Search results for "drug discovery"

Endothelial dysfunction in morbid obesity.

2013

Morbid obesity is a chronic multifunctional disease characterized by an accumulation of fat. Epidemiological studies have shown that obesity is associated with cardiovascular and metabolic disorders. Endothelial dysfunction, as defined by an imbalance between relaxing and contractile endothelial factors, plays a central role in the pathogenesis of these cardiometabolic diseases. Diminished bioavailability of nitric oxide (NO) contributes to endothelial dysfunction and impairs endothelium- dependent vasodilatation. But this is not the only mechanism that drives to endothelial dysfunction. Obesity has been associated with a chronic inflammatory process, atherosclerosis, and oxidative stress. …

Splenic respiratory gas exchange and glucose uptake in patients with splenomegaly in hypersplenism and Hodgkin's disease.

1977

Blood samples are taken from the splenic artery, vein and pulp of patients suffering from Hodgkin's disease (n=10) or hypersplenism (n=7) and undergoing splenectomy. In these samples, the relevant parameters of the respiratory gas exchange as well as glucose and lactate concentrations are determined. In hypersplenism (mean splenic wet weight: 543 g) the mean oxygen consumption of the splenic tissue amounts to 0.9 ml O2/100 g/min taking into account a mean splenic blood flow of 80 ml/100 g/min. The glucose uptake and the lactate release are 9 mg/100 g/min and 5.5 mg/100 g/min, respectively. These values are in close agreement with the results obtained in the normal and undisturbed spleen in …

�ber die unterschiedliche Wirkung von Follikelhormon und Stilbenen auf die Gonadotropinaussch�ttung der Rattenhypophyse

1955

Microbial technologies for the discovery of novel bioactive metabolites

2002

Soil microbes represent an important source of biologically active compounds. These molecules present original and unexpected structure and are selective inhibitors of their molecular targets. At Biosearch Italia, discovery of new bioactive molecules is mostly carried out through the exploitation of a proprietary strain collection of over 50000 strains, mostly unusual genera of actinomycetes and uncommon filamentous fungi. A critical element in a drug discovery based on microbial extracts is the isolation of unexploited groups of microorganisms that are at the same time good producers of secondary metabolites. Molecular genetics can assist in these efforts. We will review the development an…

Die Bildung von Leber- und Muskelglykogen aus Xylit, Sorbit und Glucose bei gesunden und alloxandiabetischen Ratten

1963

Xylit, Sorbit und Glucose konnen bei Infusion an hungernde Ratten in gleichem Umfang zur Synthese von Leberglykogen verwendet werden. Dies gilt sowohl fur gesunde als auch fur alloxandiabetische Ratten. Auch bei alloxandiabetischen Ratten wird bei dieser Versuchsanordnung Glucose unvermindert zur Synthese von Leberglykogen verwendet. Weder bei gesunden noch alloxandiabetischen Ratten findet man eine signifikante Bildung von Muskelglykogen aus Sorbit oder Xylit. Aus Glucose kann Muskelglykogen nur bei gesunden Tieren, nicht aber bei diabetischen gebildet werden.

Mechanisms underlying noise-induced hearing loss

2006

Noise-induced hearing loss (NIHL) is the worldwide leading occupational disease and presents an important socio-economic factor. Despite numerous identified details about its etiology, the underlying mechanisms, which induce NIHL, have been only partially identified. In the present article, we shall discuss possible mechanisms focusing on failure in cellular calcium regulation, leading to a rise in mitochondrial NO production and reactive oxygen species formation. In cases where radical production is significantly elevated, pathological concentrations lead to alterations of cell physiological conditions and finally contribute to NIHL. A more detailed knowledge about the induction of free ra…

The role of statins in preventing the progression of congestive heart failure in patients with metabolic syndrome.

2008

Heart Failure (CHF) is a very important public health problem in the world and certainly one of the most common debilitating diseases and cause of mortality. Current knowledge underlines that incidence rates are also influenced by the coexisting pathologic conditions that accelerate the development of disease or increase its severity. Important scientific evidence is emerging to demonstrate a strong correlation between HF and the metabolic syndrome (MetS). Hypolipemia- inducing medication offers the opportunity to discuss the possible existence of pharmacological substances that in addition to their specific targets have several demonstrated pleiotropic effects that could be beneficial in H…

Pharmacological Therapy in Children with Atrial Fibrillation and Atrial Flutter

2008

Heart rhythm disorders in children are not different, on electrocardiographic trace, from heart rhythm disorders in adults with the exception of incidence which is different according to the age. Paticularly, atrial flutter (FlA) and fibrillation (FA) are very uncommon arrhythmias in the general pediatric population. Generally atrial fibrillation and atrial flutter, in our experience, is a temporary heart rhythm disturbance connected to specifical and resovable reasons with the exception of Fontains surgical correction of congenital heart diseases or cardiopathies with dilatation of both atria. Presenting symptoms, symptom history (e.g., frequency, duration, and severity), risk assessment, …

Hereditary angioneurotic oedema and blood-coagulation: interaction between C1-esterase-inhibitor and the activation factors of the proteolytic enzyme…

1983

C-1-inactivator (C-1-INA) does not only exert its important inhibitory functions in the complement system but also in the first step in the activation of the coagulation, fibrinolytic and kallikrein system. We therefore determined in nine patients with hereditary angioneurotic oedema (HANE) with obvious quantitative or functional defects of C-1-INA, and one further patient with Quincke-type oedema of different origin, the coagulation factors of the initial phase such as Hageman factor, plasma thromboplastin antecedent (PTA) and high molecular weight kininogen (HMWK). These factors were further correlated with the concentration as well as functional activity of C-1-INA. Nine of ten patients …

Gastrin: an acid-releasing, proliferative and immunomodulatory peptide?

2010

Gastrin release is affected by gastric inflammatory conditions. Antral G cells respond to inflammatory mediators by increasing gastrin secretion. Accumulating experimental evidence suggests that gastrin exerts immunomodulatory and proinflammatory effects. Gastrin could be a contributing factor to these pathologies, which may constitute a new justification for pharmacological blockade of gastrin action.