sulfate (DS) is a glycosaminoglycan of extractive origin with a relevant antithrombotic effect; the active mechanism differs from that of heparin. Heparin, indeed has a marked anticoagulant effect, due to its activating capacity on natural antiserine/proteases, such as antithrombin (AT III), which in turn mainly inhibits Factor Xa and Factor IIa (thrombin). DS, on the other hand, is almost inactive on AT III and does not inhibit Factor Xa 1-3 but it only interacts with heparin cofactor II (HC II), another natural antiprotease, which directly and selectively inhibits thrombin, 4-9 also interfering with its formation. 10 DS can in this way effectively neutralize thrombin thus preventing fibrin formation and probably providing a relevant contribution in maintaining the blood fluid balance in vivo. Studies in animals proved its efficacy in preventing venous thrombosis in different models 8-10 and in reducing in vivo the growth of an already formed thrombus, 11 with a quite low bleeding risk. 9 ' 12 ' 13 Desmin is a low molecular weight (LMW) DS preparation, with an average molecular weight of 5.6 kDa, obtained through an original procedure (of controlled chemical depolymerization followed by chromatographic purification 14 ) by Opocrin (Modena, Italy), starting from a natural DS extracted from porcine intestinal mucosa.The substance has undergone a thorough preclinical investigation in many laboratories. This has proved its antithrombotic properties in different animal models, associated with a very low hemorrhagic risk, attributed to its peculiar pharmacological profile. 15 A greater bioavailability after subcutaneous and intramuscular administration than the native compound was also proved for the LMW derivative, again in animal experiments, 16,17 and a substantial absence of toxic effects. Desmin shows a slightly lower antithrombotic efficacy when administered intravenously on thrombosis models in rats, whereas by the subcutaneous route it is practically two times more active than the native molecule, presumably due to its very high bioavailability by this administration route.In comparison to standard unfractionated heparin (UFH), Desmin showed 15 a less potent preventive antithrombotic effect in some experimental models, but was associated with a greater ability in reducing the size of preformed thrombi in a time-and dose-dependent way. This thrombolytic effect was comparable, in the same model, to that of therapeutic doses of tissue-type plasminogen activator and urokinase plasminogen activator 18 and there is some evidence from other sources 12 of a profibrinolytic mechanism contributing to its antithrombotic capacity. The anticoagulant effect was, on the contrary, extremely limited or even absent: Desmin doses required to double activated partial thromboplastin time (APTT) values were 396 versus 2.5 µg/mL of UFH. Moreover, Desmin induced much less bleeding than heparin at the corresponding antithrombotic doses.The aim of the present work was to investigate the pharmacological profile of Desmin in man through ...

In eight normal subjects, eight patients with asthma, and six patients with chronic obstructive lung disease, the first derivative of occlusion pressure at FRC during rebreathing has been studied. The maximal dP/dt was always lower in patients. Such a behavior may depend on reduced neuronal discharge as well as on reduced effectiveness of the contraction of the respiratory muscles. Though (dP/dt)_max may provide a reliable measure of the sensitivity of the respiratory center only in a homogeneous group, the results of plotting its value against ventilation and end-tidal Pco₂ confirm the failure of the thoracomuscular system to convert the output of respiratory centers into increase of pulmonary pressure and ventilation.

The ventilatory response to CO₂ inhalation, using rebreathing method, was studied in normal subjects and in patients with bronchial asthma and chronic obstructive lung disease. The patients with lung disease had flatter CO₂ response curves. However, if the ventilation was expressed as a fraction of the maximal voluntary ventilation, the difference between normal subjects and patients disappeared. The reduced ventilatory response of these patients may be of mechanical origin and not depending on reduced CO₂ sensitivity. The high lung volume of these patients may be the mean factor of the mechanical disadvantage of thoracomuscular system.

No abstract