Sistema de administración tópica basada en microesponjas de miconazol para la dermatitis del pañal

Objetivo: La presente investigación tuvo como objetivo desarrollar y optimizar las microesponjas de nitrato de miconazol para el tratamiento de la dermatitis del pañal para un efecto terapéutico mejorado. Material y métodos: Las microesponjas fueron desarrollados por emulsión técnica de difusión del disolvente usando un diseño factorial 23. Las microesponjas fabricadas han sido optimizadas con el fin de analizar los efectos de las variables independientes sobre la eficacia de encapsulación, tamaño de partícula, la topografía de la superficie y en la liberación de fármaco in vitro. A continuación, la formulación optimizada se incorporo en un gel y se evaluó. Resultados: Se encontró que el tamaño de partículas de todas las formulaciones fue uniforme y la microscopía electrónica de barrido (SEM) indicó forma esférica y de naturaleza porosa de las microesponjas. En la liberación del fármaco, estudios in vitro de todas las formulaciones, revelaron la velocidad de liberación dentro de un intervalo de 67±0,09% a 80,6±0,68% al cabo de 12 horas. Con esta base, La formulación F8 se seleccionó y se incorporó en el gel (CF8) en el que se evaluó el pH, viscosidad, capacidad de extensión, estudios de difusión in vitro del fármaco, estudios in vitro anti hongos y estudios de estabilidad. Conclusión: El gel a base de microesponja formulado de nitrato de miconazol sería un sustituto adecuado al tratamiento tradicional para la curación fiable y económica de la dermatitis del pañal.Aim: The current investigation was aimed to develop and optimize the microsponges of miconazole nitrate for treatment of diaper dermatitis for enhanced therapeutic effect. Material and Methods: Microsponges were developed by emulsion solvent diffusion technique using 23 factorial design. Fabricated microsponges were optimized in order to analyze the effects of independent variables on the encapsulation efficiency, particle size, surface topography and in vitro drug release. The optimized formulation was then incorporated into the gel and evaluated. Results: Particle size of all formulations was found to be uniform and scanning electron microscopy (SEM) indicates spherical shape and porous nature of microsponges. In vitro drug release studies of all formulations revealed the release rate within the range of 67%±0.09 to 80.6%± 0.68 at the end of 12 hours. On its basis, formulation F8 was selected and incorporated into the gel (CF8) which was evaluated for pH, viscosity, spreadability, in vitro drug diffusion studies, in vitro anti fungal studies and stability studies. Conclusion: The formulated microsponge-based gel of miconazole nitrate would be a capable substitute to traditional treatment for reliable and economical cure of diaper dermatitis

Advances in Tissue Engineering Approaches for Craniomaxillofacial Bone Reconstruction

Trauma, congenital abnormalities and pathologies such as cancer can cause significant defects in craniofacial bone. Regeneration of the bone in the craniofacial area presents a unique set of challenges due to its complexity and association with various other tissues. Bone grafts and bone cement are the traditional treatment options but pose their own issues with regards to integration and morbidity. This has driven the search for materials which mimic the natural bone and can act as scaffolds to guide bone growth. Novel technology and computer aided manufacturing have allowed us to control material parameters such as mechanical strength and pore geometry. In this chapter, we elaborate the current status of materials and techniques used in fabrication of scaffolds for craniomaxillofacial bone tissue engineering and discuss the future prospects for advancements

Distinct GDP/GTP bound states of the tandem G-domains of EngA regulate ribosome binding

EngA, a unique GTPase containing a KH-domain preceded by two consecutive G-domains, displays distinct nucleotide binding and hydrolysis activities. So far, Escherichia coli EngA is reported to bind the 50S ribosomal subunit in the guanosine-5′-trihosphate (GTP) bound state. Here, for the first time, using mutations that allow isolating the activities of the two G-domains, GD1 and GD2, we show that apart from 50S, EngA also binds the 30S and 70S subunits. We identify that the key requirement for any EngA–ribosome association is GTP binding to GD2. In this state, EngA displays a weak 50S association, which is further stabilized when GD1 too binds GTP. Exchanging bound GTP with guanosine-5′-diphosphate (GDP), at GD1, results in interactions with 50S, 30S and 70S. Therefore, it appears that GD1 employs GTP hydrolysis as a means to regulate the differential specificity of EngA to either 50S alone or to 50S, 30S and 70S subunits. Furthermore, using constructs lacking either GD1 or both GD1 and GD2, we infer that GD1, when bound to GTP and GDP, adopts distinct conformations to mask or unmask the 30S binding site on EngA. Our results suggest a model where distinct nucleotide-bound states of the two G-domains regulate formation of specific EngA–ribosome complexes

Febuxostat Modulates MAPK/NF- κ

Xanthine oxidase and xanthine dehydrogenase have been implicated in producing myocardial damage following reperfusion of an occluded coronary artery. We investigated and compared the effect of febuxostat and allopurinol in an experimental model of ischemia-reperfusion (IR) injury with a focus on the signaling pathways involved. Male Wistar rats were orally administered vehicle (CMC) once daily (sham and IR + control), febuxostat (10 mg/kg/day; FEB10 + IR), or allopurinol (100 mg/kg/day; ALL100 + IR) for 14 days. On the 15th day, the IR-control and treatment groups were subjected to one-stage left anterior descending (LAD) coronary artery ligation for 45 minutes followed by a 60-minute reperfusion. Febuxostat and allopurinol pretreatment significantly improved cardiac function and maintained morphological alterations. They also attenuated oxidative stress and apoptosis by suppressing the expression of proapoptotic proteins (Bax and caspase-3), reducing TUNEL-positive cells, and increasing the level of antiapoptotic proteins (Bcl-2). The MAPK-based molecular mechanism revealed suppression of active JNK and p38 proteins concomitant with the rise in ERK1/ERK2, a prosurvival kinase. Additionally, a reduction in the level of inflammatory markers (TNF-α, IL-6, and NF-κB) was also observed. The changes observed with febuxostat were remarkable in comparison with those observed with allopurinol. Febuxostat protects relatively better against IR injury than allopurinol by suppressing inflammation and apoptosis mediating the MAPK/NF-κBp65/TNF-α pathway

Molecular Basis of Host-Virus Interactions to Explain Relative Transmission and Severity Caused by Omicron and Delta variants of SARS-CoV-2

In India and other affected countries, Omicron variant of SARS-CoV-2 has shown faster transmission but less clinical severities when compared to Delta strain. Present study was aimed to investigate how molecular changes in the spike proteins of Omicron variant has increased its transmission but reduced the disease severity. We report molecular interactions of Spike proteins of Delta and Omicron variants with ACE-2 receptor to explain how change in chemical and physical nature of mutated amino acids of Omicron variant has affected the internalization competence of virus into host cell. The Research Collaboratory Structural Bioinformatics (RCSB) and Protein Data Bank (PDB) were used to construct ACE2-Spike Protein interaction. The binding affinity of both omicron and delta variant spike proteins with human ACE2 receptor was observed. Spike protein of Omicron variants has revealed total number of 93 dissimilarities of amino acids from Delta strain,15 of which are in its Receptor Binding Domain (RBD). Our study showed that RBD of Delta variant contained only one hydrophobic amino acid whereas there were 6 hydrophobic amino acids in the RBD of Omicron variant. We report that increased number of Hydrophobic Amino Acids in RBD of Omicron variant affects its binding with ACE2 receptor to enter into the cell. The failure of internalization of virus has increased concentration of extracellular virions at nasopharyngeal region leading to faster expulsion of infective droplets during coughing or sneezing to increase transmission but has reduced the severity of infection. The reported observations could prove to be of public health and therapeutic significance

Chemoenzymatic synthesis, nanotization and anti- aspergillus activity of optically enriched fluconazole analogues

Despite recent advances in diagnostic and therapeutic advances in antifungal research, aspergillosis still remains a leading cause of morbidity and mortality. One strategy to address this problem is to enhance the activity spectrum of known antifungals, and we now report the first successful application of Candida antarctica lipase (CAL) for the preparation of optically enriched fluconazole analogs. Anti-Aspergillus activity was observed for an optically enriched derivative, (-)-S-2-(2’ ,4’ -difluorophenyl)-1-hexyl-amino-3-(1‴,2‴,4‴) triazol-1‴-yl-propan-2-ol, which exhibits MIC values of 15.6 μg/mL and 7.8 μg/disc in microbroth dilution and disc diffusion assays, respectively. This compound is tolerated by mammalian erythrocytes and cell lines (A549 and U87) at concentrations of up to 1000 μg/mL. When incorporated into dextran nanoparticles, the novel, optically enriched fluconazole analog exhibited improved antifungal activity against Aspergillus fumigatus (MIC = 1.63 μg/mL). These results not only demonstrate the ability of biocatalytic approaches to yield novel, optically enriched fluconazole derivatives but also suggest that enantiomerically pure fluconazole derivatives, and their nanotised counterparts, exhibiting anti-Aspergillus activity may have reduced toxicity

SPARC 2019 Fake news & home truths : Salford postgraduate annual research conference book of abstracts

Welcome to the Book of Abstracts for the 2019 SPARC conference. This year we not only celebrate the work of our PGRs but also our first ever Doctoral School Best Supervisor awards, which makes this year’s conference extra special. Once again we have received a tremendous contribution from our postgraduate research community; with over 90 presenters, the conference truly showcases a vibrant, innovative and collaborative PGR community at Salford. These abstracts provide a taster of the inspiring, relevant and impactful research in progress, and provide delegates with a reference point for networking and initiating critical debate. Find an abstract that interests you, and say “Hello” to the author. Who knows what might result from your conversation? With such wide-ranging topics being showcased, we encourage you to take up this great opportunity to engage with researchers working in different subject areas from your own. To meet global challenges, high impact research needs interdisciplinary collaboration. This is recognised and rewarded by all major research funders. Engaging with the work of others and forging collaborations across subject areas is an essential skill for the next generation of researchers. Even better, our free ice cream van means that you can have those conversations while enjoying a refreshing ice lolly

Miconazole Microsponges based topical delivery system for diaper dermatitis

Aim: The current investigation was aimed to develop and optimize the microsponges of miconazole nitrate for treatment of diaper dermatitis for enhanced therapeutic effect. Material and Methods: Microsponges were developed by emulsion solvent diffusion technique using 2³ factorial design. Fabricated microsponges were optimized in order to analyze the effects of independent variables on the encapsulation efficiency, particle size, surface topography and in vitro drug release. The optimized formulation was then incorporated into the gel and evaluated. Results: Particle size of all formulations was found to be uniform and scanning electron microscopy (SEM) indicates spherical shape and porous nature of microsponges. In vitro drug release studies of all formulations revealed the release rate within the range of 67%±0.09 to 80.6%± 0.68 at the end of 12 hours. On its basis, formulation F8 was selected and incorporated into the gel (CF8) which was evaluated for pH, viscosity, spreadability, in vitro drug diffusion studies, in vitro anti fungal studies and stability studies. Conclusion: The formulated microsponge-based gel of miconazole nitrate would be a capable substitute to traditional treatment for reliable and economical cure of diaper dermatitis