The role of bidirectional communication between the adipokines and the endogenous opioid system in an experimental mouse model of colitis-associated colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is one of the leading causes of death globally. Multiple factors may contribute to the pathogenesis of CRC, including the abnormalities in the functioning of the endogenous opioid system (EOS) or adiponectin-related signaling. The aim of our study was to evaluate if differences in the expression of opioid receptors (ORs) influence the development of CRC and if modulation of adiponectin receptors using AdipoRon, a selective AdipoR1 receptor agonist, affects colorectal carcinogenesis. METHODS: Naltrexone, an opioid receptor antagonist, was injected intraperitoneally every second day for 2 weeks, at the dose of 1 mg/kg in healthy Balb/C mice to induce changes in ORs expression. CRC was induced by a single intraperitoneal injection of azoxymethane (AOM) and the addition of dextran sodium sulfate (DSS) into drinking water in three-week cycles. The development of CRC was assessed using macro- and microscopic scoring and molecular analysis (RT qPCR, ELISA) after 14 weeks. RESULTS: Naltrexone significantly increased the mRNA expression of Oprm1, Oprd1, and Oprk1 in the mouse colon and in the brain (non-significantly). The pretreatment of mice with naltrexone aggravated the course of CRC (as indicated by tumor area, colon thickness, and spleen weight). The level of circulatory adiponectin was lowered in mice with CRC and increased in the colon as compared with healthy mice. The ß-endorphin level was increased in the plasma of mice with CRC and decreased in the colon as compared to healthy mice. AdipoRon, AdipoR1 agonist, worsened the CRC development, and pretreatment with naltrexone enhanced this negative effect in mice. CRC did not affect the expression of the Adipor1 gene, but the Adipor1 level was increased in mice pretreated with naltrexone (AOM/DSS and healthy mice). AdipoRon did not influence the expression of opioid receptors at the mRNA level in the colon of mice with CRC. The mRNA expression of Ptgs2, Il6, Nos2, Il1b, Il18, Gsdmd, and Rela was increased in mice with CRC as compared to the healthy colon. AdipoRon significantly decreased mRNA expression of Ptgs2, Il6, Il1b, and Il18 as compared to CRC mice. CONCLUSION: EOS and adiponectin-related signaling may play a role in the pathogenesis of CRC and these systems may present some additivity during carcinogenesis.

Inferior vena cava/aorta diameter index in the assessment of the body fluid status - a comparative study of measurements performed by experienced and inexperienced examiners in a group of young adults.

The assessment of the body fluid status is one the most challenging tasks in clinical practice. Although there are many methods to assess the body fluid status of patients, none of them is fully satisfactory in contemporary medical sciences. In the article below, we compare the results of measurements performed by experienced and inexperienced examiners based on the inferior vena cava/aorta diameter index in a sonographic hydration assessment. The study enrolled 50 young students at the age of 19-26 (the median age was 22.95) including 27 women and 23 men. The volunteers were examined in the supine position with GE Logiq 7 system and a convex transducer with the frequency of 2-5 MHz. The measurements were performed in the longitudinal and transverse planes by two inexperienced examiners - the authors of this paper, following a four-hour training conducted by an experienced sonographer. The longitudinal values of the inferior vena cava/aorta diameter index obtained in this study were similar to those found in the literature. The reference value for the inferior vena cava/aorta index determined by Kosiak et al., which constituted 1.2 ± 2 SD, for SD = 0.17, was similar to the values obtained by the authors of this paper which equaled 1.2286 ± 2 SD, for SD = 0.2. The article presented below proves that measuring the inferior vena cava/aorta diameter index is not a complex examination and it may be performed by physicians with no sonographic experience. Furthermore, the paper demonstrates that the inferior vena cava/aorta diameter index measured in the transverse plane is similar to the inferior vena cava/aorta diameter index determined in the longitudinal plane. Thus, both measurements may be used interchangeably to assess the hydration status of patients.