Assessment and Management of Scabies in Primary Care Settings

Scabies is an overlooked tropical illness that yet has significant worldwide effects and lasting health repercussions. The condition is caused by the mite Sarcoptes scabei var. hominis, which is a parasitic organism that dwells on the outer layer of the human skin. Scabies is prevalent in impoverished neighborhoods as a result of the high population density in locations such as nursing homes, correctional facilities, and among homeless and displaced children. Nevertheless, modern nations are also prone to scabies infestations, particularly in cases of institutional outbreaks or mini epidemics occurring after conflict or natural calamities. Scabies diagnosis can be aided by both invasive and noninvasive techniques. This paper reviews assessment diagnosis, and management of scabies in primary health care settings

Development and validation of a new preclinical analgesic assay

Current preclinical analgesic assays suffer from major weaknesses that hamper the discovery of new drugs. This thesis describes the development of a new mouse assay, the Hypertonic Saline Analgesia Assay (HSAA). Chapter 1 provides an overview for current preclinical analgesic assays and discusses their strengths and weaknesses. It also discusses the impact of sex, strain, and circadian rhythm on nociception and antinociception. Chapter 2 describes the development of the assay. We evaluated hypertonic saline (HS) as a nociceptive agent, its optimal concentration, the responses, and the optimal time for evaluation. We also assessed sex related differences and tissue damage. Chapter 3 describes the validation of the assay. Analgesics known to be effective clinically were assayed to establish the validity of the HSAA. HSAA demonstrated that responses were attenuated by a range of clinical analgesics, produces minimal tissue damage and has lower variability compared to other assays. Chapter 4 examines the refinement of the assay. We determined the effects of repeated testing, strain, sex, and diurnal rhythm on the reproducibility of HSAA. The absence of tissue damage raised the possibility of repeated testing in a mouse to reduce the number of animals. The antinociceptive action of morphine was unchanged when HSAA was used at different times in the same hind paw of a mouse. No histological damage was observed following multiple injections of HS. Repeated testing in the same mouse reduces both the number of animals required and the variance of the results. Initial development and validation were performed with CD-1 mice. To evaluate the widespread utility of HSAA, we evaluated its ability to detect analgesics in another commonly used murine strain, C57BL/6. HSAA detected the dose-dependent attenuation of responses by morphine in C57BL/6 which was equivalent to responses found with CD-1 mice. Additionally, female mice were demonstrated to have greater response than males. The diurnal cycle had little effect. In conclusion, the HSAA rapidly detects standard analgesics and is reproducible within an animal and between strains. This assay minimizes tissue damage and the number of animals required. HSAA is a useful addition to the armamentarium of preclinical analgesic assays.  Medicine, Faculty ofGraduat

An overview of ion channels therapeutics in the treatment of pain

Significance of the study: The clinical management of severe and chronic pain relies heavily on opioids that cause serious side-effects. There therefore exists an urgent need to develop safer and effective analgesics. Moreover, there has been significant progress in the understanding of pain physiology, especially the role of some ion channels in the pain process. Thus, the immense potential of ion channel therapeutics in pain management is a subject of current interest. Aim of the study: This study is a comprehensive review, focused on ion channels as potential therapeutic targets for the treatment of pain. Research methodology: A systemic search of available literature on ion channels analgesics was performed. Articles related to the drug discovery and clinical trials on relevant topics were extracted from PubMed and other databases. Major conclusion of the study: Small molecules targeted at ion channels pathways hold great promise for creating a new approach to pain treatment. Several molecules targeting TRPV1, TRPV3, TRPV4, TRPA1, TRPM8, Nav1.7, Nav1.8, CaV2.2, CaV3.2, ASIC, and P2X3 have demonstrated potential clinical benefits. However, till date US FDA has approved capsaicin, ziconotide, and pregabalin for the treatment of different pain conditions. This review highlights the possibilities for discovery and research on ion channels and their potential for pain treatment

The Impact of Autologous Platelet Concentrates on the Periapical Tissues and Root Development of Replanted Teeth: A Systematic Review

Introduction: In many cases, the replanted teeth may undergo resorption or ankyloses. Recent studies show that autologous platelet concentrates (APCs) may improve the outcomes of tooth replantation. The aim of this systematic review was to summarize and critically appraise the currently available literature on the use of APCs before tooth replantation. Methodology: An electronic search was conducted on the following research databases: PubMed/MEDLINE, ISI Web of Science, EMBASE and Scopus. The following medical subject heading (MeSH) keywords used were: ((tooth replantation) OR (replanted tooth) OR (teeth replantation) OR (replanted teeth)) AND ((autologous platelet concentrate) OR (platelet-rich plasma) OR (platelet-rich fibrin) OR (autologous platelet)). The studies’ data was extracted, and the research’ quality was rated using the CARE and ARRIVE protocols. Results: Ten case reports and three animal studies, one cell study and one study, which included both animal and in vitro experiments, were included in this review. In majority of the studies, APCs improved the outcomes of tooth replantation. However, there were various sources of bias in the most of the research, which may have influenced the results. Conclusions: Although majority of the studies indicate that APCs may improve outcomes of tooth replantation, majority of the studies contained numerous sources of bias. Additionally, the sample size of the included subjects is inadequate to predict the clinical efficacy of APCs in management of replanted teeth. Large-scale, multi-center and long-term studies are required to ascertain the efficacy of APCs in improve the outcomes of tooth replantation

Synthesis and biological evaluation of tetrazole ring incorporated oxazole-pyrimidine derivatives as anticancer agents

A new library of tetrazole rings with oxazole-pyrimidine derivatives (9a–j) has been developed and synthesized. All of the compounds were characterized using spectral data. These were then tested for in vitro anticancer activity against four human cancer cell lines: prostate cancer (PC3 & DU-145), lung cancer (A549), and breast cancer (MCF-7) using an MTT assay. Etoposide was chosen as the positive control. Most of the compounds demonstrated moderate to good activity. These compounds (9a, 9b, 9d, 9g, and 9h) demonstrated the most powerful action. Particularly, one chemical 9h had exceptional antitumor efficacy.</p

Application of 32 factorial design for loratadine-loaded nanosponge in topical gel formulation: comprehensive in-vitro and ex vivo evaluations

Loratadine (LoR) is a highly lipophilic and practically insoluble in water, hence having a low oral bioavailability. As it is formulated as topical gel, it competitively binds with the receptors, thus reducing the side-effects. The objective of this study was to prepare LoR loaded nanosponge (LoR-NS) in gel for topical delivery. Nine different formulations of emulsion were prepared by solvent evaporation method with polyvinyl alcohol (PVA), ethyl cellulose (EC), and dichloromethane (DCM). Based on 32 Full Factorial Design (FFD), optimization was carried out by varying the concentration of LOR:EC ratio and stirring rate. The preparations were subjected for the evaluation of particle size (PS), in vitro release, zeta potential (ZP) and entrapment efficiency (EE). The results revealed that the NS dispersion was nanosized with sustained release profiles and significant PS. The optimised formulation was formulated and incorporated into carbopol 934P hydrogel. The formulation was then examined to surface morphological characterizations using scanning electron microscopy (SEM) which depicted spherical NS. Stability studies, undertaken for 2 months at 40 ± 2 °C/75 ± 5% RH, concluded to the stability of the formulation. The formulation did not cause skin irritation. Therefore, the prepared NS hydrogel proved to be a promising applicant for LoR as a novel drug delivery system (NDDS) for safe, sustained and controlled topical application

Ameliorative Effect of Ethanolic Extract of <i>Moringa oleifera</i> Leaves in Combination with Curcumin against PTZ-Induced Kindled Epilepsy in Rats: In Vivo and In Silico

The ameliorative effect of ethanolic extract of M. oleifera (MOEE) leaves in combination with curcumin against seizures, cognitive impairment, and oxidative stress in the molecular docking of PTZ-induced kindled rats was performed to predict the potential phytochemical effects of MOEE and curcumin against epilepsy. The effect of pretreatment with leaves of M. oleifera ethanolic extracts (MOEE) (250 mg/kg and 500 mg/kg, orally), curcumin (200 mg/kg and 300 mg/kg, orally), valproic acid used as a standard (100 mg/kg), and the combined effect of MOEE (250 mg/kg) and curcumin (200 mg/kg) at a low dose on Pentylenetetrazole was used for (PTZ)-induced kindling For the development of kindling, individual Wistar rats (male) were injected with pentyletetrazole (40 mg/kg, i.p.) on every alternate day. Molecular docking was performed by the Auto Dock 4.2 tool to merge the ligand orientations in the binding cavity. From the RCSB website, the crystal structure of human glutathione reductase (PDB ID: 3DK9) was obtained. Curcumin and M. oleifera ethanolic extracts (MOEE) showed dose-dependent effects. The combined effects of MOEE and curcumin leaves significantly improved the seizure score and decreased the number of myoclonic jerks compared with a standard dose of valproic acid. PTZ kindling induced significant oxidative stress and cognitive impairment, which was reversed by pretreatment with MOEE and curcumin. Glutathione reductase (GR) is an enzyme that plays a key role in the cellular control of reactive oxygen species (ROS). Therefore, activating GR can uplift antioxidant properties, which leads to the inhibition of ROS-induced cell death in the brain. The combination of the ethanolic extract of M. oleifera (MOEE) leaves and curcumin has shown better results than any other combination for antiepileptic effects by virtue of antioxidant effects. As per the docking study, chlorogenic acid and quercetin treated with acombination of curcumin have much more potential

Significance and Diagnostic Role of Antimicrobial Cathelicidins (LL-37) Peptides in Oral Health

Cathelicidins are a group of oral antimicrobial peptides that play multiple vital roles in the human body, such as their antimicrobial (broad spectrum) role against oral microbes, wound healing, and angiogenesis, with recent evidences about their role in cancer regulation. Cathelicidins are present in humans and other mammals as well. By complex interactions with the microenvironment, it results in pro-inflammatory effects. Many in vitro and in vivo experiments have been conducted to ultimately conclude that these unique peptides play an essential role in innate immunity. Peptides are released in the precursor form (defensins), which after cleavage results in cathelicidins formation. Living in the era where the major focus is on non-invasive and nanotechnology, this ultimately leads to further advancements in the field of salivaomics. Based on current spotlight innovations, we have highlighted the biochemistry, mode of action, and the importance of cathelicidins in the oral cavity

Phytocompound screening, antioxidant activity and molecular docking studies of pomegranate seed: a preventive approach for SARS-CoV-2 pathogenesis

Abstract A global hazard to public health has been generated by the coronavirus infection 2019 (COVID-19), which is spreading quickly. Pomegranate is a strong source of antioxidants and has demonstrated a number of pharmacological characteristics. This work was aimed to analyze the phytochemicals present in ethanolic pomegranate seed extract (PSE) and their in vitro antioxidant potential and further in-silico evaluation for antiviral potential against crystal structure of two nucleocapsid proteins i.e., N-terminal RNA binding domain (NRBD) and C-terminal Domain (CTD) of SARS-CoV-2. The bioactive components from ethanolic extract of PSE were assessed by gas chromatography-mass spectroscopy (GC–MS). Free radical scavenging activity of PSE was determined using DPPH dye. Molecular docking was executed through the Glide module of Maestro software. Lipinski’s 5 rule was applied for drug-likeness characteristics using cheminformatics Molinspiration software while OSIRIS Data Warrior V5.5.0 was used to predict possible toxicological characteristics of components. Thirty-two phytocomponents was detected in PSE by GC–MS technique. Free radical scavenging assay revealed the high antioxidant capacity of PSE. Docking analysis showed that twenty phytocomponents from PSE exhibited good binding affinity (Docking score ≥ − 1.0 kcal/mol) towards NRBD and CTD nucleocapsid protein. This result increases the possibility that the top 20 hits could prevent the spread of SARS-CoV-2 by concentrating on both nucleocapsid proteins. Moreover, molecular dynamics (MD) simulation using GROMACS was used to check their binding efficacy and internal dynamics of top complexes with the lowest docking scores. The metrics root mean square deviation (RMSD), root mean square fluctuation (RMSF), intermolecular hydrogen bonding (H-bonds) and radius of gyration (Rg) revealed that the lead phytochemicals form an energetically stable complex with the target protein. Majority of the phytoconstituents exhibited drug-likeness with non-tumorigenic properties. Thus, the PSE phytoconstituents could be useful source of drug or nutraceutical development in SARS-CoV-2 pathogenesis