Immunomodulatory Effects of the Cyclooxygenase Inhibitor Lornoxicam on Phenotype and Function of Camel Blood Leukocytes

(1) Background: Lornoxicam is a nonsteroidal anti-inflammatory drug (NSAID) with analgesic, antiphlogistic and antipyretic effects. The improved tolerance of lornoxicam due to the relatively shorter elimination half-life in comparison to other members of the oxicams may favor its application in the management of pain and inflammation in race dromedary camels. There are no studies conducted yet on the immunomodulatory or immunotoxilogic effect of lornoxicam in camels. Therefore, the current study aimed to evaluate the immunomodulatory effects of the cyclooxygenase inhibitor lornoxicam on some phenotypic and functional properties of camel blood leukocytes; (2) Methods: Using flow cytometry, blood leukocyte composition, monocyte phenotype, and antimicrobial functions of neutrophils and monocytes were analyzed ex vivo after a single dose injection with lornoxicam. In addition, the effect of in vitro incubation of camel blood with lornoxicam on leukocyte cell vitality and antimicrobial functions were evaluated; (3) Results: The injection of camels with a single dose of lornoxicam resulted in a significant change in their leukogram with reduced numbers of total leukocytes, neutrophils, eosinophils, monocytes, and lymphocytes. Within the lymphocyte population, the numbers of CD4+ T cells, T cells, and B cells decreased significantly in blood after injection of camels with lornoxicam. In addition, injection of lornoxicam resulted in decreased abundance of major histocompatibility complex (MHC) class II molecules and increased abundance of the scavenger receptor CD163 on blood monocytes, indicating an anti-inflammatory phenotype of monocytes. Functionally, administration of lornoxicam decreased the capacity of camel neutrophils and monocytes to uptake bacteria and to produce reactive oxygen species (ROS) after bacterial stimulation. Similarly, the in vitro whole blood incubation with lornoxicam resulted in reduced phagocytosis and ROS production activity of the camel blood phagocytes. Flow cytometric analysis of cell vitality, including cell necrosis and apoptosis, revealed a pro-apoptotic effect of lornoxicam on camel leukocytes; (4) Conclusions: Lornoxicam administration, at the dose and intervals utilized herein, induces significant changes in the phenotype and function of camel blood leukocytes. The reduced cell numbers of all studied leukocyte subpopulations in lornoxicam-treated camels, which seems to be a result of enhanced cell apoptosis, indicates an inhibitory effect rather than a modulatory effect of lornoxicam on the camel immune system, which need to be considered when using lornoxicam in camel medicine.

Cisplatin-cyclooxygenase inhibitor conjugates, free and immobilised in mesoporous silica SBA-15, prove highly potent against triple-negative MDA MB 468 breast cancer cell line

For the development of anticancer drugs with higher activity and reduced toxicity, two approaches were combined: preparation of platinum(IV) complexes exhibiting higher stability compared to their platinum(II) counterparts and loading...

Characterization of cough evoked by inhaled treprostinil and treprostinil palmitil

Cough is induced by inhaled prostacyclin analogs including treprostinil (TRE), and, at higher doses, treprostinil palmitil (TP), a prodrug of TRE. In this report, we have investigated mechanisms involved with TRE- and TP-induced cough, using a dry powder formulation of TP (TPIP) to supplement previous data obtained with an aqueous suspension formulation of TP (TPIS).Experiments in guinea pigs and rats investigated the prostanoid receptor subtype producing cough and whether it involved activation of sensory nerves in the airways and vasculature. Experiments involved treatment with prostanoid, tachykinin and bradykinin receptor antagonists, a cyclooxygenase inhibitor and TRE administration to the isolated larynx or intravenously.In guinea pigs, cough with inhaled TRE (1.23 µg·kg−1) was not observed with an equivalent dose of TPIP and required higher inhaled doses (12.8 and 35.8 µg·kg) to induce cough. TRE cough was blocked with IP and tachykinin NK1 receptor antagonists but not with EP1, EP2, EP3, DP1 or bradykinin B2 antagonists or a cyclooxygenase inhibitor. TRE administered to the isolated larynx or intravenously in rats produced no apnea or swallowing, whereas citric acid, capsaicin and hypertonic saline had significant effects.The mechanisms inducing cough with inhaled TRE likely involves the activation of prostanoid IP receptors on jugular C-fibers in the tracheobronchial airways. Cough induced by inhaled dry powder and nebulised formulations of TP occurs at higher inhaled doses than TRE, presumably due to the slow, sustained release of TRE from the prodrug resulting in lower concentrations of TRE at the airway sensory nerves.

Intracanal Analgesic Solutions to Control Interappointment Pain during Root Canal Treatment in Patients with Symptomatic Irreversible Pulpitis - A Pilot Study

Mefenamic acid is a Non Steroidal Anti Inflammatory Drug belonging to anthranilic acid group while Aceclofenac is an acetic acid derivative. Aceclofenac is a non selective cyclooxygenase inhibitor while Mefenamic acid is a potent cyclooxygenase inhibitor with both central and peripheral actions. The use of Mefenamic acid and Aceclofenac has reduced due to their side effect of gastrointestinal irritation. The idea of this study is to use Mefenamic acid and Aceclofenac as intracanal agents to achieve localized action without having systemic side effects. Patients with symptomatic irreversible pulpitis with symptomatic apical periodontitis were identified and divided into three groups of 10 each. After cleaning and shaping of the root canals, 0.1ml of the analgesic solution was injected within the root canals. The pain was evaluated at the end of 6 hours. There was significant reduction in pain in patients who received intracanal Mefenamic acid followed by the group that received Aceclofenac. This proves that intracanal administration of analgesics controls inter appointment pain during endodontic treatment and also prevents systemic side effects that are likely to occur due to oral use of the drugs.