EFFECT OF ADENOSINE ON ISOPROTERENOL-INDUCED HYPERTROPHY IN VITRO. A PRELIMINARY STUDY

Persistent β1-adrenergic stimulation is thought to induce cardiac hypertrophy, alteration in calcium regulation and Cx43 over-expression. Adenosine is a negative feedback inhibitor of adrenergic stimulation in the heart, protecting it from toxic effects of overstimulation. The aim of our study evaluate the effects of adenosine administration on Cx43 and pCx43 expression and [Ca2+]i in Isoproterenol-treatedcardiomiocytesby usingH9c2 cells. Adenosine co-treatment reduced cellular hypertrophy, Cx43, pCx43 and CaMKII over-expression, and reducedintracellularCa2+ overload. These results suggest that the beneficial activity of adenosine on cardiomyocytes underlie the reduction of Cx43-dependent calcium overload and CaMKII over-expression, implying a potential therapeutic in cardiac hypertrophy

Lung cancer and Toll-like receptors.

Lung carcinoma is one of the leading causes of death worldwide. It is a non-immunogenic cancer, resistant to immune surveillance. Toll-like receptors (TLRs) connect the innate to the adaptive immune system. Given that cancerous cells evade the immune system, the activation of TLRs could represent a potential target for cancer therapy. The induction of Th1-like and cytotoxic immunity by TLR signalling could lead to tumour cell death, resulting in tumour regression or arrest. However, basic research and clinical trials revealed that the activation of specific TLRs, such as TLR2, TLR4 and TLR9, do not have any anti-tumour activity in lung carcinoma. Increasing evidence suggests that TLRs are important regulators of tumour biology; however, little is known about their function in lung cancer. Thus, in order to develop new therapeutic approaches, further studies are needed to understand the connection between TLRs and lung cancer progression. This review focuses on the potential mechanisms by which TLR ligands can facilitate or not lung cancer and lung metastases establishment/progression

Plasmacytoid Dendritic Cells: From Heart to Vessels

Cardiovascular diseases, formerly only attributed to the alterations of the stromal component, are now recognized as immune-based pathologies. Plasmacytoid Dendritic Cells (pDCs) are important immune orchestrators in heart and vessels. They highly produce IFN type I that promote the polarization of T cells towards a Th1 phenotype; however, pDCs can also participate to suppressive networks via the recruitment of T regulatory cells that downmodulate proinflammatory responses. pDCs populate the vessel wall layers during pathological conditions, such as atherosclerosis. It is thus clear that a better identification of pDCs activity in cardiovascular diseases can not only elucidate pathological mechanisms but also lead to new therapeutic approaches

Ladrilhamentos dourados da recta real

Apresentaremos a definição de sucessão dourada {r_i}. Estas sucessões possuem a propriedade de serem Fibonacci quasi-periodicas e determinam um ladrilhamento na recta real. Provaremos uma correspondência bijectiva entre: (i) sucessões douradas; (ii) Classes de conjugação diferenciáveis de difeomorfismos de Anosov na classe de conjugação topológica do automorfismo hiperbólico do toro G(x,y) =(x+y,x); (iii) Classes de conjugação diferenciáveis de difeomorfismos da circunferência com número de rotação igual ao inverso do número de ouro e que são pontos fixos do operador renormalização

Role of connexin 43 in cardiovascular diseases

Gap junctions (GJs) channels provide the basis for intercellular communication in the cardiovascular system for maintenance of the normal cardiac rhythm, regulation of vascular tone and endothelial function as well as metabolic interchange between the cells. They allow the transfer of small molecules and may enable slow calcium wave spreading, transfer of "death" or of "survival" signals. In the cardiomyocytes the most abundant isoform is Connexin 43 (Cx43). Alterations in Cx43 expression and distribution were observed in myocardium disease; i.e. in hypertrophic cardiomyopathy, heart failure and ischemia. Recent reports suggest the presence of Cx43 in the mitochondria as well, at least in the inner mitochondrial membrane, where it plays a central role in ischemic preconditioning. In this review, the current knowledge on the relationship between the remodeling of cardiac gap junctions and cardiac diseases are summarized

Impaired endothelium-dependent relaxations in rabbits subjected to aortic coarctation hypertension

Rabbits were rendered hypertensive by suprarenal coarctation of the abdominal aorta. Seven days later, endothelium-dependent and endothelium-independent vascular relaxations were examined in vascular rings taken from hypertensive (thoracic aorta, carotid artery) and normotensive (abdominal aorta) regions. Relaxation of phenylephrine-contracted rings in response to endothelium-dependent agonists (acetylcholine, A23187) was impaired, compared with that in sham-operated and intact controls, in regions exposed to the elevated blood pressure (i.e., above the coarctation). Responses to acetylcholine and A23187 in the abdominal aorta, below the coarctation, were not altered. The diminished endothelium-dependent responses in the thoracic aorta were not affected by pretreatment with the cyclooxygenase inhibitor indomethacin. In contrast to acetylcholine and A23187, responses to the endothelium-independent agonist nitroprusside were not attenuated in vessels from hypertensive regions, indicating that the defect occurred in the endothelium. The EC50 for acetylcholine-induced relaxations of thoracic aorta correlated significantly with mean arterial pressure above the coarctation, indicating that the extent to which endothelium-dependent relaxation is impaired is in proportion to the degree of blood pressure elevation. This study suggests that the diminished relaxations by endothelium-dependent agonists is a local response to the elevation of blood pressure and is not due to a circulating factor

The inhibition by hydrocortisone of prostaglandin biosynthesis in rat peritoneal leucocytes is correlated with intracellular macrocortin levels

Hydrocortisone inhibits prostaglandin generation by rat peritoneal leucocytes by releasing the polypeptide phospholipase inhibitor, macrocortin. The susceptibility of these cells to hydrocortisone is directly correlated with their intracellular macrocortin content. Cells depleted of the peptide by prior incubation with steroid cannot respond to the steroid, until a fresh intracellular store has been synthesized. In vitro, this process requires 4-5 h. Cells remain sensitive to the inhibitory action of the peptide at all times

Presence of cytochrome P-450-dependent monooxygenase in intimal cells of the hog aorta

Cytochrome P-450-dependent mixed function oxidase activity is present in vascular tissue; however, as far as we could determine, the distribution of monooxygenase activity across the blood vessel wall has not previously been assessed. The aryl-hydrocarbon hydroxylase activity was examined by metabolism of benzo[a]pyrene in microsomes prepared from intimal and smooth muscle cell scrapings of the hog thoracic aorta. Microsomes of intimal cells comprising 95% endothelial cells showed an approximately 2.5-fold increase in aryl-hydrocarbon hydroxylase activity compared with that in microsomes prepared from medial smooth muscle cells. Michaelis-Mentin kinetics for the intimal enzyme yielded an apparent Km value of 11.11 microM and an apparent Vmax of 3-OH benzo[a]pyrene of 40 pmol/mg protein/10 min. Aryl-hydrocarbon hydroxylase activity was dependent on nicotinamide adenine dinucleotide phosphate and was inhibited by 7,8 benzoflavone, SKF 525A, and carbon monoxide. The localization of cytochrome P-450-dependent mixed function oxidase primarily to the intimal surface of the aorta may indicate a role for this enzyme system in vasoregulation and the pathogenesis of atherosclerosis

Galeal Flap Based on Superficial Temporal Vessels for Oral Cavity and Pharynx Reconstruction – An Anatomical Study

PURPOSE: Despite the advances in microvascular free tissue transfer for intraoral reconstruction, this surgery is not recommended for all patients. In specific cases, the pedicled temporoparietal galeal flap may be an option for reconstructive procedures in the head and neck regions. The objective of this paper is to present the anatomical aspects of a galeal flap based on the superficial temporal vessels and to test its potential for reconstructing diverse sites of the oral cavity and pharynx. METHODS: We performed 40 dissections on 34 fresh adult cadavers. The flap vascular anatomy was studied by injecting latex into the superficial temporal vessels. A standardized square-shape flap measuring 10 x 10 cm², pedicled on the superficial temporal vessels, was raised. Oral cavity and oropharynx reconstruction simulations were performed after flap transposition into the mouth by passing it under the zygomatic arch. Hypopharyngeal reconstruction was tested by transposing the flap to the neck under the facial nerve. RESULTS: After latex injection, a rich vascular network over the temporoparietal galea was observed directly from the superficial temporal artery, and a well-vascularized flap based on this vessel was raised. In the reconstruction simulations, the flap was shown to be suitable for the coverage of hypothetical defects in most oral cavity and pharyngeal sites, mainly the retromolar trigone, tonsil area, and buccal mucosa. CONCLUSIONS: A galeal flap based on the superficial temporal vessels presents favorable anatomical characteristics for oral cavity and pharyngeal reconstruction