Site Of Metabolic Activity Research Articles

DIAGNOSTIC UTILITY OF PET/CT WITH 11C-METHIONINE IN PATIENTS WITH LYMPHOMAS

Aim: to study the role of combined positron emission and computed tomography (PET/CT) with 11C-methionine in the diagnosis of patients with different types of lymphoma. Material and methods. Uptake of 11C-methionine and 18F-FDG was studied with PeT/CT in 24 patients with histologically verified lymphoma. All patients underwent studies with both radiopharmaceuticals. A total of 48 studies were performed. Results. All 24 patients had abnormal sites of pathological uptake of 11C-methionine and 18F-FDG. Regions of abnormal sites of metabolic activity were coinciding in examinations with both radiopharmaceuticals. The average uptake rate of 18F-FDG and 11C-methionine were 9,45 ± 1,3 and 6,7 ± 0,4, (p = 0,05) respectively. In patients with Hodgkin's lymphoma (HL) and aggressive non-Hodgkin's lymphoma (NHL) in comparison with indolent NHL patients the metabolic activity of the pathological focuses in examinations with both radiopharmaceuticals had a significant difference in the accumulation rate, depending on the degree of malignancy-p = 0,01 and p = 0,001, respectively. The sensitivity and specificity of PET/CT with 11C-methionine was 94,4% and 83,3%, respectively. The threshold value of SUVmax > 5,6 (p <0,0001), allows to differentiate lymphomas according to the degree of malignancy. Conclusion. Most sites of tumor involvement in patients with HL and NHL well visualized using 11C-metnionine PET/ CT. All tumor sites had a different level of metabolic activity, higher in patients with aggressive NHL and HL. However it's utility in the abdomen is limited by uptake in normal structures.

Vascular Endothelium and Hypovolemic Shock.

Endothelium is a site of metabolic activity and has a major reservoir of multipotent stem cells. It plays a vital role in the vascular physiological, pathophysiological and reparative processes. Endothelial functions are significantly altered following hypovolemic shock due to ischemia of the endothelial cells and by reperfusion due to resuscitation with fluids. Activation of endothelial cells leads to release of vasoactive substances (nitric oxide, endothelin, platelet activating factor, prostacyclin, mitochondrial N-formyl peptide), mediators of inflammation (tumor necrosis factor α, interleukins, interferons) and thrombosis. Endothelial cell apoptosis is induced following hypovolemic shock due to deprivation of oxygen required by endothelial cell mitochondria; this lack of oxygen initiates an increase in mitochondrial reactive oxygen species (ROS) and release of apoptogenic proteins. The glycocalyx structure of endothelium is compromised which causes an impairment of the protective endothelial barrier resulting in increased permeability and leakage of fluids in to the tissue causing edema. Growth factors such as angiopoetins and vascular endothelial growth factors also contribute towards pathophysiology of hypovolemic shock. Endothelium is extremely active with numerous functions, understanding these functions will provide novel targets to design therapeutic agents for the acute management of hypovolemic shock. Hypovolemic shock also occurs in conditions such as dengue shock syndrome and Ebola hemorrhagic fever, defining the role of endothelium in the pathophysiology of these conditions will provide greater insight regarding the functions of endothelial cells in vascular regulation.

EXTRAPOLATING IN VITRO DATA ON DRUG METABOLISM TO IN VIVO PHARMACOKINETICS: EVALUATION OF THE PHARMACOKINETIC INTERACTION BETWEEN AMITRIPTYLINE AND FLUOXETINE

Recently, models have been proposed to extrapolate in vitro data on the influence of inhibitors on drug metabolism to in vivo decrement in drug clearance. Many factors influence drug clearance such as age, gender, habits, diet, environment, liver disease, heredity, and other drugs. In vitro investigation of hepatic cytochrome P450 activity has generally centered on genetic influences and interactions with other drugs. This group of enzymes is involved in many, although not all, drug interactions. The interaction of amitriptyline and fluoxetine is an example. Of the different in vitro paradigms, interaction studies utilizing human liver microsomal preparations have proved to be the most generally applicable for in vitro scaling models. Assuming Michaelis—Menten conditions and applying nonlinear regression, a hybrid inhibition constant (Ki) can be generated that allows classification of the inhibitory potency of an inhibitor toward a specific reaction. This constant is largely independent of the substrate concentration, but in vivo relevance is critically dependent on the inhibitor concentration in the site of metabolic activity, the liver cell cytosol. Many lipophilic drugs are extensively bound to plasma protein but, nonetheless, demonstrate extensive partitioning into liver tissue. This is not compatible with diffusion only of the unbound drug fraction into liver cells. The introduction of a partition factor, based on data from a number of possible sources, provided a reasonable basis for the scaling of in vitro data to in vivo conditions. Many interactions could be reconstructed or predicted with greater accuracy and clinical relevance for interactions such as terfenadine or midazolam and ketoconazole. Even for less marked interactions such as amitriptyline and fluoxetine, this model provides a forecast consistent with the clinically observed range of 22–45% reduction in oral clearance, although this interaction is complicated by the presence of two inhibitors, fluoxetine and norfluoxetine. The concept of in vitro–in vivo scaling is promising and might ultimately yield a fast and more cost-effective screening for drug interactions with reduced human drug exposure and risk.

Temporal and spatial activity in mirror segments of mature dog fibulae.

This investigation was undertaken to determine if the metabolic activity of homotypic segments of dog fibulae could be reliably compared in a thirty day period. Activities analyzed were: cumulative formation, porosity, resorption and apposition. Analyses were performed on contiguous tissue sections using microradiographic and tetracycline techniques. Spatial arrangements of the various activities were analyzed by constructing three dimensional models. The data permitted the following conclusions: 1) The mean differences between dog homotypic fibular segments are much smaller than the mean differences between heterotypic sites. 2) The use of homotypic fibular sites as valid controls should be limited to investigations in which the differences worth detecting are at least greater than 4% (apposition), 2% (resorption), 0.6% (porosity), and 2% (cumulative formation). 3) Of the four parameters measured, porosity was the most constant, showing no significant differences between mirror segments. 4) Lag correlations emphasize the importance of utilizing all available contiguous sections in a given specimen. 5) Physiologic resorption was not exclusive in old bone. 6) The sites of metabolic activity were predominantly found among specific active osteons which were primarily distributed peripherally in a strikingly similar pattern between mirror segments.