The Effect of Combined Treatment of Psilocybin and Eugenol on Lipopolysaccharide-Induced Brain Inflammation in Mice.

Inflammation is an organism's biological defense mechanism. Acute and chronic inflammation of the body triggers the production of pro- and anti-inflammatory pathways that can affect the content of cytokines in the brain and thus cause brain inflammation. Disorders such as depression and posttraumatic stress disorder (PTSD) are often associated with elevated inflammation. Recently, positive and promising clinical results of psilocybin for the treatment of depression and PTSD were reported. Thus, we decided to test whether psilocybin alone or in combination with eugenol, an anti-inflammatory and antioxidant agent, would prevent the increase in or decrease the content of cytokines in the brain of C57BL/6J mice injected with lipopolysaccharides (LPS). Two experiments were performed, one with pre-treatment of mice through gavage with psilocybin (0.88 mg/kg), eugenol (17.6 mg/kg), or combinations of psilocybin and eugenol (1:10, 1:20, or 1:50), followed by intraperitoneal injection of LPS, and the second, post-treatment, with initial injection with LPS, followed by treatment with psilocybin, eugenol, or their combination. Brain tissues were collected, and cytokines were analyzed by qRT-PCR, Western blot, and ELISA. Data were analyzed with a one-way ANOVA followed by Tukey's post hoc test or with multiple unpaired t-tests. LPS upregulated mRNA expression of COX-2, TNF-α, IL-1ß, and IL-6. All pre-treatments decreased the expression of COX-2 and TNF-α, with psilocybin alone and in 1:50 combination, with eugenol being the most effective. In the post-treatment, all combinations of psilocybin and eugenol were effective in reducing inflammation, with the 1:50 ratio displaying the most prominent results in reducing the mRNA content of tested cytokines. Western blot analysis confirmed the effect on COX-2 and IL-1ß proteins. Finally, the ELISA showed that post-treatment with psilocybin + eugenol (1:50) demonstrated the best results, decreasing the expression of multiple markers including IL-6 and IL-8. This demonstrates the anti-inflammatory effects of a combination of psilocybin and eugenol in the brain of animals with systemically induced inflammation.

Phytocannabinoids Stimulate Rejuvenation and Prevent Cellular Senescence in Human Dermal Fibroblasts.

In light of the increased popularity of phytocannabinoids (pCBs) and their appearance in beauty products without rigorous research on their rejuvenation efficacy, we decided to investigate the potential role of pCBs in skin rejuvenation. Utilizing healthy and stress-induced premature senescent (SIPS) CCD-1064Sk skin fibroblasts, the effects of pCBs on cellular viability, functional activity, metabolic function, and nuclear architecture were tested. Both delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) within the range of 0.5 µM to 2.0 µM increased cell growth in a dose-dependent manner while significantly decreasing senescence as measured by beta-galactosidase activity. Utilizing a scratch assay, both THC and CBD (2.0 µM) significantly improved wound healing in both healthy and SIPS fibroblasts. THC and CBD altered nuclear architecture and mRNA levels of cell cycle regulators and genes involved in ECM production. Subsequently, we found ELN, Cyclin D1, PCNA, and BID protein levels altered by SIPS but ameliorated after pCBs exposure in human dermal fibroblasts. Lastly, we compared the efficacy of THC and CBD with common anti-aging nutrient signaling regulators in replicative senescent adult human dermal fibroblasts, CCD-1135Sk. Both THC and CBD were found to improve wound healing better than metformin, rapamycin, and triacetylresveratrol in replicative senescent CCD-1135Sk fibroblasts. Therefore, pCBs can be a valuable source of biologically active substances used in cosmetics, and more studies using clinical trials should be performed to confirm the efficacy of phytocannabinoids.

The Role of Tranexamic Acid in the Prevention and Management of Blood Loss in Total Joint Arthroplasty.

Objective To collect data on the role played by tranexamic acid in the prevention and management of blood loss in patients undergoing total hip arthroplasty and total knee arthroplasty. Methods In the present prospective, comparative study, 30 patients undergoing total hip arthroplasty (THA) or total knee arthroplasty (TKA) were randomly allocated into 1 of 2 groups with 15 patients each. Tranexamic acid was administered by intravenous and topical routes in the study group, but it was not administered in the control group. Preoperative blood parameters, intraoperative and postoperative blood loss, and need for blood transfusion were noted. Statistical analysis was performed using the chi-squared test and the independent t -test. Results The study group had statistically significant higher postoperative hemoglobin values ( p = 0.03), less difference between pre and postoperative hemoglobin value ( p = 0.046), less difference between pre and postoperative packed-cell volume ( p = 0.06), less intraoperative measured blood loss ( p = 0.015), and less volume of blood collected in the drain ( p = 0.0291) compared with the control group. There was also reduced frequency of blood transfusions in the study group ( p = 0.0008). Conclusion Tranexamic acid is associated with reduced intra and postoperative blood loss and reduced frequency of blood transfusions in patients undergoing THA/TKA.

The Role of Tranexamic Acid in the Prevention and Management of Blood Loss in Total Joint Arthroplasty / O papel do ácido tranexâmico na prevenção e gerenciamento da perda de sangue na artroplastia total de articulação

Abstract Objective To collect data on the role played by tranexamic acid in the prevention and management of blood loss in patients undergoing total hip arthroplasty and total knee arthroplasty. Methods In the present prospective, comparative study, 30 patients undergoing total hip arthroplasty (THA) or total knee arthroplasty (TKA) were randomly allocated into 1 of 2 groups with 15 patients each. Tranexamic acid was administered by intravenous and topical routes in the study group, but it was not administered in the control group. Preoperative blood parameters, intraoperative and postoperative blood loss, and need for blood transfusion were noted. Statistical analysis was performed using the chisquared test and the independent t-test. Results The study group had statistically significant higher postoperative hemoglobin values (p = 0.03), less difference between pre and postoperative hemoglobin value (p = 0.046), less difference between pre and postoperative packed-cell volume (p = 0.06), less intraoperative measured blood loss (p = 0.015), and less volume of blood collected in the drain (p = 0.0291) compared with the control group. There was also reduced frequency of blood transfusions in the study group (p = 0.0008). Conclusion Tranexamic acid is associated with reduced intra and postoperative blood loss and reduced frequency of blood transfusions in patients undergoing THA/TKA.

Resumo Objetivo Coletar dados sobre o papel desempenhado pelo ácido tranexâmico na prevenção e gerenciamento da perda de sangue em pacientes submetidos à artroplastia total do quadril (ATQ) e à artroplastia total do joelho (ATJ). Métodos Neste estudo prospectivo e comparativo, 30 pacientes submetidos à ATQ ou à ATJ foram alocados aleatoriamente em 1 de 2 grupos com 15 pacientes. O ácido tranexâmico foi administrado por rotas intravenosas e tópicas no grupo de intervenção, mas não foi administrado no grupo controle. Foram observados parâmetros sanguíneos pré-operatórios, perda de sangue intrae pós-operatória e necessidade de transfusão de sangue. A análise estatística foi realizada utilizando-se teste do qui-quadrado e o teste-t independente. Resultados O grupo de intervenção apresentou hemoglobina mais elevada no pósoperatório de forma estatisticamente significante (p = 0,03), menor diferença entre concentração de hemoglobina pré- e pós-operatória (p = 0,046), menor diferença entre volume de células embaladas pré- e pós-operatório (p = 0,06), menor perda de sangue intraoperatória medida (p = 0,015) e menor volume de sangue coletado na drenagem (p = 0,0291) em comparação com o grupo controle. Também houve redução da frequência de transfusões de sangue no grupo de intervenção (p = 0,0008). Conclusão O ácido tranexâmico está associado à redução da perda sanguínea intraoperatória e pós-operatória e à redução da frequência de transfusões de sangue em pacientes submetidos à ATQ/ATJ.