Stereospecific deuteration of alpha-furanosyl azomycin nucleosides: a model reaction for tritium radiolabeling

Stereospecific synthesis of 1-alpha-d-(2-deuteroribofuranosyl)-2-nitroimidazole (2'-[(2)H]-alpha-AZR) is reported. This, deuteration was independent of the configuration of C-2' -OH group (arabinose or ribose) in sugar moiety of starting molecules. Slightly better yield (>37%) of the deuterated product, 6, from arabinosyl precursor in comparison to corresponding ribose precursor (29%) was obtained which may reflect better stereochemical availability of C-2' -OH in arabinose during oxidation.     

Vasoactive intestinal peptide receptor activity and specificity during enterocyte-like differentiation and retrodifferentiation of the human colonic cancerous subclone HT29-18

Commitment of HT29-18 cells to enterocyte-like differentiation by glucose removal is related to a decreased capacity to generate cAMP after treatment with vasoactive intestinal peptide (VIP), forskolin or sodium fluoride. In contrast, the potency of VIP (EC50 = 1.1 - 1.3 X 10(-10) M) and the pharmacological specificity of the VIP receptor (VIP greater than rh GRF 1-43 greater than PHI greater than secretin) are unchanged during differentiation and retrodifferentiation. These results indicate that disturbances in VIP receptor-post-receptor activity, involving cell surface VIP receptors, membrane and intracellular transducers of hormonal information, occur during enterocyte-like differentiation of the HT29-18 subclone.     

Demonstration of a sucrose-derived contrast agent for magnetic resonance imaging of the GI tract

A scaffold bearing eight terminal alkyne groups was synthesized from sucrose, and copies of an azide-terminated Gd–DOTA complex were attached via copper(I)-catalyzed azide-alkyne cycloaddition. The resulting contrast agent (CA) was administered by gavage to C3H mice. Passage of the CA through the gastrointestinal (GI) tract was followed by T₁-weighted magnetic resonance imaging (MRI) over a period of 47 h, by which time the CA had exited the GI tract. No evidence for leakage of the CA from the GI tract was observed. Thus, a new, orally administered CA for MRI of the GI tract has been developed and successfully demonstrated.     

Dose-Dependent Effects of Astaxanthin on Ischemia/Reperfusion Induced Brain Injury in MCAO Model Rat

Excitotoxicity and oxidative stress are central to the pathology of the nervous system, and inhibition of excitotoxicity induced by glutamate is one of the therapeutic goals determined for stroke. The present study aimed to investigate the effects of Astaxanthin, a potent natural antioxidant, on complications caused by acute cerebral stroke. In this research, 60 male Wistar rats were used which were divided into 5 groups as follow: (1) the sham group (vehicle), (2) the ischemic control group (vehicle), and the ischemic groups treated by Astaxanthin with doses of 25, 45, and 65 mg/kg. In the ischemic groups, ischemic model was performed by middle cerebral artery occlusion (MCAO) method, and the Astaxanthin administration was carried out after the artery occlusion and before opening the artery. The obtained results indicated that Astaxanthin could significantly reduce stroke volume, neurological deficits, and lipid peroxidation. Moreover, it was able to restore total oxidant status (TOS) and caspase 3 level to the normal level. The activity of antioxidant enzyme glutathione peroxidase (GPX), and the expression of catalase, GPx and nuclear factor kappa B (NFκb) genes, which were reduced after ischemia, were increased. This phenomenon was particularly pronounced for glutamate transporter 1 (GLT-1). Furthermore, Astaxanthin decreased the augmented pro-apoptotic gene Bax and restored the reduced Bcl2 expression to the normal level. Significant effects on the P53 and PUMA expression were not observed. Overall, the medium dosage of Astaxanthin appears to be more effective in reducing the complications of ischemia, particularly on our major study endpoints (stroke volume and neurological defects). Longer studies with a more frequent administration of Astaxanthin are required to better understand the precise mechanism of Astaxanthin.

     

Higher circulating levels of ANGPTL8 are associated with body mass index,triglycerides, and endothelial dysfunction in patients with coronary artery disease

Molecular and Cellular Biochemistry - Bac Coronary artery disease (CAD) is the leading cause of death worldwide and most commonly develops as a result of atherosclerosis. ANGPTL8 is a secreted...     

Release of Cyt c from the model membrane due to conformational change induced by anticancer palladium complex

Cytochrome C (Cyt c) is an electron transporting protein that resides within the inter-membrane space of the mitochondria. It plays a critical role as an electron carrier in the process of oxidative phosphorylation and production of cellular ATP. Cyt c is also involved in the apoptosis process and functions as a death messenger. On the other hand, it is well known that the metallo-pharmaceuticals such as palladium complex offer potential as anti-tumor agents to fight cancer. In order to identify the role of anticancer Pd complex in release of Cyt c from the biological membrane, an artificial monolayer was assembled which is able to adsorb Cyt c. A monolayer containing a mixture of two long chain thiols (mercapto-undecanoic acid and mercapto-undecanol) was self-assembled on the surface of a gold electrode. Due to the existence of both hydrophobic and electrostatic interactions between Cyt c and the assembled monolayer, this membrane could be considered as a rough analogue of the biological membrane to study the release of Cyt c by Pd complex. The electrochemical and spectroscopic studies showed that bounding of Pd complex to Cyt c causes a conformational change which leads to the release of Cyt c from the model membrane.     

Activation of adenylyl cyclases, regulation of insulin status, and cell survival by G(alpha)olf in pancreatic beta-cells

Because we recently identified the G(alpha)olf subunit in rat pancreatic beta-cells, we investigated the downstream effectors and the biological functions of this G protein in HEK-293T cells and the insulin-secreting mouse betaTC-3 cell line. With the use of transient transfection of HEK-293T cells with constitutively activated G(alpha)olf (G(alpha)olfQ214L, i.e., AG(alpha)olf), together with expression vectors encoding the adenylyl cyclase (AC) isoforms (AC-I to -VIII and soluble AC), compared with cotransfections using AG(alphas) (G(alphas)R201C), we observed that AG(alpha)olf preferentially activates AC-I and -VIII, which are also expressed in beta-cells. Stable overexpression of wild-type or AG(alpha)olf in betaTC-3 cells resulted in partial attenuation of insulin secretion and biosynthesis, suggesting that chronic activation of the G(alpha)olf-signaling pathway is associated with beta-cell desensitization. In agreement, transfected betaTC-3 cells present a decreased insulin content with respect to parental cells, whereas the proinsulin convertases PC-1 and PC-2 were unaffected. Furthermore, betaTC-3-AG(alpha)olf cells are resistant to serum starvation-induced apoptosis. Our findings suggest that G(alpha)olf is involved in insulin status, cell survival, and regeneration of the insulin-secreting beta-cells during development and diabetes.     

A comparison of the effects of sodium nitroprusside and insulin on the control of metabolism in rat isolated adipocytes

Sodium nitroprusside, a known activator of guanylate cyclase within cells, was used as a probe to investigate the possible role of cyclic GMP in the control of metabolism within rat isolated white adipocytes. Over the concentration range 0-0.1 mM, it increased intracellular cyclic GMP concentrations up to 6-fold within 2 min. Over the same concentration range, it increased the incorporation of 14C from D-[U-14C]glucose into triacylglycerol and of L-[14C]leucine into protein. It also inhibited adrenalin -stimulated lipolysis in the cells, but had no effect on the transport of glucose into the cells. The effects of sodium nitroprusside were compared with those elicited by insulin under identical conditions, as this hormone was shown to cause a similar, but transient, rise in intracellular cyclic GMP concentrations within these cells. Nor insulin, neither sodium nitroprusside were able to increase cyclic AMP levels in adipocytes, whereas adrenalin (0.3 microM) stimulated this production. It is suggested that cyclic GMP may have a role in the control of some part of metabolism 'glucose or amino acids' in adipocytes, and that sodium nitroprusside is a useful probe to investigate this. The limitation of its use are discussed.     

Pesticide handling practices,health risks,and determinants of safety behavior among Iranian apple farmers

Common safety practices in pesticide use were assessed among apple farmers in Ardabil Province, Iran. With reference to the place of storing pesticides, most farmers (60%) stated that they store the pesticides in stalls and warehouses, while 8.5% stated that they store the pesticides in their houses. The majority of the farmers (71.5%) stated that they prepare the pesticide sprays in the orchards or next to irrigation wells. Almost one out of three farmers (32.8 %) reported that they dump the empty containers in the orchard fields and almost an equal proportion (30.2%) reported that they usually bury the empty containers. Irritating (burning) eyes and blurred vision were symptoms that the majority of respondents had experienced. Most farmers used trousers, long-sleeved blouses/shirts, and gloves when spraying, but coveralls and goggles were rarely used. Age and farming experience negatively affected PPE use and safety behavior, namely old and experienced farmers did not follow safety rules. On the contrary, education, information about pesticides, and farming as the main profession promoted safety behavior. Overall, significant levels of exposure among farmers can be concluded due to pesticide use. The extension services should aim human safety in relation to pesticide use in agriculture.