Potential of Chemical and Physical Enhancers for Transungual Delivery of Amorolfine Hydrochloride

Topical monotherapy of nail infection is limited by poor drug permeability into the human nail plate. Numerous substances and methods are applied to improve the antifungal agent delivery across the nail plate. This work aimed to evaluate the effect of chemical and physical enhancers on the accumulation and permeation of amorolfine hydrochloride through human nail clippings. Polymeric nail lacquers with Eudragit E100 were developed as a potentially suitable delivery system for amorolfine hydrochloride. Incorporating thioglycolic acid and urea into formulations provided increased accumulation of antifungal agent in nail layers of up to 100% and 57%, respectively. Structural changes of nail barrier, induced by fractional CO2 laser, were visualized by microscopy. The permeation of amorolfine hydrochloride through the nail increased twofold when thioglycolic acid-containing formulation was applied and the nail was pretreated with a fractional CO2 laser. The results suggest that this novel combination of enhancers has the potential to be an effective option for topical drug delivery through the nail, and increased the efficacy of treatment

River-sourced Cladophora glomerata macroalgal biomass as a more sustainable and functional feed raw material for growing rabbits

Animal scientists actively seek strategies for ensuring the sustainable viability of animal ecosystems, with a focus on exploring alternative feed raw materials to reduce reliance on traditional ones. So, this study aims to analyse the impact of river-sourced Cladophora glomerata macroalgal biomass on the growth, slaughter performance, and physiological development of rabbits. Thirty weaned (52 days of age) Californian rabbits were assigned to three dietary treatments: standard compound diet (SCD), SCD enriched with 4% C. glomerata (CG4), and SCD enriched with 8% C. glomerata (CG8). Growth performance was recorded throughout the feeding trial, and at its conclusion (122 days of age), rabbits were euthanized, slaughtered, and subjected to intestinal analysis. Incorporation of CG diets showed no significant impact on body weight or average daily gain (p > 0.05); however, CG8 significantly lowered daily feed intake and feed conversion ratio (p < 0.05). The SCD resulted in a significantly higher lung percentage (p < 0.05), while CG diets had minimal effects on remaining slaughter performance traits. In duodenal content, CG-enriched diets increased acetic and propionic acid levels but reduced lactic (p < 0.05). Duodenal villus height remained stable, while in the ileum, CG4 inclusion resulted in a significantly higher villus (p < 0.05). Duodenal crypt depth increased with biomass supplementation; conversely, in the ileum, increased biomass led to decreased crypt depth (p < 0.05). In general, recent research suggests that adding C. glomerata to rabbit diets can be an effective alternative without adverse effects on growth, slaughter performance, or physiologial development

CAN FRESHWATER CLADOPHORA GLOMERATA MACROALGAL BIOMASS BE COMBINED IN RABBIT DIETS TO ENHANCE NOT ONLY RABBIT MEAT QUALITY BUT ALSO RABBIT HEALTH?

Despite numerous challenges and rising consumer demands, strategies for growing healthy animals and improving sustainability are being pursued, such as using natural, renewable sources to replace traditional feed materials. Thus, the aim of this study was to analyse the impact of macroalgal C. glomerata biomass on rabbit physiological features. The feeding trial (52-122 days) was carried out with twenty male Californian rabbits assigned to two dietary treatments (n=10 rabbits/treatment) and fed standard compound diet (SCD) and SCD + 4% C. glomerata (CG4). Macroalgal biomass was collected from the Lithuanian River Šventoji. At the end of the feeding trial, twelve rabbits (n=6 rabbits/treatment) were randomly selected and euthanized; samples were collected post-portem. A comprehensive analysis of rabbit organ development, histomorphometry, short-chain fatty acids (SCFA), and ammoniacal nitrogen (NH3-N) accumulation in intestinal contents was performed. The CG4 treatment had no impact on organ or intestinal development or the concentration of NH3-N in the duodenum (P>0.05). However, the crypt depth was significantly lower in the duodenum of CG4 compared to SCD, but 14.40 μm deeper in the ileum (P<0.05). Although CG4 had no impact on villus height, it had an impact on the villus/crypt ratio (V/C), which was higher in the duodenum in CG4 but lower in the ileum in SCD (P<0.05). After examining the gut contents from the duodenum, CG4 significantly reduced the lactic acid concentration, which was almost four times lower compared to SCD (P<0.05). Overall, C. glomerata in rabbit diets can improve the crypt depth in the ileum and therefore the absorption of nutrients that remain digested; nevertheless, it can reduce the crypt depth in the duodenum and thus the digestive area required to carry out the primary nutrient absorption. Moreover, such inclusion can reduce the concentration of lactic acid, whose decrease can affect weaker peristalsis and bowel movements

Effect of betaine, a methyl group donor, on broiler chicken growth performance, breast muscle quality characteristics, oxidative status and amino acid content

This study was aimed to investigate the effect of feed supplemented with betaine on broiler chickens’ growth and slaughter performance, breast muscle histomorphometric and physicochemical properties, oxidative status and amino acid content. A total of 1000 1-day-old Ross 308 broiler chickens were divided into four treatments. Control group chickens were fed with standard compound diet (SCD), the chickens from experimental groups B1, B2 and B3 receiving SCD supplemented with 1 g/kg (B1), 2 g/kg (B2) and 3 g/kg (B3) betaine anhydrous, respectively. Each treatment had five replicate pens. Feeding test results showed that betaine reduced broilers’ mortality but increased feed conversion ratio (p < .05). Forty broiler chickens (5 weeks old) were slaughtered and slaughter performance showed that 2 g/kg betaine inclusion improved breast muscle percentage and yield (p < .05). Betaine dosage of 1 g/kg into feed increased breast muscle fibre areas (p < .05). Betaine affected some physicochemical properties: higher a and the highest drip loss in B2; the highest cooking losses in B1, B2; the highest shear force and fat content in SCD; the highest amounts of ashes in B1, B2 (p < .05). Lower malondialdehyde levels were observed in all betaine-treated groups (p < .05), except B1 fresh meat samples. The highest total amino acid content and a greater amount of essential amino acids were obtained in SCD breast muscles (p < .05), except equally highest amounts of methionine were found in both SCD and B3 samples (p < .05). However, according to our study results, betaine, as a methyl group donor, in broiler chicken diets cannot replace methionine as an essential amino acid

Synthesis, ADMET properties, and in vitro antimicrobial and antibiofilm activity of 5-nitro-2-thiophenecarbaldehyde N-((E)-(5-nitrothienyl)methylidene)hydrazone (KTU-286) against Staphylococcus aureus with defined resistance mechanisms

The emergence of drug-resistant Staphylococcus aureus is responsible for high morbidity and mortality worldwide. New therapeutic options are needed to fight the increasing antimicrobial resistance among S. aureus in the clinical setting. We, therefore, characterized the in silico absorption, distribution, metabolism, elimination, and toxicity (ADMET) and in vitro antimicrobial activity of 5-nitro-2-thiophenecarbaldehyde N-((E)-(5-nitrothienyl)methylidene)hydrazone (KTU-286) against drug-resistant S. aureus strains with genetically defined resistance mechanisms. The antimicrobial activity of KTU-286 was determined by CLSI recommendations. The ADMET properties were estimated by using in silico modeling. The activity on biofilm integrity was examined by crystal violet assay. KTU-286 demonstrated low estimated toxicity and low skin permeability. The highest antimicrobial activity was observed among pan-susceptible (Pan-S) S. aureus (minimal inhibitory concentration (MIC) 0.5–2.0 µg/mL, IC50 = 0.460 µg/mL), followed by vancomycin resistant S. aureus (VRSA) (MIC 4.0 µg/mL, IC50 = 1.697 µg/mL) and methicillin-resistant S. aureus (MRSA) (MIC 1.0–16.0 µg/mL, IC50 = 2.282 µg/mL). KTU-286 resulted in significant (p < 0.05) loss of S. aureus biofilm integrity in vitro. Further studies are needed for a better understanding of safety, synergistic relationship, and therapeutic potency of KTU-286

Functionalized Electrospun Scaffold&ndash;Human-Muscle-Derived Stem Cell Construct Promotes In Vivo Neocartilage Formation

Polycaprolactone (PCL) is a non-cytotoxic, completely biodegradable biomaterial, ideal for cartilage tissue engineering. Despite drawbacks such as low hydrophilicity and lack of functional groups necessary for incorporating growth factors, it provides a proper environment for different cells, including stem cells. In our study, we aimed to improve properties of scaffolds for better cell adherence and cartilage regeneration. Thus, electrospun PCL&ndash;scaffolds were functionalized with ozone and loaded with TGF-&beta;3. Together, human-muscle-derived stem cells (hMDSCs) were isolated and assessed for their phenotype and potential to differentiate into specific lineages. Then, hMDSCs were seeded on ozonated (O) and non-ozonated (&ldquo;na&iuml;ve&rdquo; (NO)) scaffolds with or without protein and submitted for in vitro and in vivo experiments. In vitro studies showed that hMDSC and control cells (human chondrocyte) could be tracked for at least 14 days. We observed better proliferation of hMDSCs in O scaffolds compared to NO scaffolds from day 7 to day 28. Protein analysis revealed slightly higher expression of type II collagen (Coll2) on O scaffolds compared to NO on days 21 and 28. We detected more pronounced formation of glycosaminoglycans in the O scaffolds containing TGF-&beta;3 and hMDSC compared to NO and scaffolds without TGF-&beta;3 in in vivo animal experiments. Coll2-positive extracellular matrix was observed within O and NO scaffolds containing TGF-&beta;3 and hMDSC for up to 8 weeks after implantation. These findings suggest that ozone-treated, TGF-&beta;3-loaded scaffold with hMDSC is a promising tool in neocartilage formation

CT- and MRI-based assessment of body composition and pancreatic fibrosis reveals high incidence of clinically significant metabolic changes that affect the quality of life and treatment outcomes of patients with chronic pancreatitis and pancreatic cancer

Background and Objectives: Both chronic pancreatitis (CP) and pancreatic ductal adenocarcinoma (PDAC) may lead to cachexia, sarcopenia, and osteoporosis due to di erent mechanisms. Neither patient gender, age, nor body weight are good predictors of these metabolic changes having a significant negative impact on the quality of life (QOL) and treatment outcomes. The aim of this study was to evaluate radiological changes in body composition and to compare them with manifestations of exocrine and endocrine pancreatic insu ciency, body mass, and QOL among patients with CP and PDAC. Materials and Methods: Prospectively collected data of 100 patients with diagnosed CP or PDAC were used for analysis. All patients underwent dual-energy X-ray absorptiometry (DXA), computed tomography (CT), and magnetic resonance imaging (MRI). The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30) was used to assess QOL. Diabetes and changes in fecal elastase-1 were also assessed. Results: There was no significant di erence in skeletal muscle mass (SMM) among patients with CP and PDAC (p=0.85). Significantly more underweight patients had low SMM (p=0.002). Patients with CP had more pronounced pancreatic fibrosis (PF) (p<0.001). Data showed a significant relationship between a high degree of PF and occurrence of diabetes (p=0.006) and low fecal elastase-1 levels (p=0.013). A statistically significant lower QOL was determined in patients with PF 50% and in the CP group. Conclusions: Sarcopenia and osteoporosis/osteopenia are highly prevalent among patients with chronic pancreatitis and pancreatic cancer, and CT- and MRI-based assessment of body composition and pancreatic fibrosis could be a potentially useful tool for routine detection of these significant metabolic changes