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Biomedical subjects

L Di Bari

Publications and source records attributed to L Di Bari.

17 recordsLinked to original sources
PubMed2001

Determination of absolute configuration of acyclic 1,2-diols with Mo2(OAc)4. 1. Snatzke's method revisited.

The method employing dimolybdenum tetraacetate for the assignment of the absolute configuration of optically active 1,2-diols is thoroughly revisited and applied to several compounds, some of which were synthesized by asymmetric cis-dihydroxylation. No exceptions were found to the empirical rule relating the sign of the induced CD spectrum and the configuration of the substrate, whatever its structure and sterical requirements. To broaden the scope of the method, its applicability to critical situations commonly encountered with synthetic products is tested. It is demonstrated that the method can be applied on samples with low chemical and optical purity, and that it may lend itself as a means to estimate the ee. The roles of the water content of the sample and of the diol-to-dimolybdenum ratio are investigated.

Circular Dichroism↗
PubMed2001

Antioxidant principles from Bauhinia tarapotensis.

A new cyclohexenone (1) and a new caffeoyl ester derivative (2), together with the known compounds (-)-isolariciresinol 3-alpha-O-beta-D-glucopyranoside (3), (+)-1-hydroxypinoresinol 1-O-beta-D-glucopyranoside (4), isoacteoside (5), luteolin 4'-O-beta-D-glucopyranoside (6), and indole-3-carboxylic acid (7), were isolated from the leaves of Bauhinia tarapotensis. The structures of these new compounds were determined by spectroscopic data analysis. The antioxidant activities of 1-7 were determined by measuring their free radical scavenging effects, using the 1,1-diphenyl-2-dipicrylhydrazyl free radical (DPPH) and Trolox equivalent antioxidant activity (TEAC) methods, and the coupled oxidation of beta-carotene and linoleic acid. Compounds 3-5 showed good activities in the DPPH and TEAC tests, while compounds 1 and 2 were active in the coupled oxidation of beta-carotene and linoleic acid bioassay.

Antioxidants↗
PubMed2000

Beneficial effects of postmenopausal hormone replacement therapy with transdermal estradiol on sensitivity to activated protein C.

Many hemostatic and fibrinolytic parameters have been evaluated following hormone replacement therapy (HRT) but little is known about its influence on the anticoagulant response to activated protein C (APC-sensitivity). For this purpose, we studied the effect of transdermal 17-beta-estradiol (50 microg/24 h) by a continuous regimen on the APC-sensitivity, in 28 postmenopausal hysterectomized women (mean age, 47 years; range, 44-65 years). We also measured the plasma proteins directly involved in the protein C anticoagulant pathway, such as activities of factor VIII (VIII:C), factor V and free protein S. Von Willebrand factor (vWF) antigen, the carrier protein of factor VIII, was also determined. Blood sampling was done at baseline and after 16-week therapy. A significant increase in the normalized APC-sensitivity ratio (n-APC-SR) values (mean +/- SD: pre-trial, 0.88 +/- 0.14; post-trial, 1.01 +/- 0.12; P < 0.001) and a significant decrease of factor VIII:C plasma levels (pre-trial, 1.13 +/- 0.29 IU/ml; post-trial, 0.98 +/- 0.20 IU/ ml; P = 0.001) were found. No difference was observed in factor V, protein S and vWF plasma levels. Correlation studies demonstrated only a significant negative correlation between the percent change in n-APC-SR and the percent change in factor VIII:C (r = -0.574; P = 0.001). Our findings clearly show that HRT with transdermal estradiol improves the anticoagulant response to APC, probably as a result of a decreased factor VIII:C. We also suggest that a similar but opposite mechanism may occur for perorally administered estrogens used in the HRT. These results may have some clinical implications about the reported increase of the risk for venous thromboembolism following HRT.

Activated Protein C Resistance↗
PubMed1999

Treatment with recombinant activated factor VII in a patient with hemophilia A and an inhibitor: advantages of administration by continuous infusion over bolus intermittent injections.

Recent studies have shown that treatment with a continuous infusion of recombinant activated factor VII (rFVIIa) is far more convenient than administration by bolus intermittent injections and may allow a substantial reduction in the dose. We present the case of a 26-year-old patient with hemophilia A, who had a high-titer inhibitor to both human and porcine factor VIII, and who had recently been admitted to hospital because of a bilateral severe ilio-psoas hematoma. Two subsequent courses of treatment with rFVIIa by bolus intermittent injection showed only a partial efficacy. A further administration of rFVIIa was therefore carried out using a continuous infusion regimen that proved to be fully efficacious. During the continuous infusion course levels of factor VII coagulant activity were in the range 18.2-5.2 U/ml, while the prothrombin time, expressed as an International Normalized Ratio, remained within the range 0.57-0.71. The continuous infusion, compared with the administration of the bolus intermittent infusion, reduced the amount of rFVIIa required by approximately 40-50%. Statistical analysis demonstrated that there was a strong positive correlation between the rate of infusion of rFVIIa and levels of factor VII coagulant activity (r = +0.941; P < 0.001), and a very significant negative correlation between levels of factor VII coagulant activity and prothrombin time values (r = -0.897; P < 0.001). In accordance with previous findings, our experience confirms that, when prolonged therapy is required, treatment with rFVIIa by continuous infusion is more convenient than administration of bolus intermittent injections, and may allow the saving of a large amount of drug. Moreover, we suggest potential additional advantages of the continuous infusion regimen over bolus intermittent injections, such as a better efficacy and a stronger correlation between prothrombin time and factor VII coagulant activity levels.

Adult↗
PubMed1999

Influence of factor VIII/von Willebrand complex on the activated protein C-resistance phenotype and on the risk for venous thromboembolism in heterozygous carriers of the factor V Leiden mutation.

High factor VIII plasma levels have been shown to represent a common increased risk for venous thromboembolism (VTE) and may cause an activated protein C (APC) resistance in the absence of the factor V Leiden mutation, but there are no studies specifically aimed to establish if high factor VIII and von Willebrand factor (vWF) concentrations may influence the APC sensitivity ratio (APC-SR) and increase the risk for VTE in the presence of the factor V Leiden mutation. For this purpose, we performed a retrospective case-control study to investigate the influence of the procoagulant factor VIII (VIII:C) and the antigen of vWF (vWF:Ag) on the normalized APC-SR (n-APC-SR) and on the risk for VTE, in two selected groups of 30 symptomatic (Group I) and 32 asymptomatic (Group II) related heterozygotes for the factor V Leiden mutation. Differences between the two groups (Group I versus Group II) were: n-APC-SR, 0.57+/-0.06 versus 0.63+/-0.08, P = 0.001; factor VIII:C, 1.49+/-0.42 versus 1.13+/-0.28 IU/ml, P<0.001; vWF:Ag, 1.46+/-0.53 versus 1.26+/-0.32 IU/ml, NS. As a whole (Group I + Group II), Pearson correlation coefficients were: n-APC-SR versus factor VIII:C, r = -0.410, P = 0.001; n-APC-SR versus vWF:Ag, r = -0.309, P = 0.01; factor VIII:C versus vWF:Ag, r = +0.640, P<0.0001. The relative risk for VTE in individuals with the factor VIII:C concentration > 1.5 IU/ml was 2.5 (95% confidence interval 1.6-3.9). We concluded that high factor VIII:C levels, probably in the effect of vWF, play a determinant role in worsening the APC-resistance phenotype and represent a common additional risk factor for VTE in heterozygous carriers of the factor V Leiden mutation.

Adult↗
PubMed1998

Use of CD and FT-IR to determine the secondary structure of purified proteins in the low-microgram range.

The spectroscopic characterization of protein secondary structure is often partially unreliable when samples are not extremely pure and abundant. This problem may be overcome by the combination of circular dichroism (CD) and Fourier transform infrared spectroscopy (FT-IR). We used these methods to characterize the secondary structure of two proteins of neurobiological interest, calexcitin (CE) and the cellular isoform of prion protein (PrPC). Both proteins were purified with multiple chromatographic steps and were obtained in buffer with high purity (> 95%) and in low amount (approximately 2 micrograms). The samples were analyzed by circular dichroism (down to 184 or 182 nm), recovered, and deposited on films for infrared analysis. The spectral deconvolution from the two methods yielded secondary structures in good agreement with each other as well as with theoretical predictions based on amino acid sequence. The conformation of CE was found to be dependent on its concentration and on calcium binding. The secondary structure of cellular native PrP varied dramatically with the detergent used. In conclusion, the combination of CD and FT-IR analysis is suitable for the characterization of the conformational changes induced by ligand binding and/or by different solvent conditions when the protein of interest is only scarcely available. The methods used here provide valuable insights into the putative correlation between protein structure and activity.

Algorithms↗
PubMed1997

Increase in both pro-thrombotic and anti-thrombotic factors in obese premenopausal women: relationship with body fat distribution.

OBJECTIVES: To examine the relationship of obesity, body fat distribution, and fasting plasma insulin concentrations with the plasma levels of both pro-thrombotic and anti-thrombotic factors in premenopausal women. SUBJECTS: 32 obese women with BMI > 28 and 33 age-matched non-obese = women with BMI < 25. MEASUREMENTS: (i) plasma concentrations of plasminogen activator inhibitor-1 antigen (PAI-1 Ag), plasminogen activator inhibitor-1 activity (PAI-1 activity), fibrinogen, von Willebrand factor antigen (vWF Ag), von Willebrand factor activity (vWF activity), and factor VII activity as pro-thrombotic factors; (ii) plasma concentrations of tissue plasminogen activator antigen (t-PA Ag), protein C, and antithrombin III as anti-thrombotic factors; (iii) fasting plasma insulin and glucose concentrations, and the lipid pattern (triglycerides, total and HDL-cholesterol) as metabolic parameters. The body fat distribution was evaluated by measuring the waist circumference and the waist-to-hip ratio (WHR). RESULTS: Obese subjects had higher plasma concentrations of all pro-thrombotic factors as compared to non-obese controls (PAI-1 Ag, P < 0.001; PAI-1 activity, P < 0.05; fibrinogen, P < 0.001; vWF Ag, P < 0.001; vWF activity, P < 0.05; factor VII, P < 0.05). The plasma concentrations of PAI-1 Ag and vWF Ag were directly correlated with the waist circumference independently of other metabolic and non-metabolic variables (P < 0.05). Obese women were also characterized by higher plasma concentrations of anti-thrombotic factors such as t-PA Ag and protein C as compared to non-obese controls (P < 0.001 and P < 0.001, respectively), although these factors were not independently correlated with the waist circumference or the WHR. CONCLUSION: Plasma concentrations of the pro-thrombotic factors are increased in obese women as compared to non-obese controls, and plasma levels of PAI-1 Ag and vWF Ag correlate with central fat accumulation specifically. Plasma concentrations of anti-thrombotic factors (namely protein C and t-PA Ag) are also raised in obese women, but they are not correlated with parameters of body fat distribution. The increase in protein C levels may represent a protective response partly counteracting the increase in pro-thrombotic factors in these individuals.

Adipose Tissue↗
PubMed1996

A versatile mechanical ventilator (DIGIT) with high flow stability and a programmable inspiratory phase flow pattern.

The paper describes the general characteristics of a newly developed nonconstant-flow generator for automatic ventilation of the lungs. It is known that the application of very high pressure to high internal resistance leads to a very stable flow, in that the flow itself is unaffected by external load (patient) variations. The stability of the flow means that the inspiratory process can be controlled by means of the ventilated volume, thus extending DIGIT utilization to high resistance patients. The modulation of the flow is implemented via a digital electromechanical system, which allows the ventilator functions to be accurately programmed. The desired flow waveform is obtained by means of a series of pneumatic valves, the apertures of which are digitally controlled. The design is innovative in that it allows the flow waveform in each of the ten digitalized time steps into which each inspiratory phase is divided to be both programmed and controlled. Other ventilators commercially available and currently in use do not have this functional capability, as they are all designed to model the integral flow of the inspiratory waveform without being able to modify the subunit time steps of a single inspiratory phase. The paper also discusses the results of fundamental tests concerning the performance characteristics of the ventilator.

Airway Resistance↗
PubMed1995

The binding of 5-fluorouracil to native and modified human serum albumin: UV, CD, and 1H and 19F NMR investigation.

5-Fluorouracil (FU) is an important and widely used antineoplastic drug that is carried in the serum by plasma proteins. Protein binding studies of this drug to human serum albumin (HSA) have been carried out by several spectroscopic techniques. Difference circular dichroism and UV studies provided information on the class of binding sites involved in the interaction. In particular, displacement experiments showed that FU has at least one secondary binding site in the coumarin binding area, but does not interact with the benzodiazepine binding area. Binding was also investigated by difference 1H NMR and by measuring the increase in the 19F NMR signal of FU when bound to HSA. Finally, evidence was obtained that chemical acetylation of Lys199 results in a decreased apparent binding affinity constant (nK) for FU. Such a modification is induced under physiological conditions by aspirin.

Acetylation↗
PubMed1980

[An information survey on the automatic operation of intensive therapy units in Italy].

A fact finding study was carried out in 58 resuscitation centres and 78 intensive care units to evaluate the current application of computerised techniques in the monitoring and processing of various parameters relating to hospitalised patients. The enquiry revealed a marked interest in the use of computerised systems, particularly in the electrophysiological and haemodynamic field. Promising results were reported from some centres. Some adverse criticisms and points of discussion still exist. International and national experiences matured so far, however, while primarily directed towards scientific research and technological development, open up significant perspectives for the future, for the rational handling of the data collected, and the extension of current knowledge on matters of physiopathology, electrophysiology, and pharmacokinetics.

Computers↗