Common medicines for the treatment of toxoplasmosis have limited efficacy and unwanted side effects. Opiates can effect both innate and cell-mediated immunity and stimulate the immune responses in different parasitic infections. In this work, preventive and therapeutic effects of morphine were evaluated on the tachyzoites of and infected macrophages and in a murine model. Different concentrations of morphine (0.1 and 0.01 μg/ml) were evaluated on mortality rate of by direct counting after 3 and 24 hours. The cytotoxic and apoptotic effects of these drugs were measured by the MTT assays and flow cytometry analysis, respectively. The same procedures were assessed in -infected macrophages. The parasite loads were determined using quantitative polymerase chain reaction (qPCR). For in assessment, BALB/c mice treated with morphine before or after infection with tachyzoites. The survival rate of animals, parasite load in the spleen, and the IFN-γ and IL-4 cytokines levels were measured. Morphine was effective on tachyzoites of and had a reverse relationship with its concentration. The results of flow cytometry showed that the toxic effects of morphine on tachyzoites after 3 hours was not statistically significant (<0.05). Also, apoptosis in infected MQs rose with a decreasing concentration of morphine. The parasitic load in MQs treated with morphine before infection was lower than that in cells treated after infection and the differences were statistically significant (<0.01). In mice that received morphine before infection, survival rate, parasite load and the IFN-γ level were significantly lower than in mice treated after infection (<0.01). The results of this study have shown that morphine in the pre-treatment group had higher anti- activity than morphine in post-treatment and in murine model.
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http://dx.doi.org/10.17179/excli2019-1961 | DOI Listing |
Anesth Analg
January 2025
Department of Anesthesiology and Critical Care Medicine, Johns Hopkins, All Children's Hospital, St Petersburg, Florida.
Background: Optimal perioperative pain management is unknown for adolescent patients undergoing anterior cruciate ligament reconstruction (ACLR). The study aimed to determine the association of nerve blocks with short- and long-term pain outcomes and factors influencing self-reported neurological symptoms.
Methods: We performed a multisite, prospective observational study of adolescent patients undergoing ACLR.
Pain
January 2025
Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States.
Reviews of the effectiveness of medicinal cannabis for chronic pain vary in their conclusions. IASP has identified that a key missing evidence in this debate is data from observational cohort studies, analyzed with comparative effectiveness methods. In a medically supervised context to the use of marijuana for chronic pain, we identified 440 patients certified for medical marijuana by pain specialists in a single healthcare system.
View Article and Find Full Text PDFAims: We measured the association between prescribed stimulant medications and overdose among individuals receiving opioid agonist therapy (OAT) for opioid use disorder.
Design: Retrospective cohort study using the British Columbia Provincial Overdose Cohort, a linked administrative database.
Setting: We used data from British Columbia, Canada, from January 2015 through February 2020.
Fentanyl is a potent synthetic opioid widely used perioperatively and illicitly as a drug of abuse . It is well established that fentanyl acts as a μ-opioid receptor agonist, signaling through Gα intracellular pathways to inhibit electrical excitability, resulting in analgesia and respiratory depression . However, fentanyl uniquely also triggers muscle rigidity, including respiratory muscles, hindering the ability to execute central respiratory commands or to receive external resuscitation.
View Article and Find Full Text PDFLarge library docking of tangible molecules has revealed potent ligands across many targets. While make-on-demand libraries now exceed 75 billion enumerated molecules, their synthetic routes are dominated by a few reaction types, reducing diversity and inevitably leaving many interesting bioactive-like chemotypes unexplored. Here, we investigate the large-scale enumeration and targeted docking of isoquinuclidines.
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