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BMC Veterinary Research May 2024Gray horses are predisposed to equine malignant melanoma (EMM) with advancing age. Depending on the tumor's location and size, they can cause severe problems (e.g.,... (Comparative Study)
Comparative Study
Potent drug delivery enhancement of betulinic acid and NVX-207 into equine skin in vitro - a comparison between a novel oxygen flow-assisted transdermal application device and microemulsion gels.
BACKGROUND
Gray horses are predisposed to equine malignant melanoma (EMM) with advancing age. Depending on the tumor's location and size, they can cause severe problems (e.g., defaecation, urination, feeding). A feasible therapy for EMM has not yet been established and surgical excision can be difficult depending on the location of the melanoma. Thus, an effective and safe therapy is needed. Naturally occurring betulinic acid (BA), a pentacyclic triterpene and its synthetic derivate, NVX-207 (3-acetyl-betulinic acid-2-amino-3-hydroxy-2-hydroxymethyl-propanoate) are known for their cytotoxic properties against melanomas and other tumors and have already shown good safety and tolerability in vivo. In this study, BA and NVX-207 were tested for their permeation potential into equine skin in vitro in Franz-type diffusion cell (FDC) experiments after incubation of 5 min, 30 min and 24 h, aiming to use these formulations for prospective in vivo studies as a treatment for early melanoma stages. Potent permeation was defined as reaching or exceeding the half maximal inhibitory concentrations (IC) of BA or NVX-207 for equine melanoma cells in equine skin samples. The active ingredients were either dissolved in a microemulsion (ME) or in a microemulsion gel (MEG). All of the formulations were transdermally applied but the oil-in-water microemulsion was administered with a novel oxygen flow-assisted (OFA) applicator (DERMADROP TDA).
RESULTS
All tested formulations exceeded the IC values for equine melanoma cells for BA and NVX-207 in equine skin samples, independently of the incubation time NVX-207 applied with the OFA applicator showed a significant time-dependent accumulation and depot-effect in the skin after 30 min and 24 h (P < 0.05).
CONCLUSIONS
All tested substances showed promising results. Additionally, OFA administration showed a significant accumulation of NVX-207 after 30 min and 24 h of incubation. Further in vivo trials with OFA application are recommended.
Topics: Animals; Horses; Betulinic Acid; Pentacyclic Triterpenes; Triterpenes; Administration, Cutaneous; Emulsions; Skin; Drug Delivery Systems; Gels; Melanoma; Oxygen; Skin Absorption; Horse Diseases; Propanolamines
PubMed: 38755639
DOI: 10.1186/s12917-024-04064-1 -
Scientific Reports May 2024Antimicrobial resistance in fungal pathogens (both human and plant) is increasing alarmingly, leading to massive economic crises. The existing anti-fungal agents are...
Antimicrobial resistance in fungal pathogens (both human and plant) is increasing alarmingly, leading to massive economic crises. The existing anti-fungal agents are becoming ineffective, and the situation worsens on a logarithmic scale. Novel antifungals from unique natural sources are highly sought to cope sustainably with the situation. Metabolites from endophytic microbes are the best-fitted alternatives in this case. Endophytes are the untapped sources of 'plants' internal microbial population' and are promising sources of effective bio-therapeutic agents. Fungal endophytes were isolated from Tropaeolum majus and checked for antifungal activity against selected plant and human pathogens. Bioactive metabolites were identified through chromatographic techniques. The mode of action of those metabolites was evaluated through various spectroscopic techniques. The production of antifungal metabolite was optimized also. In particular VOCs (volatile organic compounds) of TML9 were tested in vitro for their anti-phytopathogenic activity. Ethyl acetate (EA) extract of cell-free culture components of Colletotrichum aenigma TML3 exhibited broad-spectrum antifungal activity against four species of Candida and the major constituents reported were 6-pentyl-2H-pyran-2-one, 2-Nonanone, 1 propanol 2-amino. The volatile metabolites, trans-ocimene, geraniol, and 4-terpinyl acetate, produced from Curvularia lunata TML9, inhibited the growth of some selected phyto pathogens. EA extract hampered the biofilm formation, minimised the haemolytic effect, and blocked the transformation of Candida albicans (MTCC 4748) from yeast to hyphal form with a Minimum Fungicidal Concentration (MFC) of 200-600 µg mL. Central carbohydrate metabolism, ergosterol synthesis, and membrane permeability were adversely affected and caused the lethal leakage of necessary macromolecules of C. albicans. Volatile metabolites inhibited the growth of phytopathogens i.e., Rhizoctonia solani, Alternaria alternata, Botrytis cinerea, Cercospora beticola, Penicillium digitatum, Aspergillus fumigatus, Ceratocystis ulmi, Pythium ultimum up to 89% with an IC value of 21.3-69.6 µL 50 mL and caused leakage of soluble proteins and other intracellular molecules. Citrusy sweet odor volatiles of TML9 cultured in wheat-husk minimised the infections of Penicillium digitatum (green mold), in VOC-exposed sweet oranges (Citrus sinensis). Volatile and non-volatile antifungal metabolites of these two T. majus endophytes hold agricultural and pharmaceutical interests. Metabolites of TML3 have strong anti-Candida activity and require further assessment for therapeutic applications. Also, volatile metabolites of TML9 can be further studied as a source of antifungals. The present investigational outcomes bio-prospects the efficacy of fungal endophytes of Garden Nasturtium.
Topics: Volatile Organic Compounds; Antifungal Agents; Endophytes; Microbial Sensitivity Tests; Colletotrichum; Fungi; Alternaria; Rhizoctonia; Humans; Candida
PubMed: 38755187
DOI: 10.1038/s41598-024-60948-0 -
Environmental Science and Pollution... May 2024Developing the Co-based catalysts with high reactivity for the sulfate radical (SO·)-based advanced oxidation processes (SR-AOPs) has been attracting numerous...
Developing the Co-based catalysts with high reactivity for the sulfate radical (SO·)-based advanced oxidation processes (SR-AOPs) has been attracting numerous attentions. To improve the peroxymonosulfate (PMS) activation process, a novel Co-based catalyst simultaneously modified by bamboo carbon (BC) and vanadium (V@CoO-BC) was fabricated through a simple solvothermal method. The atenolol (ATL) degradation experiments in V@CoO-BC/PMS system showed that the obtained V@CoO-BC exhibited much higher performance on PMS activation than pure CoO, and the V@CoO-BC/PMS system could fully degrade ATL within 5 min via the destruction of both radicals (SO· and O·) and non-radicals (O). The quenching experiments and electrochemical tests revealed that the enhancing mechanism of bamboo carbon and V modification involved four aspects: (i) promoting the PMS and Co ion adsorption on the surface of V@CoO-BC; (ii) enhancing the electron transfer efficiency between V@CoO-BC and PMS; (iii) activating PMS with V species; (iv) accelerating the circulation of Co and Co, leading to the enhanced yield of reactive oxygen species (ROS). Furthermore, the V@CoO-BC/PMS system also exhibited satisfactory stability under broad pH (3-9) and good efficiency in the presence of co-existing components (HCO, NO, Cl, and HA) in water. This study provides new insights to designing high-performance, environment-friendly bimetal catalysts and some basis for the remediation of antibiotic contaminants with SR-AOPs.
Topics: Atenolol; Catalysis; Carbon; Peroxides; Vanadium; Oxidation-Reduction; Water Pollutants, Chemical
PubMed: 38753235
DOI: 10.1007/s11356-024-33657-4 -
The Journal of Physical Chemistry. B May 2024Surfactant-free microemulsion (SFME) represents a class of fluid mixtures that can form microheterogeneous structures without detergents, offering an environmentally...
Kirkwood-Buff Analysis of Binary and Ternary Systems Consisting of Alcohols (Methanol, Ethanol, 1-Propanol, and 2-Propanol), Water, and -Hexane to Understand the Formation of Surfactant-Free Microemulsions.
Surfactant-free microemulsion (SFME) represents a class of fluid mixtures that can form microheterogeneous structures without detergents, offering an environmentally benign alternative to traditional microemulsions. However, the formation mechanism is still elusive. This work applies the Kirkwood-Buff theory to mixtures of alcohols, water, and -hexane to elucidate the SFME formation mechanism. To ensure robust calculation of the Kirkwood-Buff integrals (KBIs), we construct a data set of densities and excess free energies of binary and ternary systems. Multiple excess Gibbs free energy models are assessed against this data set to select the most suitable model reproducing the experimental results. In addition, we introduce statistical methods to determine the optimal polynomial order of the Redlich-Kister correlation for the excess volume data. We first validate our methodology in binary systems. Then, we extend the calculation method to ternary mixtures. The KBI calculation results reveal that the alcohol-hexane and water-hexane interactions do not significantly affect SFME formation. In contrast, the interplay among water-water, water-alcohol, and alcohol-alcohol interactions critically influences the ability of a liquid mixture to form SFME structures. SFME systems exhibit the facile formation of water aggregates enveloped by alcohols, whereas non-SFME systems demonstrate homogeneous alcohol/water droplets dispersed in an oil continuous medium.
PubMed: 38743587
DOI: 10.1021/acs.jpcb.4c01563 -
Vestnik Oftalmologii 2024The management protocol for patients with neovascular age-related macular degeneration (nAMD) involves multiple intravitreal injections (IVI) of anti-VEGF drugs. The...
UNLABELLED
The management protocol for patients with neovascular age-related macular degeneration (nAMD) involves multiple intravitreal injections (IVI) of anti-VEGF drugs. The ability to reduce the peak intraocular pressure (IOP) rise is greatly important in clinical practice.
PURPOSE
This study evaluates the effect of topical hypotensive drugs on the short-term IOP rise after IVI of anti-VEGF drugs in patients with nAMD.
MATERIAL AND METHODS
The prospective study included 80 patients with newly diagnosed nAMD. Before the start of treatment, the patients were divided into 4 groups of 20 people each: 1st - controls, who received no prophylactic drugs, in the 2nd, 3rd and 4th groups local instillations of one drop of hypotensive drugs brinzolamide 1%, brinzolamide-timolol, brimonidine-timolol were performed in the conjunctival sac twice: 1 day before the injection (at 20:00) and on the day of the injection 2 hours before the manipulation (at 08:00), respectively. IOP was measured in each patient using ICare Pro non-contact tonometer before injection, as well as 1 min, 30 and 60 min after injection.
RESULTS
Prophylactic use of hypotensive drugs was associated with a significant decrease in IOP immediately after IVI compared to the same parameter in the 1st group (<0.001), the maximum decrease in IOP values was observed when using a fixed combination of brimonidine-timolol by 12.1 mm Hg compared to the controls (<0.001), the combination of brinzolamide-timolol reduced IOP by 8.5 mm Hg (<0.001), brinzolamide 1% led to the smallest decrease in IOP - by 5.1 mm Hg (<0.001).
CONCLUSION
Study patients that received instillations of brimonidine-timolol combination of one drop into the conjunctival sac 1 day before the injection and on the day of the injection showed the maximum decrease in IOP compared to patients of the other groups.
Topics: Humans; Male; Intravitreal Injections; Female; Aged; Intraocular Pressure; Ocular Hypertension; Angiogenesis Inhibitors; Prospective Studies; Sulfonamides; Treatment Outcome; Antihypertensive Agents; Vascular Endothelial Growth Factor A; Tonometry, Ocular; Middle Aged; Timolol; Brimonidine Tartrate; Ophthalmic Solutions; Thiazines; Macular Degeneration
PubMed: 38739134
DOI: 10.17116/oftalma202414002273 -
Chemistry (Weinheim An Der Bergstrasse,... May 2024Crystallophores are lanthanide complexes that have demonstrated outstanding induction of crystallization for various proteins. This article explores the effect of...
Crystallophores are lanthanide complexes that have demonstrated outstanding induction of crystallization for various proteins. This article explores the effect of tailored modifications of the crystallophore first generation and their impact on the nucleating properties and protein crystal structures. Through high-throughput crystallization experiments and dataset analysis, we evaluated the effectiveness of these variants, in comparison to the first crystallophore generation G. In particular, the V variant, featuring a propanol pendant arm, demonstrated the ability to produce new crystallization conditions for the proteins tested (hen-egg white lysozyme, proteinase K and thaumatin). Structural analysis performed in the case of hen egg-white lysozyme along with Molecular Dynamics simulations, highlights V's unique behavior, taking advantage of the flexibility of its propanol arm to explore different protein surfaces and form versatile supramolecular interactions.
PubMed: 38738452
DOI: 10.1002/chem.202400900 -
Se Pu = Chinese Journal of... Apr 2024The applications of organic-amine desulfurization have steadily increased owing to its high efficiency, low cost, and low energy consumption. Different proportions of...
The applications of organic-amine desulfurization have steadily increased owing to its high efficiency, low cost, and low energy consumption. Different proportions of organic amines exert different effects on sulfur dioxide removal. Therefore, the accurate determination of different organic amines in the desulfurization solution is of great importance. The ion-chromatographic method for the detection of organic amines does not require a derivatization step, has simple pretreatment procedures, and allows for the simultaneous determination of many types of organic amines. In this study, a method based on ion chromatography was developed for the simultaneous determination of ethanolamine (MEA), diethylethanolamine (DEEA), -methyldiethanolamine (MDEA), 2-amino-2-methyl-1-propanol (AMP), hydroxyethylethylenediamine (AEEA), piperazine (PZ), -hydroxyethylpiperazine (HEPZ), and diethylenetriamine (DETA). The separation efficiency of the eight organic amines in different types of columns, leaching solutions, and column temperatures were compared. The determination was performed using an IonPac CS17 column with column temperature of 35 ℃ and gradient leaching with methyl sulfonic acid (MSA) solution via the inhibition conductance method. Samples of the desulfurization solution were analyzed using ultrapure water filtered through a 0.22 μm nylon microporous filter membrane and an OnGuard Ⅱ RP column; thus, the pretreatment steps are simple. The eight organic amines showed a good linear relationship within a certain concentration range, and the coefficient of determinations () were greater than 0.998. The limits of detection (LODs) and quantification (LOQs) were determined from the mass concentrations of the organic amines corresponding to signal-to-noise ratios () of 3 and 10, respectively. LODs of 0.02-0.08 mg/L and LOQs of 0.07-0.27 mg/L were determined from a 1.0 μL sample injection. The actual recoveries ranged from 93.0% to 111%, and the relative standard deviations (RSDs, =5) ranged from 0.31% to 1.2%. The results indicated that the proposed method has good accuracy and precision; thus, it is suitable for the determination of various organic amines in desulfurization solution.
PubMed: 38736388
DOI: 10.3724/SP.J.1123.2023.09024 -
The Journal of the Association of... Dec 2023In India, heart failure (HF) is an important health concern affecting younger age groups than the western population. A limited number of Indian patients receive...
In India, heart failure (HF) is an important health concern affecting younger age groups than the western population. A limited number of Indian patients receive guideline-directed medical therapy (GDMT). Selective β-1 blockers (BB) are one of the GDMTs in HF and play an important role by decreasing the sympathetic overdrive. The BB reduces heart rate (HR) reverse the adverse cardiac (both ventricular and atrial), vascular, and renovascular remodeling seen in HF. Bisoprolol, a β-1 blocker, has several advantages and can be used across a wide spectrum of HF presentations and in patients with HF and comorbid conditions such as coronary artery disease (CAD), atrial fibrillation (AF), post-myocardial infarction (MI), uncontrolled diabetes, uncontrolled hypertension, and renal impairment. Despite its advantages, bisoprolol is not optimally utilized for managing HF in India. This consensus builds on updated evidence on the efficacy and safety of bisoprolol in HF and recommends its place in therapy with a focus on Indian patients with HF.
Topics: Humans; Bisoprolol; Heart Failure; India; Adrenergic beta-1 Receptor Antagonists; Consensus
PubMed: 38736057
DOI: 10.59556/japi.71.0426 -
Journal of Veterinary Cardiology : the... Jun 2024A nine-year-old spayed female domestic shorthair cat with a previous diagnosis of hypertrophic cardiomyopathy and treated for one month with atenolol (6.25 mg q 12 h)...
A nine-year-old spayed female domestic shorthair cat with a previous diagnosis of hypertrophic cardiomyopathy and treated for one month with atenolol (6.25 mg q 12 h) was referred for respiratory distress and anorexia. The cat was diagnosed with pulmonary oedema secondary to obstructive hypertrophic cardiomyopathy. After stabilisation, she was discharged with furosemide (1 mg/kg q 12 h), clopidogrel (18.75 mg q 24 h), atenolol (6.25 mg q 12 h), and mirtazapine (2 mg/cat q 24 h) to increase appetite. At recheck, the cat was lethargic and presented with severe bradycardia with a junctional escape rhythm and ventriculoatrial conduction. The mirtazapine was discontinued due to its possible side-effects on cardiac rhythm. After three days, the atenolol was halved because the bradyarrhythmia was still present. After 10 days, the rhythm returned to sinus; atenolol was reintroduced twice daily with no further side-effects. The absence of a sinus rhythm with a junctional escape rhythm and P' retroconduction is compatible with a third-degree sinus block or a sinus standstill; the differentiation of these rhythm disturbances is impossible, based on the surface electrocardiogram (ECG). The sinus rhythm was restored after mirtazapine was withdrawn. However, it is not possible to rule out the role of the atenolol or the combined effect of the two drugs. The cat was affected by hypertrophic cardiomyopathy, and the role of myocardial remodelling cannot be excluded. This is the first time that a bradyarrhythmia consequent to the treatment with atenolol and mirtazapine was described in a cat.
Topics: Female; Mirtazapine; Animals; Atenolol; Cats; Cat Diseases; Cardiomyopathy, Hypertrophic; Bradycardia; Mianserin; Adrenergic beta-1 Receptor Antagonists
PubMed: 38735230
DOI: 10.1016/j.jvc.2024.03.003 -
Thrombosis Research Jun 2024Nonselective β blockers (NSBBs) facilitate the development of portal vein thrombosis (PVT) in liver cirrhosis. Considering the potential effect of NSBBs on neutrophils...
BACKGROUND & AIMS
Nonselective β blockers (NSBBs) facilitate the development of portal vein thrombosis (PVT) in liver cirrhosis. Considering the potential effect of NSBBs on neutrophils and neutrophil extracellular traps (NETs), we speculated that NSBBs might promote the development of PVT by stimulating neutrophils to release NETs.
MATERIALS AND METHODS
Serum NETs biomarkers were measured, use of NSBBs was recorded, and PVT was evaluated in cirrhotic patients. Carbon tetrachloride and ferric chloride (FeCl) were used to induce liver fibrosis and PVT in mice, respectively. After treatment with propranolol and DNase I, neutrophils in peripheral blood, colocalization and expression of NETs in PVT specimens, and NETs biomarkers in serum were measured. Ex vivo clots lysis analysis was performed and portal vein velocity and coagulation parameters were tested.
RESULTS
Serum MPO-DNA level was significantly higher in cirrhotic patients treated with NSBBs, and serum H3Cit and MPO-DNA levels were significantly higher in those with PVT. In fibrotic mice, following treatment with propranolol, DNase I significantly shortened the time of FeCl-induced PVT formation, lowered the peripheral blood neutrophils labelled by CD11b/Ly6G, inhibited the positive staining of H3Cit and the expression of H3Cit and MPO proteins in PVT tissues, and reduced serum nucleosome level. Furthermore, the addition of DNase I to tissue plasminogen activator (tPA) significantly accelerated clots lysis as compared with tPA alone. Propranolol reduced portal vein velocity in fibrotic mice, but did not influence coagulation parameters.
CONCLUSION
Our study provides a clue to the potential impact of NETs formation on the association of NSBBs with the development of PVT.
Topics: Extracellular Traps; Propranolol; Humans; Animals; Portal Vein; Venous Thrombosis; Male; Mice; Female; Middle Aged; Neutrophils; Liver Cirrhosis; Mice, Inbred C57BL; Adult; Aged
PubMed: 38733693
DOI: 10.1016/j.thromres.2024.04.030