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1.
Annu Rev Genomics Hum Genet ; 24: 347-368, 2023 08 25.
Article in English | MEDLINE | ID: mdl-37253596

ABSTRACT

Continued advances in precision medicine rely on the widespread sharing of data that relate human genetic variation to disease. However, data sharing is severely limited by legal, regulatory, and ethical restrictions that safeguard patient privacy. Federated analysis addresses this problem by transferring the code to the data-providing the technical and legal capability to analyze the data within their secure home environment rather than transferring the data to another institution for analysis. This allows researchers to gain new insights from data that cannot be moved, while respecting patient privacy and the data stewards' legal obligations. Because federated analysis is a technical solution to the legal challenges inherent in data sharing, the technology and policy implications must be evaluated together. Here, we summarize the technical approaches to federated analysis and provide a legal analysis of their policy implications.


Subject(s)
Fenbendazole , Privacy , Humans , Health Facilities , Information Dissemination , Policy
2.
BMC Vet Res ; 20(1): 214, 2024 May 20.
Article in English | MEDLINE | ID: mdl-38769544

ABSTRACT

As an orally effective benzimidazole anthelmintic agent, fenbendazole was not only widely used in agriculture and animal husbandry to prevent and treat parasites, but also shows anti-cancer effects against several types of cancer, exhibits anti-cancer effects in paclitaxel and doxorubicin-resistant cancer cells. However, fenbendazole's poor in water solubility (0.3 µg/mL), limits its clinical applications. Even great efforts were made toward increasing its water solubility, the results were not significant to reach anti-cancer drug delivery requirement (5-10 mg/mL). Through single factor and orthogonal strategy, many complex conditions were designed and used to prepare the complexes, the inclusion complex with methyl-ß-cyclodextrin with 29.2 % of inclusion rate and 89.5% of inclusion yield can increase drug's water solubility to 20.21 mg/mL, which is the best result so far. Its structure was confirmed by differential scanning calorimetry, scanning electron microscopic image, 1D and 2D NMR spectra in D2O. In its in vitro pharmacokinetic study, fenbendazole was 75% released in 15 min., in its in vivo pharmacokinetic study, the bio-availabilities of fenbendazole, its major metabolic anthelmintic agent oxfendazole and its minor metabolic anthelmintic agent oxfendazole were increased to 138%, 149% and 169% respectively, which would allow for fewer drug doses to achieve the same therapeutic effect and suggest that the complex can be used as a potential anticancer agent.


Subject(s)
Fenbendazole , Solubility , beta-Cyclodextrins , Fenbendazole/pharmacokinetics , Fenbendazole/therapeutic use , Fenbendazole/chemistry , Animals , beta-Cyclodextrins/chemistry , Antineoplastic Agents/pharmacokinetics , Antineoplastic Agents/chemistry , Antineoplastic Agents/administration & dosage , Male , Anthelmintics/pharmacokinetics , Anthelmintics/chemistry , Anthelmintics/administration & dosage
3.
Exp Parasitol ; 258: 108714, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38367946

ABSTRACT

Helminth infections pose a significant economic threat to livestock production, causing productivity declines and, in severe cases, mortality. Conventional anthelmintics, exemplified by fenbendazole, face challenges related to low solubility and the necessity for high doses. This study explores the potential of supramolecular complexes, created through mechanochemical modifications, to address these limitations. The study focuses on two key anthelmintics, praziquantel (PZQ) and fenbendazole (FBZ), employing mechanochemical techniques to enhance their solubility and efficacy. Solid dispersions (SD) of PZQ with polymers and dioctyl sulfosuccine sodium (DSS) and fenbendazole with licorice extract (ES) and DSS were prepared. The helminthicidal activity of these complexes was assessed through helminthological dissections of sheep infected with Schistosoma turkestanicum, moniesiasis, and parabronemosis. In the assessment of supramolecular complex of FBZ (SMCF) at doses ranging from 1.0 to 3.0 mg/kg for the active substance (AS), optimal efficacy was observed with the fenbendazole formulation containing arabinogalactan and polyvinylpyrrolidone at a 3.0 mg/kg dosage. At this concentration, the formulation demonstrated a remarkable 100% efficacy in treating spontaneous monieziosis in sheep, caused by Moniezia expansa (Rudolphi, 1810) and M. benedenii (Moniez, 1879). Furthermore, the SMCF, administered at doses of 1.0, 2.0, and 3.0 mg/kg, exhibited efficacy rates of 42.8%, 85.7%, and 100%, respectively, against the causative agent of parabronemosis (Parabronema skrjabini Rassowska, 1924). Mechanochemical modifications, yielding supramolecular complexes of PZQ and FBZ, present a breakthrough in anthelmintic development. These complexes address solubility issues and significantly reduce required doses, offering a practical solution for combating helminth infections in livestock. The study underscores the potential of supramolecular formulations for revolutionizing helminthiasis management, thereby enhancing the overall health and productivity of livestock.


Subject(s)
Anthelmintics , Cestode Infections , Schistosomiasis , Animals , Sheep , Fenbendazole/therapeutic use , Anthelmintics/pharmacology , Anthelmintics/therapeutic use , Praziquantel/therapeutic use , Cestode Infections/drug therapy
4.
Proc Natl Acad Sci U S A ; 118(3)2021 01 19.
Article in English | MEDLINE | ID: mdl-33431676

ABSTRACT

Pathogen interactions arising during coinfection can exacerbate disease severity, for example when the immune response mounted against one pathogen negatively affects defense of another. It is also possible that host immune responses to a pathogen, shaped by historical evolutionary interactions between host and pathogen, may modify host immune defenses in ways that have repercussions for other pathogens. In this case, negative interactions between two pathogens could emerge even in the absence of concurrent infection. Parasitic worms and tuberculosis (TB) are involved in one of the most geographically extensive of pathogen interactions, and during coinfection worms can exacerbate TB disease outcomes. Here, we show that in a wild mammal natural resistance to worms affects bovine tuberculosis (BTB) severity independently of active worm infection. We found that worm-resistant individuals were more likely to die of BTB than were nonresistant individuals, and their disease progressed more quickly. Anthelmintic treatment moderated, but did not eliminate, the resistance effect, and the effects of resistance and treatment were opposite and additive, with untreated, resistant individuals experiencing the highest mortality. Furthermore, resistance and anthelmintic treatment had nonoverlapping effects on BTB pathology. The effects of resistance manifested in the lungs (the primary site of BTB infection), while the effects of treatment manifested almost entirely in the lymph nodes (the site of disseminated disease), suggesting that resistance and active worm infection affect BTB progression via distinct mechanisms. Our findings reveal that interactions between pathogens can occur as a consequence of processes arising on very different timescales.


Subject(s)
Buffaloes/immunology , Disease Resistance , Haemonchiasis/microbiology , Lung/immunology , Lymph Nodes/immunology , Trichostrongylosis/microbiology , Tuberculosis, Bovine/microbiology , Animals , Antinematodal Agents/pharmacology , Buffaloes/microbiology , Buffaloes/parasitology , Cattle , Coinfection , Disease Progression , Eosinophils/drug effects , Eosinophils/immunology , Eosinophils/microbiology , Eosinophils/parasitology , Feces/parasitology , Female , Fenbendazole/pharmacology , Haemonchiasis/drug therapy , Haemonchiasis/mortality , Haemonchiasis/parasitology , Haemonchus/drug effects , Haemonchus/genetics , Haemonchus/pathogenicity , Immunoglobulin A/blood , Lung/drug effects , Lung/microbiology , Lung/parasitology , Lymph Nodes/drug effects , Lymph Nodes/microbiology , Lymph Nodes/parasitology , Mast Cells/drug effects , Mast Cells/immunology , Mast Cells/microbiology , Mast Cells/parasitology , Mycobacterium bovis/growth & development , Mycobacterium bovis/pathogenicity , Severity of Illness Index , Survival Analysis , Trichostrongylosis/drug therapy , Trichostrongylosis/mortality , Trichostrongylosis/parasitology , Trichostrongylus/drug effects , Trichostrongylus/genetics , Trichostrongylus/pathogenicity , Tuberculosis, Bovine/drug therapy , Tuberculosis, Bovine/mortality , Tuberculosis, Bovine/parasitology
5.
Parasitol Res ; 123(5): 207, 2024 May 07.
Article in English | MEDLINE | ID: mdl-38713234

ABSTRACT

Biomarkers are specific molecular, histological, or physiological characteristics of normal or pathogenic biological processes and are promising in the diagnosis of gastrointestinal nematodes (GINs). Although some biomarkers have been validated for infection by Ostertagia sp. in cattle raised in temperate regions, there is a lack of information for tropical regions. The aim of this project was to assess potential biomarkers and validate the most promising. In the first study, 36 bovines (Nelore breed) naturally infected by GINs were distributed into two groups: infected (not treated with anthelmintic) and treated (treated with fenbendazole on days 0, 7, 14, 21, 28, 42, and 56). The variables of interest were live weight, fecal egg count, hemogram, serum biochemical markers, phosphorus, gastrin, and pepsinogen. In the second step, pepsinogen was assessed in cattle of the Nelore breed distributed among three groups: infected (not treated with anthelmintic), MOX (treated with moxidectin), and IVM + BZD (treated with ivermectin + albendazole). In the first study, no difference between groups was found for weight, albumin, hematocrit (corpuscular volume [CV]), erythrocytes, or hemoglobin. Negative correlations were found between pepsinogen and both CV and albumin, and albumin was negatively correlated with the percentage of Haemonchus sp. in the fecal culture. Among the biomarkers, only pepsinogen differentiated treated and infected (beginning with the 28th day of the study). In the second study, a reduction in pepsinogen was found after anthelmintic treatment. Therefore, pepsinogen is a promising biomarker of worms in cattle naturally infected by the genera Haemonchus and Cooperia in tropical areas.


Subject(s)
Biomarkers , Cattle Diseases , Feces , Nematode Infections , Tropical Climate , Animals , Cattle , Cattle Diseases/parasitology , Cattle Diseases/drug therapy , Biomarkers/blood , Nematode Infections/veterinary , Nematode Infections/parasitology , Nematode Infections/drug therapy , Feces/parasitology , Parasite Egg Count , Anthelmintics/therapeutic use , Nematoda/isolation & purification , Nematoda/classification , Nematoda/drug effects , Gastrointestinal Diseases/parasitology , Gastrointestinal Diseases/veterinary , Intestinal Diseases, Parasitic/veterinary , Intestinal Diseases, Parasitic/parasitology , Fenbendazole/therapeutic use
6.
Chem Biodivers ; 21(4): e202302081, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38318954

ABSTRACT

In this work, the cytotoxicity of monoclonal antibody (Cetuximab, Ce) and Fenbendazole (Fen), as well as their combination therapy were tested with the MTT assay. On the other side, Ce, Fen, and a combination between them were subjected to a colchicine-tubulin binding test, which was conducted and compared to Colchicine as a reference standard. Besides, Ce, Fen, and the combination of them were tested against the VEGFR-2 target receptor, compared to Sorafenib as the standard medication. Moreover, the qRT-PCR technique was used to investigate the levels of apoptotic genes (p53 and Bax) and anti-apoptotic gene (Bcl-2) as well. Also, the effect of Ce, Fen, and the combination of them on the level of ROS was studied. Furthermore, the cell cycle analysis and Annexin V apoptosis assay were carried out for Ce, Fen, and a combination of them. In addition, the molecular docking studies were used to describe the molecular levels of interactions for both (Fen and colchicine) or (Fen and sorafenib) within the binding pockets of the colchicine binding site (CBS) and vascular endothelial growth factor-2 receptor (VEGFR-2), respectively.


Subject(s)
Antineoplastic Agents , Cetuximab/pharmacology , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Vascular Endothelial Growth Factor Receptor-2 , Fenbendazole/pharmacology , Molecular Docking Simulation , Sorafenib/pharmacology , Vascular Endothelial Growth Factor A/pharmacology , Cell Proliferation , Binding Sites , Receptors, Vascular Endothelial Growth Factor , Apoptosis , Colchicine/pharmacology , Structure-Activity Relationship , Protein Kinase Inhibitors/chemistry , Molecular Structure , Drug Screening Assays, Antitumor
7.
N Z Vet J ; 72(3): 133-140, 2024 May.
Article in English | MEDLINE | ID: mdl-38369301

ABSTRACT

AIMS: To determine the concentration, in comparison with the maximum residue limit (MRL), of anthelmintic marker residues in the target tissues (liver and fat) of sheep treated concurrently with two oral drenches, one containing monepantel and abamectin and the other oxfendazole and levamisole. METHODS: On day 0 of the study, 12 sheep (six male and six female; 8-9-months old) were dosed according to individual body weight determined the day prior. Zolvix Plus (dual-active oral drench containing 25 g/L monepantel and 2 g/L abamectin) was administered to all animals prior to administration of Scanda (dual-active oral drench containing 80 g/L levamisole hydrochloride and 45.3 g/L oxfendazole). Six sheep (three male and three female) were slaughtered 21 and 28 days after treatment and renal fat and liver samples were collected.Using validated methods, analyses for monepantel sulfone, abamectin, levamisole and oxfendazole (expressed as total fenbendazole sulfone following conversion of the combined concentrations of oxfendazole, fenbendazole and fenbendazole sulfone) were performed on liver samples while renal fat specimens were analysed for monepantel sulfone and abamectin residues only. Detected concentrations were compared to the established MRL in sheep for each analyte determined by the Ministry for Primary Industries. RESULTS: All residues detected in samples of liver and fat collected 21 and 28 days after treatment were below the MRL for each analyte. All liver samples collected on day 21 had detectable monepantel sulfone (mean 232 (min 110, max 388) µg/kg) and oxfendazole (mean 98.7 (min 51.3, max 165) µg/kg) residues below the MRL (5,000 and 500 µg/kg, respectively). Monepantel sulfone (mean 644 (min 242, max 1,119) µg/kg; MRL 7,000 µg/kg) residues were detected in 6/6 renal fat samples. Levamisole residues were detected in 3/6 livers (mean 40.0 (min 14.3, max 78.3) µg/kg; MRL 100 µg/kg), and abamectin residues in 1/6 livers (0.795 µg/kg; MRL 25 µg/kg) and 2/6 fat samples, (mean 0.987 (min 0.514, max 1.46) µg/kg; MRL 50 µg/kg) 21 days after treatment. CONCLUSION AND CLINICAL RELEVANCE: These results suggest that concurrent administration of Zolvix Plus and Scanda to sheep is unlikely to result in an extended residue profile for any of the active ingredients, with all analytes measured being under the approved New Zealand MRL 21 days after treatment. This work was not completed in line with guidance for establishing official residue profiles, nor is it sufficient to propose a new withholding period.


Subject(s)
Aminoacetonitrile/analogs & derivatives , Anthelmintics , Benzimidazoles , Ivermectin/analogs & derivatives , Sheep Diseases , Animals , Male , Female , Sheep , Levamisole/therapeutic use , Fenbendazole/therapeutic use , Anthelmintics/therapeutic use , Sulfones/therapeutic use , Sheep Diseases/drug therapy
8.
AAPS PharmSciTech ; 25(7): 199, 2024 Aug 28.
Article in English | MEDLINE | ID: mdl-39198340

ABSTRACT

Fenbendazole is an antiparasitic drug widely used in veterinary medicine to treat parasitic infections caused in animals like cattle, horses, sheep, and dogs. Recently, it has been repositioned as a potential alternative for cancer treatment. However, it is a highly hydrophobic molecule (0.9 ug/mL), which can compromise its dissolution rate and absorption. Thus, this work aimed to apply a nanotechnological approach to improve drug solubility and dissolution performance. Fenbendazole nanoparticles stabilized by different poloxamers were obtained by lyophilization without cryoprotectants. The behavior of the drug in the solid state was analyzed by X-ray diffractometry, differential scanning calorimetry, and infrared spectroscopy. The nanosystems were also evaluated for solubility and dissolution rate. A long-term stability evaluation was performed for three years at room temperature. The yields of the lyophilization ranged between 75 and 81% for each lot. The nanoparticles showed a submicron size (< 340 nm) and a low polydispersity depending on the stabilizer. The physicochemical properties of the prepared systems indicated a remarkable amorphization of the drug, which influenced its solubility and dissolution performance. The drug dissolution from both the fresh and aged nanosystems was significantly higher than that of the raw drug. In particular, nanoparticles prepared with poloxamer 407 showed no significant modifications in their particle size in three years of storage. Physical stability studies indicated that the obtained systems prepared with P188, P237, and P407 suffered certain recrystallization during long storage at 25 °C. These findings confirm that selected poloxamers exhibited an important effect in formulating fenbendazole nanosystems with improved dissolution.


Subject(s)
Drug Stability , Fenbendazole , Freeze Drying , Nanoparticles , Solubility , Nanoparticles/chemistry , Fenbendazole/chemistry , Freeze Drying/methods , Calorimetry, Differential Scanning/methods , Drug Storage , Particle Size , X-Ray Diffraction/methods , Drug Liberation , Chemistry, Pharmaceutical/methods , Poloxamer/chemistry , Cryoprotective Agents/chemistry
9.
J Exp Biol ; 226(5)2023 03 01.
Article in English | MEDLINE | ID: mdl-36806418

ABSTRACT

Working memory, the ability to actively maintain and manipulate information across time, is key to intelligent behavior. Because of the limited capacity of working memory, relevant information needs to be protected against distracting representations. Whether birds can resist distractors and safeguard memorized relevant information is unclear. We trained carrion crows in a delayed match-to-sample task to memorize an image while resisting other, interfering stimuli. We found that the repetition of the sample stimulus during the memory delay improved performance accuracy and accelerated reaction time relative to a reference condition with a neutral interfering stimulus. In contrast, the presentation of the image that constituted the subsequent non-match test stimulus mildly weakened performance. However, the crows' robust performance in this most demanding distractor condition indicates that sample information was actively protected from being overwritten by the distractor. These data show that crows can cognitively control and safeguard behaviorally relevant working memory contents.


Subject(s)
Crows , Memory, Short-Term , Animals , Cognition , Behavior, Animal , Fenbendazole
10.
Exp Parasitol ; 245: 108458, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36592712

ABSTRACT

Dentostomella translucida is an oxyurid nematode that was first discovered in the Mongolian gerbil but has also been detected in other wild and housed rodents. In conventional laboratory animals, oxyurid nematode parasites are widespread infections. A proven treatment strategy for pinworm eradication is the oral application of benzimidazoles, such as fenbendazole. In general, this drug is regarded as safe with minimal side effects. Nevertheless, in Sprague Dawley rats, a significantly reduced litter size could be seen after longer treatment with fenbendazole. Even though Dentostomella translucida was already described in Syrian golden hamsters (Mesocricetus auratus), data on treatment with fenbendazole and its effects on reproduction is lacking. Therefore, the main purposes of the study were (1) the verification of the effectiveness of fenbendazole as medicated feed (150 ppm) against this parasite in naturally infected Syrian golden hamsters in conventional husbandry and (2) monitoring of possible effects on reproduction during the treatment. Results show that fenbendazole treatment was highly effective against Dentostomella translucida, as numbers of pinworm eggs in the faeces were significantly reduced already after the first week of treatment in all animals. After four weeks of treatment, eggs were eradicated entirely. Interestingly, the average weaning weight was significantly reduced during treatment, but the litters were in good health.


Subject(s)
Fenbendazole , Nematoda , Animals , Rats , Cricetinae , Mesocricetus , Fenbendazole/therapeutic use , Rats, Sprague-Dawley , Gerbillinae/parasitology
11.
Biomed Chromatogr ; 37(8): e5637, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37002730

ABSTRACT

The Northern Bobwhite (Colinus virginianus) is an economically important game bird within the Rolling Plains Ecoregion. Within this region, bobwhite is experiencing extreme cyclic population fluctuations which are resulting in a net decline in total population. It is suspected that within this region two helminth parasites, an eyeworm (Oxyspirura petrowi) and a cecal worm (Aulonocephalus pennula), are contributing to this phenomenon. However, this has been difficult to study as the primary mode of investigation would be the deployment of anthelmintic treatment. Unfortunately, no registered treatments for wild bobwhite currently exist. Thus, utilizing an anthelmintictreatment for wild bobwhite would require registration of that treatment with the U.S. Food and Drug Administration (FDA). As bobwhite are game birds that are hunted, they are considered food-producing animals to the FDA, and as such require the assessment for the withdrawal of the drug residues to be assessed for human food safety. In this study, we optimized and validated a bioanalytical method for the quantification of fenbendazole sulfone in bobwhite following the U.S. FDA Center for Veterinary Medicine Guidance for Industry #208 [VICH GL 49 (R)] for assessment of fenbendazole sulfone drug residue in Northern bobwhite liver. The official method for quantifying fenbendazole sulfone in domestic chicken (Gallus gallus) was adapted for use in bobwhite. The validated method quantitation range is 2.5-30 ng/mL for fenbendazole with an average recovery of 89.9% in bobwhite liver.


Subject(s)
Bird Diseases , Colinus , Drug Residues , Thelazioidea , Animals , Humans , Colinus/parasitology , Fenbendazole , Chromatography, Liquid , Bird Diseases/epidemiology , Bird Diseases/parasitology , Tandem Mass Spectrometry , Chickens , Liver , Sulfones
12.
Parasitol Res ; 123(1): 70, 2023 Dec 23.
Article in English | MEDLINE | ID: mdl-38135838

ABSTRACT

Fasciolosis is an important zoonotic disease caused by the trematode Fasciola hepatica, and it causes great losses in bovine production. The anthelmintic resistance is a major problem in the control of fasciolosis. In this study, the F. hepatica egg development and hatching test (EDHT) was used for the evaluation of the ovicidal activity of commercial drugs, commonly used for treating infected cattle, which reflects F. hepatica anthelminthic resistance in infected bovines, according to recent literature. Bile samples from F. hepatica naturally parasitized cattle were obtained from slaughterhouses in the cities of Lages and Otacílio Costa, Santa Catarina State, Brazil. The bile was washed, the eggs were recovered, quantified, and distributed in universal collectors, with a minimum of 1,000 eggs per vial. Four commercial drugs were used in this study, containing albendazole sulfoxide (ABDZ), closantel (CSTL), nitroxynil (NTXL), and triclabendazole with fenbendazole (TBZF). The drugs were diluted according to the manufacturer instructions. All drugs, and the respective control, were tested in triplicates, with the quantity of recovered eggs determining the number of drugs to be tested. The vials were incubated for 28 days at 27 °C, and the eggs were classified according to their degree of development under a stereomicroscope. In total, 121 egg samples were analyzed. Two samples were identified as resistant to TBZF. Undetermined resistance/susceptibility has been found in two isolates treated with ABDZ, one treated with NTXL and six treated with TBZF. CSTL did not present ovicidal activity and cannot be used in EDHT. This is the first time that commercial drugs were used in F. hepatica EDHT.


Subject(s)
Anthelmintics , Cattle Diseases , Fasciola hepatica , Fascioliasis , Cattle , Animals , Drug Resistance , Anthelmintics/pharmacology , Anthelmintics/therapeutic use , Triclabendazole , Fascioliasis/drug therapy , Fascioliasis/veterinary , Nitroxinil/therapeutic use , Fenbendazole/therapeutic use , Cattle Diseases/drug therapy , Feces
13.
J Vet Pharmacol Ther ; 46(1): 34-41, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36189621

ABSTRACT

The combination of oxfendazole and oxyclozanide is used to provide activity against fluke and gastrointestinal nematodes. This study aimed to determine both the pharmacokinetics of oxfendazole (7.5 mg/kg) and oxyclozanide (15 mg/kg) tablet formulation administered orally to sheep and whether there is a pharmacokinetic interaction between these two drugs. The study was conducted in a three-period, crossover pharmacokinetic design and on six healthy Awassi sheep 1-3 years of age. The plasma concentrations of oxfendazole and its metabolites (fenbendazole and fenbendazole sulphone) and oxyclozanide were determined by high-performance liquid chromatography using an ultraviolet detector. Compounds recovered in plasma when oxfendazole was administered alone or combined with oxyclozanide were oxfendazole, fenbendazole sulphone, and fenbendazole, respectively. When oxfendazole was administered alone and co-administered with oxyclozanide, the AUCFBZ /AUCOFZ was 0.26 and 0.23, respectively, and the AUCFBZSO2 /AUCOFZ was 0.35 and 0.32, respectively. The volume of distribution (Vz/F) of oxfendazole was large in both groups. Oxyclozanide did not change the plasma disposition of oxfendazole. When the oxyclozanide tablet formulation was administered alone, the elimination half-life (21.35 h) and the Vz/F (940.17 ml/kg) were long and large, respectively. The area under the curve (AUC) and the maximum plasma concentration of oxyclozanide were significantly larger and higher, respectively, in the oxyclozanide plus oxfendazole group (1146.61 h × µg/ml and 29.80 µg/ml) compared with the oxyclozanide group (491.44 h × µg/ml and 14.24 µg/ml) while a significant decrease in apparent Vz/F (940.17 vs 379.14 ml/kg) and total clearance (30.52 vs 13.08 ml/h/kg) was detected. In conclusion, co-administration with oxfendazole causing an increase in the plasma profile of oxyclozanide may increase the antiparasitic activity of oxyclozanide.


Subject(s)
Anthelmintics , Fenbendazole , Animals , Sheep , Fenbendazole/pharmacokinetics , Oxyclozanide , Anthelmintics/pharmacokinetics , Tablets , Administration, Oral
14.
J Vet Pharmacol Ther ; 46(3): 170-176, 2023 May.
Article in English | MEDLINE | ID: mdl-36065517

ABSTRACT

The pharmacokinetics and bioavailability of fenbendazole and levamisole were determined in Caspian turtles after a single intravenous (i.v.) and subcutaneous (s.c.) administration. Thirty turtles diagnosed as naturally infected with Serpinema microcephalus and Falcaustra armenica nematodes received fenbendazole (50 mg/kg) or levamisole (10 mg/kg) by i.v. and s.c. administrations. Blood samples were collected at time 0, 0.125, 0.25, 0.5, 1, 2, 4, 8, 12, 24, and 48 h after drug administration. Plasma drug concentrations were determined by a validated high-performance liquid chromatography method. Data were analyzed by noncompartmental methods. The mean elimination half-life of levamisole was 5.16 h and 12.03 h for i.v. and s.c. routes, respectively, and for fenbendazole, the mean elimination half-life was 25.38 h (i.v.) and 29.77 h (s.c.). The total clearance and volume of distribution at steady-state for levamisole and fenbendazole following i.v. administration were 0.22, 0.44 ml/g/h, and 1.06 and 7.35 ml/g, respectively. For the s.c. route, the peak plasma concentration of levamisole and fenbendazole was 10.53 and 5.24 µg/mL, respectively. The s.c. bioavailability of levamisole and fenbendazole was complete. Considering high anthelmintic efficacy and bioavailability after s.c. administration of levamisole and fenbendazole, and the absence of adverse effects, this route of administration is an easy and efficacious way of treating nematodes in Caspian turtles.


Subject(s)
Anthelmintics , Helminths , Turtles , Animals , Fenbendazole/therapeutic use , Levamisole/therapeutic use , Anthelmintics/therapeutic use
15.
J Esthet Restor Dent ; 35(7): 1098-1102, 2023 10.
Article in English | MEDLINE | ID: mdl-37017291

ABSTRACT

OBJECTIVE: This article provides an overview of the implications of ChatGPT and other large language models (LLMs) for dental medicine. OVERVIEW: ChatGPT, a LLM trained on massive amounts of textual data, is adept at fulfilling various language-related tasks. Despite its impressive capabilities, ChatGPT has serious limitations, such as occasionally giving incorrect answers, producing nonsensical content, and presenting misinformation as fact. Dental practitioners, assistants, and hygienists are not likely to be significantly impacted by LLMs. However, LLMs could affect the work of administrative personnel and the provision of dental telemedicine. LLMs offer potential for clinical decision support, text summarization, efficient writing, and multilingual communication. As more people seek health information from LLMs, it is crucial to safeguard against inaccurate, outdated, and biased responses to health-related queries. LLMs pose challenges for patient data confidentiality and cybersecurity that must be tackled. In dental education, LLMs present fewer challenges than in other academic fields. LLMs can enhance academic writing fluency, but acceptable usage boundaries in science need to be established. CONCLUSIONS: While LLMs such as ChatGPT may have various useful applications in dental medicine, they come with risks of malicious use and serious limitations, including the potential for misinformation. CLINICAL SIGNIFICANCE: Along with the potential benefits of using LLMs as an additional tool in dental medicine, it is crucial to carefully consider the limitations and potential risks inherent in such artificial intelligence technologies.


Subject(s)
Artificial Intelligence , Dentists , Humans , Professional Role , Language , Fenbendazole
16.
Sci Eng Ethics ; 29(2): 9, 2023 03 07.
Article in English | MEDLINE | ID: mdl-36882674

ABSTRACT

Synthetic biologists design and engineer organisms for a better and more sustainable future. While the manifold prospects are encouraging, concerns about the uncertain risks of genome editing affect public opinion as well as local regulations. As a consequence, biosafety and associated concepts, such as the Safe-by-design framework and genetic safeguard technologies, have gained notoriety and occupy a central position in the conversation about genetically modified organisms. Yet, as regulatory interest and academic research in genetic safeguard technologies advance, the implementation in industrial biotechnology, a sector that is already employing engineered microorganisms, lags behind. The main goal of this work is to explore the utilization of genetic safeguard technologies for designing biosafety in industrial biotechnology. Based on our results, we posit that biosafety is a case of a changing value, by means of further specification of how to realize biosafety. Our investigation is inspired by the Value Sensitive Design framework, to investigate scientific and technological choices in their appropriate social context. Our findings discuss stakeholder norms for biosafety, reasonings about genetic safeguards, and how these impact the practice of designing for biosafety. We show that tensions between stakeholders occur at the level of norms, and that prior stakeholder alignment is crucial for value specification to happen in practice. Finally, we elaborate in different reasonings about genetic safeguards for biosafety and conclude that, in absence of a common multi-stakeholder effort, the differences in informal biosafety norms and the disparity in biosafety thinking could end up leading to design requirements for compliance instead of for safety.


Subject(s)
Biotechnology , Containment of Biohazards , Humans , Communication , Engineering , Fenbendazole
17.
Vet Radiol Ultrasound ; 64(6): E83-E87, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37798816

ABSTRACT

A 16-month-old Sarplaninac Shepherd cross dog presented for a 1-month history of a productive cough that was unresponsive to an empirical 10-day course of cephalexin. Thoracic computed tomography (CT) showed multifocal, well-defined, smoothly marginated, soft tissue attenuating, minimally contrast enhancing nodular airway mural thickenings protruding into the airway lumen in the caudal trachea and principal bronchi. These nodules were also visualized on bronchoscopy, and cytology revealed parasitic larvae consistent with Oslerus osleri. The dog was treated with oral fenbendazole for 26 days. Clinical signs resolved within 3 weeks of treatment initiation and had not relapsed at 7-month follow-up.


Subject(s)
Dog Diseases , Metastrongyloidea , Animals , Dogs , Dog Diseases/diagnostic imaging , Dog Diseases/drug therapy , Trachea , Fenbendazole/therapeutic use , Bronchi , Bronchoscopy/veterinary
18.
J Zoo Wildl Med ; 54(2): 282-291, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37428690

ABSTRACT

An outbreak of the nematode Strongyloides sp. occurred in a population of 18 male and 29 female panther chameleons (Furcifer pardalis) at the Singapore Zoo. The parasite was first detected in one individual during routine microscopic examination of feces using the direct examination and magnesium sulfate flotation methods. The parasite was later found to have a closest match (98.96%) with Strongyloides sp. Okayama by DNA sequencing. Over a period of 6 mon, 97.9% (46/47) of the panther chameleons tested positive for the parasite, and 25.5% (12/47) of the animals died due to the disease. All the animals that died were female. Of the positive tests, magnesium sulfate flotation identified the parasite 98.1% (105/107) of the time, compared to direct fecal microscopy, which identified the parasite only 43.9% (47/107) of the time. Parasite eggs were detected in 100% (105/105) of the positive magnesium sulfate flotation tests but only 66.0% (31/47) of the positive direct fecal microscopy tests. Parasite larvae were detected in 61.7% (29/47) of the positive direct fecal microscopy tests but only 9.5% (10/105) of the magnesium sulfate flotation tests. Treatments with fenbendazole and pyrantel pamoate at published doses were ineffective at eliminating the parasite. Ivermectin (0.2 mg/kg PO q2wk for two doses) was successful at treating the parasite, with all animals testing negative for the parasite at the end of the treatment course without any observed adverse reactions. However, complete eradication of the parasite could not be achieved, as Strongyloides sp. could still be detected in the population on routine coproscopy intermittently over 3 yr. There were no further mortalities due to the disease with prompt treatment with ivermectin. Strongyloidiasis may cause high morbidity in panther chameleons, but severe disease leading to mortality can be prevented with the use of ivermectin.


Subject(s)
Lizards , Strongyloidiasis , Male , Female , Animals , Ivermectin/therapeutic use , Strongyloidiasis/drug therapy , Strongyloidiasis/epidemiology , Strongyloidiasis/veterinary , Magnesium Sulfate , Pyrantel Pamoate/therapeutic use , Fenbendazole/therapeutic use , Feces/parasitology
19.
Med Lav ; 114(3): e2023024, 2023 Jun 12.
Article in English | MEDLINE | ID: mdl-37309882

ABSTRACT

BACKGROUND: The construction industry has a percentage of work-related injuries and fatalities. Workers' perception of occupational hazards exposure can be a proactive management tool in knowing the state of construction site safety performance. This study aimed to assess the hazard perception of on-site construction workers in Ghana. METHODS: Using a structured questionnaire, data was collected from 197 construction workers at live building sites in the Ho Municipality. The data were analyzed using the Relative Importance Index (RII) approach. RESULTS: The study revealed that on-site construction workers perceived ergonomic hazards as the most frequent, followed by physical, phycological, biological, and chemical hazards. The importance level of RII revealed that long working hours and bending or twisting back during task performance were perceived as the most severe hazards. Long working hours had the highest overall RII ranking, followed by bending or twisting back during task performance, manual lifting of objects or loads, scorching temperatures, and lengthy standing for prolonged periods. CONCLUSIONS: Given the adverse health effects of working for long hours, the management of Ghanaian construction industries needs to reinforce the legislation on working hours to safeguard workers' occupational health. Safety professionals can use the study's findings to improve safety performance in the Ghanaian construction industry.


Subject(s)
Construction Industry , Humans , Ghana , Ergonomics , Fenbendazole , Perception
20.
J Sports Sci Med ; 22(4): 707-725, 2023 Dec.
Article in English | MEDLINE | ID: mdl-38045740

ABSTRACT

While the tactical behavior of soccer players differs between specific phases of play (offense, defense, offensive transition, defensive transition), little is known about successful behavior of players during defensive transition (switching behavior from offense to defense). Therefore, this study aims to analyze the group tactic of rest defense (despite in ball possession, certain players safeguard quick counterattacks in case of ball loss) in defensive transition. A mixed-methods approach was used, involving both qualitative and quantitative analysis. Semi-structured expert interviews with seven professional soccer coaches were conducted to define rest defense. In the quantitative analysis, several KPIs were calculated, based on tracking and event data of 153 games of the 2020/21 German Bundesliga season, to predict the success of rest defense situations in a machine learning approach. The qualitative interviews indicated that rest defense can be defined as the positioning of the deepest defenders during ball possession to prevent an opposing counterattack after a ball loss. For instance, the rest defending players created a numerical superiority of 1.69 ± 1.00 and allowed a space control of the attacking team of 11.51 ± 9.82 [%] in the area of rest defense. The final machine learning model showed satisfactory prediction performance of the success of rest defense (Accuracy: 0.97, Precision: 0.73, f1-Score: 0.64, AUC: 0.60). Analysis of the individual KPIs revealed insights into successful behavior of players in rest defense, including controlling deep spaces and dangerous counterattackers. The study concludes regaining possession as fast as possible after a ball loss is the most important success factor in defensive transition.


Subject(s)
Athletic Performance , Soccer , Humans , Achievement , Fenbendazole , Machine Learning
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