-
Prevalence and drug susceptibility of clinical species in nasopharyngeal cancer patients in Vietnam.One Health (Amsterdam, Netherlands) Jun 2024In the nature, species are normal inhabitants and can be observed in a wide variety of vertebrates. In humans, especially for cancer patients who fall prey to...
In the nature, species are normal inhabitants and can be observed in a wide variety of vertebrates. In humans, especially for cancer patients who fall prey to opportunistic pathogens, this group of susceptible multi-drug resistant and biofilm-forming yeasts, are among the commonest ones. In this study, species in 76 oral lesion samples from Vietnamese nasopharyngeal-cancer patients were isolated, morphologically identified using CHROMagar™, germ tube formation, and chlamydospore formation tests, and molecularly confirmed by PCR-RFLP. The drug susceptibility of these isolates was then tested, and the gene was DNA sequenced to investigate the mechanism of resistance. The results showed that remained the most prevalent species (63.16% of the cases), followed by , , and . The rates of resistance of for tested drugs were 85.71%, 53.57%, and 57.14% to fluconazole, clotrimazole, and miconazole, respectively. Although the drug-resistance rate of was lower than that of , it was higher than expected, suggesting an emerging drug-resistance phenomenon. Furthermore, DNA sequencing revealed different mutations (especially K128T), implying the presence of multiple resistance mechanisms. Altogether, the results indicate an alarming drug-resistance situation in species in Vietnamese cancer patients and emphasize the importance of species identification and their drug susceptibility prior to treatment.
PubMed: 38179314
DOI: 10.1016/j.onehlt.2023.100659 -
ACS Medicinal Chemistry Letters Dec 2023Serotogenic toxicity is a major hurdle associated with Linezolid in the treatment of drug-resistant tuberculosis (TB) due to the inhibition of monoamine oxidase (MAO)...
Serotogenic toxicity is a major hurdle associated with Linezolid in the treatment of drug-resistant tuberculosis (TB) due to the inhibition of monoamine oxidase (MAO) enzymes. Azole compounds demonstrate structural similarities to the recognized anti-TB drug Linezolid, making them intriguing candidates for repurposing. Therefore, we have repurposed azoles (Posaconazole, Itraconazole, Miconazole, and Clotrimazole) for the treatment of drug-resistant TB with the anticipation of their selectivity in sparing the MAO enzyme. The results of repurposing revealed that Clotrimazole showed equipotent activity against the () HRv strain compared to Linezolid, with a minimal inhibitory concentration (MIC) of 2.26 μM. Additionally, Clotrimazole exhibited reasonable MIC values of 0.17 μM, 1.72 μM, 1.53 μM, and 5.07 μM against the promoter+, , , and MDR clinical isolates, respectively, compared to Linezolid. Clotrimazole also exhibited 3.90-fold less inhibition of MAO-A and 50.35-fold less inhibition of MAO-B compared to Linezolid, suggesting a reduced serotonergic toxicity burden.
PubMed: 38116435
DOI: 10.1021/acsmedchemlett.3c00406 -
Journal of Advanced Pharmaceutical... 2023The reason for conducting this study is to prolong release of miconazole in the ocular site of action by ocular-based gels (OBGs) formulations. The formulation factors...
The reason for conducting this study is to prolong release of miconazole in the ocular site of action by ocular-based gels (OBGs) formulations. The formulation factors affecting on the release from OBG should be studied using various gelling agents in various concentrations to achieve the improvement in retention and residence time in response to prolonged release. In this study, the formulations were prepared using carbopol 940, pectin, sodium alginate, poloxamer 407, and poly(methacrylic acid) at 0.5%, 1%, and 1.5% w/v, respectively. Hydroxypropyl methylcellulose E5 (HPMC E5) 1% was added as thickening agent/viscosity builder. The formulation containing carbopol 940, pectin and sodium alginate at 1.5% w/v, displayed a noticable improvement in viscosity, gelling capacity, and extended release for 7 h in comparison with the reference drug. Overall, the release showed that the sodium alginate with HPMC E5 form gel which had longer time of release reach to 12 h compared with other polymers. the release of miconazole from the OBGs affected significantly by two factors includes gelling capacity and viscosity builder. The novelty of this study is supporting the delivery of ocular drugs through a cornea as an important key of the eye instead of dependence on an internal blood supply using an oral or a parental administration.
PubMed: 38107457
DOI: 10.4103/japtr.japtr_91_23 -
Molecular Informatics Feb 2024Fungal infections caused by Candida are still a public health concern. Particularly, the resistance to traditional chemotherapeutic agents is a major issue that requires...
Fungal infections caused by Candida are still a public health concern. Particularly, the resistance to traditional chemotherapeutic agents is a major issue that requires efforts to develop new therapies. One of the most interesting approaches to finding new active compounds is drug repurposing aided by computational methods. In this work, two databases containing anticandidal agents and drugs were studied employing cheminformatics and compared by similarity methods. The results showed 36 drugs with high similarities to some candicidals. From these drugs, trimetozin, osalmid and metochalcone were evaluated against C. albicans (18804), C. glabrata (90030), and miconazole-resistant strain C. glabrata (32554). Osalmid and metochalcone were the best, with activity in the micromolar range. These findings represent an opportunity to continue with the research on the potential antifungal application of osalmid and metochalcone as well as the design of structurally related derivatives.
Topics: Drug Repositioning; Antifungal Agents; Candida; Chalcones; Candida albicans
PubMed: 38095132
DOI: 10.1002/minf.202300206 -
Veterinary Dermatology Apr 2024Erythemato-ceruminous otitis externa (ECOE) is frequently seen in dogs affected with an allergic skin disease, with recurrent secondary bacteria and yeast overgrowths...
Efficacy and safety of a hydrocortisone aceponate-containing ear spray solution in dogs with erythemato-ceruminous otitis externa: A randomised, multicentric, single-blinded, controlled trial.
BACKGROUND
Erythemato-ceruminous otitis externa (ECOE) is frequently seen in dogs affected with an allergic skin disease, with recurrent secondary bacteria and yeast overgrowths (detected on cytological examination).
OBJECTIVES
The objective of the study was to compare the efficacy and safety of an ear spray containing only hydrocortisone aceponate glucocorticoid diester (HCA) to a control product (CTRL), an approved otic formulation containing prednisolone-miconazole-polymyxin combination, in dogs with ECOE.
ANIMALS
In total, 97 and 104 dogs with ECOE were respectively randomly assigned to the tested ear treatment product group (HCA) or the commercially available ear treatment control product group (CTRL).
MATERIALS AND METHODS
Dogs were treated for 7-14 days, as needed. At Day (D)0, D7, D14, D28 and D42, Otitis Index Score-3, hearing test, pruritus and pain visual analogue scales, and cytological scores were graded. The overall response to treatment also was assessed.
RESULTS
All clinical parameters decreased rapidly and in a similar way without any significant difference at any time between treatment groups. A good-to-excellent response to treatment was seen in >90% of dogs of both groups as early as D14. The treatment was considered safe in all dogs.
CONCLUSIONS AND CLINICAL RELEVANCE
A 7- to 14-day ear topical application of HCA alone to dogs with ECOE accompanied with bacterial and/or fungal (yeast) overgrowth was safe and led to no statistical difference in improvement of clinical scores relative to the CTRL combination. Based on these results, it may be necessary to reconsider the routine use of antimicrobial drugs such as antibiotics and antifungals as a first-line treatment for ECOE that is likely to have been caused by an allergic reaction.
Topics: Animals; Dogs; Dog Diseases; Hydrocortisone; Otitis Externa; Saccharomyces cerevisiae
PubMed: 38093088
DOI: 10.1111/vde.13224 -
Journal of Medicinal Chemistry Dec 2023Developing drugs for brain infection by is an unmet medical need. We used a combination of cheminformatics, target-, and phenotypic-based drug discovery methods to...
Developing drugs for brain infection by is an unmet medical need. We used a combination of cheminformatics, target-, and phenotypic-based drug discovery methods to identify inhibitors that target an essential enzyme, sterol 14-demethylase (NfCYP51). A total of 124 compounds preselected were tested against . Nine primary hits with EC ≤ 10 μM were phenotypically identified. Cocrystallization with NfCYP51 focused attention on one primary hit, miconazole-like compound . The -enantiomer of produced a 1.74 Å cocrystal structure. A set of analogues was then synthesized and evaluated to confirm the superiority of the -configuration over the -configuration and the advantage of an ether linkage over an ester linkage. The two compounds, - and -, had an improved EC and compared to . Importantly, both were readily taken up into the brain. The brain-to-plasma distribution coefficient of - was 1.02 ± 0.12, suggesting further evaluation as a lead for primary amoebic meningoencephalitis.
Topics: Miconazole; 14-alpha Demethylase Inhibitors; Naegleria fowleri; Drug Discovery
PubMed: 38085955
DOI: 10.1021/acs.jmedchem.3c01898 -
Environmental Science & Technology Dec 2023The ubiquitous presence of pharmaceuticals and personal care products (PPCPs) in environments has aroused global concerns; however, minimal information is available...
The ubiquitous presence of pharmaceuticals and personal care products (PPCPs) in environments has aroused global concerns; however, minimal information is available regarding their multimedia distribution, bioaccumulation, and trophic transfer in marine environments. Herein, we analyzed 77 representative PPCPs in samples of surface and bottom seawater, surface sediments, and benthic biota from the Bohai Sea. PPCPs were pervasively detected in seawater, sediments, and benthic biota, with antioxidants being the most abundant PPCPs. PPCP concentrations positively correlated between the surface and bottom water with a decreasing trend from the coast to the central oceans. Higher PPCP concentrations in sediment were found in the Yellow River estuary, and the variations in the physicochemical properties of PPCPs and sediment produced a different distribution pattern of PPCPs in sediment from seawater. The log , but not log , showed a linear and positive relationship with bioaccumulation and trophic magnification factors and a parabolic relationship with biota-sediment accumulation factors. The trophodynamics of miconazole and acetophenone are reported for the first time. This study provides novel insights into the multimedia distribution and biomagnification potential of PPCPs and suggests that log is a better indicator of their bioaccumulation and trophic magnification.
Topics: Water Pollutants, Chemical; Environmental Monitoring; Seawater; Cosmetics; Pharmaceutical Preparations; China
PubMed: 38078887
DOI: 10.1021/acs.est.3c06522 -
American Journal of Physiology. Cell... Feb 2024Small organic molecules in the intestinal lumen, particularly short-chain fatty acids (SCFAs) and glucose, have long been postulated to enhance calcium absorption. Here,...
Small organic molecules in the intestinal lumen, particularly short-chain fatty acids (SCFAs) and glucose, have long been postulated to enhance calcium absorption. Here, we used Ca radioactive tracer to determine calcium fluxes across the rat intestine after exposure to glucose and SCFAs. Confirming previous reports, glucose was found to increase the apical-to-basolateral calcium flux in the cecum. Under apical glucose-free conditions, SCFAs (e.g., butyrate) stimulated the cecal calcium fluxes by approximately twofold, while having no effect on proximal colon. Since SCFAs could be absorbed into the circulation, we further determined whether basolateral SCFA exposure rendered some positive actions. It was found that exposure of duodenum and cecum on the basolateral side to acetate or butyrate increased calcium fluxes. Under butyrate-rich conditions, cecal calcium transport was partially diminished by Na/H exchanger 3 (NHE3) inhibitor (tenapanor) and nonselective transient receptor potential vanilloid subfamily 6 (TRPV6) inhibitor (miconazole). To confirm the contribution of TRPV6 to SCFA-stimulated calcium transport, we synthesized another TRPV6 inhibitor that was demonstrated by in silico molecular docking and molecular dynamics to occlude TRPV6 pore and diminish the glucose- and butyrate-induced calcium fluxes. Therefore, besides corroborating the importance of luminal molecules in calcium absorption, our findings provided foundation for development of more effective calcium-rich nutraceuticals in combination with various absorptive enhancers, e.g., glucose and SCFAs. Organic molecules in the intestinal lumen, e.g., glucose and short-chain fatty acids (SCFAs), the latter of which are normally produced by microfloral fermentation, can stimulate calcium absorption dependent on transient receptor potential vanilloid subfamily 6 (TRPV6) and Na/H exchanger 3 (NHE3). A selective TRPV6 inhibitor synthesized and demonstrated by in silico docking and molecular dynamics to specifically bind to the pore domain of TRPV6 was used to confirm a significant contribution of this channel. Our findings corroborate physiological significance of nutrients and SCFAs in enhancing calcium absorption.
Topics: Rats; Animals; Sodium-Hydrogen Exchanger 3; Calcium; Molecular Docking Simulation; Fatty Acids, Volatile; Butyrates; Carrier Proteins; Duodenum; Glucose; Intestinal Absorption
PubMed: 38073487
DOI: 10.1152/ajpcell.00330.2023 -
Journal of the American Veterinary... Mar 2024Albumins are protein molecules that account for 50% of total plasma protein. They are imperative in maintaining intravascular colloidal oncotic pressure, act as key...
OBJECTIVE
Albumins are protein molecules that account for 50% of total plasma protein. They are imperative in maintaining intravascular colloidal oncotic pressure, act as key scavenger molecules for oxygen free radicals, and perform a major role in transporting numerous substances and in wound healing. Hypoalbuminemia has been reported as the consequence of decreased intake, increased loss, decreased production, and redistribution. While anecdotal evidence of tyrosine kinase inhibitors causing hypoalbuminemia in canine patients exists, to the author's knowledge there is no formal report to this effect to date. This case report aims to bridge the gap between anecdotal evidence and literature.
ANIMAL
3-year-old neutered male hound-mix canine.
CLINICAL PRESENTATION, PROGRESSION, AND PROCEDURES
The patient was presented for recurrent otitis externa refractory to treatments with orbifloxacin/mometasone/posaconazole otic suspension, miconazole/polymyxin B/prednisolone otic suspension, ketoconazole/TrizEDTA, and gentamicin/mometasone/clotrimazole, which prompted consideration of oral antifungals. Baseline blood work prior to initiation of fluconazole showed elevated alkaline phosphatase. Treatment was initiated with fluconazole, and blood work was rechecked and revealed hypoalbuminemia. Multiple diagnostic tests failed to reveal a cause of hypoalbuminemia.
TREATMENT AND OUTCOME
Discontinuation of oclacitinib that the patient was being administered resulted in normalization of serum albumin.
CLINICAL RELEVANCE
It is unclear whether hypoalbuminemia associated with oclacitinib administration is associated with worse outcomes for pathologies in canine patients; however, this seems to be the case in humans according to some reports. This report aims to take a step in the direction of this knowledge.
Topics: Humans; Male; Dogs; Animals; Hypoalbuminemia; Fluconazole; Pyrimidines; Mometasone Furoate; Dog Diseases; Sulfonamides
PubMed: 38064895
DOI: 10.2460/javma.23.10.0600 -
Mikrochimica Acta Dec 2023With a view to improving applicability as a sorbent while overcoming the challenges associated with its powdery nature, cobalt-doped zeolitic imidazolate framework (ZIF...
ZIF67-derived porous carbon-reinforced electrospun nanofiber as an extractive phase for on-chip micro-solid-phase extraction of antifungals from biological fluids prior to liquid chromatography tandem mass spectrometry.
With a view to improving applicability as a sorbent while overcoming the challenges associated with its powdery nature, cobalt-doped zeolitic imidazolate framework (ZIF 67)-derived nanoporous carbon (Co-NPC) was employed as an additive in nanofiber through the process of electrospinning. X-ray diffraction (XRD), Fourier transform infrared (FT-IR) spectroscopy, scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), and Brunauer-Emmett-Teller (BET) surface area analysis were used to characterize the resulting nanocomposite. A microfluidic chip device with four layers, including two layers entailing spiral channels, was designed and employed to assess the analytical performance of the fabricated Co-NPC-reinforced electrospun composite. To do so, a folded piece of electrospun composite was sandwiched between two layers with spiral channels. Therefore, both sides of the folded composite acted as a sorptive phase to extract antifungal drugs as target analytes. The significant factors affecting the efficiency of the extraction process were investigated and optimized. Subsequently, the technique was verified through the utilization of liquid chromatography-tandem mass spectrometry (LC-MS/MS) by employing optimal parameters. The optimal conditions were applied to evaluate the figures of merit. A linear range was obtained for antifungal drugs within the range 0.25-200.0 ng ml with an R value of ≥ 0.9914. The method demonstrated detection limits ranging between 0.08 and 0.40 ng ml. The intra-day and inter-day precisions were less than 6.9%. Relative recoveries exhibited variations between 91.4-106.8%, 95.9-103.6%, and 96.4-109.3% for ketoconazole, clotrimazole, and miconazole, respectively. The proposed approach yielded satisfactory results, demonstrating its efficiency.
Topics: Carbon; Chromatography, Liquid; Antifungal Agents; Nanofibers; Porosity; Spectroscopy, Fourier Transform Infrared; Tandem Mass Spectrometry; Solid Phase Extraction
PubMed: 38052979
DOI: 10.1007/s00604-023-06103-4