Development of a rapid, sensitive, and selective LC-MS/MS method for quantifying curcumin levels in healthy human urine: Effect of pepper on curcumin bioavailability.

Curcumin (CCM), a culinary spice, is widely consumed for its health benefits for managing oxidative and inflammatory conditions, metabolic syndrome, arthritis, and hyperlipidemia. However, due to its extensive metabolism, the oral bioavailability of CCM is very low. In this study, we developed a rapid, sensitive, and selective assay to examine the hypothesis that piperine improves CCM bioavailability after piperine co-ingestion.

Renin-Angiotensin System Components and Arachidonic Acid Metabolites as Biomarkers of COVID-19.

Through the ACE2, a main enzyme of the renin-angiotensin system (RAS), SARS-CoV-2 gains access into the cell, resulting in different complications which may extend beyond the RAS and impact the Arachidonic Acid (ArA) pathway. The contribution of the RAS through ArA pathways metabolites in the pathogenesis of COVID-19 is unknown. We investigated whether RAS components and ArA metabolites can be considered biomarkers of COVID-19.

Circadian Modulation of the Antioxidant Effect of Grape Consumption: A Randomized Controlled Trial.

Grape consumption acts on the immune system to produce antioxidant and anti-inflammatory effects. Since immune activity demonstrates circadian rhythmicity, with peak activity occurring during waking hours, the timing of grape intake may influence the magnitude of its antioxidant effect. This study followed a 2 × 2 factorial randomized, controlled design wherein healthy men and women ( = 32) consumed either a grape or placebo drink with a high-fat meal in the morning or evening.

Anti-Inflammatory Effects of Ang-(1-7) Bone-Targeting Conjugate in an Adjuvant-Induced Arthritis Rat Model.

Rheumatoid arthritis (RA) is a chronic inflammatory condition of synovial joints that causes disability and systemic complications. Ang-(1-7), one of the main peptides in the renin-angiotensin (Ang) system (RAS), imposes its protective effects through Mas receptor (MasR) signaling. It has a short half-life, limiting its feasibility as a therapeutic agent.

Bone-Targeted Delivery of Novokinin as an Alternative Treatment Option for Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is an autoimmune inflammatory bone destructive disorder that is orchestrated by multiple systems in the body, including Renin-Angiotensin System (RAS) and arachidonic acid (ArA) pathway. Current therapeutic options are not highly effective and are associated with severe side effects, including cardiovascular complications. Therefore, new safe and effective disease modulators are seriously needed.

Formulation, Characterization, and In Vitro/In Vivo Efficacy Studies of a Novel Liposomal Drug Delivery System of Amphiphilic Jaspine B for Treatment of Synovial Sarcoma.

Sphingomyelin is a cell membrane sphingolipid that is upregulated in synovial sarcoma (SS). Jaspine B has been shown to inhibit sphingomyelin synthase, which synthesizes sphingomyelin from ceramide, a critical signal transducer; however, jaspine B's low bioavailability limits its application as a promising treatment option. To address this shortcoming, we used microfluidics to develop a liposomal delivery system with increased anticancer efficacy.

Plasma angiotensin peptides as biomarkers of rheumatoid arthritis are correlated with anti-ACE2 auto-antibodies level and disease intensity.

Background: This study aimed to explore a correlation between plasma angiotensin II/(1-7) (Ang II/Ang-(1-7)) ratio, anti-ACE2 autoantibodies level and disease activity in rheumatoid arthritis (RA) patients.

Methods: In a pilot study, the plasma level of Ang II, Ang-(1-7), and anti-ACE2 autoantibodies of twelve RA patients (five in active stage and seven in remission) were measured using an LC-MS/MS method and an ELISA kit, respectively.

Results: The Ang-(1-7) level was significantly higher in the remission group than in the active RA patients (7.

Tissue Engineering Through 3D Bioprinting to Recreate and Study Bone Disease.

The applications of 3D bioprinting are becoming more commonplace. Since the advent of tissue engineering, bone has received much attention for the ability to engineer normal bone for tissue engraftment or replacement. While there are still debates on what materials comprise the most durable and natural replacement of normal tissue, little attention is given to recreating diseased states within the bone.

Update on Angiotensin II Subtype 2 Receptor: Focus on Peptide and Nonpeptide Agonists.

Angiotensin II (Ang II) is the most dominant effector component of the renin-angiotensin system (RAS) that generally acts through binding to two main classes of G protein-coupled receptors, namely Ang II subtype 1 receptor (AT1R) and angiotensin II subtype 2 receptor (AT2R). Despite some controversial reports, the activation of AT2R generally antagonizes the effects of Ang II binding on AT1R. Studying AT2R signaling, function, and its specific ligands in cell culture or animal studies has confirmed its beneficial effects throughout the body.

Improved pharmacokinetics and bone tissue accumulation of Angiotensin-(1-7) peptide through bisphosphonate conjugation.

The renin-angiotensin system (RAS) has a central role in renal and cardiovascular homeostasis. Angiotensin-(1-7) (Ang1-7), one of the RAS active peptides, exerts beneficial effects through different mechanisms. These biological actions suggest that Ang1-7 is an effective therapeutic agent for treating various diseases associated with activated RAS.

Targeting the Protective Arm of the Renin-Angiotensin System: Focused on Angiotensin-(1-7).

The in vivo application and efficacy of many therapeutic peptides is limited because of their instability and proteolytic degradation. Novel strategies for developing therapeutic peptides with higher stability toward proteolytic degradation would be extremely valuable. Such approaches could improve systemic bioavailability and enhance therapeutic effects.

Drug-Disease Interaction: Effect of Inflammation and Nonsteroidal Anti-Inflammatory Drugs on Cytochrome P450 Metabolites of Arachidonic Acid.

Inflammatory conditions increase cardiovascular (CV) risk. Some nonsteroidal anti-inflammatory drugs (NSAIDs) that are used to treat pain and inflammation are also associated with CV complications. Inflammation, but not NSAIDs, disrupts the balance of vasodilator and vasoconstrictor components of the renin-angiotensin system within the heart.

Bone-targeting parathyroid hormone conjugates outperform unmodified PTH in the anabolic treatment of osteoporosis in rats.

Synthetic parathyroid hormone (PTH) is clinically indicated for the treatment of osteoporosis, through its anabolic effects on parathyroid hormone receptors (PTHRs), located on osteoblast cells. However, the bioavailability of PTH for bone cells is restricted by the short half-life of PTH and the widespread distribution of PTHRs in non-skeletal tissues. To impart affinity for mineralized bone surfaces, bisphosphonate (BP)-mediated PTH analogues were synthesized, characterized, and evaluated in vitro and in vivo.

Cardiovascular effect of inflammation and nonsteroidal anti-inflammatory drugs on renin-angiotensin system in experimental arthritis.

A co-morbidity of inflammatory conditions is increased cardio-renal risks. Additionally, nonsteroidal anti-inflammatory drugs (NSAIDs) which are used to treat pain and inflammation are also associated with increase in such risks. We hypothesized that inflammation and NSAIDs impose the cardio-renal risk through the activation of the renin-angiotensin-system (RAS), a regulating pathway of the renal and cardiovascular homeostasis.

Disease specific modeling: Simulation of the pharmacokinetics of meloxicam and ibuprofen in disease state vs. healthy conditions.

Purpose: Studies have shown altered pharmacokinetic patterns (PK) in patient suffering from acute pain. Thus, we aimed to simulate pharmacokinetics of meloxicam and ibuprofen in pain and pain-free states using a physiological based software program to identify the underlining mechanistic changes for the observed differences.

Method: Published in vivo data of meloxicam and ibuprofen were used for the simulations.

Transdermal drug delivery: feasibility for treatment of superficial bone stress fractures.

Transdermal drug delivery offers the promise of effective drug therapy at selective sites of pathology whilst reducing systemic exposure to the pharmaceutical agents in off-target organs and tissues. However, that strategy is often limited to cells comprising superficial tissues of the body (rarely to deeper bony structures) and mostly indicated with small hydrophobic pharmacological agents, such as steroid hormones and anti-inflammatory gels to skin, muscle, and joints. Nonetheless, advances in transdermal liposomal formulation have rendered the ability to readily incorporate pharmacologically active hydrophilic drug molecules and small peptide biologics into transdermal dosage forms to impart the effective delivery of those bioactive agents across the skin barrier to underlying superficial tissue structures including bone, often enhanced by some form of electrical, chemical, and mechanical facilitation.

Simultaneous determination of selected eicosanoids by reversed-phase HPLC method using fluorescence detection and application to rat and human plasma, and rat heart and kidney samples.

Eicosanoids are biologically active lipid-derived oxidative metabolites of arachidonic acid. We, herein, present an improved sensitive, selective and robust high performance liquid chromatography (HPLC)-fluorescence assay for simultaneous quantification of eicosanoids in human plasma and rat tissues. Aliquots of 200 μL of plasma or 30 mg of heart or kidney tissues were spiked with 16-hydroxydecanoic acid as internal standard, and extracted with anhydrous acetonitrile using solid phase cartridges.

The impact of implementation of the Canadian regulatory requirements on the quality of natural health products: the glucosamine case.

Purpose: We investigated whether the recent implementation of the regulatory requirements for the entry to the Canadian market of natural products has resulted in improved quality of the available glucosamine products.

Methods: Eleven available products, of which 8 had been tested in 2002 (7 had contained substantially lower than the label claim of the active ingredient), and a European pharmaceutical grade tablet were assayed for their glucosamine content. The potassium and sodium contents of the products were also tested.

Glucosamine dose/concentration-effect correlation in the rat with adjuvant arthritis.

There is a debate on the dose dependency, concentration-effect, hence, the beneficial effect of glucosamine (GlcN), a widely used anti-inflammatory natural product. We investigated dose/concentration-effect relationship and determined its minimum effective dose/concentration in rats with adjuvant arthritis (AA, Mycobacterium butyricum in squalene) both as preventive and ameliorating interventions. To control already emerged arthritis, rats received oral doses of placebo or 160 mg/kg.

Absorption and bioavailability of glucosamine in the rat.

The objective of this study was to determine reasons behind the low oral (p.o.) bioavailability of glucosamine.

The glucosamine controversy; a pharmacokinetic issue.

Glucosamine (GlcN) is a naturally occurring aminosugar that is widely used to treat osteoarthritis despite controversial clinical trial results. Animal studies, on the other hand, unequivocally suggest anti-inflammatory and disease modifying effects for GlcN. Many explanations have been offered as to the root of the controversy.

Pharmacokinetics of meloxicam administered as regular and fast dissolving formulations to the rat: influence of gastrointestinal dysfunction on the relative bioavailability of two formulations.

It is believed that acute pain suppresses nervus vagus, thereby, influencing gastrointestinal secretion and motility, which are the two factors that are necessary for disintegration and dissolution of solid dosage forms. We studied the pharmacokinetics of meloxicam and the effect of vagal suppression on the oral bioavailability and bioequivalence using a marketed (Brand) and a fast dissolving (FD) formulation. In simulated gastric juice, FD was disintegrated in 30s and released 30% of its meloxicam in 15 min and 60% in 2h.

Single dose pharmacokinetics and bioavailability of butyryl glucosamine in the rat.

Purpose: To study single dose pharmacokinetics and bioavailability of the synthetic glucosamine analogue, N-butyryl glucosamine (GLcNBu) after different routes of administration, and also the effect of food following oral doses of GLcNBu in the rat, and stability and absorption of GLcNBu across the rat everted intestine.

Method: GLcNBu was administered intravenously (i.v.

Extent of renal effect of cyclo-oxygenase-2-selective inhibitors is pharmacokinetic dependent.

Non-steroidal anti-inflammatory drugs (NSAIDs) cause renal side-effects. In the present study, we tested the hypothesis that the extent of the renal effects of cyclo-oxygenase (COX)-2-selective NSAIDs is linked to their pharmacokinetics. A single oral dose of rofecoxib (10 mg/kg), celecoxib (40 mg/kg), meloxicam (3 mg/kg) or placebo was administered to rats.