Effect of the compound L-mimosine in an in vivo model of chronic granuloma formation induced by potassium permanganate (KMNO4).

The plant amino acid L-mimosine has recently been suggested to inhibit cells at a regulatory step in late G phase before establishment of active DNA replication forks. In addition, L-mimosine is an extremely effective inhibitor of DNA replication in chromosomes of mammalian nuclei. In this work, the effect of L-mimosine on chronic inflammation induced by dorsal injections of 0.2 ml of a 1:40 saturated crystal solution of potassium permanganate in mice, was studied. Seven days afterwards, all mice developed a subcutaneous granulomatous tissue indicative of chronic inflammatory response at the site of infection. The intraperitoneal administration of L-mimosine (200 μg/dose) to the potassium permanganate treated mice for 5 consecutive days (the first at the same time of inoculation of the KMnO4), produced a significant decrease in size and weight of the granuloma when compared to mice not treated with L-mimosine (controls). In addition, in all mice treated with L-mimosine, there was a strong inhibition of tumor necrosis factor alpha that was revealed in the serum (P<0.05) and in the minced granulomas. Interleukin-6 was not detected in the serum of treated and untreated mice. These findings show for the first time, that L-mimosine may have an anti-inflammatory effect on chronic inflammation and an inhibitory effect on tumor necrosis factor alpha and interleukin-6 generation in supernatant fluids of minced granulomas

Predictors of health-related quality of life in type II diabetic patients in Greece

<p>Abstract</p> <p>Background</p> <p>Diabetes Mellitus (DM) is a major cause of morbidity and mortality affecting millions of people worldwide, while placing a noteworthy strain on public health funding. The aim of this study was to assess health-related quality of life (HRQOL) of Greek Type II DM patients and to identify significant predictors of the disease in this patient population.</p> <p>Methods</p> <p>The sample (N = 229, 52.8% female, 70.0 years mean age) lived in a rural community of Lesvos, an island in the northeast of the Aegean Archipelagos. The generic SF-36 instrument, administered by trainee physicians, was used to measure HRQOL. Scale scores were compared with non-parametric Mann-Whitney and Kruskal-Wallis tests and multivariate stepwise linear regression analyses were used to investigate the effect of sociodemographic and diabetes-related variables on HRQOL.</p> <p>Results</p> <p>The most important predictors of impaired HRQOL were female gender, diabetic complications, non-diabetic comorbidity and years with diabetes. Older age, lower education, being unmarried, obesity, hypertension and hyperlipidaemia were also associated with impaired HRQOL in at least one SF-36 subscale. Multivariate regression analyses produced models explaining significant portions of the variance in SF-36 subscales, especially physical functioning (R²= 42%), and also showed that diabetes-related indicators were more important disease predictors, compared to sociodemographic variables.</p> <p>Conclusion</p> <p>The findings could have implications for health promotion in rural medical practice in Greece. In order to preserve a good HRQOL, it is obviously important to prevent diabetes complications and properly manage concomitant chronic diseases. Furthermore, the gender difference is interesting and requires further elucidation. Modifying screening methods and medical interventions or formulating educational programs for the local population appear to be steps in the correct direction.</p

Microarray Analysis of NF-κB Signaling Pathways in PBMC of Mice Infected by <i>Trichinella Spiralis</i>

The NF-κB pathway gene expression profiles were compared between 10, 20 and 39 days after Trichinella spiralis experimental infection in BALB/c mice. Out of 128 genes, 19 (14.8%) genes were present in non-infected and post-infected mice. The expression of 7 (36.8%) genes was downregulated 10 and 20 days post-infection while 3 (15.8%) genes were upregulated 39 days post-infection. The present study lists the candidate genes of the NF-κB signaling pathway that were commonly and differentially expressed between the specific points of T. spiralis infection, thus suggesting that these genes need to be further investigated to reveal the mechanism of the T. spiralis modulation of the NF-κB signaling pathways. </jats:p

Prevalence of IgG Antibodies against Borrelia Burgdorferi

The aim of this study was to evaluate the prevalence (seroprevalence) of antibodies against Borrelia burgdorferi and Ehrlichia phagocytophila among patients resident in Lazio, a region of central Italy. Of a sample of 1,050 patients, which presented clinical manifestations related to Lyme disease, 34 (3.2%) were Borrelia-seropositive (Lyme index value ≥ 1.2). The sera of 25 out of the 34 patients that were Borrelia-positive were also analysed for the presence of antibodies against E. phagocytophila and 3 (12%) were found Ehrlichia-positive (titres >1:64). No Ehrlichia-positive samples were found among sera of 250 Borrelia-negative patients. Since both B. burgdorferi s.l. and Ehrlichia species share the same tick vector ( Ixodes ricinus), our results indicate that concurrent transmission of these microbial pathogens might have been occurred among the patients included in this study

DIFFERENT SIGNALS INDUCE MAST CELL INFLAMMATORY ACTIVITY: INHIBITORY EFFECT OF VITAMIN E

Vitamin supplementation in disease reduces morbidity and mortality in humans by promoting the activation of different genes which influence several pathways. The purpose of this article is to clarify the role of vitamin E in mast cell inflammation. Vitamin E is a fat soluble antioxidant which protects from low-density lipoprotein (LDL) oxidation. Vitamin E promotes a barrier function and anti-inflammatory responses by binding the regulatory domain of protein kinase C alpha (PKC alpha) (a regulator and antagonist of heart failure) and decreases the activation of NF-kappa B, a proinflammatory transcription factor, causing the generation of cytokines/chemokines and mast cell activation. Mast cells participate in innate and acquired immunity and inflammation. Several factors, including cytokines and chemokines, regulate the development and migration of activated mast cells. Mast cells generate and release inflammatory compounds in asthma and allergic diseases and have a detrimental effect on the vessel wall, which can be inhibited by vitamin E. Vitamin E inhibits histamine release generated in activated mast cells, increases calcium Ca2+ uptake and prevents the oxidation of unsaturated fatty acids. Vitamin E is relatively non-toxic, however, administered at very high doses may suppress normal hematological response as well as causing other adverse effects. Therefore, vitamin E may be beneficial in the prevention of diseases mediated by mast cells and can have special value in the treatment of asthma and allergic diseases; however, the exact mechanism by which vitamin E acts is still unclear, thus warranting future research

Different signals induce mast cell inflammatory activity: inhibitory effect of Vitamin E

Vitamin supplementation in disease reduces morbidity and mortality in humans by promoting the activation of different genes which influence several pathways. The purpose of this article is to clarify the role of vitamin E in mast cell inflammation. Vitamin E is a fat soluble antioxidant which protects from low-density lipoprotein (LDL) oxidation. Vitamin E promotes a barrier function and anti-inflammatory responses by binding the regulatory domain of protein kinase Cα (pkcα) (a regulator and antagonist of heart failure) and decreases the activation of NF-қb, a proinflammatory transcription factor, causing the generation of cytokines/chemokines and mast cell activation. Mast cells participate in innate and acquired immunity and inflammation. Several factors, including cytokines and chemokines, regulate the development and migration of activated mast cells. Mast cells generate and release inflammatory compounds in asthma and allergic diseases and have a detrimental effect on the vessel wall, which can be inhibited by vitamin E. Vitamin E inhibits histamine release generated in activated mast cells, increases calcium Ca2+ uptake and prevents the oxidation of unsaturated fatty acids. Vitamin E is relatively non-toxic, however, administered at very high doses may suppress normal hematological response as well as causing other adverse effects. Therefore, vitamin E may be beneficial in the prevention of diseases mediated by mast cells and can have special value in the treatment of asthma and allergic diseases; however, the exact mechanism by which vitamin E acts is still unclear, thus warranting future research

Induction of pro-inflammatory cytokines (IL-1 and IL-6) and lung inflammation by COVID-19: anti-inflammatory strategies

Coronavirus-19 (COVI-19) involves humans as well as animals and may cause serious damage to the respiratory tract, including the lung: coronavirus disease (COVID-19). This pathogenic virus has been identified in swabs performed on the throat and nose of patients who suffer from or are suspected of the disease. When COVI-19 infect the upper and lower respiratory tract it can cause mild or highly acute respiratory syndrome with consequent release of pro-inflammatory cytokines, including interleukin (IL)-1β and IL-6. The binding of COVI-19 to the Toll Like Receptor (TLR) causes the release of pro-IL-1β which is cleaved by caspase-1, followed by inflammasome activation and production of active mature IL-1β which is a mediator of lung inflammation, fever and fibrosis. Suppression of pro-inflammatory IL-1 family members and IL-6 have been shown to have a therapeutic effect in many inflammatory diseases, including viral infections. Cytokine IL-37 has the ability to suppress innate and acquired immune response and also has the capacity to inhibit inflammation by acting on IL-18Rα receptor. IL-37 performs its immunosuppressive activity by acting on mTOR and increasing the adenosine monophosphate (AMP) kinase. This cytokine inhibits class II histocompatibility complex (MHC) molecules and inflammation in inflammatory diseases by suppressing MyD88 and subsequently IL-1β, IL-6, TNF and CCL2. The suppression of IL-1β by IL-37 in inflammatory state induced by coronavirus-19 can have a new therapeutic effect previously unknown. Another inhibitory cytokine is IL-38, the newest cytokine of the IL-1 family members, produced by several immune cells including B cells and macrophages. IL-38 is also a suppressor cytokine which inhibits IL-1β and other pro-inflammatory IL-family members. IL-38 is a potential therapeutic cytokine which inhibits inflammation in viral infections including that caused by coronavirus-19, providing a new relevant strategy