Home About us Contact
|
Home About us Contact | ||
|
|
||
Several Pathological Conditions (several + pathological_condition)
Selected AbstractsA case of multiple metastasis in Late Holocene hunter-gatherers from the Argentine Pampean regionINTERNATIONAL JOURNAL OF OSTEOARCHAEOLOGY, Issue 5 2008L. H. Luna Abstract Chenque I site is a prehistoric cemetery located in Lihué Calel National Park (La Pampa province) in the Western Pampean region of Argentina. Hunter-gatherer societies made use of this site during the Final Late Holocene for at least 700 years (1030,370,BP). Currently 41 burial structures have been excavated, and more than 150 individuals have been recovered. There is great variability in mortuary patterns at the site (simple, multiple, primary, secondary burials, and also a variant not previously observed in the region). The life-ways of this population have been investigated through the evaluation of several biological and cultural factors. Several pathological conditions have also been identified in this cemetery. Burial no. 12 contains a skeleton of an adult male that shows multiple pathological lesions, compatible with a neoplastic disease. These lesions have been analysed using several methodological strategies: macroscopic, radiological and microscopic. This is the first time that this kind of disease has been identified from a prehistoric burial in Argentina. In this paper the location and characteristics of the lesions are evaluated, and the different neoplastic diseases that could have produced them are discussed. Since the people buried in this cemetery belonged to highly mobile societies, a key issue is to infer the consequences that this disease would have had on the dynamics of the group in which this person lived, because of the gradual deterioration of his health and physical strength. Copyright © 2007 John Wiley & Sons, Ltd. [source] Effects of diabetes on plasma nitrotyrosine levelsDIABETIC MEDICINE, Issue 6 2004X. L. Wang Abstract Background Oxidative stress plays a major role in disease processes such as atherosclerosis and diabetes. Peroxynitrite is a reaction product of nitric oxide (NO) and superoxide and a potent oxidant. The peroxynitrite-mediated tyrosine nitration, which forms nitrotyrosine (NT), is associated with several pathological conditions. Methods We measured plasma NT levels using the HPLC method in 40 Mexican Americans with diabetes, but not taking medications, and 40 age- and sex-matched euglycaemic controls. Results Plasma-free NT levels were not different between subjects with diabetes (11.0 ± 1.7 nmol/l, n = 40) and with non-diabetes (10.4 ± 1.5 nmol/l, n = 40). There was also no association with levels of fasting glucose (r = ,0.049, P = 0.663) or 2-h glucose (r = ,0.099, P = 0.390). However, females had significantly lower free NT level (7.6 ± 1.4 nmol/l, n = 40) than males (13.8 ± 1.7 nmol/l, n = 40, P = 0.005), which were not affected by age, smoking status, BMI and glucose levels. Conclusions In contrast to some earlier reports, our study shows that diabetes has no effect on plasma NT levels in Mexican Americans. We have also demonstrated lower free NT levels in females than males, which may partly explain the lower risk profile to vascular disease in women. [source] Thrombin-mediated impairment of fibroblast growth factor-2 activityFEBS JOURNAL, Issue 12 2009Pierangela Totta Thrombin generation increases in several pathological conditions, including cancer, thromboembolism, diabetes and myeloproliferative syndromes. During tumor development, thrombin levels increase along with several other molecules, including cytokines and angiogenic factors. Under such conditions, it is reasonable to predict that thrombin may recognize new low-affinity substrates that usually are not recognized under low-expression levels conditions. In the present study, we hypothesized that fibroblast growth factor (FGF)-2 may be cleaved by thrombin and that such action may lead to an impairment of its biological activity. The evidence collected in the present study indicates that FGF-2-induced proliferation and chemotaxis/invasion of SK-MEL-110 human melanoma cells were significantly reduced when FGF-2 was pre-incubated with active thrombin. The inhibition of proliferation was not influenced by heparin. Phe-Pro-Arg-chloromethyl ketone, a specific inhibitor of the enzymatic activity of thrombin, abolished the thrombin-induced observed effects. Accordingly, both FGF-2-binding to cell membranes as well as FGF-2-induced extracellular signal-regulated kinase phosphorylation were decreased in the presence of thrombin. Finally, HPLC analyses demonstrated that FGF-2 is cleaved by thrombin at the peptide bond between residues Arg42 and Ile43 of the mature human FGF-2 sequence. The apparent kcat/Km of FGF-2 hydrolysis was 1.1 × 104 m,1·s,1, which is comparable to other known low-affinity thrombin substrates. Taken together, these results demonstrate that thrombin digests FGF-2 at the site Arg42-Ile43 and impairs FGF-2 activity in vitro, indicating that FGF-2 is a novel thrombin substrate. [source] Involvement of ,1 integrin in microglial chemotaxis and proliferation on fibronectin: Different regulations by ADP through PKAGLIA, Issue 2 2005Kaoru Nasu-Tada Abstract Microglia are immune cells in the brain; their activation, migration, and proliferation have pivotal roles in brain injuries and diseases. Microglia are known to attach firmly to fibronectin, the upregulation of which is associated with several pathological conditions in the CNS, through ,1 integrin and become activated. Extracellular nucleotides can serve as potent signaling molecules. Recently, ATP and ADP were revealed to possess chemoattractive properties to microglia via Gi-coupled P2Y receptors. In the present study, we report that the ADP-induced chemotaxis of microglia is mediated by P2Y12/13 receptors and is ,1 integrin-dependent in the presence of fibronectin. Signals from P2Y12/13 receptors also cause ,1 integrin translocation to the membrane ruffle regions, but this redistribution was lost when the intracellular cyclic AMP (cAMP) was increased by forskolin or dibutyryl cAMP. This inhibitory effect of cAMP-elevating agents did not appear when microglia were co-incubated with a protein kinase A (PKA) inhibitor, KT-5720, suggesting that PKA is a negative regulator of the ,1 integrin translocation. We also show that the engagement of ,1 integrin enhanced microglial proliferation. Signals from P2Y12/13 receptors attenuated the proliferation, whereas ADP itself had no effect on microglial growth. Furthermore, ,1 integrin-induced proliferation is positively regulated by the cAMP-dependent PKA. Together, these results indicate the involvement of ,1 integrin in microglial proliferation and chemotaxis, both of which have clinical importance. The data also suggest that PKA is inversely involved in these two cellular functions. © 2005 Wiley-Liss, Inc. [source] ,,,-Cyclopentaneglycine Dipeptides Capped with Biaryls as Tachykinin NK2 Receptor AntagonistsCHEMMEDCHEM, Issue 7 2008Marina Porcelloni Dr. Abstract The NK2 receptor belongs to the family of tachykinin neurotransmitters. It has been reported to be involved in several pathological conditions, and selective antagonists are potentially useful drugs for the treatment of asthma, irritable bowel syndrome, cystitis, and depression. Starting from in-house capped dipeptide libraries, we were able to identify a number of molecules with sub-nanomolar binding affinity for the hNK2 receptor. All were characterized by a rigid core structure with a strong constraint induced by an ,,,-cyclopentaneglycine fragment. Herein we report the further elaboration of three initial basic structures. The planar benzothiophene group was substituted with a series of biphenyl and heterobiphenyl moieties that are well tolerated in terms of receptor affinity. The new compounds also maintained good antagonist potency in an in,vitro functional assay, and a number of them showed significant in,vivo activity after intravenous administration in our guinea pig model. [source] | ||||||||||