Changes induced by KI administration on plasma heparinic activity in healthy subjects

Other researches WE HAVE carried out show how it is possible to correct the high level of neutral fats in subjects with high trygliceridemia, with the administration of KI. We wished to ascertain whether the capacity of KI to reduce trygliceridemia when this is increased should be correlated to a possible change induced by this salt on PHA. Our researches has been carried out on 11 subjects who received a daily dose of 28 mg/Kg of b.w. of KI for a period of 10 days. The result we have obtained indicates that the administration of KI does not cause any significant change of PHA both after load and after prolonged treatment with KI.     

Plasmatic inheritance

The Botanical Review - It may be said in conclusion that the question of plasmatic inheritance is becoming of greater importance, not only from a theoretical point of view, but also as it concerns...     

Marked enhancement in antithrombotic activity of isocarbacyclin following its incorporation into lipid microspheres

Isocarbacyclin, (+)-9(O)-methano-delta 6 (9 alpha)-PGI1 (TEI 7165) and its methyl ester (TEI 9090) were incorporated in lipid microspheres (LM) with a diameter of 0.2 micron, in an attempt to increase their efficacy, possibly by way of targeting the drugs to the site of vascular damage. When the two LM-preparations were incubated in 2% bovine serum albumin solution, it was shown that TEI 7165 was released rapidly from LM, while the release of TEI 9090 was slow. Thus, TEI 9090 in LM, injected intravenously, may not be released largely in plasma before the distribution of LM to the target sites. The antithrombotic activity of the LM preparation of TEI 9090 was then compared with that of TEI 9090 as such in the hamster cheek pouch model. It was found that TEI 9090 incorporated in LM was more than 500 times more potent as an inhibitor of ADP-induced thrombus growth. These data suggest that prostacyclin analogues incorporated in LM may be used safely as potent antithrombotic agents in the clinical application.     

Marked enhancement in antithrombotic activity of isocarbacyclin following its incorporation into lipid microspheres

Isocarbacyclin, (+)-9(0)-methano-Δ^6(9α)-PGI₁ (TEI 7165) and its methyl ester (TEI 9090) were incorporated in lipid microspheres (LM) with a diameter of 0.2 μm, in an attempt to increase their efficacy, possibly by way of targeting the drugs to the site of vascular damage. When the two LM-preparations were incubated in 2% bovine serum albumin solution, it was shown that TEI 7165 was slow. rapidly from LM, while the release of TEI 9090 was slow. Thus, TEI 9090 in LM, injected intravenously, may not be released largely in plasma before the distribution of LM to the target sites. The antithrombotic activity of the LM preparation of TEI 9090 was then compared with that of TEI 9090 as such in the hamster cheek pouch model. It was found that TEI 9090 incorporated in LM was more than 500 times more potent as an inhibitor of ADP-induced thrombus growth. These data suggest that prostacyclin analogues incorporated in LM may be used safely as potent antithrombotic agents in the clinical application.     

Plasmatic fibronectin in malignancies.

Plasmatic fibronectin has been studied in tumor patients on the basis of the role that unspecific opsonin may play in tumor growth and spreading. Alterations in fibronectin levels might be used as a biological marker and our purpose has been to evaluate the significance of this test in the biological diagnosis of cancer. When comparing the levels found in the control group (22.86 +/- 1.40 mg/dl) and in tumor patients (23.80 +/- 1.90 mg/dl), we observed no difference in the overall group. However, in relation to the localization of tumors, a significant increase was found in breast cancer (31.83 +/- 3.83 mg/dl) and a significant decrease in squamous cell carcinoma of the head and neck (9.56 +/- 1.68 mg/dl). These results suggest that plasmatic fibronectin could be useful as a biomarker in some types of tumors. Our conclusion was confirmed by analysis of ROC curves related to every one of the studied tumors.     

Inhibitory effect of intracellular lipid load on macroautophagy

Degradation of intracellular components via macroautophagy is a complex multi-step process that starts with the sequestration of cytosolic cargo in a de novo formed double-membrane vesicle or autophagosome. This compartment acquires the hydrolases required for cargo digestion by fusion with lysosomes. In contrast to the detailed molecular dissection of the components that participate in the induction, regulation and execution of the early steps in macroautophagy, through the engulfment of cargo in autophagosomes, the mechanisms involved in the lysosomal clearance of autophagosomes have been poorly characterized in mammals. One of the major limitations in this respect has been the fact that autophagosome-lysosome fusion in intact cells involves several independent steps, namely binding of the molecular motors associated to the surface of the vesicles with the cytoskeletal network, directional vesicular trafficking and fusion between the two vesicular compartments. Furthermore, both lysosomes and autophagosomes are very dynamic organelles that can fuse with different vesicular structures involved in macroautophagy, but also along the endocytic and phagocytic pathways. To resolve these limitations and directly analyze the fusion step between autophagosomes and different compartments of the endocytic-lysosomal pathway, we have recently developed an in vitro fusion assay with autophagosomes, lysosomes and endosomes isolated from cells or tissues. Fluorescent labeling of these compartments allows for the tracking of fusion events by fluorescence microscopy or by fluorescence activated cell sorting (FACS). Labeling of either membrane proteins on the surface of the organelles or dye-loading of the vesicles permits the monitoring of hemi-membrane fusion and complete vesicular fusion (cargo mixing).     

Plasmatic exosomes from prostate cancer patients show increased carbonic anhydrase IX expression and activity and low pH

Abstract

Acidity, hypoxia and increased release of exosomes are severe phenotypes of tumours. The regulation of pH in tumours involves the interaction of several proteins, including the carbonic anhydrases which catalyze the formation of bicarbonate and protons from carbon dioxide and water. Among CA isoforms, CA IX is over-expressed in a large number of solid tumours, conferring to cancer cells a survival advantage in hypoxic and acidic microenvironment, but there isn’t evidence that CA IX expression could have a real clinical impact. Therefore, in this study for the first time the expression and activity of CA IX have been investigated in the plasmatic exosomes obtained from patients with prostate carcinoma (PCa). For this purpose, the study was performed through different methodological approaches, such as NTA, western blot analysis, enzyme activity assay, Nanoscale flow cytometry, ELISA, confocal microscopy. The results showed that PCa exosomes significantly overexpressed CA IX levels and related activity as compared to healthy donors. Furthermore, CA IX expression and activity were correlated to the exosome intraluminal pH, demonstrating for the first time that PCa exosomes are acidic. Our data suggest the possible use of the exosomal CA IX expression and activity as a biomarker of cancer progression in PCa.     

Plasmatic markers of muscular stress in isokinetic exercise

In this paper we examined the variations of plasmatic concentrations of hypoxanthine and xanthine, and their relation with other important indicators of muscular stress creatine-kinase (CK), myoglobin, uric acid, leucocytes, in prolonged, isokynetic physical exercise, performed in a concentric mode at different joint excursion. Twenty healthy male subjects performed isokinetic exercises in concentric-concentric mode, with joint excursion of 30, 60, 90 deg/sec. Blood samples were drawn at rest, immediately after exercise and after 45 min of recovery. The plasmatic concentration of hypoxanthine increased at the end of physical exercise, compared to the rest value of about 1,5 micromol/L, up to a level of greater than 19 micromol/L; the values were higher after a period of recovery of 45 min and the increase varies considerably according to the type of exercise that was performed. Myoglobin has a slight but sensible increment too, with the same trend as hypoxanthine, while CK increase without correlation to the type of exercises. The relation with other indicators of muscular activity demonstrates that in none of the different isokinetic exercises, performed at concentric mode, was there ultrastructural damage, while it is possible to come across a considerable metabolic stress, which is dissimilar in the different kinds of exercises. The results suggest that hypoxanthine can be useful in monitoring the effectiveness of a work load and the metabolic stress consequences on the muscle tissue in training or rehabilitation programs. The results also suggest that even myoglobin, at small concentrations, can have the same function.     

Plasmatic regulation of vascular prostacyclin in pregnancy.

Activity of prostacyclin-stimulating factor was measured in six normal, non-pregnant women, six women in early normal pregnancy, six in late normal pregnancy, and six in late pregnancy complicated by severe pre-eclampsia. The activity was lower in the women in late pregnancy than in those in early pregnancy and the controls but was about normal in those with severe pre-eclampsia. These results may be relevant to the physiology of pregnancy and the pathogenesis of pre-eclampsia.     

Alterations in rat lipid metabolism following ecdysterone treatment

The influence of ecdysterone on the lipid metabolism in liver and adipose tissue from rat was investigated using 14C-acetate and 32P-orthophosphate as precursors. Ecdysterone produced an increase in 14C-acetate incorporation into triglycerides. A concomitant decrease in free fatty acids and diglycerides was observed. The effect of ecdysterone on triglyceride lipase activity was investigated and a significant decrease was found. Ecdysterone produced a significant increase in the specific activity of phosphatidylethanolamine and phosphatidylserine in liver. On the contrary, the specific activity of phosphatidylcholine was reduced. In adipose tissue, the most evident effect observed was the increase of specific activity of phosphatidylcholine. These results contribute to knowledge of the heterophylic action of ecdysterone.