C-reactive protein and lipid parameters in older persons aged 80 years and older.

OBJECTIVES: Aims of the study were 1) to investigate the association of C-reactive protein (CRP) with lipid (i.e. total, LDL, and HDL cholesterol, triglycerides) concentrations, and to evaluate their predictive value for mortality in very old subjects. DESIGN: Cross-sectional and longitudinal analyses in a prospective cohort study. SETTING: Participants. Data are from 336 community-dwelling subjects aged > or = 80 years old enrolled in the "Invecchiamento e Longevità nel Sirente" (ilSIRENTE) study. MEASUREMENTS: High sensitivity CRP and lipid concentrations were measured at the baseline clinical visit. High sensitivity CRP concentrations were measured by ELISA assessment. Mortality outcome was evaluated over a 24-month follow-up. RESULTS: Participants had a mean age of 85.8 (SD 4.8) years old. Spearman's correlations showed significant (p values < 0.01) inverse correlations between CRP and lipid parameters (except triglycerides). Adjusted linear regressions between CRP and lipid parameters concentrations showed no significant association in participants aged lower than 85 years old (all p values > 0.5). In the older age group, significant inverse associations of CRP with total (p=0.002), LDL (p=0.007), and HDL cholesterol (p=0.002) were found, even after adjustment for potential confounders. Adjusted Cox proportional hazard models demonstrated that CRP was the only biomarker significantly predictive of mortality, independently of age and lipid parameters. CONCLUSION: An inverse relationship of total, LDL, and HDL cholesterol with CRP is present in very old persons. The prognostic value of CRP is particularly important among very old persons whereas lipid parameters tend to lose their capacity to predict events.

Lifetime occupation and physical function: a prospective cohort study on persons aged 80 years and older living in a community.

BACKGROUND: Several studies have reported predictors for loss of mobility and impairments of physical performance among frail elderly people. AIM: To evaluate the relationship between lifetime occupation and physical function in persons aged 80 years or older. METHODS: Data are from baseline evaluation of 364 subjects enrolled in the ilSIRENTE study (a prospective cohort study performed in a mountain community in Central Italy). Physical performance was assessed using the physical performance battery score, which is based on three timed tests: 4-metre walking speed, balance, and chair stand tests. Muscle strength was measured by hand grip strength. Lifetime occupation was categorised as manual or non-manual work. RESULTS: Mean age of participants was 85.9 (SD 4.9) years. Of the total sample, 273 subjects (75%) had a history of manual work and 91 subjects (25%) a history of non-manual work. Manual workers had significant lower grip strength and physical performance battery score (indicating worse performance) than non-manual workers. After adjustment for potential confounders (including age, gender, education, depression, cognitive performance scale score, physical activity, number of diseases, hearing impairment, history of alcohol abuse, smoking habit, and haemoglobin level), manual workers had significantly worse physical function (hand grip strength: non-manual workers 32.5 kg, SE 1.4, manual workers 28.2 kg, SE 0.8; physical performance battery score: non-manual workers 7.1, SE 0.4, manual workers 6.1, SE 0.2). CONCLUSIONS: A history of manual work, especially when associated with high physical stress, is independently associated with low physical function and muscle strength in older persons.

Functional decline in frail community-dwelling stroke patients.

Patients who suffer a stroke event are at high risk of functional decline after the post-acute rehabilitation period. The aim of the present study was the evaluation of factors associated with functional decline in a large sample of older patients with stroke living in the community. The study population consisted of all patients admitted to home care programs after a post-acute rehabilitation program--with at least 1 year of follow-up--in twenty-two Italian Home Health Agencies from 2000 to 2002 (n=1338). For the present study we selected 355 (26%) patients with diagnosis of stroke. After 1 year of in-home care program, 149 out of 355 stroke survivors (42%) had presented a worsening in the activities of daily living (ADL) scale score. In the final adjusted model, patients with cognitive impairment (OR 2.59, 95% CI, 1.45-4.64), pressure ulcer (OR 2.74, 95% CI, 1.45-5.18), urinary incontinence (OR 1.64, 95% CI, 1.01-3.29), or hearing impairment (OR 1.83, 95% CI, 1.02-3.29) were more likely to significantly decline in physical functioning after a period of 1 year in-home care program. Our study documents that functional decline of stroke patients was largely dependent on specific subjects' clinical characteristics. Three of four concomitant disabling conditions associated in our sample with functional decline--pressure ulcer, urinary incontinence, hearing--can be prevented and eventually treated or modified. Appropriate post-acute rehabilitation programs and adequate home care interventions focused on the prevention and treatment of these conditions might be correlated to better outcomes in older post-stroke patients.

Antithrombotic drugs in secondary stroke prevention among a community dwelling older population.

BACKGROUND: Patients who suffer a cerebrovascular event are at high risk of a recurrence. Secondary prevention is crucial in reducing the burden of cerebrovascular disease. OBJECTIVE: To estimate the percentage of stroke survivors receiving antiplatelet or anticoagulant drugs and to identify factors associated with such treatment. DESIGN: Cross sectional retrospective cohort study. METHODS: Data were analysed from a large collaborative observational study, the Italian "silver network" home care project, which collected data (from 1997 to 2001) on patients admitted to home care programmes (n = 5372). Twenty two home health agencies participated in evaluating the implementation of the minimum dataset for home care (MDS-HC) instrument. For the present study, 648 individuals with a diagnosis of stroke were selected and the initial MDS-HC assessment reported. RESULTS: 70% of stroke survivors did not receive any antiplatelet or anticoagulant drugs (95% confidence interval (CI), 66.5 to 73.5). Among all age categories, aspirin and ticlopidine were the two most commonly prescribed drugs. Living alone (odds ratio (OR), 0.49 (95% CI, 0.24 to 0.89)), dependency in activities of daily living (0.66 (0.40 to 0.99)), cognitive impairment (0.58 (0.38 to 0.86)), and low educational level (0.58 (0.34 to 0.98)) were associated with a reduced likelihood of receiving secondary stroke prevention treatment. Cardiac arrhythmias, coronary artery disease, heart failure, and peripheral vascular disease were associated with the use of antiplatelet or anticoagulant treatment. CONCLUSIONS: Negative attitudes among physicians with respect to secondary stroke prevention are prevalent and reinforce the need for increased awareness of existing data on the risks and benefits for elderly individuals. Social problems and functional impairment may be issues concerning physicians when deciding whether or not the risks of treatment exceed the benefit.

Sulodexide in the treatment of intermittent claudication. Results of a randomized, double-blind, multicentre, placebo-controlled study.

AIMS: Patients with peripheral arterial obstructive disease require treatment to prevent major cardiovascular events and to relieve intermittent claudication. The walking performance of peripheral arterial obstructive disease patients was used to evaluate the usefulness of sulodexide, a glycosaminoglycan containing fast moving heparin and dermatan sulphate. METHODS AND RESULTS: A randomized, multicentre, double-blind, placebo-controlled study was performed in 286 patients with Leriche-Fontaine stage II peripheral arterial obstructive disease. Patients received placebo (n=143) or sulodexide (n=143) for 27 weeks. The primary end-point was the doubling of the pain-free walking distance at the end of treatment, and this was achieved by 23.8% of patients treated with sulodexide and 9.1% of those on placebo (P=0.001). The pain-free walking distance increased on average (+/-SE) by 83.2+/-8.6 m (+64.7% from baseline) with sulodexide and 36.7+/-6.2 m (+29.9% from baseline) with placebo (P=0.001). The maximum walking distance increased by 142.3+/-15.8 m (+76.0% from baseline) and 54.5+/-8.4 m (+27.9% from baseline) (P<0.001), respectively. Results for patients with type II diabetes were similar to those for non-diabetic patients. Plasma fibrinogen decreased with sulodexide, but increased with placebo. CONCLUSION: Sulodexide improved the walking ability of peripheral arterial obstructive disease patients to a significantly greater extent than placebo, with a concurrent significant decrease in fibrinogen. The treatment was well tolerated.

Crystal structures of two human pyrophosphorylase isoforms in complexes with UDPGlc(Gal)NAc: role of the alternatively spliced insert in the enzyme oligomeric assembly and active site architecture.

The recently published human genome with its relatively modest number of genes has highlighted the importance of post-transcriptional and post-translational modifications, such as alternative splicing or glycosylation, in generating the complexities of human biology. The human UDP-N-acetylglucosamine (UDPGlcNAc) pyrophosphorylases AGX1 and AGX2, which differ in sequence by an alternatively spliced 17 residue peptide, are key enzymes synthesizing UDPGlcNAc, an essential precursor for protein glycosylation. To better understand the catalytic mechanism of these enzymes and the role of the alternatively spliced segment, we have solved the crystal structures of AGX1 and AGX2 in complexes with UDPGlcNAc (at 1.9 and 2.4 A resolution, respectively) and UDPGalNAc (at 2.2 and 2.3 A resolution, respectively). Comparison with known structures classifies AGX1 and AGX2 as two new members of the SpsA-GnT I Core superfamily and, together with mutagenesis analysis, helps identify residues critical for catalysis. Most importantly, our combined structural and biochemical data provide evidence for a change in the oligomeric assembly accompanied by a significant modification of the active site architecture, a result suggesting that the two isoforms generated by alternative splicing may have distinct catalytic properties.

The location of the ligand-binding site of carbohydrate-binding modules that have evolved from a common sequence is not conserved.

Polysaccharide-degrading enzymes are generally modular proteins that contain non-catalytic carbohydrate-binding modules (CBMs), which potentiate the activity of the catalytic module. CBMs have been grouped into sequence-based families, and three-dimensional structural data are available for half of these families. Clostridium thermocellum xylanase 11A is a modular enzyme that contains a CBM from family 6 (CBM6), for which no structural data are available. We have determined the crystal structure of this module to a resolution of 2.1 A. The protein is a beta-sandwich that contains two potential ligand-binding clefts designated cleft A and B. The CBM interacts primarily with xylan, and NMR spectroscopy coupled with site-directed mutagenesis identified cleft A, containing Trp-92, Tyr-34, and Asn-120, as the ligand-binding site. The overall fold of CBM6 is similar to proteins in CBM families 4 and 22, although surprisingly the ligand-binding site in CBM4 and CBM22 is equivalent to cleft B in CBM6. These structural data define a superfamily of CBMs, comprising CBM4, CBM6, and CBM22, and demonstrate that, although CBMs have evolved from a relatively small number of ancestors, the structural elements involved in ligand recognition have been assembled at different locations on the ancestral scaffold.

Domain swing upon His to Ala mutation in nitrite reductase of Pseudomonas aeruginosa.

The nitrite reductase (NIR) from Pseudomonas aeruginosa (NIR-Pa) is a soluble enzyme catalysing the reduction of nitrite (NO2(-)) to nitric oxide (NO). The enzyme is a 120 kDa homodimer, in which the monomers carry a c-heme domain and a d(1)-heme domain. The structures of the enzyme in both the oxidised and reduced state were solved previously and indicate His327 and His369 as putative catalytic residues. The kinetic characterisation of site-directed mutants has shown that the substitution of either one of these two His with Ala dramatically reduces the physiologically relevant reactivity towards nitrite, leaving the reactivity towards oxygen unaffected. The three-dimensional structures of P. aeruginosa NIR mutant H327A, and H369A in complex with NO have been solved by multiple wavelength anomalous dispersion (MAD), using the iron anomalous signal, and molecular replacement techniques. In both refined crystal structures the c-heme domain, whilst preserving its classical c-type cytochrome fold, has undergone a 60 degrees rigid-body rotation around an axis parallel with the pseudo 8-fold axis of the beta-propeller, and passing through residue Gln115. Even though the distance between the Fe ions of the c and d(1)-heme remains 21 A, the edge-to-edge distance between the two hemes has increased by 5 A. Furthermore the distal side of the d(1)-heme pocket appears to have undergone structural re-arrangement and Tyr10 has moved out of the active site. In the H369A-NO complex, the position and orientation of NO is significantly different from that of the NO bound to the reduced wild-type structure. Our results provide insight into the flexibility of the enzyme and the distinction between nitrite and oxidase reduction mechanisms. Moreover they demonstrate that the two histidine residues play a crucial role in the physiological activity of nitrite reduction, ligand binding and in the structural organisation of nitrite reductase from P. aeruginosa.

Crystal structure of a monocotyledon (maize ZMGlu1) beta-glucosidase and a model of its complex with p-nitrophenyl beta-D-thioglucoside.

The maize beta-glucosidase isoenzymes ZMGlu1 and ZMGlu2 hydrolyse the abundant natural substrate DIMBOAGlc (2-O-beta-D-glucopyranosyl-4-hydroxy-7-methoxy-1,4-benzoxazin-3-one), whose aglycone DIMBOA (2,4-hydroxy-7-methoxy-1,4-benzoxazin-3-one) is the major defence chemical protecting seedlings and young plant parts against herbivores and other pests. The two isoenzymes hydrolyse DIMBOAGlc with similar kinetics but differ from each other and their sorghum homologues with respect to specificity towards other substrates. To gain insights into the mechanism of substrate (i.e. aglycone) specificity between the two maize isoenzymes and their sorghum homologues, ZMGlu1 was produced in Escherichia coli, purified, crystallized and its structure solved at 2.5 Angstrom resolution by X-ray crystallography. In addition, the complex of ZMGlu1 with the non-hydrolysable inhibitor p-nitrophenyl beta-D-thioglucoside was crystallized and, based on the partial electron density, a model for the inhibitor molecule within the active site is proposed. The inhibitor is located in a slot-like active site where its aromatic aglycone is held by stacking interactions with Trp-378. Whereas some of the atoms on the non-reducing end of the glucose moiety can be modelled on the basis of the electron density, most of the inhibitor atoms are highly disordered. This is attributed to the requirement of the enzyme to accommodate two different species, namely the substrate in its ground state and in its distorted conformation, for catalysis.

The mechanism of substrate (aglycone) specificity in beta -glucosidases is revealed by crystal structures of mutant maize beta -glucosidase-DIMBOA, -DIMBOAGlc, and -dhurrin complexes.

The mechanism and the site of substrate (i.e., aglycone) recognition and specificity were investigated in maize beta-glucosidase (Glu1) by x-ray crystallography by using crystals of a catalytically inactive mutant (Glu1E191D) in complex with the natural substrate 2-O-beta-d-glucopyranosyl-4-hydroxy-7-methoxy-1,4-benzoxazin-3-one (DIMBOAGlc), the free aglycone DIMBOA, and competitive inhibitor para-hydroxy-S-mandelonitrile beta-glucoside (dhurrin). The structures of these complexes and of the free enzyme were solved at 2.1-, 2.1-, 2.0-, and 2.2-A resolution, respectively. The structural data from the complexes allowed us to visualize an intact substrate, free aglycone, or a competitive inhibitor in the slot-like active site of a beta-glucosidase. These data show that the aglycone moiety of the substrate is sandwiched between W378 on one side and F198, F205, and F466 on the other. Thus, specific conformations of these four hydrophobic amino acids and the shape of the aglycone-binding site they form determine aglycone recognition and substrate specificity in Glu1. In addition to these four residues, A467 interacts with the 7-methoxy group of DIMBOA. All residues but W378 are variable among beta-glucosidases that differ in substrate specificity, supporting the conclusion that these sites are the basis of aglycone recognition and binding (i.e., substrate specificity) in beta-glucosidases. The data also provide a plausible explanation for the competitive binding of dhurrin to maize beta-glucosidases with high affinity without being hydrolyzed.

Helianthus tuberosus lectin reveals a widespread scaffold for mannose-binding lectins.

BACKGROUND: Heltuba, a tuber lectin from the Jerusalem artichoke Helianthus tuberosus, belongs to the mannose-binding subgroup of the family of jacalin-related plant lectins. Heltuba is highly specific for the disaccharides Man alpha 1-3Man or Man alpha 1-2Man, two carbohydrates that are particularly abundant in the glycoconjugates exposed on the surface of viruses, bacteria and fungi, and on the epithelial cells along the gastrointestinal tract of lower animals. Heltuba is therefore a good candidate as a defense protein against plant pathogens or predators. RESULTS: The 2.0 A resolution structure of Heltuba exhibits a threefold symmetric beta-prism fold made up of three four-stranded beta sheets. The crystal structures of Heltuba in complex with Man alpha 1-3Man and Man alpha 1-2Man, solved at 2.35 A and 2.45 A resolution respectively, reveal the carbohydrate-binding site and the residues required for the specificity towards alpha 1-3 or alpha 1-2 mannose linkages. In addition, the crystal packing reveals a remarkable, donut-shaped, octahedral assembly of subunits with the mannose moieties at the periphery, suggesting possible cross-linking interactions with branched oligomannosides. CONCLUSIONS: The structure of Heltuba, which is the prototype for an extended family of mannose-binding agglutinins, shares the carbohydrate-binding site and beta-prism topology of its galactose-binding counterparts jacalin and Maclura pomifera lectin. However, the beta-prism elements recruited to form the octameric interface of Heltuba, and the strategy used to forge the mannose-binding site, are unique and markedly dissimilar to those described for jacalin. The present structure highlights a hitherto unrecognized adaptability of the beta-prism building block in the evolution of plant proteins.

Efficacy of an intravenous low-molecular-weight dermatan sulphate (Desmin) in patients with acute proximal deep venous thrombosis and silent pulmonary embolism. A pilot study.

Ten patients affected by proximal deep venous thrombosis were treated in an open study with a low-molecular-weight dermatan sulphate (Desmin), administered at doses of 400 mg (intravenous bolus) followed by 1200 mg/day infused intravenously for 10 days, without activated partial thromboplastin adjustment. The evolution of the deep vein thrombosis and the presence of silent pulmonary embolism were evaluated by phleboscintigraphy and lung scan, performed before treatment and after 10 days of treatment, and by repeated echocolour-Doppler examination (every 2 days during treatment). The evolution of deep vein thrombosis showed a considerable improvement; similarly, lung scan showed a substantial reperfusion of lung, with regression of perfusional deficit. Repeated echocolour-Doppler examination of the deep venous system during treatment did not document further thrombus extension in any patient. Tolerance and safety were excellent. No adverse effects were observed. These preliminary results indicate that the tested dose of Desmin can be effective in treating deep vein thrombosis and silent pulmonary embolism.

Assessment of the efficacy of a last-generation polyvalent immunoglobulin in the treatment of idiopathic thrombocytopenic purpura.

High-dose intravenous immunogammaglobulin (h.d.IgG) has been proposed as a treatment of idiopathic thrombocytopenic purpura (ITP), but the clinical effect is usually short and adverse reactions have been reported in clinical studies using different immunoglobulin (Ig) preparations. In this study, the efficacy of a last-generation polyvalent immunoglobulin in the treatment of ITP in adults and the incidences of adverse reactions of this therapy were evaluated. The reported data were based on various clinical and laboratory parameters evaluated before, during and after therapy, with a follow-up of 6 months. The data showed administration of 400 mg/kg d of intravenous polyvalent intact IgG for 5 days significantly increased the platelet count in all 15 patients, the maximum level occurring on Day 10 and being maintained in some patients for 6 months. Its very rapid onset of action suggests it may be useful for correcting life-threatening thrombocytopenia where bleeding complicates the clinical course, and for severe ITP in seriously immunosuppressed or infected patients in whom corticosteroids or immunosuppressive agents cannot be safely administered. The treatment was also well tolerated. In conclusion, polyvalent Ig may be useful in ITP steroid-refractory patients; further studies are required to evaluate clinical-laboratory parameters related to the long-term response of patients.

Bioavailability of Desmin, a low molecular weight dermatan sulfate, after subcutaneous administration to healthy volunteers.

The bioavailability of two different s.c. doses of Desmin (a new low molecular weight dermatan sulfate) was evaluated in 12 healthy volunteers (6 men, 6 women aged 22-45 years) who were injected, on 3 separate days and with a wash-out period of at least 21 days between each administration, with 200 and 300 mg of Desmin by the s.c. route and 200 mg by the i.v. route. Immediately before injection and at various times thereafter (after 15 min and 30 min for i.v. only and after 1, 2, 3, 4, 6, 8, 12, and 24 h for both s.c. and i.v. dosing), blood samples were drawn to investigate bioavailability by measuring several coagulation parameters: activated partial thromboplastin time, thrombin time, inhibition of factor Xa, Heptest, and heparin cofactor II. Furthermore the local tolerance of the s.c. and i.v. injections were investigated. The s.c. administration of the two Desmin doses had a negligible effect on the activated partial thromboplastin time and a very small effect on the thrombin time, measured with human thrombin; in contrast, Heptest, heparin cofactor II, and anti-Xa activities increased, with a good drug bioavailability (more than 100%). The plasma effects of Desmin were dose dependent only when measured by Heptest, which also gave a greater response after the s.c. administrations. There were no symptoms of intolerance or pain at the injection site after single i.v. and s.c. Desmin administration.

The treatment of deep vein thrombosis with continuous intravenous low-molecular-weight dermatan sulphate (Desmin). A pilot study.

Eight patients with femoro-popliteal or sural DVT, confirmed by phlebography, were treated with intravenous Desmin (LMW-dermatan sulphate): on the first day, after an initial i.v. injection of 400 mg, all patients received an infusion of 800 mg in 500 ml of saline, during 24 hours; this infusion was repeated in each of the subsequent 9 days (global treatment period: 10 days). To monitor efficacy of the antithrombotic treatment a phlebography, with calculation of Marder score, was repeated at the end of treatment. Laboratory tests monitoring blood coagulation were carried out: aPTT, TT, PT. Factor Xa inhibition (by chronometric and chromogenic method), Stachrom DS, fibrinogen, prothrombin fragments F1 + 2 and TAT. Seven patients completed the ten-day treatment: 6 patients evidenced good improvement of the phlebographic patterns, 1 remained stationary and 1 patient was withdrawn due to adverse events. During the ten days treatment we did not observe any variation of blood coagulation tests. Desmin tolerability was good and no haemorrhagic episodes were registered. The collected results point to a good antithrombotic activity of the new LMW-dermatan sulphate, that deserves to be further evaluated with controlled investigations on larger number of patients.

Postphlebitic syndrome: clinical activity and tolerability of desmin, new LMW dermatan sulfate.

One hundred patients suffering from postphlebitic syndrome of the lower limbs were enrolled in an open, randomized, and multicenter (six centers) trial for a period of eighteen months. Patients were randomly assigned to three treatment groups to receive (for ninety consecutive days) Desmin, a new low-molecular-weight dermatan sulfate, at the dose, respectively, of 100 mg once daily by subcutaneous (SC) route (36 patients), 100 mg twice a day by SC route (33 patients), and 200 mg once daily by intramuscular (IM) route (31 patients). The general and local tolerability and the clinical efficacy of the drug were evaluated by means of clinical, instrumental, and laboratory parameters. Desmin is effective in the decompensation stage of postphlebitic syndrome; this was demonstrated by a significant reduction in the severity of a number of typical symptoms as well as by the drug's positive effect on venous tone as confirmed by phlebotensiometric examination. The daily dose of 200 mg (either SC or IM) was more effective than the 100 mg dose. The results obtained at the end of the trial (ninety days) were statistically better than those obtained after thirty days of treatment. This trial demonstrated that both the systemic and the local (at the site of injection) tolerability of the drug, administered for three months, were good and without significant variations in the laboratory parameters monitored.

Tolerability and clinical efficacy of desmin in the treatment of superficial thrombovaricophlebitis.

Fifty-six patients with superficial thrombovaricophlebitis of the lower limbs were enrolled in an open and multicenter (4 centers) trial for a period of thirty days. Patients were randomly allocated to three treatment groups to receive a new low-molecular-weight dermatan sulfate (Desmin) at the dose, respectively, of 100 mg once daily by subcutaneous (SC) route, 100 mg twice a day SC, and 200 mg once daily by intramuscular (IM) route. The general and local tolerability and the clinical efficacy of the drug were evaluated by means of clinical, instrumental, and laboratory parameters. Desmin proved capable of effectively improving the symptoms of patients affected by thrombovaricophlebitis, inducing rapid regression by the tenth day of treatment. The daily dose of 200 mg (either SC or IM) was more effective than the 100 mg dose. The systemic tolerability of the drug, administered for the first time for one month, was extremely good, without significant variations in the relevant laboratory tests. Local tolerance (at the site of injection) of the drug was also good.

Pharmacology of desmin (low molecular weight dermatan sulphate) in healthy volunteers following intravenous bolus administration of different dosages (200, 400, 800 mg).

Eight healthy volunteers (6 males, 2 females, mean age 31.6 yrs), were administered--on three separate days--200, 400 and 800 mg of a new low molecular weight Dermatan sulphate (Desmin), given as a single i.v. bolus (2 min.) injection. Before each administration and 10, 20, 30 min., 1, 2, 4, 8, 12, 24 hours after, blood samples were drawn and the following coagulative assays performed: aPTT (activated Partial Thromboplastin Time), TT (Thrombin Time), anti Xa (Xa Factor inhibition), Heptest, Stachrom D.S.. Furthermore, a kinetic analysis was performed on the activity curves calculated on the Heptest and Stachrom data. Plasma peak values and half lives of the parameters checked showed a clear dose-effect relationship. aPTT and TT showed very short-lasting variations and the inhibition of Factor Xa was moderate, but significant. The most evident and specific effects of Desmin were those on Heptest and Stachrom D.S.: both tests were influenced in a clear-cut and dose-dependent way, mainly as a consequence of the action of Desmin on HCII, with partially different kinetic patterns. A series of in vitro experiments proved an anti Xa effect of Desmin, mediated by antithrombin III, well above the possible interference of the small (< 1%) heparin contaminants in Desmin. An even more marked anti Xa activity was seen in the in vivo study, an observation so far unrecognized for this type of drug: some possible interpretations of this fact are discussed.