Vol 30, No 7 (2024)

Immunology, Inflammation & Allergy

Anticoagulation in Patients with Atrial High-rate Episodes Detected by Cardiac Implantable Electronic Devices

Spartalis M., Kontogiannis C., Spartalis E., Iliopoulos D., Siasos G.

Abstract

Atrial high-rate episodes (AHRE) are atrial tachyarrhythmias that are identified by the use of continuous rhythm monitoring devices such as pacemakers, defibrillators, or implantable cardiac monitors. Nevertheless, the therapeutic implications of these rhythm disturbances remain uncertain. The presence of AHRE is associated with an increased risk of stroke as compared to patients who do not exhibit AHRE. The utilisation of oral anticoagulation has the ability to mitigate the likelihood of stroke occurrence in patients with AHRE. However, it is important to note that this treatment approach is also linked to a severe bleeding rate of approximately 2% per year. The stroke rate among individuals diagnosed with AHRE appears to be comparatively lower when compared to patients diagnosed with atrial fibrillation. The efficacy and safety of anticoagulation in patients with AHRE have yet to be definitively established. Further research is required to provide a comprehensive understanding of the effectiveness and safety of oral anticoagulation in individuals with AHRE.

Current Pharmaceutical Design. 2024;30(7):485-488
pages 485-488 views

Organogels: "GelVolution" in Topical Drug Delivery - Present and Beyond

Shirur K., Pandey A., Mutalik S., Nikam A., Roy A., Raychaudhuri R., Navti P., Soman S., Kulkarni S.

Abstract

Topical drug delivery holds immense significance in dermatological treatments due to its non-invasive nature and direct application to the target site. Organogels, a promising class of topical drug delivery systems, have acquired substantial attention for enhancing drug delivery efficiency. This review article aims to explore the advantages of organogels, including enhanced drug solubility, controlled release, improved skin penetration, non-greasy formulations, and ease of application. The mechanism of organogel permeation into the skin is discussed, along with formulation strategies, which encompass the selection of gelling agents, cogelling agents, and additives while considering the influence of temperature and pH on gel formation. Various types of organogelators and organogels and their properties, such as viscoelasticity, non-birefringence, thermal stability, and optical clarity, are presented. Moreover, the biomedical applications of organogels in targeting skin cancer, anti-inflammatory drug delivery, and antifungal drug delivery are discussed. Characterization parameters, biocompatibility, safety considerations, and future directions in optimizing skin permeation, ensuring long-term stability, addressing regulatory challenges, and exploring potential combination therapies are thoroughly examined. Overall, this review highlights the immense potential of organogels in redefining topical drug delivery and their significant impact on the field of dermatological treatments, thus paving the way for exciting prospects in the domain.

Current Pharmaceutical Design. 2024;30(7):489-518
pages 489-518 views

Traditional Uses, Phytochemistry, and Pharmacological Activities of Coleus amboinicus: A Comprehensive Review

Paul K., Gowda B., Hani U., Chandan R., Mohanto S., Ahmed M., Ashique S., Kesharwani P.

Abstract

Coleus amboinicus Benth., also known as Plectranthus amboinicus (Lour.) Spreng., is a perennial plant from the Lamiaceae family commonly found in tropical and warm regions of Africa, Asia, and Australia. Folk medicine commonly employs this remedy to address various ailments, including but not limited to asthma, headaches, skin disorders, coughs, constipation, colds, and fevers. Several phytoconstituents from various phytochemical classes, such as phenolics, terpenoids, phenolic acids, flavonoids, flavones, and tannins, have been identified in Coleus amboinicus up to the present time. Numerous pharmacological properties of Coleus amboinicus crude extracts have been documented through both in vitro and in vivo studies, including but not limited to antitumor, antibacterial, antifungal, antiprotozoal, anti-inflammatory, antioxidant, antidiabetic, wound healing, analgesic, antirheumatic, and various other therapeutic effects. Due to its extensive history of traditional usage, the diverse array of bioactive phytochemicals, and numerous established pharmacological activities, Coleus amboinicus is widely regarded as having significant potential for clinical applications and warrants further exploration, development, and exploitation through research. With this context, the present study gathers information on the occurrence, biological description, cultivation, and nutritional values of Coleus amboinicus. Furthermore, it thoroughly discusses various phytoconstituents, along with their classes, present in Coleus amboinicus, followed by detailed descriptions of their pharmacological activities based on recent literature.

Current Pharmaceutical Design. 2024;30(7):519-535
pages 519-535 views

Effects of High Efficacy Multiple Sclerosis Disease Modifying Drugs on the Immune Synapse: A Systematic Review

Deftereos S., Vavougios G., Bakirtzis C., Hadjigeorgiou G., Grigoriadis N.

Abstract

Background::Co-signaling and adhesion molecules are important elements for creating immune synapses between T lymphocytes and antigen-presenting cells; they positively or negatively regulate the interaction between a T cell receptor with its cognate antigen, presented by the major histocompatibility complex.

Objectives::We conducted a systematic review on the effects of High Efficacy Disease Modifying Drugs (HEDMDs) for Multiple Sclerosis (MS) on the co-signaling and adhesion molecules that form the immune synapse.

Methods::We searched EMBASE, MEDLINE, and other sources to identify clinical or preclinical reports on the effects of HEDMDs on co-signaling and adhesion molecules that participate in the formation of immune synapses in patients with MS or other autoimmune disorders. We included reports on cladribine tablets, anti- CD20 monoclonal antibodies, S1P modulators, inhibitors of Bruton’s Tyrosine Kinase, and natalizumab.

Results::In 56 eligible reports among 7340 total publications, limited relevant evidence was uncovered. Not all co-signaling and adhesion molecules have been studied in relation to every HEDMD, with more data being available on the anti-CD20 monoclonal antibodies (that affect CD80, CD86, GITR and TIGIT), cladribine tablets (affecting CD28, CD40, ICAM-1, LFA-1) and the S1P modulators (affecting CD86, ICAM-1 and LFA-1) and less on Natalizumab (affecting CD80, CD86, CD40, LFA-1, VLA-4) and Alemtuzumab (affecting GITR and CTLA-4).

Conclusion::The puzzle of HEDMD effects on the immune synapse is far from complete. The available evidence suggests that distinguishing differences exist between drugs and are worth pursuing further.

Current Pharmaceutical Design. 2024;30(7):536-551
pages 536-551 views

A New Cell Model Overexpressing sTGFBR3 for Studying Alzheimer's Disease In vitro

Chen J., Zhou L., Zhao Q., Qi Z.

Abstract

Background::Recent studies have suggested that abnormal microglial hyperactivation has an important role in the progression of Alzheimer's disease (AD). sTGFBR3 (a shed extracellular domain of the transforming growth factor type III receptor) is a newly identified target of microglia polarization dysregulation, whose overexpression can cause abnormal accumulation of transforming growth factor β1 (TGF-β1), promoting Aβ, tau, and neuroinflammatory pathology.

Objective::The objective of this study is to develop and validate a new cell model overexpressing sTGFBR3 for studying AD in vitro.

Methods::BV2 cells (a microglial cell derived from C57/BL6 murine) were used as a cell model. Cells were then treated with different concentrations of lipopolysaccharide (LPS) (0, 1, or 0.3 µg/mL) for 12, 24, or 48h and then with or without sodium pervanadate (100 µM) for 30 min. Next, the effect surface optimization method was used to determine optimal experimental conditions. Finally, the optimized model was used to assess the effect of ZQX series compounds and vasicine on cell viability and protein expression. Expression of TGFBR3 and TNF-α was assessed using Western blot. MTT assay was used to assess cell viability, and enzyme- linked immunosorbent assay (ELISA) was employed to evaluate extracellular TGF-β1 and sTGFBR3

Results::LPS (0.3 µg/mL) treatment for 11 h at a cell density of 60% and pervanadate concentration (100 µM) incubation for 30 min were the optimal experimental conditions for increasing membrane protein TGFBR3 overexpression, as well as extracellular sTGFBR3 and TGF-β1. Applying ZQX-5 and vasicine reversed this process by reducing extracellular TGF-β1, promoting the phosphorylation of Smad2/3, a protein downstream of TGF-β1, and inhibiting the release of the inflammatory factor TNF-α.

Conclusion::This new in vitro model may be a useful cell model for studying Alzheimer's disease in vitro

Current Pharmaceutical Design. 2024;30(7):552-563
pages 552-563 views