Spontaneous cytotoxicity of macrophages against pancreatic islet cells

Activated peritoneal macrophages were found to lyse syngeneic [3H]leucine-labeled pancreatic islet cells or rat insulinoma cells after 15 h of coculture at 37 degrees C. Lysis was verified by electron microscopic analysis. Islet cell lysis was dependent on the T:E ratio and was comparable with P815 and L929 tumor cells used as targets. The cytotoxic activity was localized in the adherent fraction of Corynebacterium parvum activated peritoneal cells and was destroyed by incubation of cells with macrophage-toxic silica particles. Syngeneic thyrocytes and hepatocytes were found to be resistant to the cytolytic action of activated macrophages. It has been shown previously that macrophages contribute to pancreatic islet inflammation. The present in vitro analysis demonstrates that macrophages can function as effector cells in islet destruction.     

Curcumin prevents liver fat accumulation and serum fetuin-A increase in rats fed a high-fat diet

Fetuin-A is synthesized in the liver and is secreted into the bloodstream. Clinical studies suggest involvement of fetuin-A in metabolic disorders such as visceral obesity, insulin resistance, diabetes, and fatty liver. Curcumin is extracted from the rhizome Curcuma longa and has been shown to possess potent antioxidant, anticarcinogenic, anti-inflammatory, and hypoglycemic properties. In this study, we investigated the effect of curcumin treatment on serum fetuin-A levels as well as hepatic lipids and prooxidant–antioxidant status in rats fed a high-fat diet (HFD). Male Sprague–Dawley rats were divided into six groups. Group 1 was fed control diet (10 % of total calories from fat). Groups 2 and 3 were given curcumin (100 and 400 mg/kg bw/day, respectively ) by gavage for 8 weeks and were fed control diet. Group 4 was fed with HFD (60 % of total calories from fat). Groups 5 and 6 received HFD together with the two doses of curcumin, respectively. Curcumin treatment appeared to be effective in reducing liver triglycerides and serum fetuin-A levels. These findings suggest that the reduction of fetuin-A may contribute to the beneficial effects of curcumin in the pathogenesis of obesity.     

Pepsin Digest of Wheat Gliadin Fraction Increases Production of IL-1β via TLR4/MyD88/TRIF/MAPK/NF-κB Signaling Pathway and an NLRP3 Inflammasome Activation

Celiac disease (CD) is a gluten-responsive, chronic inflammatory enteropathy. IL-1 cytokine family members IL-1β and IL-18 have been associated with the inflammatory conditions in CD patients. However, the mechanisms of IL-1 molecule activation in CD have not yet been elucidated. We show in this study that peripheral blood mononuclear cells (PBMC) and monocytes from celiac patients responded to pepsin digest of wheat gliadin fraction (PDWGF) by a robust secretion of IL-1β and IL-1α and a slightly elevated production of IL-18. The analysis of the upstream mechanisms underlying PDWGF-induced IL-1β production in celiac PBMC show that PDWGF-induced de novo pro-IL-1β synthesis, followed by a caspase-1 dependent processing and the secretion of mature IL-1β. This was promoted by K+ efflux and oxidative stress, and was independent of P2X7 receptor signaling. The PDWGF-induced IL-1β release was dependent on Nod-like receptor family containing pyrin domain 3 (NLRP3) and apoptosis-associated speck like protein (ASC) as shown by stimulation of bone marrow derived dendritic cells (BMDC) from NLRP3^−/− and ASC^−/− knockout mice. Moreover, treatment of human PBMC as well as MyD88^−/− and Toll-interleukin-1 receptor domain-containing adaptor-inducing interferon-β (TRIF)^−/− BMDC illustrated that prior to the activation of caspase-1, the PDWGF-triggered signal constitutes the activation of the MyD88/TRIF/MAPK/NF-κB pathway. Moreover, our results indicate that the combined action of TLR2 and TLR4 may be required for optimal induction of IL-1β in response to PDWGF. Thus, innate immune pathways, such as TLR2/4/MyD88/TRIF/MAPK/NF-κB and an NLRP3 inflammasome activation are involved in wheat proteins signaling and may play an important role in the pathogenesis of CD.     

Identifying uniformly mutated segments within repeats

Given a long string of characters from a constant size alphabet we present an algorithm to determine whether its characters have been generated by a single i.i.d. random source. More specifically, consider all possible n-coin models for generating a binary string S, where each bit of S is generated via an independent toss of one of the n coins in the model. The choice of which coin to toss is decided by a random walk on the set of coins where the probability of a coin change is much lower than the probability of using the same coin repeatedly. We present a procedure to evaluate the likelihood of a n-coin model for given S, subject a uniform prior distribution over the parameters of the model (that represent mutation rates and probabilities of copying events). In the absence of detailed prior knowledge of these parameters, the algorithm can be used to determine whether the a posteriori probability for n=1 is higher than for any other n>1. Our algorithm runs in time O(l4logl), where l is the length of S, through a dynamic programming approach which exploits the assumed convexity of the a posteriori probability for n. Our test can be used in the analysis of long alignments between pairs of genomic sequences in a number of ways. For example, functional regions in genome sequences exhibit much lower mutation rates than non-functional regions. Because our test provides means for determining variations in the mutation rate, it may be used to distinguish functional regions from non-functional ones. Another application is in determining whether two highly similar, thus evolutionarily related, genome segments are the result of a single copy event or of a complex series of copy events. This is particularly an issue in evolutionary studies of genome regions rich with repeat segments (especially tandemly repeated segments).     

Chemical composition of Cystoseira crinita Bory from the Eastern Mediterranean

The chemical composition of the brown alga Cystoseira crinita Bory from the Eastern Mediterranean was investigated. Fourteen sterols have been identified, five of them for the first time in algae. The structure of one new sterol was established. The origin of seven sterols with short side chains was discussed. In the volatile fraction 19 compounds and in the polar fraction 15 compounds were identified. The main lipid classes were isolated and their fatty acid composition was established.     

Levels of zinc and lipid peroxidation in acute coronary syndrome

The present study was carried out on 20 female patients diagnosed with acute coronary syndrome (ACS). The control group was composed of 20 healthy female volunteers. Plasma malondialdehyde (MDA) levels and serum zinc (Zn), total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and VLDL-cholesterol, Lp(a), Apo-A₁, and Apo-B were determined in all patients and controls. Plasma MDA levels were determined to be significantly high in patients with ACS compared to the controls (1.75±0.27 vs 0.8±0.43 nmol/mL; p<0.05). On the other hand, Zn levels in patients with ACS were determined to be significantly low compared to the control group (67.9±14.8 vs 101.8±22.4 mg/dL; p<0.05). There was a statistically significant negative correlation between MDA and Zn levels in patients with ACS (r=−0.678, p<0.05). Other lipid parameters were significantly altered in patients with ACS compared to the controls (p<0.05). In conclusion, Zn and lipid peroxidation levels are important in patients with ACS and they must be monitored during diagnosis and treatment of these patients.     

Lipid peroxidation and scavenging enzyme levels in the liver of streptozotocin-induced diabetic rats

In this study, alterations in the liver antioxidant enzymes status and lipid peroxidation in short-term (8-weeks) and long-term (24-weeks) diabetic rats were examined. Glutathione peroxidase (GSH-Px) activity and malondialdehyde (MDA) levels were significantly increased, but superoxide dismutase (SOD) activity was significantly reduced in 8-weeks diabetic rats, compared to control. Catalase (CAT) activity, however, was found unchanged. In 24-weeks diabetic rats, while GSH-Px activity was unchanged, but SOD and CAT activities and MDA levels were significantly increased, compared to control. These results suggest that diabetes-induced alterations in tissue antioxidant system may reflect a generalized increase in tissue oxidative stress. It can be concluded that lipid peroxidation and antioxidant enzyme levels are elevated in diabetic condition. Hence, diabetes mellitus, if left untreated, may increase degenerative processes due to accumulation of oxidative free radicals.     

Histological changes in the uterus of the hens after embryonic exposure to bisphenol A and diethylstilbestrol

Many employed chemicals in industries have estrogenic hormone effects on organisms, and these are called as environmental estrogens. Environmental estrogens have adverse effects on development and function of reproductive organs of the birds. Bisphenol A (BPA) is one of the best known environmental estrogens widely found in plastic products. In this study, we injected BPA and the synthetic estrogen diethylstilbestrol (DES) in ovo and then examined and compared the effects of those on the uteri (shell gland) of the adult hens by histological methods. Five groups have been designed in the current study. Only vehicle substance was given in ovo to the control group and BPA (67 or 134 μg/g egg) and DES (0.02 or 0.2 μg/g egg) were administered in the experimental groups. Tissue specimens were taken from uteri of hens at 21 weeks of age, prior to the laying period. Estrogen receptor alpha (ERα) was immunohistochemically stained. It was observed that the hatching proportion in BPA (67 μg and 134 μg/g) was lesser than the other groups (P?<?0.01). Uterine tubular glandular density and thickness of tunica mucosa were found to have reduced (P?<?0.01) in BPA (134 μg/g) and DES (0.2 μg/g) groups, in comparison with those of the control and the other experimental groups. Uterine gland epithelium revealed positive immunoreaction for ERα. These findings suggested that administration of BPA and DES at high doses affected embryonic development in a negative way, and this adverse effect was seen less in adult period.