Pharmacokinetic Pattern of Menbutone in Calves after Single Intravenous and Intramuscular Administration.

Menbutone is a choleretic agent currently used in Europe to treat digestive disorders in livestock and dogs. Pharmacokinetic parameters were established in 4-month Holstein calves after intravenous (IV) and intramuscular (IM) administration. The drug was administered to 12 animals (10 mg/kg) for both IV and IM routes following a crossover design. Plasma samples were collected at various time points over 24 h and analyzed by reverse-phase high-performance liquid chromatography with a photodiode-array detector, following a method validated according to European Medicines Agency guidelines. Pharmacokinetic parameters were calculated using compartmental and non-compartmental methods. Menbutone followed a two-compartment open model after IV injection, with a total clearance (Cl) of 71.9 ± 13.5 mL/h/kg, an elimination half-life (t½ß) of 4.53 ± 2.45 h, and a volume of distribution at steady-state (Vss) of 310.4 ± 106.4 mL/kg. Non-compartmental elimination half-life (t½λ) was 4.2 ± 1.1 h. After IM administration, drug pharmacokinetics was best described by a one-compartment open model. The peak plasma concentration (Cmax) was 15.1 ± 4.3 µg/mL; the time to reach Cmax (tmax), 1.66 ± 0.55 h; and the mean absorption time (MAT), 2.50 ± 1.42 h. Absorption was high, with a fraction of the dose absorbed (F) of 83.5 ± 22.4%. Menbutone was rapidly eliminated from plasma for both routes of administration, with a fast and high IM bioavailability.

Tribulus terrestris and Sport Performance: A Quantitative and Qualitative Evaluation of Its Advertisement and Availability via Online Shopping in Six Different Countries.

Dietary supplements are commonly used among athletes, and the Internet may be an easy source of these products. Tribulus terrestris is an herbal supplement with multiple properties. Of interest to athletes are reports that its consumption can lead to muscle mass gain and a faster recovery process. The objective of this cross-sectional study was to determine the availability of Tribulus terrestris via the Internet in six countries (Canada, Puerto Rico, Russia, Spain, Ukraine, and the United States of America) via a specifically designed computer program. The characteristics of the websites selling this substance, the country from which it can be purchased, the route of administration, and recommendations for its use were analyzed. The results of the study show that this supplement is marketed mainly in Russia, Ukraine, and Spain on many websites that are mostly dedicated to sports products. Just over half of the webpages (59.14%) identified only distribute this supplement within the same country. The main claims for its consumption refer to sports performance benefits, but there are also claims that it may improve male hormone levels and sexual function. Athletes should be encouraged to seek professional advice prior to ingesting this supplement to ensure that it is suitable for their specific training and sports objectives.

Benchmark Outcomes for Distal Pancreatectomy: A Multicenter Prospective Snapshot Study from the Spanish Distal Pancreatectomy Project (SPANDISPAN).

BACKGROUND: Improving the quality of care is a priority for health systems to obtain better care and reduce costs. One of the tools for measuring quality is benchmarking (BM). We presented a 1-country prospective study of distal pancreatectomies (DPs) and determined BM. STUDY DESIGN: Prospective, multicenter, observational snapshot study of DP carried out at Spanish hepatopancreatobiliary centers for a year (February 1, 2022, to January 31, 2023). Hepatopancreatobiliary centers were defined as high volume if they performed more than 10 DPs per year. Inclusion criteria include any scheduled DP for any diagnosis and age older than 18 years. The low-risk group was defined following the criteria given by Durin and colleagues and major complications as Clavien-Dindo ≥III. RESULTS: A total of 313 patients from 42 centers and 46.6% from high-volume centers were included. Median DP by center was 7 (interquartile range 5 to 10), median age was 65 years (interquartile range 55 to 74), and 53.4% were female. The surgical approach was minimally invasive in 69.3%. Major complications were 21.1%. Postoperative pancreatic fistula grade B/C rate was 20.1%, and 90-day mortality was 1.6%. One hundred forty-three patients were in low-risk group (43.8%). Compared with previous BM data, an increasing MIS rate and fewer hospital stay were obtained. CONCLUSIONS: We present the first determination of DP-BM in a prospective series, obtaining similar results to the previous ones, but our BM values include a shorter hospital stay and a higher percentage of minimally invasive surgery probably related to Enhanced Recovery after Surgery protocols and prospective data collection. BM is a multiparameter valuable tool for reporting outcomes, comparing centers, and identifying the points to improve surgical care.

Pathogenicity of microsclerotia from Metarhizium robertsii against Aedes aegypti larvae and antimicrobial peptides expression by mosquitoes during fungal-host interaction.

Aedes aegypti is a vector of various disease-causing arboviruses. Chemical insecticide-based methods for mosquito control have increased resistance in different parts of the world. Thus, alternative control agents such as the entomopathogenic fungi are excellent candidates to control mosquitoes as part of an ecofriendly strategy. There is evidence of the potential of entomopathogenic fungal conidia and blastospores for biological control of eggs, larval and adult stages, as well as the pathogenicity of fungal microsclerotia against adults and eggs. However, there are no studies on the pathogenicity of microsclerotia against either aquatic insects or insects that develop part of their life cycle in the water, such as the A. aegypti larvae. In this study, we assayed the production of microsclerotia and their pathogenicity against A. aegypti larvae of two isolates of Metarhizium robertsii, i.e., CEP 423 isolated in La Plata, Argentina, and the model ARSEF 2575. Both isolates significantly reduced the survival of A. aegypti exposed to their microsclerotia. The fungus-larva interaction resulted in a delayed response in the host. This was evidenced by the expression of some humoral immune system genes such as defensins and cecropin on the 9th day post-infection, when the fungal infection was consolidated as a successful process that culminates in larvae mortality. In conclusion, M. robertsii microsclerotia are promising propagules to be applied as biological control agents against mosquitoes since they produce pathogenic conidia against A. aegypti larvae.

Online information and availability of three doping substances (anabolic agents) in sports: role of pharmacies.

Background: The Internet has become an important source for easy access to doping substances, where people and athletes may acquire, outside pharmacies and without a (medical) prescription. These online websites do not always offer quality-assured products, and are outside the regular distribution channels of medicines. The aim of this study was to estimate the availability and accessible information on the Internet about the sale of three doping substances (oxandrolone, DHEA, androstenedione). Methods: Cross-sectional exploratory study, being an observation at a point in time of the online availability of these three doping substances (WADA S1 category: anabolic agents), purchased from Spain, Puerto Rico, Canada, United States, Ukraine and Russia. The characteristics of the websites, the countries the webs sold to, the pharmaceutical forms offered and the recommendations for its use were analyzed by using a computer tool designed ad hoc. Results: There were significant differences between countries in the number of webpages that sold the products (Chi-square test, p < 0.05). Oxandrolone was available for purchase mainly when buying from Spain (27.12%) and Ukraine (26.58%), in websites dedicated to sports (77.26%). For DHEA, most of the pages offered it if the search was done from Canada (23.34%) and Russia (21.44%). Products containing androstenedione or DHEA are claimed to enhance sports performance or for sports use without providing details. Compared to the total number of websites checked, the proportion of pharmacies offering these products was low, ranging from 4.86% for DHEA to 15.79% for androstenedione. Conclusion: The three substances selected are easily available without control through the Internet. Only a small number of websites offering them were online pharmacies, and requested a prescription. Most of the doping substances are purchased from the country where they are requested. Product information described benefits for sports performance, but did not do the same with their side effects. It would be advisable for these products to be sold through pharmacies, to guarantee their quality and provide evidence-based information on their safe use, benefits and risks, and only with a prescription. Athletes should be encouraged to consult health professionals about those supplements suitable for their type of training and sports objectives.

Distantly related Alteromonas bacteriophages share tail fibers exhibiting properties of transient chaperone caps.

The host recognition modules encoding the injection machinery and receptor binding proteins (RBPs) of bacteriophages are predisposed to mutation and recombination to maintain infectivity towards co-evolving bacterial hosts. In this study, we reveal how Alteromonas mediterranea schitovirus A5 shares its host recognition module, including tail fiber and cognate chaperone, with phages from distantly related families including Alteromonas myovirus V22. While the V22 chaperone is essential for producing active tail fibers, here we demonstrate production of functional A5 tail fibers regardless of chaperone co-expression. AlphaFold-generated models of tail fiber and chaperone pairs from phages A5, V22, and other Alteromonas phages reveal how amino acid insertions within both A5-like proteins results in a knob domain duplication in the tail fiber and a chaperone ß-hairpin "tentacle" extension. These structural modifications are linked to differences in chaperone dependency between the A5 and V22 tail fibers. Structural similarity between the chaperones and intramolecular chaperone domains of other phage RBPs suggests an additional function of these chaperones as transient fiber "caps". Finally, our identification of homologous host recognition modules from morphologically distinct phages implies that horizontal gene transfer and recombination events between unrelated phages may be a more common process than previously thought among Caudoviricetes phages.

Evolutionary pathways for deep-sea adaptation in marine planktonic Actinobacteriota.

The deep ocean, one of the largest ecosystems on earth, is dominated by microorganisms that are keystones in the regulation of biogeochemical cycles. However, the evolutionary pathways underlying the specific adaptations required (e.g., high pressure and low temperature) by this unique niche remain understudied. Here, we analyzed the first representatives belonging to the order Acidimicrobiales, a group of marine planktonic Actinobacteriota, that specifically inhabits the aphotic zone of the oceanic water column (>200 m). Compared with their epipelagic counterparts, deep-sea representatives showed the same evolution in genome architecture with higher GC content, longer intergenic spaces as well as higher nitrogen (N-ARSC) and lower carbon (C-ARSC) content in encoded amino acid residue side chains consistent with the higher nitrogen concentration and lower carbon concentration in deep waters compared to the photic zone. Metagenomic recruitment showed distribution patterns that allowed the description of different ecogenomic units within the three deep water-associated genera defined by our phylogenomic analyses (UBA3125, S20-B6 and UBA9410). The entire genus UBA3125 was found exclusively associated with oxygen minimum zones linked to the acquisition of genes involved in denitrification. Genomospecies of genus S20-B6 recruited in samples from both mesopelagic (200-1,000 m) and bathypelagic (1000-4,000 m) zones, including polar regions. Diversity in the genus UBA9410 was higher, with genomospecies widely distributed in temperate zones, others in polar regions, and the only genomospecies associated with abyssal zones (>4,000 m). At the functional level, groups beyond the epipelagic zone have a more complex transcriptional regulation including in their genomes a unique WhiB paralog. In addition, they showed higher metabolic potential for organic carbon and carbohydrate degradation as well as the ability to accumulate glycogen as a source of carbon and energy. This could compensate for energy metabolism in the absence of rhodopsins, which is only present in genomes associated with the photic zone. The abundance in deep samples of cytochrome P450 monooxygenases associated with the genomes of this order suggests an important role in remineralization of recalcitrant compounds throughout the water column.

Association between soluble angiotensin-converting enzyme 2 in saliva and SARS-CoV-2 infection: a cross-sectional study.

This study aimed to investigate the association between saliva soluble angiotensin-converting enzyme 2 (sACE2) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children and adults. We selected a convenience sample of adults with post-acute SARS-CoV-2 infection and their household children living in quarantined family households of the metropolitan Barcelona region (Spain) during the spring 2020 pandemic national lockdown. Participants were tested for saliva sACE2 quantification by western blot and nasopharyngeal SARS-CoV-2 RT-PCR detection. A total of 161 saliva samples [82 (50.9%) from children; 79 (49.1%) from females] yielded valid western blot and RT-PCR results. Saliva sACE2 was detected in 79 (96.3%) children and 76 (96.2%) convalescent adults. Twenty (24.4%) children and 20 (25.3%) convalescent adults were positive for SARS-CoV-2 in nasopharynx by RT-PCR. SARS-CoV-2 RT-PCR-negative children had a significantly higher mean proportional level of saliva sACE2 (0.540 × 10-3%) than RT-PCR-positive children (0.192 × 10-3%, p < 0.001) and convalescent adults (0.173 × 10-3%, p < 0.001). In conclusion, children negative for nasopharyngeal SARS-CoV-2 RT-PCR appear to exhibit a higher concentration of saliva sACE2 than SARS-CoV-2 RT-PCR-positive children and convalescent adults. Release of adequate levels of sACE2 in saliva could play a protective role against SARS-CoV-2.

Single-amplified genomes reveal most streamlined free-living marine bacteria.

Evolutionary adaptations of prokaryotes to the environment sometimes result in genome reduction. Our knowledge of this phenomenon among free-living bacteria remains scarce. We address the dynamics and limits of genome reduction by examining one of the most abundant bacteria in the ocean, the SAR86 clade. Despite its abundance, comparative genomics has been limited by the absence of pure cultures and the poor representation in metagenome-assembled genomes. We co-assembled multiple previously available single-amplified genomes to obtain the first complete genomes from members of the four families. All families showed a convergent evolutionary trajectory with characteristic features of streamlined genomes, most pronounced in the TMED112 family. This family has a genome size of ca. 1 Mb and only 1 bp as median intergenic distance, exceeding values found in other abundant microbes such as SAR11, OM43 and Prochlorococcus. This genomic simplification led to a reduction in the biosynthesis of essential molecules, DNA repair-related genes, and the ability to sense and respond to environmental factors, which could suggest an evolutionary dependence on other co-occurring microbes for survival (Black Queen hypothesis). Therefore, these reconstructed genomes within the SAR86 clade provide new insights into the limits of genome reduction in free-living marine bacteria.

Quantification of the flexural rigidity of endovascular surgical devices using three-point bending tests.

Endovascular surgical procedures require the navigation of catheters and wires through the vasculature to reach distal target sites. Quantitative frameworks for device selection hold the potential to improve the tracking of endovascular devices through vascular anatomy by personalizing the device flexural rigidity to an individual's anatomy. However, data are lacking to facilitate this technology, in part because typical endovascular devices have intricate spatial variations in mechanical properties that are challenging and tedious to quantify repeatably. We therefore developed a three-point bend test methodology using a custom rig and applied it to measure lengthwise flexural rigidity profiles of endovascular devices that are used to target the cerebral vasculature. The methodology demonstrated high repeatability and was able to characterize transition zones. We applied the methodology to generate the first comprehensive, quantitative library of device flexural rigidities, spanning guidewires, intermediate guides, and long sheaths. We observed that these three classes of device have properties that fall into distinct ranges. Additional plots examining relationships between flexural rigidity, device diameter, and length revealed application-specific trends in flexural properties. This methodology and the data allow for standardized characterization and comparisons to aid device selection, and have the potential to both enhance surgical planning and inform future innovation.

Elucidating the picocyanobacteria salinity divide through ecogenomics of new freshwater isolates.

BACKGROUND: Cyanobacteria are the major prokaryotic primary producers occupying a range of aquatic habitats worldwide that differ in levels of salinity, making them a group of interest to study one of the major unresolved conundrums in aquatic microbiology which is what distinguishes a marine microbe from a freshwater one? We address this question using ecogenomics of a group of picocyanobacteria (cluster 5) that have recently evolved to inhabit geographically disparate salinity niches. Our analysis is made possible by the sequencing of 58 new genomes from freshwater representatives of this group that are presented here, representing a 6-fold increase in the available genomic data. RESULTS: Overall, freshwater strains had larger genomes (≈2.9 Mb) and %GC content (≈64%) compared to brackish (2.69 Mb and 64%) and marine (2.5 Mb and 58.5%) isolates. Genomic novelties/differences across the salinity divide highlighted acidic proteomes and specific salt adaptation pathways in marine isolates (e.g., osmolytes/compatible solutes - glycine betaine/ggp/gpg/gmg clusters and glycerolipids glpK/glpA), while freshwater strains possessed distinct ion/potassium channels, permeases (aquaporin Z), fatty acid desaturases, and more neutral/basic proteomes. Sulfur, nitrogen, phosphorus, carbon (photosynthesis), or stress tolerance metabolism while showing distinct genomic footprints between habitats, e.g., different types of transporters, did not obviously translate into major functionality differences between environments. Brackish microbes show a mixture of marine (salt adaptation pathways) and freshwater features, highlighting their transitional nature. CONCLUSIONS: The plethora of freshwater isolates provided here, in terms of trophic status preference and genetic diversity, exemplifies their ability to colonize ecologically diverse waters across the globe. Moreover, a trend towards larger and more flexible/adaptive genomes in freshwater picocyanobacteria may hint at a wider number of ecological niches in this environment compared to the relatively homogeneous marine system.

Pharmacokinetics of menbutone after intravenous and intramuscular administration to sheep.

Menbutone is a drug currently approved in several European Union (EU) countries to treat digestive disorders in different animal species. The objective of this study was to establish the pharmacokinetic parameters resulting from intravenous (IV) and intramuscular (IM) administration of this drug in sheep. Menbutone was administered to 12 animals at the dose of 10 mg/kg for both IV and IM routes. Plasma samples were collected up to 24 h (15 points, IV route; 14 points, IM route). Concentrations were determined using high-performance liquid chromatography with photodiode-array (PDA) detection, following a method validated according to the EMEA/CHMP/EWP/192217/2009 guideline. Pharmacokinetic data were analyzed by non-compartmental methods. After IV administration, a total clearance (Cl) of 63.6 ± 13.6 mL/h/kg, a volume of distribution at steady-state (Vss) of 259.6 ± 52.7 mL/kg, and an elimination half-life (t½λ) of 6.08 ± 2.48 h were calculated. After IM administration, menbutone peak plasma concentration (Cmax) was 18.8 ± 1.9 µg/mL, the time to reach Cmax (tmax) 3.75 ± 0.45 h, the mean absorption time (MAT) 3.31 ± 1.36 h, and the fraction of dose absorbed (F) 103.1 ± 23.0 %. The results obtained indicate that menbutone absorption after IM administration is quick and complete.

Impact of COVID-19 Lockdown on the Nasopharyngeal Microbiota of Children and Adults Self-Confined at Home.

The increased incidence of COVID-19 cases and deaths in Spain in March 2020 led to the declaration by the Spanish government of a state of emergency imposing strict confinement measures on the population. The objective of this study was to characterize the nasopharyngeal microbiota of children and adults and its relation to SARS-CoV-2 infection and COVID-19 severity during the pandemic lockdown in Spain. This cross-sectional study included family households located in metropolitan Barcelona, Spain, with one adult with a previous confirmed COVID-19 episode and one or more exposed co-habiting child contacts. Nasopharyngeal swabs were used to determine SARS-CoV-2 infection status, characterize the nasopharyngeal microbiota and determine common respiratory DNA/RNA viral co-infections. A total of 173 adult cases and 470 exposed children were included. Overall, a predominance of Corynebacterium and Dolosigranulum and a limited abundance of common pathobionts including Haemophilus and Streptococcus were found both among adults and children. Children with current SARS-CoV-2 infection presented higher bacterial richness and increased Fusobacterium, Streptococcus and Prevotella abundance than non-infected children. Among adults, persistent SARS-CoV-2 RNA was associated with an increased abundance of an unclassified member of the Actinomycetales order. COVID-19 severity was associated with increased Staphylococcus and reduced Dolosigranulum abundance. The stringent COVID-19 lockdown in Spain had a significant impact on the nasopharyngeal microbiota of children, reflected in the limited abundance of common respiratory pathobionts and the predominance of Corynebacterium, regardless of SARS-CoV-2 detection. COVID-19 severity in adults was associated with decreased nasopharynx levels of healthy commensal bacteria.

Herbs as an Active Ingredient in Sport: Availability and Information on the Internet.

The use of supplements containing herbal active ingredients in sport has increased in recent years. Their consumption is explained by the benefits they may provide and because their natural origin do not involve health complications, from the point of view of the consumers. The aim of this study is to analyze the availability of four supplements (caffeine, turmeric, ginseng, cannabidiol) on the internet and understand the nature of these websites. A descriptive, observational, and cross-sectional study design was used. A detailed search was carried out with specifically developed software. The searches and data evaluation took 10 days. The websites consulted correspond to those that sell supplements, or some sport websites in the case of the Spanish ones, whereas those in English belong to pharmacies, parapharmacies, or herbalists. It is concluded that the websites do not provide adequate information to ensure proper consumption and lack advice on the choices of supplements and their administration guidelines.

Potentially Inappropriate Medication and Polypharmacy in Nursing Home Residents: A Cross-Sectional Study.

Inappropriate prescribing in the elderly is a risk factor for higher adverse drugs reactions, hospitalisation, and mortality rates. Therefore, it is necessary to identify irrational prescriptions and implement interventions to improve geriatric clinical practices in nursing homes. This study aimed to examine and compare the prevalence of potentially inappropriate medications in nursing home residents using three different updated criteria: 2019 Beers criteria, PRISCUS list, and v2 STOPP criteria, and to determine the prevalence of potential prescribing omissions according to v2 START criteria. A descriptive, observational, and cross-sectional study design was used. A total of 218 residents were involved in this study. Data on drug use were collected from medical charts. Information was screened with the software CheckTheMeds. Potentially inappropriate medications were present in 96.3%, 90.8%, and 35.3% of residents, according to the STOPP, Beers, and PRISCUS criteria or list, respectively. Inappropriate medication was found to be significantly associated with polypharmacy and severe or moderate drug-drug interactions with the three tools and with pathologies and unnecessary drugs only for STOPP criteria. The most frequent inappropriate medications were benzodiazepines and proton pump inhibitors. A regular use of software to review medications in nursing home residents would help to reduce the risk of these drug-related problems.

α-cyanobacteria possessing form IA RuBisCO globally dominate aquatic habitats.

RuBisCO (ribulose 1,5-bisphosphate carboxylase/oxygenase) is one the most abundant enzymes on Earth. Virtually all food webs depend on its activity to supply fixed carbon. In aerobic environments, RuBisCO struggles to distinguish efficiently between CO2 and O2. To compensate, organisms have evolved convergent solutions to concentrate CO2 around the active site. The genetic engineering of such inorganic carbon concentrating mechanisms (CCMs) into plants could help facilitate future global food security for humankind. In bacteria, the carboxysome represents one such CCM component, of which two independent forms exist: α and ß. Cyanobacteria are important players in the planet's carbon cycle and the vast majority of the phylum possess a ß-carboxysome, including most cyanobacteria used as laboratory models. The exceptions are the exclusively marine Prochlorococcus and Synechococcus that numerically dominate open ocean systems. However, the reason why marine systems favor an α-form is currently unknown. Here, we report the genomes of 58 cyanobacteria, closely related to marine Synechococcus that were isolated from freshwater lakes across the globe. We find all these isolates possess α-carboxysomes accompanied by a form 1A RuBisCO. Moreover, we demonstrate α-cyanobacteria dominate freshwater lakes worldwide. Hence, the paradigm of a separation in carboxysome type across the salinity divide does not hold true, and instead the α-form dominates all aquatic systems. We thus question the relevance of ß-cyanobacteria as models for aquatic systems at large and pose a hypothesis for the reason for the success of the α-form in nature.

Drug-Related Problems and Polypharmacy in Nursing Home Residents: A Cross-Sectional Study.

At present, 19.2% of the Spanish population is aged 65 or older. Polypharmacy is a frequent condition among the elderly, especially in those living in nursing homes, which is associated with adverse outcomes, such as adverse drug events or drug-drug interactions. This study aimed to assess the pattern of polypharmacy in a nursing home in Leon, one of Spain's most ageing regions, and its relationship with different drug-related problems. A descriptive, observational, and cross-sectional study design was used; 222 residents were involved in this study. Data on drug use were collected from medical charts. Information was screened with the software CheckTheMeds, BOT PLUS and Drug-Reax. Residents were on a median of 7 medicines. Polypharmacy and inappropriate medications were present in 78.8% and 96.8% of residents, respectively. Drug-related problems were present in almost all the populations evaluated. Drug-drug interactions were very common in participants (81.1%), being severe/moderate in 24.7%. A high prevalence of polypharmacy and drug-related problems in the nursing home population assessed has been observed. A significantly higher risk of suffering drug-drug interactions was revealed for increasing polypharmacy and anticholinergic risk. A regular evaluation of drug prescribing in nursing home residents is necessary to minimize drug-related problems risk.

Melatonin in the Prophylaxis of SARS-CoV-2 Infection in Healthcare Workers (MeCOVID): A Randomised Clinical Trial.

We evaluated in this randomised, double-blind clinical trial the efficacy of melatonin as a prophylactic treatment for prevention of SARS-CoV-2 infection among healthcare workers at high risk of SARS-CoV-2 exposure. Healthcare workers fulfilling inclusion criteria were recruited in five hospitals in Spain and were randomised 1:1 to receive melatonin 2 mg administered orally for 12 weeks or placebo. The main outcome was the number of SARS-CoV-2 infections. A total of 344 volunteers were screened, and 314 were randomised: 151 to placebo and 163 to melatonin; 308 received the study treatment (148 placebo; 160 melatonin). We detected 13 SARS-CoV-2 infections, 2.6% in the placebo arm and 5.5% in the melatonin arm (p = 0.200). A total of 294 adverse events were detected in 127 participants (139 in placebo; 155 in melatonin). We found a statistically significant difference in the incidence of adverse events related to treatment: 43 in the placebo arm and 67 in the melatonin arm (p = 0.040), and in the number of participants suffering from somnolence related to treatment: 8.8% (n = 14) in the melatonin versus 1.4% (n = 2) in the placebo arm (p = 0.008). No severe adverse events related to treatment were reported. We cannot confirm our hypothesis that administration of melatonin prevents the development of SARS-CoV-2 infection in healthcare workers.

Improvement of Albendazole Bioavailability with Menbutone Administration in Sheep.

The pharmacokinetic interaction between a benzimidazole (albendazole, ABZ) and a choleretic drug (menbutone, MEN) was evaluated in sheep. The plasma disposition of albendazole sulfoxide (ABZSO, active metabolite) and albendazole sulfone (ABZSO2, inactive metabolite) was investigated following an oral administration of albendazole (ABZ) (5 mg/kg) alone or with menbutone (MEN) (intramuscular, 10 mg/kg). Blood samples were collected over 3 days post-treatment, and drug plasma concentrations were measured by high performance liquid chromatography (HPLC). ABZSO was measured from 0.5 to 48 h, and ABZSO2 from 2 to 60 h. No parent drug was detected at any sampling time. Mean maximum plasma concentration (Cmax) and the area under the plasma concentration-time curve (AUC) were 12.8% and 21.5% higher for ABZSO when ABZ and MEN were administered together, which indicates a significant increase in the amount absorbed. The rate of absorption was not modified, with similar values for the time to reach Cmax (tmax) (11.5 h with ABZ + MEN and 10.7 h with ABZ treatment), although no significant differences were observed for these latter pharmacokinetic parameters. Regarding ABZSO2, Cmax, AUC and tmax values were similar after both treatments (ABZ or ABZ + MEN). The results obtained indicate that co-administration of ABZ and MEN may be an interesting and practical option to increase the efficacy of this anthelmintic.