levels such a system should be able to inform or warn the operator when dose thresholds have been exceeded or even better inform the operator about possible excess dosages before an examination. Depending on the information provided by the modality, dose management systems can operate at different levels in the picture archiving and communication system (PACS), radiological and hospital information systems (RIS/HIS) or with the header information of a digital imaging and communications in medicine (DICOM) image and evaluate and analyze this data.
CONCLUSION
A practicable use of such systems is only possible by close cooperation of medical personnel, medical physicists and information technology (IT) administrators. Various systems are available commercially or free but an individual adaptation of these systems is useful and necessary, depending on the requirements of the radiology practice or hospital.
Topics: Diagnostic Imaging; Europe; Humans; Patient Safety; Practice Guidelines as Topic; Radiation Dosage; Radiation Protection; Radiometry
PubMed: 26296803
DOI: 10.1007/s00117-015-2817-9 -
Research in Veterinary Science Oct 2021This study aimed to evaluate the preliminary safety of self-developed meloxicam (MEL) oil suspension and determine the comparative pharmacokinetics of it at 0.8 and...
This study aimed to evaluate the preliminary safety of self-developed meloxicam (MEL) oil suspension and determine the comparative pharmacokinetics of it at 0.8 and 2mg/kg body weight (b.w.) dosages in pigs following a single intramuscular administration. Six rabbits were used for the study of preliminary safety and six healthy pigs were used for pharmacokinetics study by a crossover design in two periods. The muscle irritation results showed that both of the MEL oil suspension and the conventional injection had no significant changes at the dosage of 0.4 mg/kg b.w.. However, at the dosage of 2 mg/kg b.w., both of the self-developed MEL oil suspension and the MEL conventional injection showed mild irritation to muscle. Plasma concentrations of MEL were measured by ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The MEL plasma concentrations were quantified up to 30 h and 72 h after intramuscular administration at the low- and high-dosage, respectively. The difference was statistically significant (P < 0.05) between different dosages in pharmacokinetic parameters of t, C, AUC, AUC, MRT, and V. The C values of MEL were 1.92 ± 0.34 μg/ml and 3.03 ± 1.25 μg/ml at dosages of 0.8 and 2 mg/kg b.w. while the t values were 3.25 ± 1.04 h and 4.00 ± 1.26 h, respectively. The pharmacokinetics results of self-developed MEL oil suspension demonstrated that the retention time of it in pigs was prolonged, showing the sustained-release effect. Therefore, Oil suspension was an ideal new drug loading form of MEL.
Topics: Animals; Area Under Curve; Chromatography, Liquid; Cross-Over Studies; Injections, Intramuscular; Meloxicam; Rabbits; Swine; Tandem Mass Spectrometry
PubMed: 34333251
DOI: 10.1016/j.rvsc.2021.07.017 -
Interactive Cardiovascular and Thoracic... Apr 2021A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was 'Does routine topical antimicrobial administration... (Review)
Review
A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was 'Does routine topical antimicrobial administration prevent sternal wound infection (SWI) after cardiac surgery? Altogether >238 papers were found using the reported search, of which 11 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. Several different antimicrobial agents, dosages and application protocols were found in the literature. Regarding topical vancomycin use, a meta-analysis by Kowalewski et al. demonstrated a 76% risk reduction in any SWI. Collagen-gentamicin sponge application was associated with a 38% risk reduction in SWI in another meta-analysis by Kowalewski et al., which included 4 randomized control trials and >23 000 patients. Lower evidence observational studies found benefit in the use of different regimes, including: combination of vancomycin paste and subcutaneous gentamycin; combined cefazoline and gentamicin spray; isolated cefazolin; bacitracin ointment; and rifampicin irrigation. We conclude that, in light of the body of evidence available, topical antibiotic application prevents SWI, including both superficial and deep SWI. The strongest evidence, derived from 2 meta-analyses, is related to the use of gentamicin-collagen sponges and topical vancomycin. Heterogeneity throughout studies regarding antibiotic agents, dosages, application protocols and SWI definition makes providing general recommendations challenging.
Topics: Administration, Topical; Anti-Infective Agents; Cardiac Surgical Procedures; Gentamicins; Humans; Meta-Analysis as Topic; Sternotomy; Sternum; Surgical Wound Infection; Treatment Outcome; Vancomycin
PubMed: 33346346
DOI: 10.1093/icvts/ivaa292 -
Nanomaterials (Basel, Switzerland) Nov 2023Nanoparticles are increasingly being used by industry to enhance the outcomes of various chemical processes. In many cases, these processes involve over-dosages that...
Nanoparticles are increasingly being used by industry to enhance the outcomes of various chemical processes. In many cases, these processes involve over-dosages that compensate for particle losses. At best, these unique waste streams end up in landfills. This circumstance is inefficient and coupled with uncertain impacts on the environment. Pozzolanic nanoparticle treatments have been found to provide remarkable benefits for strength restoration and the mitigation of durability problems in ordinary Portland cement and concrete. These treatments have been accompanied by significant particle losses stemming from over-dosages and instability of the colloidal suspensions that are used to deliver these materials into the pore structure. In this study, new methods involving simple tools have been developed to monitor and sustain suspension stability. Turbidity measurement was introduced to monitor the progress of electrokinetic nanoparticle treatment. This tool made it possible to amend a given dosing strategy in real time while it remains possible to make effective treatment adjustments. By monitoring the particle stability and using pH and electric field controls to avoid suspension collapse, successful electrokinetic treatment dosage strategies were demonstrated using 20 nm NALCO 1056 alumina-coated silica particles. These trials indicated that turbidity measurements could track the visually imperceptible phenomena of particle flocking early on at the inception of its development. Suspensions of these nanoparticles were successfully delivered into 5 cm diameter by 10 cm tall hardended cement paste (HCP) specimens by monitoring fluid turbidity along with the specific gravity and using these values to guide the active management of the treatment dosage and pH. Under this new strategy, these losses were reduced to 5% as compared to the 80% losses associated with other treatment approaches. The relationship between the turbidity and the specific gravity was found to be linear. These plots indicated regions of turbidity and specific gravity that were associated with particle flocking. The tools, guidelines, and strategies developed in this work made it possible to manage efficient (low-particle-loss) electrokinetic nanoparticle treatments by signaling in real time when adjustments to electric field, pH, and particle dosage increments were needed.
PubMed: 38063741
DOI: 10.3390/nano13233045