Synthesis and Cytotoxic Evaluation of Novel Thiazolocarbazoles. Part II1

Novel thiazolocarbazole derivatives have been synthesized via the corresponding imino-1,2,3-dithiazoles. In vitro antitumor activity of these polyheterocyclic compounds was studied.     

Microwave-assisted Synthesis of Novel Thiazolocarbazoles and Evaluation as Potential Anticancer Agents. Part III

Novel 6-substituted thiazolocarbazole derivatives have been synthesized under microwave irradiation via the corresponding imino-1,2,3-dithiazoles. In vitro antitumor potential of these polyheterocyclic compounds was evaluated. Among all the tested thiazolocarbazoles, compound 10 is the most effective in inhibiting cell growth.     

Synthesis and Cytotoxic Evaluation of Novel Thiazolocarbazoles

Novel thiazolocarbazole derivatives 4 and 5 have been synthesized via the corresponding imino-1,2,3-dithiazoles 3. In vitro antitumor activity of these polyheterocyclic compounds was studied and the results show that 2-cyano derivatives exhibit a medium in vitro antiproliferative effect.     

The octadecaneuropeptide ODN prevents 6‐hydroxydopamine‐induced apoptosis of cerebellar granule neurons through a PKC‐MAPK‐dependent pathway

Oxidative stress, induced by various neurodegenerative diseases, initiates a cascade of events leading to apoptosis, and thus plays a critical role in neuronal injury. In this study, we have investigated the potential neuroprotective effect of the octadecaneuropeptide (ODN) on 6‐hydroxydopamine (6‐OHDA)‐induced oxidative stress and apoptosis in cerebellar granule neurons (CGN). ODN, which is produced by astrocytes, is an endogenous ligand for both central‐type benzodiazepine receptors (CBR) and a metabotropic receptor. Incubation of neurons with subnanomolar concentrations of ODN (10^?18 to 10^?12 M) inhibited 6‐OHDA‐evoked cell death in a concentration‐dependent manner. The effect of ODN on neuronal survival was abrogated by the metabotropic receptor antagonist, cyclo_1–8[DLeu⁵]OP, but not by a CBR antagonist. ODN stimulated polyphosphoinositide turnover and ERK phosphorylation in CGN. The protective effect of ODN against 6‐OHDA toxicity involved the phospholipase C/ERK MAPK transduction cascade. 6‐OHDA treatment induced an accumulation of reactive oxygen species, an increase of the expression of the pro‐apoptotic gene Bax, a drop of the mitochondrial membrane potential and a stimulation of caspase‐3 activity. Exposure of 6‐OHDA‐treated cells to ODN blocked all the deleterious effects of the toxin. Taken together, these data demonstrate for the first time that ODN is a neuroprotective agent that prevents 6‐OHDA‐induced oxidative stress and apoptotic cell death.     

Characterization of genetic variation in and phylogenetic relationships among diploid<Emphasis Type="Italic"> Aegilops</Emphasis> species by AFLP: incongruity of chloroplast and nuclear data

Intra- and inter-specific genetic variation was investigated in seven diploid Aegilops species using the amplified fragment length polymorphism (AFLP) technique. Of the seven species, the cross-pollinating Aegilops speltoides and Aegilops mutica showed high levels of intraspecific variation whereas the remaining five self-pollinating species showed low levels. Aegilops bicornis, Aegilops searsii and Ae. speltoides formed one cluster in the dendrograms, while Aegilops caudata and Aegilops umbellulata formed another. Relationships among the species inferred were more consistent with the relationships inferred from studies of chromosome pairing in interspecific hybrids, and previous molecular phylogenetic reconstructions based on nuclear DNA, than they were with those based on molecular plasmon analysis, suggesting that the nuclear genome has evolved differently from the cytoplasmic genome in the genus Aegilops.Communicated by J. Dvorak     

Synthesis and cytotoxic evaluation of novel thiazolocarbazoles. Part III

Novel thiazolocarbazole derivatives have been synthesized via the corresponding imino-1,2,3-dithiazoles. In vitro antitumor activity of these polyheterocyclic compounds was studied.     

Human articular chondrocytes express 15-lipoxygenase-1 and -2: potential role in osteoarthritis

Introduction

Although cardiovascular morbidity and mortality are increased in rheumatoid arthritis, little is known about the burden of subclinical coronary atherosclerosis in these patients.

Methods

Using computed tomography, coronary artery calcification was measured in 195 men and women with rheumatoid arthritis aged 45 to 84 years without clinical cardiovascular disease and compared with 1,073 controls without rheumatoid arthritis enrolled in the Baltimore cohort of the Multi-Ethnic Study of Atherosclerosis.

Results

The prevalence of coronary calcification (Agatston score > 0) was significantly higher in men, but not women, with rheumatoid arthritis after adjusting for sociodemographic and cardiovascular risk factors (prevalence ratio = 1.19; P = 0.012). Among participants with prevalent calcification, those with rheumatoid arthritis had adjusted mean Agatston scores 53 units higher than controls (P = 0.002); a difference greater for men than women (P for interaction = 0.017). In all analyses, serum IL-6 attenuated the association between rheumatoid arthritis and coronary calcification, suggesting its role as a potential mediator of enhanced atherosclerosis. Notably, increasing severity of rheumatoid arthritis was associated with a higher prevalence and extent of coronary calcification among both men and women with rheumatoid arthritis, and for all age categories. The largest percentage difference in coronary arterial calcification between rheumatoid arthritis patients and their nonrheumatoid arthritis counterparts was observed in the youngest age category.

Conclusions

Increasing rheumatoid arthritis disease severity was associated with a higher prevalence and greater extent of coronary artery calcification, potentially mediated through an atherogenic effect of chronic systemic inflammation. Gender and age differences in association with coronary calcification suggest that preventive measures should be emphasized in men with rheumatoid arthritis, and considered even in younger rheumatoid arthritis patients with low levels of traditional cardiovascular risk factors.     

Effect of n-3 and n-6 polyunsaturated fatty acids on lymphocyte proliferation, interleukin production and phospholipid fatty acids composition in type 2 diabetic and healthy subjects in Jordan people

Dietary lipid manipulation may affect a great number of immune parameters, such as lymphocyte proliferation, cytokine synthesis. In this study, lymphocytes of diabetic type 2 were incubated with different polyunsaturated fatty acid (docosahexaenoic, eicosapentaenoic, arachidonic acid) for investigated their effect on lymphoproliferation response, the concentration of interleukin 2 produced in each essay and phospholipid fatty acid composition of lymphocyte membrane. Our results found that the concanavalin A and insulin increase significantly the proliferative response while eicosapentaenoic, arachidonic and docosahexaenoic acid inhibited that by different degrees: 47%, 37% and 19%, respectively, for healthy subjects and 39%, 29% and 13% for diabetes. However, the concentration of IL-2 produced in presence of either docosahexaenoic, eicosapentaenoic or arachidonic acid was significantly reduced by 36%, 32% and 39%, respectively, in controls while 16%, 15% and 23%, respectively, in diabetics. On the other hand, the tested fatty acids demonstrated a major impact on the fatty acid composition of different phospholipid fractions of lymphocyte membrane but these fractions were different in their response to each fatty acid examined. For instance, the addition of docosahexaenoic acid to culture media was accompanied with a predominant composition of docosahexaenoic acid in phospholipid fractions. Also, our results showed a notable increased proportion of arachidonic, eicosapentaenoic and docosahexaenoic acids in control phospholipid fractions than those of diabetic.