The Sensitivity of <Emphasis Type="Italic">In Vitro</Emphasis> Permeation Tests to Chemical Penetration Enhancer Concentration Changes in Fentanyl Transdermal Delivery Systems

Chemical penetration enhancers (CPEs) are frequently incorporated into transdermal delivery systems (TDSs) to improve drug delivery and to reduce the required drug load in formulations. However, the minimum detectable effect of formulation changes to CPE-containing TDSs using in vitro permeation tests (IVPT), a widely used method to characterize permeation of topically applied drug products, remains unclear. The objective of the current exploratory study was to investigate the sensitivity of IVPT in assessing permeation changes with CPE concentration modifications and subsequently the feasibility of IVPT’s use for support of quality control related to relative CPE concentration variation in a given formulation. A series of drug-in-adhesive (DIA) fentanyl TDSs with different amounts of CPEs were prepared, and IVPT studies utilizing porcine and human skin were performed. Although IVPT could discern TDSs with different amounts of CPE by significant differences in flux profiles, maximum flux (J_max) values, and total permeation amounts, the magnitudes of the CPE increment needed to see such significant differences were very high (43–300%) indicating that IVPT may have limitations in detecting small changes in CPE amounts in some TDSs. Possible reasons for such limitations include formulation polymer and/or other excipients, type of CPE, variability associated with IVPT, skin type used, and disrupted stratum corneum (SC) barrier effects caused by CPEs.     

Chlorophyll <Emphasis Type="Italic">a</Emphasis> fluorescence as a tool to monitor physiological status of plants under abiotic stress conditions

Plants living under natural conditions are exposed to many adverse factors that interfere with the photosynthetic process, leading to declines in growth, development, and yield. The recent development of Chlorophyll a fluorescence (ChlF) represents a potentially valuable new approach to study the photochemical efficiency of leaves. Specifically, the analysis of fluorescence signals provides detailed information on the status and function of Photosystem II (PSII) reaction centers, light-harvesting antenna complexes, and both the donor and acceptor sides of PSII. Here, we review the results of fast ChlF analyses of photosynthetic responses to environmental stresses, and discuss the potential scientific and practical applications of this innovative methodology. The recent availability of portable devices has significantly expanded the potential utilization of ChlF techniques, especially for the purposes of crop phenotyping and monitoring.     

Effect of biofertilizers and putrescine amine on the physiological features and productivity of date palm (<Emphasis Type="Italic">Phoenix dactylifera,</Emphasis> L.) grown on reclaimed-salinized soil

Key message

Plant growth promoting rhizobia bacteria and mycorrhizae in the presence of putrescine allows and/or enables date palm to increase its adaptation to reclaimed/salinized areas.

Abstract

Amines and biofertilizers play an important role in a plant’s response to adverse environmental conditions including salt and osmotic stress. This study investigates the integration effect of putrescine amine (Put), biofertilizers, and mycorrhizae (My) on the date palm zaghloul genotype irrigated by saline water and grown in reclaimed saline soil. The data collected indicates that selected plant growth promoting rhizobacteria, in the presence of Put, enables the date palm zaghloul genotype to increase its tolerance and adapt to stress conditions in the reclaimed saline soil. Overall, treatments reduced salt-induced oxidative damage in the date palm, resulting in increased productivity and improved fruit quality. The results observed may be a consequence of the increase in photosynthetic pigments, activities of antioxidant enzymes, organic solutes and/or promoting growth substances such as gibberellic acid (GA₃), auxins (IAA) and cytokinin. Moreover, a decrease in the levels of lipid peroxidation and inhibitor substances such as abscisic acid (ABA) may be related. The most effective interaction treatments were seen at 2.5 mM Put due to an increase in the activities of ascorbate peroxidase (APX), glutathione reductase (GR) and superoxide dismutase (SOD) while a decrease in lipid peroxidation was noticed. The combination of Put with plant growth promoting rhizobacteria (PGPR) at a 5 mM concentration as biofertilizer increased diamine oxidase (DAO) and polyamine oxidase (PAO) activities when compared to the other treatments. The activity of these two enzymes can produce hydrogen peroxide (H₂O₂), which may act in structural defense as a signal molecule and decrease the production of polyamines against salt-induced oxidative damage in date palm. We believe that further investigation is needed to understand the tolerance/adaptation mechanisms in date palm grown under stress condition.

     

Low PSI content limits the photoprotection of PSI and PSII in early growth stages of chlorophyll b-deficient wheat mutant lines

Photosynthesis Research - In vivo analyses of electron and proton transport-related processes as well as photoprotective responses were carried out at different stages of growth in chlorophyll b...     

The alanine-serine-cysteine-1 (Asc-1) transporter controls glycine levels in the brain and is required for glycinergic inhibitory transmission

Asc-1 (SLC7A10) is an amino acid transporter whose deletion causes neurological abnormalities and early postnatal death in mice. Using metabolomics and behavioral and electrophysiological methods, we demonstrate that Asc-1 knockout mice display a marked decrease in glycine levels in the brain and spinal cord along with impairment of glycinergic inhibitory transmission, and a hyperekplexia-like phenotype that is rescued by replenishing brain glycine. Asc-1 works as a glycine and L-serine transporter, and its transport activity is required for the subsequent conversion of L-serine into glycine in vivo. Asc-1 is a novel regulator of glycine metabolism and a candidate for hyperekplexia disorders.     

Opioids and efflux transporters. Part 1: P-glycoprotein substrate activity of N-substituted analogs of meperidine

P-Glycoprotein (P-gp) is an efflux transporter which is up-regulated at the blood-brain barrier in both morphine- and oxycodone-tolerant rats. Numerous studies have shown that many clinically employed opioid analgesics are substrates for P-gp, suggesting that up-regulation of P-gp may contribute to the development of central tolerance to opioids. The studies herein focus on the development of SAR for P-gp substrate activity in the meperidine series of compounds, and show that a meperidine analog of greater potency, N-phenylbutyl-N-normeperidine, has low activity as a P-gp substrate and has the potential to be utilized as a tool to study the contribution of P-gp to the development of central tolerance to opioids.     

Prevalence of T790M mutation among TKI-therapy resistant Lebanese lung cancer patients based on liquid biopsy analysis: a first report from a major tertiary care center

Molecular Biology Reports - Lung adenocarcinoma patients have variable prognosis due to many factors. Detection of epidermal growth factor receptor (EGFR) activating mutations is one of the factors...     

Seed priming of plants aiding in drought stress tolerance and faster recovery: a review

Plant Growth Regulation - Drought stress exposure adversely affects plant growth and productivity. Various seed priming techniques are experimented to mitigate the adverse effect of drought stress...     

Topo II inhibition and DNA intercalation by new phthalazine-based derivatives as potent anticancer agents: design,synthesis, anti-proliferative,docking, and in vivo studies

This research presents the design and synthesis of a novel series of phthalazine derivatives as Topo II inhibitors, DNA intercalators, and cytotoxic agents. In vitro testing of the new compounds against HepG-2, MCF-7, and HCT-116 cell lines confirmed their potent cytotoxic activity with low IC₅₀ values. Topo II inhibition and DNA intercalating activities were evaluated for the most cytotoxic members. IC₅₀ values determination demonstrated Topo II inhibitory activities and DNA intercalating affinities of the tested compounds at a micromolar level. Amongst, compound 9d was the most potent member. It inhibited Topo II enzyme at IC₅₀ value of 7.02 ± 0.54 µM with DNA intercalating IC₅₀ of 26.19 ± 1.14 µM. Compound 9d was then subjected to an in vivo antitumor examination. It inhibited tumour proliferation reducing solid tumour volume and mass. Additionally, it restored liver enzymes, proteins, and CBC parameters near-normal, indicating a remarkable amelioration in their functions along with histopathological examinations.     

Stem cell applications for pathologies of the urinary bladder

New stem cell based therapies are undergoing intense research and are widely investigated in clinical fields including the urinary system. The urinary bladder performs critical complex functions that rely on its highly coordinated anatomical composition and multiplex of regulatory mechanisms. Bladder pathologies resulting in severe dysfunction are common clinical encounter and often cause significant impairment of patient’s quality of life. Current surgical and medical interventions to correct urinary dysfunction or to replace an absent or defective bladder are sub-optimal and are associated with notable complications. As a result, stem cell based therapies for the urinary bladder are hoped to offer new venues that could make up for limitations of existing therapies. In this article, we review research efforts that describe the use of different types of stem cells in bladder reconstruction, urinary incontinence and retention disorders. In particular, stress urinary incontinence has been a popular target for stem cell based therapies in reported clinical trials. Furthermore, we discuss the relevance of the cancer stem cell hypothesis to the development of bladder cancer. A key subject that should not be overlooked is the safety and quality of stem cell based therapies introduced to human subjects either in a research or a clinical context.