Mobile-Based Augmented Reality Application in Pharmacy Schools Implemented in Pharmaceutical Compounding Laboratories: Students' Benefits and Reception.

Background: Augmented reality (AR) is a technological approach which combines virtual objects such as text, pictures or videos with physical objects (real-world). The study aimed to design, implement and validate a mobile-based AR application, as a self-paced, interactive, student-centered learning tool be used in the pharmaceutical compounding laboratory course for first year pharmacy students.

Method: A mobile-based AR application (Amplified Rx app; HeyPayLess Inc) compatible with iOS and android operating system was developed.

The novel piperazino-enaminone JOAB-40 reduced colitis severity in mice via inhibition tumor necrosis factor-α and interleukin-1β.

Brief Introduction: The synthetic compound enaminone E121 has an established role as a potent anti-tussive, bronchodilator and anti-inflammatory agent in asthma, cough, and colitis induced animal models. The addition of an N-alkylated piperazine motif to the terminal end of E121 lead to the generation of various analogues such as JOAB-40. JOAB-40 was shown to be more potent than the lead compound E121 in inhibiting the expression of the chemokine receptor CCR2, ERK1/2 phosphorylation, and the release of pro-inflammatory cytokines in vitro.

Nutraceuticals' Novel Formulations: The Good, the Bad, the Unknown and Patents Involved.

Traditional nutraceuticals and cosmeceuticals hold pragmatic nature with respect to their definitions, claims, purposes and marketing strategies. Their definitions are not well established worldwide. They also have different regulatory definitions and registration regulatory processes in different parts of the world.

Novel Piperazino-Enaminones Decrease Pro-inflammatory Cytokines Following Hemarthrosis in a Hemophilia Mouse Model.

Hemarthrosis is the primary cause of hemophiliac arthropathy (HA). Pro-inflammatory cytokines are thought to play an important role in the pathogenesis of HA, and thus, anti-cytokine approaches may be used as an adjuvant therapy. A novel series of enaminone compounds (JODI), that contain the N-aryl piperazino motif, have been shown in vitro to reduce pro-inflammatory cytokines and thus may be efficacious in vivo.

Design, synthesis and biological evaluation of piperazino-enaminones as novel suppressants of pro-Inflammatory cytokines.

Infection triggers the release of pro-inflammatory cytokines (TNF-alpha and IL-6). Over-production, however, cause tissue injury seen in severe asthma. The ability of enaminone E121 to reduce pro-inflammatory cytokines in our laboratory encouraged further examination of its structural scaffold.

Current and novel anti-inflammatory drug targets for inhibition of cytokines and leucocyte recruitment in rheumatic diseases.

Objectives: Many studies of disease state mechanisms reveal that unbridled inflammation is to blame for many of the symptoms associated with autoimmune diseases such as Crohn's and Rheumatoid Arthritis (RA). While therapies aimed at decreasing levels of pro-inflammatory cytokines exist, some have failed clinically or have extensive adverse effects. The aim of this review is to discuss common drug targets for anti-inflammatory therapies as well as explore potential mechanisms of action for new therapies.

Anti-Inflammatory Properties of the Enaminone E121 in the Dextran Sulfate Sodium (DSS) Colitis Model.

Background: Enaminones are synthetic compounds with an established role in the prevention of various forms of seizures. Recent evidence suggests potent anti-tussive, bronchodilation and anti-inflammatory properties. Pre-treatment with particularly E121 compound resulted in a decrease in leukocyte recruitment in the ovalbumin induced-model of asthma, immune cell proliferation and cytokine release in vitro.

Novel Piperazino-Enaminones Suppress Pro-Inflammatory Cytokines and Inhibit Chemokine Receptor CCR2.

Pro-inflammatory mediators including TNF-alpha, IL-6, and nitric oxide are important for the regulation of the immune response when an infection is present, but when overproduced, it can be responsible for the development of tissue and organ injury seen in sepsis, as well as severe asthma, and autoimmune diseases such as Crohn's disease and rheumatoid arthritis. Data from our lab to characterize the novel compound enaminone E121 have suggested that macrophages stimulated with lipopolysaccharide (LPS) release significantly decreased levels of TNF-alpha and IL-6 as measured by enzyme-linked immunosorbent assay as compared to the DMSO control group. Additionally, functional experiments in a mouse model of asthma have shown that E121 is efficacious in decreasing airway hyperresponsiveness.

Paclitaxel Causes Electrophysiological Changes in the Anterior Cingulate Cortex via Modulation of the γ-Aminobutyric Acid-ergic System.

Objective: The aim of this study was to elucidate any electrophysiological changes that may contribute to the development of neuropathic pain during treatment with the anticancer drug paclitaxel, particularly in the γ-aminobutyric acid (GABA) system.

Materials And Methods: One hundred and eight Sprague-Dawley rats were used (untreated control: 43; vehicle-treated: 21, and paclitaxel-treated: 44). Paclitaxel (8 mg/kg) was administered intraperitoneally on 2 alternate days to induce mechanical allodynia.

Evaluation of the antinociceptive activities of enaminone compounds on the formalin and hot plate tests in mice.

Recently, we found that methyl 4-(4'-bromophenyl)aminocyclohex-3-en-6-methyl-2-oxo-1-oate (E139), an anticonvulsant enaminone, has antinociceptive activity in the hot plate test. In this study we evaluated the antinociceptive activity of five anilino enaminones E139, ethyl 4-(4'-chlorophenyl)amino-6-methyl-2-oxocyclohex-3-en-1-oate (E121), ethyl 4-(4'-bromophenyl)amino-6-methyl-2-oxocyclohex-3-en-1-oate (E122), methyl 4-(4'-chlorophenyl)amino-6-methyl-2-oxocyclohex-3-en-1-oate (E138) and ethyl 4-(4'-fluorophenyl)amino-6-methyl-2-oxocyclohex-3-en-1-oate (BRG 19) using the formalin and hot plate tests. E139 has been reported to exert its effects via enhancement of extracellular GABA levels, thus tiagabine, a GABA transporter inhibitor, was evaluated as a control together with indomethacin.

Evaluation of anticonvulsant actions of dibromophenyl enaminones using in vitro and in vivo seizure models.

Epilepsy and other seizure disorders are not adequately managed with currently available drugs. We recently synthesized a series of dibromophenyl enaminones and demonstrated that AK6 and E249 were equipotent to previous analogs but more efficacious in suppressing neuronal excitation. Here we examined the actions of these lead compounds on in vitro and in vivo seizure models.

Antiallergic and antiasthmatic effects of a novel enhydrazinone ester (CEE-1): inhibition of activation of both mast cells and eosinophils.

Activation of mast cells and eosinophils is a fundamental process in the pathophysiology of allergic diseases. We have previously reported that the novel enhydrazinone ester CEE-1 (ethyl 4-phenylhydrazinocyclohex-3-en-2-oxo-6-phenyl-1-oate) possesses potent anti-inflammatory activity. We have now tested whether the compound also possesses antiallergic and antiasthmatic effects in vitro and in vivo.

Synthesis, neuronal activity and mechanisms of action of halogenated enaminones.

Due to the excellent anticonvulsant activity of previously synthesized halogenated enaminones, more disubstituted analogs were synthesized and evaluated in vitro. The new enaminones either had no effect, depressed, or enhanced population spike (PS) amplitude in the rat hippocampus in a concentration-dependent manner. Structure-activity relationship (SAR) analysis indicated that compounds 21 and 25 (with dibromo substituents) were equipotent, and more potent than compound 2 (with dichloro substituents), with compound 25 being the most efficacious of all tested compounds.

The anticonvulsant enaminone E139 attenuates paclitaxel-induced neuropathic pain in rodents.

The enaminone methyl 4-(4'-bromophenyl)aminocyclohex-3-en-6-methyl-2-oxo-1-oate (E139) has anticonvulsant activities. It has been reported to have a better safety profile than some anticonvulsant drugs. Since some anticonvulsant drugs are used in the management of neuropathic pain, we evaluated the effects of E139 in rodent models of acute pain and paclitaxel-induced neuropathic pain.

Anti-tussive and bronchodilator mechanisms of action for the enaminone E121.

Aims: In this study, we investigated whether the enaminone, E121, has anti-tussive effects in a guinea pig model of cough, and if so, whether this effect is mediated via a central or peripheral site of action. We also assessed whether E121 has bronchodilator effects and the molecular mechanisms underlying any anti-tussive and/or bronchodilator effects.

Main Methods: Whole body plethysmography was used to assess both cough and airway obstruction.

Selenium as a chemoprotective anti-cancer agent: reality or wishful thinking?

It is generally accepted that selenium (Se) plays an important role in maintaining equilibrium of a healthy organism. It also participates in processes related to carcinogenesis such as inhibition of tumor formation and regression. Scientific data accumulated so far using experimental animal models and from clinical studies devoted to investigating the effects of Se confirm strong relationship or correlation between Se supplementation and tumor frequency of prostate, lungs, liver and colon.

Liquid chromatography-tandem mass spectrometric method for determination of E121 in mouse plasma and its application to pharmacokinetics.

A rapid LC-MS/MS method for quantification of an enaminone analog, E121 in mouse plasma using E118 as an internal standard (IS) has been developed and validated. The analyte was analyzed on C(18) column using a mobile phase of acetonitrile/methanol/ammonium acetate/formic acid (60:20:20:0.025, v/v/v/v) at a flow rate of 0.

Anti-inflammatory and immunosuppressive effects of the enaminone E121.

Asthma is a chronic inflammatory disease of the airways. The treatment of asthma is far from optimal and hence the need for novel therapeutic agents exists. The purpose of this study was to assess the anti-asthma effects of an enaminone, E121, and also its effects on human peripheral blood mononuclear cell proliferation and cytokine release.

Synthesis, antibacterial and anticonvulsant evaluations of some cyclic enaminones.

Several cyclic enaminone esters were synthesized, characterized, and evaluated for anticonvulsant and antibacterial activities using standardized tests. A series of enaminones were mainly phenyl analogs of anticonvulsant enaminones, while a second series comprised of compounds bearing the oxazolidinone pharmacophoric moiety found in the synthetic antibacterial linezolid. The enaminone ester bearing an unsubstituted anilino analog showed class 2 anticonvulsant activity.

Norepinephrine and E139 interactions on epileptiform activity in the rat hippocampus in vitro.

Objectives: We tested if E139, an anticonvulsant enaminone, interacts with norepinephrine (NE) to suppress population responses and chemically induced in vitro seizures in the rat hippocampus.

Materials And Methods: Evoked field population spikes (PS) were recorded in the hippocampal CA1 area, and in vitro seizures were generated chemically using the zero Mg(2+) model.

Results: Low concentrations of E139 (or=100 microM) enhanced them.

Anticonvulsant enaminone E139 suppresses epileptiform activity in rat hippocampal slices.

Some enaminones are reported to have in vivo anticonvulsant activity. We asked if methyl 4-(4'-bromophenyl)aminocyclohex-3-en-6-methyl-2-oxo-1-oate (E139), one of such enaminones produced in vitro effects that may underlie or explain these in vivo anticonvulsant actions by testing if E139 suppressed in vitro seizures. In vitro seizures were generated chemically in hippocampal slices using picrotoxin and zero Mg(2+) buffer and electrically by high frequency stimulation (HFS).

Enaminones: Exploring additional therapeutic activities.

Enaminones, enamines of beta-dicarbonyl compounds, have been known for many years. Their early use has been relegated to serving as synthetic intermediates in organic synthesis and of late, in pharmaceutical development. Recently, the therapeutic potential of these entities has been realized.

Enaminones and norepinephrine employ convergent mechanisms to depress excitatory synaptic transmission in the rat nucleus accumbens in vitro.

We recently reported that anticonvulsant anilino enaminones depress excitatory postsynaptic currents (EPSCs) in the nucleus accumbens (NAc) indirectly via gamma-aminobutyric acid (GABA) acting on GABA(B) receptors [S.B. Kombian et al.

Concentration-dependent effects of anticonvulsant enaminone methyl 4-(4'-bromophenyl)aminocyclohex-3-en-6-methyl-2-oxo-1-oate on neuronal excitability in vitro.

Enaminones are a novel group of compounds some of which possess anticonvulsant activity in in vivo animal models of seizures. We recently reported that some enaminones, including methyl 4-(4'-bromophenyl)aminocyclohex-3-en-6-methyl-2-oxo-1-oate, depress glutamate-mediated excitatory synaptic transmission and that this may contribute to their anticonvulsant activity [Kombian SB, Edafiogho IO, Ananthalakshmi KVV (2005) Anticonvulsant enaminones depress excitatory synaptic transmission in the rat brain by enhancing extracellular GABA levels. Br J Pharmacol 145:945-953].

Anticonvulsant evaluation and mechanism of action of benzylamino enaminones.

The mechanism of anticonvulsant action was evaluated for the benzylamino enaminones. The most potent enaminone in this series was the unsubstituted benzylamine analog (30; methyl 4-benzylamino-6-methyl-2-oxocyclohex-3-en-1-oate) which had an oral effective dose (ED50) in rats of 27 mg/kg against maximal electroshock seizures, and a concentration 10-fold less than this dose depressed excitatory synaptic transmission, and action potential firing in the rat brain in vitro.