New prospective insecticidal agents based on thiazolo[4,5-b]quinoxaline derivatives against cotton leafworm Spodoptera litura (Fabricius): Design, synthesis, toxicological, morphology, histological, and biomedical studies.

In this study, a new series of thiazolo[4,5-b]quinoxaline derivatives 3-8 were synthesized by treating 2,3-dichloroquinoxaline with thiosemicarbazone and thiourea derivatives under reflux conditions. The chemical structure of the newly designed derivatives was conducted using spectroscopic techniques. The insecticidal bioassay of the designed derivatives was evaluated against the 2nd and 4th larvae of S. litura after five days as toxicity agents via median lethal concentration (LC50) and the lethal time values (LT50). The results indicated that all the tested compounds had insecticidal effects against both instar larvae of S. litura with variable values. Among them, thiazolo[4,5-b]quinoxaline derivative 3 was the most toxic, with LC50 = 261.88 and 433.68 ppm against 2nd and 4th instar larvae, respectively. Moreover, the thiazolo[4,5-b]quinoxaline derivative 3 required the least time to kill the 50% population (LT50) of 2nd larvae were 20.88, 13.2, and 15.84 hs with 625, 1250, and 2500 ppm, respectively, while for the 4th larval instar were 2.75, 2.08, and 1.76 days with concentrations of 625, 1250, and 2500 ppm, respectively. Larvae's morphological and histological studies for the most active derivative 3 were investigated. According to SEM analysis, the exterior morphology of the cuticle and head capsule was affected. In addition, there were some histological alterations in the cuticle layers and the midgut tissues. Columnar cells began breaking down, and vacuolization occurred in the peritrophic membrane. Moreover, treating 4th S litura larvae hemolymph with compound 3 showed significant changes in biochemical analysis, such as total proteins, GPT, GOT, acetylcholinesterase (AChE), and alkaline phosphatase (AlP). Finally, the toxicity prediction of the most active derivative revealed non-corrosive, non-irritant to the eye, non-respiratory toxicity, non-sensitivity to the skin, non-hepatotoxic, and don't have toxicity on minnow toxicity and T. pyriformis indicating a good toxicity profile for human.

High frequency of larval abnormalities of the toad Rhinella arenarum (Anura: Bufonidae) in an Argentinian agroecosystem

Introduction: The frequent use of pesticides is currently considered a cause of environmental pollution due to the high rate of entry of these substances into agroecosystems. This constitutes a risk for the species that inhabit these ecosystems, in particular anurans whose characteristics make them prone to exposure to and interaction with environmental pollutants. Objective: To report the occurrence of abnormalities in larvae of the common toad Rhinella arenarum inhabiting ponds surrounded by agroecosystems. Methods: In two consecutive springs (2015 and 2016), reproductive events of common toads were monitored in temporary pond systems in agricultural and non-agricultural areas, located near the city of La Plata (Buenos Aires, Argentina). The physicochemical parameters of the ponds were measured, and the stage of each reproductive event was recorded, such as the numbers of adult toads, amplexus and clutches. In the laboratory, the larvae were measured and photographed, their stage of development was recorded, and their morphology was examined under a stereomicroscope. Representative samples (normal and abnormal) from each pond studied were processed for histopathological analysis. Results: In the field studies carried out on a population of R. arenarum collected in an agroecosystem, a lower number of reproductive adults and clutches were observed in relation to the population of a non-agricultural pond. A total of 1 910 larvae were collected: 529 and 1 381 larvae from ponds located in non-agricultural and agricultural areas, respectively. Larvae from the agroecosystem showed two types of abnormalities: severe tail flexure and abdominal bloating. In addition, five degrees of severity could be determined in relation to abdominal bloating. Conclusions: This work reports the high frequency and severity of abnormalities observed in the early stages of R. arenarum larvae living within an agroecosystem, providing evidence of the negative impact that agricultural activities cause on aquatic ecosystems surrounded by farming areas.

Introducción: El uso frecuente de plaguicidas es considerado actualmente una causa de contaminación ambiental debido a las altas tasas de ingreso de estas sustancias a los agroecosistemas. Esta situación es un riesgo para las especies que habitan en estos ecosistemas, en particular los anuros cuyas características los hacen propensos a la exposición e interacción con contaminantes ambientales. Objetivo: Informar la presencia de anormalidades en larvas del sapo común Rhinella arenarum que habitan en estanques rodeados por un agroecosistema. Métodos: En dos primaveras consecutivas (2015 y 2016), se monitorearon los eventos reproductivos del sapo común proveniente de sistemas de estanques temporales ubicados en zonas agrícolas y no agrícolas, cerca de la ciudad de La Plata (Buenos Aires, Argentina). Se midieron los parámetros fisicoquímicos de los estanques y se registraron las etapas de cada evento reproductivo como el número de sapos adultos, amplexos y nidadas. En el laboratorio, las larvas fueron medidas y fotografiadas, se registró su estado de desarrollo y se examinó la morfología de cada una bajo microscopio estereoscópico. Se procesaron muestras representativas (normales y anormales) de cada estanque estudiado para análisis histopatológico. Resultados: En la población de R. arenarum que vive dentro de un agroecosistema, se observó un menor número de adultos reproductores y puestas en relación con la del estanque en la zona no agrícola. Se recolectaron un total de 1 910 larvas: 529 y 1 381 larvas de estanques ubicados en zonas no agrícolas y agrícolas, respectivamente. Las larvas del agroecosistema mostraron dos tipos de anormalidades: severa flexión de la cola y distensión abdominal. Además, se pudo determinar cinco grados de gravedad en relación con la distensión abdominal. Conclusiones: Una alta frecuencia y severidad de anormalidades en los estadios tempranos de larvas de R. arenarum que viven dentro de un agroecosistema proporciona evidencia del impacto negativo que las actividades agrícolas causan en los ecosistemas acuáticos rodeados por áreas de cultivo.

Simvastatin-Loaded Nanostructured Lipid Carriers as Topical Drug Delivery System for Wound Healing Purposes: Preparation, Characterization, and In Vivo Histopathological Studies.

Purpose: Simvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, is a commonly used drug to reduce total cholesterol and low-density lipoprotein (LDL) levels. Furthermore, several mechanisms showed the wound-healing potential of statins, especially simvastatin. Simvastatin is a lipophilic drug, therefore, it has low water solubility with limited skin permeability potential. In this regard, nanostructured lipid carriers (NLCs) were recruited as novel topical drug delivery systems to enhance skin adhesion and film formation, maintain skin integrity, sustain the release of simvastatin, and prolong simvastatin skin deposition to help pressure ulcers healing and regeneration. Methods: NLCs were fabricated using the solvent diffusion evaporation technique. Drug loading, in vitro drug release, and morphological assessment on the optimized formulation were considered. Furthermore, in vivo effect of simvastatin-loaded NLCs gel on pressure ulcer healing was assessed using a rat skin model. Histopathological assessments were compared with conventional simvastatin gel and drug-free NLCs gel. Results: Simvastatin-loaded NLC with an average diameter of 100 nm was considered as the optimum formulation. According to the results entrapment efficiency of simvastatin within the NLCs was about 99.4%. Drug release studies revealed sustained drug release from NLCs in which about 87% of the drug was slowly released during 48 hours. Animal study results confirmed that simvastatin-loaded NLCs gel has better efficacy on pressure ulcers and could significantly reduce inflammation, and promote skin regeneration compared to both drug-free NLCs and conventional simvastatin gels. Conclusion: Simvastatin-loaded NLCs with an average particle size of 100 nm would be a promising novel topical drug delivery system with sustained drug release potential for pressure ulcer treatment.

Ultra-Performance Liquid Chromatography Coupled with Mass Metabolic Profiling of Ammi majus Roots as Waste Product with Isolation and Assessment of Oral Mucosal Toxicity of Its Psoralen Component Xanthotoxin.

Ammi majus, a well-established member of the Umbelliferae (Apiaceae) family, is endogenous to Egypt. The main parts of this plant that are used are the fruits, which contain coumarins and flavonoids as major active constituents. The roots are usually considered by-products that are discarded and not fed to cattle because of coumarins' potential toxicity. The goal of this study was to ensure the sustainability of the plant, investigate the active metabolites present in the roots using UPLC/MS-MS, isolate and elucidate the major coumarin Xanthotoxin, and predict its oral bioavailability and its potential biological impact on tongue papillae. The results revealed coumarins as the dominant chemical class in a positive acquisition mode, with bergaptol-O-hexoside 5%, Xanthotoxin 5.5%, and isoarnoittinin 6% being the major compounds. However, phenolics ruled in the negative mode, with p-coumaroyl tartaric acid 7%, 3,7-dimethyl quercetin 6%, and hesperidin 5% being the most prominent metabolites. Fractionation and purification of the chloroform fraction yielded Xanthotoxin as one of the main compounds, which appeared as white needle crystals (20 mg). ADME studies for oral bioavailability were performed to predict the potential properties of the compound if used orally. It was noted that it followed Lipinski's rule of five, had just one parameter outside of the pink area in the radar plot, and was detected inside the threshold area using the boiled egg approach. In vivo, histopathological studies performed on rats showed a notable decrease in the tongue's keratin thickness from an average of 51.1 µm to 9.1 µm and an average of 51.8 µm to 9.8 µm in fungiform and filiform cells, respectively. The results indicated that although Xanthotoxin is a well-known medical agent with several potential therapeutic activities in oral therapy, it may cause a destructive effect on the structure of the specialized mucosa of the tongue.

Evaluation of inactivated avian influenza virus and Newcastle disease virus bivalent vaccination program against newly circulated H5N8 and NDV strains.

Avian influenza virus (AIV) and Newcastle disease virus (NDV) are respiratory illness syndromes that have recently been detected in vaccinated flocks and are causing major financial losses in the chicken farming industry. The objective was to evaluate the efficacy of Valley Vac H5Plus NDVg7 vaccine in protecting chickens against the H5N8 and NDV strains that have recently been circulating in comparison with the efficacy of the commercially available bivalent H5+ND7 vaccine. In contrast to the H5+ND7 vaccine, which was made of genetically distinct H5N8/2018 clade 2.3.4.4b genotype group (G5), H9N2/2016, H5N1/2017, and genetically comparable NDV genotype VII 1.1/2019 of the recently circulating challenge viruses, the Valley Vac H5Plus NDVg7 vaccine consisted of the recently isolated (RG HPAI H5N1 AIV/2015 Clade 2.2.1.2, RG HPAIV H5N8/2020 Clade 2.3.4.4b genotype group 6 (G6), and NDV genotype VII 1.1/2012) which were genetically similar to challenged strains. To determine the effectiveness of the Valley Vac H5Plus NDVg7 vaccine, a total of 70-day-old commercial chicks were divided into 7 groups of 10 birds each. Groups (G1 and G4) received Valley Vac H5Plus NDVg7 vaccine. Groups (G2 and G5) groups received commercial H5+ND7 vaccine. While groups (G3 and G6) were kept nonvaccinated, and group (G7) was kept as a nonchallenged and nonvaccinated. After 3-wk post vaccination (WPV), groups G1, G2, and G3 were challenged with A/Duck/ Egypt/SMG4/2019(H5N8) genotype G6. On the other hand, groups G4, G5, G6 were challenged with NDV/EGYPT/18629F/2018 genotype VII 1.1 with an intranasal injection of 0.1 mL. Antibody titer was calculated at the first 3 wk after vaccination, and the viral shedding titer was calculated at 3-, 5-, and 7-days post challenge. Mortality and morbidity rates were monitored daily during the experiment, and for the first 10 d after the challenge, to provide an estimate of the protection rate. The results showed that a single dosage of 0.5 mL per bird of Valley Vac H5Plus NDVg7 vaccine provides 80% protection against both H5N8 and NDV, compared to the bivalent H5+ND7 vaccine, which provided 20 and 80% protection against H5N8 and NDV, respectively. In addition, 0.5 mL per bird of Valley Vac H5Plus NDVg7 vaccine produced a greater immune response against both viruses than commercial vaccination at 1 to 3 WPV with a significant difference at 1 WPV for H5N8 and a comparatively higher immune response for NDV. Furthermore, it reduced virus shedding of H5N8 on the third, fifth, seventh, and tenth days lower than H5+ND7 vaccine with a significant difference on the third day for H5N8 and relatively lower than bivalent H5+ND7 vaccine for NDV with a significant difference on the fifth day. The Valley vaccinated group demonstrated more tissue intactness compared to the commercially vaccinated group against the H5N8 challenge, however the bivalent commercially vaccinated group showed the similar level of tissue integrity against NDV. In conclusion, Valley Vac H5Plus NDVg7  that contains the  genetically similar strain to recently circulating challenged virus (H5N8 genotype G6) provided better protection with greater immune response and decreased the amount of virus shed against H5N8 genotype G6 and showed less histopathological alteration than the commercial bivalent H5+ND7 vaccine that contain genetically distinct (H5N8 genotype G5). However the Valley Vac H5Plus NDVg7 provided the same protection with relatively high immune response and  relatively decreased the amount of virus shed and showed equal tissue integrity than the commercial bivalent H5+ND7 vaccine against NDV genotype VII 1.1 that contain the same genotype of NDV genotype VII 1.1.

Central composite design-based optimization, fabrication, and pharmacodynamic assessment of sulfasalazine-loaded lipoidal nanoparticle-based hydrogel for the management of rheumatoid arthritis.

Rheumatoid arthritis is a progressive, chronic, immunological, and inflammatory disorder that is distinguished by joint inflammation, joint tenderness, and synovial joint destruction. The study aimed to fabricate sulfasalazine-loaded solid lipid nanoparticle (SLN)-based gels for rheumatoid arthritis management. The SLNs were fabricated with the melt emulsification technique by employing central composite design (CCD) for SLNs optimization. The optimized formulation of SLNs (FF-1) showed particle size and drug entrapment efficiency of 117.25 nm ± 1.67 and 94.05% ± 1.05, respectively. To scrutinize the outcome of the independent variable on responses; model graphs and the polynomial equation obtained from the Design-Expert were used. The surface morphology studies of SLNs revealed a smooth surface with a slightly asymmetric shape. In vitro drug release of the optimized formulation (FF1) had shown a maximum release of up to ~ 91.89% ± 2.12 over 24 h. The optimized FF1 formulation was subsequently gelled using 1% w/v Carbopol 934 and subjected to ex vivo permeation that displayed 8.01 mg/cm2 ± 0.24 and 7.49 mg/cm2 ± 0.86 amount of drug permeated up to 24 h and 10 h from SLNs gel and plain gel, respectively. In vivo studies manifested a considerable reduction in the paw thickness (*p < 0.0001) and an arthritic score (*p < 0.0001) of the sulfasalazine SLN gel as compared to plain gel. Further, pro-inflammatory cytokines, viz. TNF-α, IL-1, and IL-6 levels, were significantly inhibited (p < 0.0001) by sulfasalazine SLN-based gel that exhibited substantial anti-inflammatory effects. In conclusion, sulfasalazine-loaded SLN-based gel showed sustained release of drug for up to 24 h and can be considered suitable as a topical application for rheumatoid arthritis management.

Ameliorative role of nanocurcumin against the toxicological effects of novel forms of Cuo as nanopesticides: a comparative study.

Copper oxide nanoparticles (CuONPs) have a wide range of uses in agricultural applications. Nanocurcumin (NCur) acts as an antioxidant treatment. The goal of the study is to reduce the toxicity resulting from the use of CuONPs as nanopesticides on living organisms by inducing changes in the morphological shape of CuONPs or treating it with NCur. So, we induced a comparative study between three shapes of CuONPs: CuO nanosphere (CuONSp), CuO nanosheet (CuONS), and CuO nanoflower (CuONF). We characterize each nano-form by using X-ray diffraction (XRD), scanning electron microscope (SEM), transmission electron microscope (HRTEM), and Zetasizer HT device; 36 rats were divided into six groups (n = 6): 1st group was the control group; 2nd group received 50 mg/kg/day of NCur orally for 30 days; 3rd, 4th, and 5th groups received orally 50 mg/kg/day of CuONSp, CuONS, and CuONF, respectively, for 30 days; 6th group received 50 mg/kg/day CuONSp plus 50 mg/kg/day of NCur orally for 30 days. An elevation occurred in malondialdehyde (MDA), liver and kidney functions, tumor necrosis factor-alpha (TNF-α), and B-cell lymphoma 2 (Bcl2) by CuONSp > CuONS > CuONF, respectively. An inhibition occurred in glutathione (GSH), superoxidase (SOD) catalase (CAT), apoptotic Bax gene (Bax), histopathological, and ultrastructural alterations by CuONSp < CuONS < CuONF, respectively. NCur ameliorated these alternations. In conclusion, CuONF is a better form compared to other forms of nanopesticide in agriculture due to its lower toxicity. NCur decreased the biological alternations which induced by CuONSp due to its antioxidant and anti-apoptotic properties.

Sperm quality and testicular histopathology of Wistar albino male rats treated with hydroethanolic extract of Cordia dichotoma fruits.

CONTEXT: Cordia dichotoma Forst. (Boraginaceae) has potent pharmacological impact. Meanwhile, its effect on fertility is unclear. OBJECTIVE: This study investigates the effect of Cordia fresh fruits hydroethanolic extract on fertility. MATERIALS AND METHODS: 120 Wistar albino male rats were divided into four groups (n = 30). The first group was negative control, and the second, third, and fourth groups received 125, 250, and 500 mg extract/kg bodyweight for 56 days. After 56 days, Cordia force-feeding stopped, and all groups were kept under laboratory conditions for another month to study the recovering effect. RESULTS: After day 56, extract at 500 mg/kg significantly reduced sperm total count, motility%, and alive%, to 47.60 ± 2.27 × 106 sperm/mL, 43.33% ± 1.49, and 63.67% ± 1.19, respectively, abnormalities% increased considerably (26.67% ± 0.54), compared to the negative control. Also, significant depletion on follicle-stimulating hormone (2.66 ± 0.21 mIU/L), luteinizing hormone (1.07 ± 0.06 mIU/L), and testosterone (2.69 ± 0.13 nmol/L) level was recorded, compared to the negative control. Cordia negative effect showed on histopathological studies of testes, prostate, and seminal vesicles. Fortunately, these adverse effects of Cordia recovered remarkably after stopping administration for one month. CONCLUSIONS: Cordia antifertility effect may be due to its hypocholesterolemic effect, where cholesterol, the steroid cycle precursor, was significantly reduced. This study can be incorporated in clinical research after being repeated on another small experimental animal, their offspring, and one large experimental animal, then going to a clinical study that we plan to do in the future.

Vitamin D2 protects acute and repeated noise stress induced behavioral, biochemical, and histopathological alterations: Possible antioxidant effect.

Noise is an environmental stressor which causes distress and hearing loss in individuals residing in urban areas. Psychological deficits such as anxiety, depression, impaired memory and cognitive decline are caused by noise stress. Different vitamins have been used as a potential antioxidant for neuronal protection. In this study we investigate the anxiolytic, antidepressant and memory enhancing effect of vitamin D2 (Vit D2) following noise stress. Thirty-six albino rats were randomly divided into six groups. (i) Unstressed + corn oil (ii) Unstressed + Vit D2 (iii) Acute noise stress + corn oil (iv) Acute noise stress + Vit D2 (v) Repeated noise stress + corn oil (vi) Repeated noise stress + Vit D2. 600 IU/kg body weight of Vit D2 dosage was prepared in corn oil. Corn oil is used as vehicle and all the drugs administered via oral gavage till end of the experiment (day 16). Recorded sound of generator which was amplified by speakers and had 100 dB intensity was used as noise stress. Repeated stressed animals were exposed to noise (4-hrs) daily for 14 days, while acute stressed animals were exposed to noise (4-hrs) once after 14 days. Behavioral tests (elevated plus maze, light dark box, tail suspension test and Morris water maze) of all groups were performed after15 days treatment period. After behavioral tests rats received their last dosage and decapitated after 1-hr. Brain of all animals was removed and used for biochemical (oxidative stress biomarker, antioxidant enzymes and acetylcholinesterase) and histopathological estimations. Results show that Vit D2 decreased time spent in light box and open arm of light dark activity box and elevated plus maze test respectively (used for anxiety evaluation), decreased immobility time in tail suspension test (for depression) and improved cognitive ability evaluated by Morris water maze test in acute and repeated noise stressed rats. Furthermore, increased antioxidant enzymes activity, decreased lipid peroxidation and acetylcholinesterase activity were also observed in Vit D2 treated animals following acute and repeated noise stress. Normalization in histopathological studies was also observed in Vit D2 treated following acute and repeated noise stress. It is concluded that Vit D2 protects from noise stress induced behavioral, biochemical and histopathological impairment through its antioxidant potential.

Exposure of Mactra corallina to acute doses of lead: effects on redox status, fatty acid composition and histomorphological aspect.

The aim of this study is to elucidate the toxicity induced by PbCl2, administered in graded doses (1; 2.5; 5 mg/L), in the redox state, in the fatty acid composition and in the histological structure of Mactra corallina digestive glands. Our findings showed a progressive accumulation of Pb in the M. corallina digestive glands in all treated groups. After 5 days of treatment with PbCl2, an increase in H2O2, MDA, PCO, GSH, NPSH and MT levels was observed in the digestive glands of treated groups. Moreover, activities of antioxidant enzymes, such as GPx and CAT, increased while SOD activity decreased in all treated groups, indicating a failure of the antioxidant defense system. Furthermore, the cholinergic function was evaluated by assessing the acetylcholinesterase activity, which was inhibited in all the treated digestive glands compared to the control group. In our experiment, the levels of n-3 (Omega-3) and n-6 (Omega-6) polyunsaturated fatty acids were greatly altered in the groups treated with 5 mg/L of PbCl2 (p < 0.001). Indeed, DHA and EPA decreased significantly in the digestive glands treated with 2.5 and 5 mg/L of PbCl2, respectively. On the other hand, under exposure to the medium and high doses (2.5 and 5 mg/L), arachidonic acid (ARA) and linoleic acid (LA) significantly increased (p < 0.001). These changes in PUFA were confirmed by significant modifications in the polyene and peroxidation indices. The histological findings confirmed the biochemical results.HighlightsIntegrated parameters were used to explore the toxic effect of PbCl2 graded doses in Mactra corallina digestive gland.Metals accumulation in digestive glands of M. corallina was greatly dependent to dose of PbCl2.Metabolic and macromolecules damaging of clams digestive glands were more sensitive at higher PbCl2 doses.Fatty acids composition especially polyunsaturated fatty acids (PUFA) and essentials fatty acids such as docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) in clams digestive glands were intensively altered at higher PbCl2 doses.Inflammation responses revealed in studied tissue.

Preclinical assessment of nanostructured liquid crystalline particles for the management of bacterial keratitis: in vivo and pharmacokinetics study.

The research work was driven to develop, optimize, and characterize novel nanostructured liquid crystalline particles as carriers for the ocular delivery of vancomycin. The formulations were developed by fragmenting the cubic crystalline phase of glycerol monooleate, water, and poloxamer 407. A four-factor, three-level Taguchi statistical experimental design was constructed to optimize the formulation. Formulations exhibited internal-cubic structure of the vesicles with particle size in the range of 51.11 ± 0.96 nm to 158.73 ± 0.46 nm and negative zeta potential. Ex vivo transcorneal permeation studies demonstrated that the optimized cubosomes had a 2.4-fold increase in apparent permeability co-efficient as compared to vancomycin solution, whereas in vivo studies in rabbits demonstrated that the severity of keratitis was considerably lowered on day 3 with optimized cubosomes. Ocular pharmacokinetic studies evaluated the level of drug in aqueous humor, and results revealed that the time to peak concentration (Tmax) of vancomycin-loaded cubosomal formulation was about 1.9-fold higher and mean residence time was 2.2-fold greater than vancomycin solution. Furthermore, histological examination revealed that the corneal layers displayed well-maintained morphology without any stromal swelling, consequently indicating the safety of formulation. It could be concluded that the developed nanostructured liquid crystalline particles of vancomycin demonstrated improved pre-ocular residence time, increased permeability, reduced dosing frequency, controlled drug release, and reduced systemic side-effects. Results manifested that the developed vancomycin-loaded cubosomes could be a promising novel ocular carrier and an ideal substitute for conventional eye drops for the management of bacterial-keratitis.

Design of transfersomal nanocarriers of nystatin for combating vulvovaginal candidiasis; A different prospective.

The objective of this study was to prepare and evaluate Nystatin (NYS) loaded transfersomes to achieve better treatment of vulvovaginal candidiasis. Nystatin transferosomes were formulated utilizing thin film hydration method. A 32 full factorial design was employed to evaluate the effect of different formulation variables. Two independent variables were chosen; the ratio between lecithin surfactant (X1) was set at three levels (10-40), and the type of surfactants (X2) was set at three levels (Span 60, Span 85 and Pluronic F-127). The dependent responses were; entrapment efficiency (Y1: EE %), vesicles size (Y2: VS) and release rate (Y3: RR). Design Expert® software was utilized to statistically optimize formulation variables. The vesicles revealed high NYS encapsulation efficiency ranging from 97.35 ± 0.03 to 98.01 ± 0.20% whereas vesicle size ranged from 194.8 ± 20.42 to 400.8 ± 42.09 nm. High negative zeta potential values indicated good stability of the prepared formulations. NYS release from transfersomes was biphasic and the release pattern followed Higuchi's model. The optimized formulation (F7) exhibited spherical morphology under transmission electron microscopy (TEM). In-vitro and in-vivo antifungal efficiency studies revealed that the optimized formula F7 exhibited significant eradication of candida infestation in comparison to free NYS. The results revealed that the developed NYS transfersomes could be a promising drug delivery system to enhance antifungal efficacy of NYS.

Cyto-histopathological and protein polymorphism alterations in five populations of Nile tilapia (Oreochromis niloticus) as biomonitor for water heavy metal pollution.

Cytological, histopathological and sodium dodecyl sulphate polyacrylamide gel analyses were carried out on five populations of common Nile tilapia fish (Oreochromis niloticus) occurring in five sites - River Nile (reference site), Bahr Yusef canal, Ibrahimia canal, Irrigation drain and El Moheet drain of El Minia Province, Egypt - to evaluate the usability of Nile tilapia as a biomonitor for water heavy metal contaminants. Water surface samples were collected from the five sites, and lead (Pb) concentration was shown to surpass the limits defined by WHO. Ni and Cd levels were shown to be elevated in Ibrahimia canal samples. Moreover, the concentration of heavy metals in fish muscles collected from Bahr Yusef canal and El Moheet drain was the highest in comparison with those of the other water sites. Cytological examinations of blood smears showed not only a significant percentage of micronuclei in Irrigation drain population but also a significant percentage of binucleated cells in Ibrahimia canal and El Moheet drain populations. In addition, pathological alteration was observed in blood cells, especially in samples collected from Irrigation drain and El Moheet drain. Histopathological changes were strongly observed in the liver and the kidneys of El Moheet and Irrigation drain population. Moreover, total protein band pattern profiles showed extra bands in both Ibrahimia canal and Irrigation drain more than that recorded for the River Nile population. In conclusion, cyto-histopathological and total protein band pattern results confirmed that O. niloticus responds sensitively to the excess of heavy metals present in the water.

Pharmacokinetics of Bio-shell-silver-core Nanoparticles (AgNP) in Sprague-Dawley Rats - In Vivo Study.

BACKGROUND: Silver nanoparticles have been widely used in the field of nanomedicine. A comprehensive understanding of their pharmacokinetics is crucial for proper risk assessment and safe biomedical applications. OBJECTIVES: The purpose of this study was to investigate the safety of silver nanoparticles by determining their potential toxicity following 28 days of administration in Sprague-Dawley rats. METHODS: The silver nanoparticles were administered by intravenous injection at the doses of 100, 200 and 500 µg/kg body weight for 28 consecutive days. Animals in the control group were received sterile water for injection. Each group consists of 10 male and 10 female rats. RESULTS: No treatment-related effects were seen in any of the parameters monitored in rats given 100, 200 and 500 µg/kg body weight/day of silver nanoparticles. CONCLUSION: The study proved that the use of up to 500 µg/kg body weight biosynthesized silver nanoparticles have no toxic effect on the target organs and found safe. However, the safety of the nanoparticles might be attributed to the covering of biological moieties on nanoparticles. Hence, the biofunctionalized nanoparticles can be safely used by selecting the required size and dose in medicines and drug delivery systems.

Chemical Profile of Launaea nudicaulis Ethanolic Extract and Its Antidiabetic Effect in Streptozotocin-Induced Rats.

Launaea nudicaulis is used in folk medicine worldwide to treat several diseases. The present study aimed to assess the antidiabetic activity of L. nudicaulis ethanolic extract and its effect on diabetic complications in streptozotocin-induced hyperglycemic rats. The extract was orally administrated at 250 and 500 mg/kg/day for 5-weeks and compared to glibenclamide as a reference drug at a dose of 5 mg/kg/day. Administration of the extract exhibited a potential hypoglycemic effect manifested by a significant depletion of serum blood glucose concurrent with a significant elevation in serum insulin secretion. After 5-weeks, extract at 250 and 500 mg/kg/day decreased blood glucose levels by about 53.8 and 68.1%, respectively, compared to the initial values (p ≤ 0.05). The extract at the two dosages prevented weight loss of rats from the 2nd week till the end of the experiment, compared to diabetic control rats. The extract further exhibited marked improvement in diabetic complications including liver, kidney and testis performance, oxidative stress, and relative weight of vital organs, with respect to diabetic control. Histopathological examinations confirmed the previous biochemical analysis, where the extract showed a protective effect on the pancreas, liver, kidney, and testis that degenerated in diabetic control rats. To characterize extract composition, UPLC-ESI-qTOF-MS identified 85 chromatographic peaks belonging to flavonoids, phenolics, acyl glycerols, nitrogenous compounds, and fatty acids, with four novel phenolics reported. The potential anti-diabetic effect warrants its inclusion in further studies and or isolation of the main bioactive agent(s).

Preventive role of probiotic bacteria against gastrointestinal diseases in mice caused by Giardia lamblia.

Giardiasis is one of the most prevalent gastrointestinal diseases in the world. It is caused by Giardia, Giardia lamblia, a common and opportunistic zoonotic parasite. The aim of our work is to find a natural and safe alternative treatment for giardiasis, specifically, to determine if probiotic bacteria (Lactobacillus acidophilus, Bifidobacterium bifidum, and Lactobacillus helveticus) can contribute to treatment, and act as preventives. Sixty weanling albino mice, Mus musculus, were divided into control and experimental, probiotic-fed groups. We determined infection intensity, and cure and prevention rates of giardiasis through ELISA (enzyme-linked immunosorbent assay) of stool samples and histopathological comparison of intestinal tissue. In experimental groups, there was a significant reduction in infection intensity (P<0.001) on days 10, 15, and 20, while cure rate reached 87.5%. The control group showed no signs of reduced infection or cure and only the group treated with probiotics prior to infection showed significant prevention rates. In the experimental groups, intestinal changes due to giardiasis appeared 7 days post-infection. However, almost all of these changes disappeared by the 25th day. Our results suggest a beneficial and significant effect of probiotics in the prevention and treatment of giardiasis in mice.

Development of nano-silver alkaline protease bio-conjugate depilating eco-benign formulation by utilizing potato peel based medium.

A new bio-conjugate nano-silver enzyme conjugate complex (BC-nAg-Akp) was formulated containing alkaline protease (Akp). The present research involved synthesis of nAg particles in acetone concentrated enzyme sol using 0.005 M AgNO3 solution formed within interaction time of 24 h through photo catalysis. The BC-nAG-Akp composite exhibited 1.9-fold increase in enzyme activity. The formulation was characterized using techniques viz., SEM, SEM-EDS, TEM, and DLS spectroscopy. The TEM analysis revealed synthesis of silver nano rods with size dimensions ranging from 40 to 80 nm. Likewise, the mean hydrodynamic diameter was 114 nm with polydispersity index of 0.260 and had the largest diffusion constant of 4.28 × 108 amongst the three forms of the formulation (crude, acetone concentrated and partially purified) on DLS characterization. The SEM-EDS analysis showed occurrence of 18.32 and 3.79%weight and %atom of Ag element respectively. The prepared formulation was investigated for its dehairing performance. The ideal dehairing was achieved at 37 °C after 12 h of treatment. The histopathological studies revealed that complete dehairing with minimal rarefication was achieved and was found perform better compared to the commercial Akp and control (crude enzyme) formulations.

Multi-vessel coronary artery aneurysms in a patient with Parry Romberg syndrome: a case report.

BACKGROUND: Coronary artery aneurysms (CAAs) are a very rare finding on coronary angiograms with multiple known aetiologies. Parry Romberg syndrome (PRS) is also a very rare disease, and the underlying aetiology remains unknown. We present a rare case of CAAs in a patient with PRS, and discuss possible implications regarding the primary pathophysiological cause for both of these diseases. CASE SUMMARY: A 48-year-old woman with a history of PRS presented with atypical and non-exertional chest pain. Initial evaluation demonstrated a rising troponin without associated electrocardiogram changes, and as such she was taken for left heart catheterization. Left heart catheterization demonstrated diffuse aneurysmal and ectatic disease of multiple coronary arteries. Further evaluation with magnetic resonance angiogram and autoantibody panel did not demonstrate other vascular anomalies or rheumatologic disease, respectively. She was treated with dual anti-platelet therapy and statin, and at 1 year follow-up, she had resolution of her symptoms. DISCUSSION: It has been postulated that the underlying mechanism causing CAA is intravascular inflammation. Parry Romberg syndrome is theorized to be a neurovasculopathy, as evidenced by cases of associated intracranial aneurysms. Intravascular inflammation may play a key pathological role in CAA, and an association between CAA and PRS may exist.

Mucoadhesive olaminosomes: A novel prolonged release nanocarrier of agomelatine for the treatment of ocular hypertension.

Mucoadhesive olaminosomes are novel nanocarriers designed to control agomelatine release and enhance its bioavailability. Olaminosomes were prepared using oleic acid, oleylamine and sorbitan monooleate adopting thin film hydration technique. Chitosan HCl was added to impart the mucoadhesive properties to the olaminosomes. Mucoadhesive olaminosomes were characterized for their particle size, in-vitro drug release and irritation potentiality in rabbit eyes. The reduction in intraocular pressure (IOP) through 8 h in male New Zealand Albino rabbits was measured after administration of the selected formulations. Histopathological changes in rabbits' eye were also evaluated. Results revealed that increasing the amount of the added oleylamine decreased the particle size of the resulted vesicles and increased the drug release rate. Olaminosomes showed enhanced drug absorption, hence more reduction in IOP was observed. Moreover, using chitosan HCl might increase the residence time of the formulation in the eye and hence improved the absorption of the drug. No histopathological changes in rabbits' eye were detected after the application of mucoadhesive olaminosomes concluding their safety on the ocular tissues. In conclusion, mucoadhesive olaminosomes succeeded in enhancing agomelatine bioavailability in rabbits' eyes confirming the development of a novel ocular nanocarrier for insoluble drugs.