In vivo evaluation of a mucoadhesive polymeric caplet for intravaginal anti-HIV-1 delivery and development of a molecular mechanistic model for thermochemical characterization

Context and objective: The aim of this study was to develop, characterize and evaluate a mucoadhesive caplet resulting from a polymeric blend (polymeric caplet) for intravaginal anti-HIV-1 delivery.

Materials and methods: Poly(lactic-co-glycolic) acid, ethylcellulose, poly(vinylalcohol), polyacrylic acid and modified polyamide 6, 10 polymers were blended and compressed to a caplet-shaped device, with and without two model drugs 3′-azido-3′-deoxythymidine (AZT) and polystyrene sulfonate (PSS). Thermal analysis, infrared spectroscopy and microscopic analysis were carried out on the caplets employing temperature-modulated DSC (TMDSC), Fourier transform infra-red (FTIR) spectrometer and scanning electron microscope, respectively. In vitro and in vivo drug release analyses as well as the histopathological toxicity studies were carried out on the drug-loaded caplets. Furthermore, molecular mechanics (MM) simulations were carried out on the drug-loaded caplets to corroborate the experimental findings.

Results and discussion: There was a big deviation between the T_g of the polymeric caplet from the T_g's of the constituent polymers indicating a strong interaction between constituent polymers. FTIR spectroscopy confirmed the presence of specific ionic and non-ionic interactions within the caplet. A controlled near zero-order drug release was obtained for AZT (20 d) and PSS (28 d). In vivo results, i.e. the drug concentration in plasma ranged between 0.012–0.332?mg/mL and 0.009–0.256?mg/mL for AZT and PSS over 1–28 d.

Conclusion: The obtained results, which were corroborated by MM simulations, attested that the developed system has the potential for effective delivery of anti-HIV-agents.     

Activation of extracellular matrix metalloproteinases in equine laminitis

Samples of connective tissue obtained from the hoof of six laminitic and eight non-laminitic adult horses were analysed zymographically to investigate whether connective tissue matrix metalloproteinases are activated or induced during laminitis. The activity or matrix metalloproteinases was substantially greater in the tissues from the laminitic horses than in the tissues from the non-laminitic horses. A comparison of the collagenolytic activity in the laminitic and control tissues showed that collagenolytic activities corresponding to the 92 kDa (P < 0.001), 72 kDa (P < 0.01) and 66 kDa (P < 0.01) bands were induced in the laminitic tissues.     

Comparison of the generation of oil by the extraction and the hydropyrolysis of biomass

This paper discusses the maximisation of the yields of useful bio-oils generated from seeds and nut-shells both by extraction and by hydropyrolysis. The formation and the composition of the bio-oils are also discussed.Powdered (<0.25 mm diameter) Rapeseed, Linseed and Safflower seed and Hazel nut and Walnut shells, that is, fresh precursors of liptinite, have been characterised by their elemental analyses, infra-red and NMR spectra. Bio-oils obtained both by extraction and by slow hydropyrolysis to 520 °C at moderate pressure in the presence of ammonium dioxydithiomolybdate have been compared by the same analyses and by gas chromatography. Consistent with previous work [Hardy JA. A greener future with biodiesel. Green Chem 2001 G56-G57], extraction of the seeds with organic solvents, including Diesel oil, gave yields of up to 40% together with an uninteresting residue. However, subsequent saponification of the residues gave further yields of oil. Hydropyrolysis removed oxygen from the seeds as water and as oxides of carbon to generate bio-oil in yields of up to 75%. Whereas little oil could be extracted from the nut-shells, hydropyrolysis gave oil yields of ∼40%. Some char was also formed, suggesting that optimisation of the hydropyrolysis might give even larger yields of oil.     

CONCENTRATION POLARIZATION OCCURRING INSIDE THE MEMBRANE DURING STEADY STATE PERVAPORATION

Experimental profiles of a single penetrant (water) across the membrane have been established at different downstream pressures during steady state pervaporation. The profiles ofacetic acid-water binary penetrant system across the membrane were also measured at different downstream pressures, temperatures and compositions during steady state pervaporation. A stack of identical pre-characterized symmetric aromatic polyamide membranes was used for the profile study. The theoretical prediction of concentration polarization from mathematical equations has been confirmed by the experimental profile data for a binary penetrant system.     

Formation of Nanocrystalline Calcia by the Decomposition of Calcite

Formation of nanocrystalline calcia from calcite has been studied in situ via transmission electron microscopy. The crystallographic transformation occurred via two mechanisms: the first is by distortion of the cleaved rhombohedron of calcite, formed by {104} planes in hexagonal coordinates, into a cube. This produced a microstructure of oriented, elongated nanocrystals of calcia with planar boundaries. In the second mechanism, the micrometer-sized parent calcite particles broke up into nano-sized grains as the decomposition began, leading to irregularly shaped, randomly oriented nanocrystals of calcia.     

An Improved Multifactor User Authentication Scheme for Wireless Sensor Networks

Wireless Personal Communications - Wireless Sensor Networks (WSNs) are used to collect and transmitted the data in various applications from normal to those which requires significant security...     

Development of a framework for truss-braced wing conceptual MDO

The paper describes the development of a multidisciplinary design optimization framework for conceptual design of truss-braced wing configurations. This unconventional configuration requires specialized analysis tools supported by a modular and flexible framework to accommodate different configurations. While the previous framework developed at Virginia Tech was a monolithic Fortran-77 code, the need for more flexibility for complex truss-braced wing configurations was addressed by the development of this new framework, which is based on Phoenix Integration ModelCenter^TM environment. The framework uses updated structural and aerodynamic design modules that enable a more general geometry definition. The new framework, thus, provides a foundation for future design concepts, especially multi-member truss-braced wing configurations. The fuel saving potential of these truss-braced wing configurations is presented by comparing different truss designs with gradually increased level of complexity.     

COVID-19 Mimics Pulmonary Dysfunction in Muscular Dystrophy as a Post-Acute Syndrome in Patients

Although progressive wasting and weakness of respiratory muscles are the prominent hallmarks of Duchenne muscular dystrophy (DMD) and long-COVID (also referred as the post-acute sequelae of COVID-19 syndrome); however, the underlying mechanism(s) leading to respiratory failure in both conditions remain unclear. We put together the latest relevant literature to further understand the plausible mechanism(s) behind diaphragm malfunctioning in COVID-19 and DMD conditions. Previously, we have shown the role of matrix metalloproteinase-9 (MMP9) in skeletal muscle fibrosis via a substantial increase in the levels of tumor necrosis factor-α (TNF-α) employing a DMD mouse model that was crossed-bred with MMP9-knockout (MMP9-KO or MMP9^-/-) strain. Interestingly, recent observations from clinical studies show a robust increase in neopterin (NPT) levels during COVID-19 which is often observed in patients having DMD. What seems to be common in both (DMD and COVID-19) is the involvement of neopterin (NPT). We know that NPT is generated by activated white blood cells (WBCs) especially the M1 macrophages in response to inducible nitric oxide synthase (iNOS), tetrahydrobiopterin (BH4), and tetrahydrofolate (FH4) pathways, i.e., folate one-carbon metabolism (FOCM) in conjunction with epigenetics underpinning as an immune surveillance protection. Studies from our laboratory, and others researching DMD and the genetically engineered humanized (hACE2) mice that were administered with the spike protein (SP) of SARS-CoV-2 revealed an increase in the levels of NPT, TNF-α, HDAC, IL-1β, CD147, and MMP9 in the lung tissue of the animals that were subsequently accompanied by fibrosis of the diaphragm depicting a decreased oscillation phenotype. Therefore, it is of interest to understand how regulatory processes such as epigenetics involvement affect DNMT, HDAC, MTHFS, and iNOS that help generate NPT in the long-COVID patients.     

Effect of tanniniferous Terminalia chebula extract on rumen biohydrogenation, ∆(9)-desaturase activity, CLA content and fatty acid composition in longissimus dorsi muscle of kids

Conjugated linoleic acid, a fatty acid found in milk fat and ruminant meat is one of the functional food components. Modifying fatty acid composition so as to increase CLA and other beneficial PUFA/MUFA level and reducing SFA levels might be a key to enhance the neutraceutical and therapeutic value of ruminant-derived food products. In the present experiment, the effect of supplementation of polyphenol rich Terminalia chebula plant extract at different concentrations (1.06 g/kg and 3.18 g/kg of body weight in T1 and T2 groups, respectively) was investigated on fatty acid composition of rumen fluid, plasma, intramuscular fat and Δ9-desaturase activity in longissimus dorsi muscle of crossbred kids. Total MUFA and PUFA content in muscle were enhanced by 25 and 35%, respectively, whereas SFA was reduced by 20% thereby improving the desaturation index. Δ9-desaturase activity also increased by 47% resulting in an enhancement of total CLA content (58.73%) in muscle.