Biomedical subjects

Laura Sabatini

Publications and source records attributed to Laura Sabatini.

12 recordsLinked to original sources

PubMed2006

Increased plasma concentrations of antiprothrombin antibodies in women with recurrent spontaneous abortions.

BACKGROUND: Antiphospholipid antibodies are associated with recurrent fetal loss, but the clinical relevance of antiprothrombin (aPT) antibodies remains controversial. This study was designed to evaluate the relationship of plasma concentrations of aPT antibodies (IgG, IgM, and IgA isotypes) and recurrent spontaneous abortion (RSA) not associated with antiphospholipid-antibody syndrome. METHODS: In this retrospective case-control study, we measured plasma aPT antibodies in 100 pregnant women at 8-12 weeks of gestation who had histories of recurrent abortion not associated with antiphospholipid-antibody syndrome. The controls were 200 healthy gestational-age-matched women with uncomplicated gestations. RESULTS: The mean (SD) plasma aPT concentrations were significantly (P <0.001) higher in women with histories of recurrent abortion than in healthy controls [7.97 (0.79) and 2.08 (0.07) kU/L]. Similarly, the concentrations of IgM aPT were significantly (P <0.001) higher in patients than in controls [5.73 (0.85) and 1.83 (0.05) kU/L]. No differences were found for IgA aPT (P = 0.358). CONCLUSIONS: High concentrations of aPT antibodies (IgG and IgM isotypes) are associated with pregnancy loss in women with RSA. We suggest that the antibodies may have a relevant role in the etiology and pathogenesis of the condition.

Abortion, Spontaneous↗

PubMed2006

Development and validation of a sensitive HPLC-ESI-MS/MS method for the direct determination of glucosamine in human plasma.

A sensitive and specific HPLC-ESI-MS/MS method for the direct determination of glucosamine in human plasma has been developed and validated. Plasma samples were analyzed after a simple, one-step protein precipitation clean-up with trichloroacetic acid using a polymer-based amino high-performance liquid chromatography (HPLC) column and a water/acetonitrile mobile phase elution gradient, with d-[1-(13)C]glucosamine as the internal standard. Detection was performed by mass spectrometry, using an electrospray source and employing multiple reaction monitoring to separately monitor glucosamine and the internal standard. The limit of quantification of the method was 10ng/ml of glucosamine and the calibration curve showed a good linearity up to 1000ng/ml. The precision (R.S.D.) and the accuracy (bias) of the method at the limit of quantification were 13.8 and 4.0%, respectively, and the mean recovery of glucosamine at three concentration levels was 101.6+/-5.7%. The method was applied for the determination of glucosamine concentrations in human plasma samples collected from untreated healthy volunteers and, in a separate bioavailability study, to evaluate plasma glucosamine pharmacokinetics profiles after oral administration of crystalline glucosamine sulfate.

Biological Availability↗

PubMed2006

Simultaneous determination of low levels of methotrexate and cyclophosphamide in human urine by micro liquid chromatography/electrospray ionization tandem mass spectrometry.

The aim of this study was to develop and validate a novel solid-phase extraction (SPE) liquid chromatography/tandem mass spectrometry (LC/MS/MS) method for the simultaneous determination of two antineoplastic drugs, cyclophosphamide (CP) and methotrexate (MTX), in human urine using trophosphamide as internal standard. The method showed good precision and accuracy (mean RSD 2.8% and 0.9%; bias 2.7% and 2.4% for MTX and CP, respectively). The lower limits of detection obtained, 0.2 microg/L(urine) for MTX and 0.04 microg/L(urine) for CP, were lower than the best previously reported values. The use of a 96-well SPE plate for matrix purification ensures a high throughput (50 samples/day), allowing the routine biological monitoring of CP and MTX as measures of occupational exposure at very low levels.

Antineoplastic Agents↗

PubMed2005

A new high-performance liquid chromatographic/electrospray ionization tandem mass spectrometric method for the simultaneous determination of cyclophosphamide, methotrexate and 5-fluorouracil as markers of surface contamination for occupational exposure monitoring.

A new high-performance liquid chromatographic/electrospray ionization tandem mass spectrometric (HPLC/ESI-MS/MS) method was developed for the simultaneous quantification of 5-fluorouracil (5FU), methotrexate (MTX) and cyclophosphamide (CP) in environmental samples. These compounds, commonly used in the treatment of cancer, are recognized as genotoxic. In order to estimate the occupational exposure of hospital personnel handling these drugs, wipe samples were taken from the working surfaces and directly analyzed (with trophosphamide as internal standard) using a reversed-phase capillary column and MS/MS detection. This is the first HPLC/MS/MS method for the simultaneous determination of 5FU, MTX and CP. The present method offers high sensitivity, with detection limits of 1.1 microg l(-1) for MTX and CP and 33.3 microg l(-1) for 5FU, avoiding any sample preconcentration procedure. Rapidity, specificity, high accuracy (mean values between 92.4 and 99.9%) and precision (mean RSD values between 3.4 and 12.1%) make the method suitable for the routine determination of these three antineoplastic drugs.

Air Pollutants, Occupational↗

PubMed2005

A method for routine quantitation of urinary 8-hydroxy-2'-deoxyguanosine based on solid-phase extraction and micro-high-performance liquid chromatography/electrospray ionization tandem mass spectrometry.

8-Hydroxy-2'-deoxyguanosine (8OHdG), one of the major oxidative DNA lesions induced by radical agents, is commonly used as a biomarker for oxidative stress, nowadays preferably in urine. In the absence of a commercially available internal standard a micro-high-performance liquid chromatography/electrospray ionization tandem mass spectrometry (micro-HPLC/ESI-MS/MS) method, suitable for routine analysis of 8OHdG in human urine using external calibration, was developed. Evaluation of the matrix effect showed that the method allows highly sensitive and accurate quantitation despite the absence of an internal standard. HPLC analysis was performed using gradient elution at a flow rate of 10 microL min(-1) using a capillary reversed-phase column and an injection volume of 0.5 microL, with detection of 8OHdG in positive multiple reaction monitoring (MRM) mode. The absolute limit of detection was 0.35 fmol using m/z 168 as a quantifier (fragment) ion. A linear (R2> 0.999) calibration curve in urine was obtained over a range 0.2-10 ng mL(-1). This method is about 20 times more sensitive than previously described procedures, and is characterized by high accuracy (mean 90%) and good reproducibility (RSD <10%). The optimized method was applied to determination of 8OHdG in 18 urinary samples derived from three healthy volunteers. 8OHdG urinary excretion ranged from 3.0-7.9 microg/day, and a large intra-individual variation was found. This method, which effectively circumvents the need for isotopically labeled 8OHdG (internal standard), is suitable for routine monitoring of exposure to DNA-damaging factors in a large number of subjects.

8-Hydroxy-2'-Deoxyguanosine↗

PubMed2005

Development and validation of a capillary high-performance liquid chromatography/electrospray tandem mass spectrometric method for the quantification of bisphenol A in air samples.

Bisphenol A (BPA) is a toxic industrial chemical that affects the endocrine system even at low concentrations. A new method, based on capillary high-performance liquid chromatography/electrospray ionization tandem mass spectrometry (HPLC/ESI-MS/MS) analysis, has been developed to determine BPA in atmospheric samples. The method involves collection of air samples (typically 2 m(3)) on glass fiber filters, with ultrasonic extraction and sample concentration under vacuum before analysis. HPLC analysis was performed isocratically at a flow rate of 10 microL min(-1) using a capillary reversed-phase column and MS/MS analysis in negative ion multiple reaction monitoring (MRM) mode, using BPA-d(16) as internal standard. The present method provides linear response in the range 0.007-3.5 microg/filter (R(2) > 0.999) and is characterized by high accuracy (mean bias 2%) and good reproducibility (mean RSD 5%). High sensitivity (LOD = 2 ng/m(3) based on 2 m(3) of air collected), specificity, and speed of the analysis make the present method suitable for routine determination of BPA in the atmosphere, both for ambient and personnel monitoring.

Air Pollutants, Occupational↗

PubMed2005

Factor II: C activity and uterine artery Doppler evaluation to improve the early prediction of pre-eclampsia on women with gestational hypertension.

OBJECTIVE: To evaluate whether the determination of maternal plasma Factor II:C (FII:C) and mean uterine artery resistance index may be useful to early predict pre-eclampsia in patients with gestational hypertension. DESIGN: Prospective study. SETTING: Consecutive enrollment in a public tertiary clinical care centre. PATIENTS: A total of 65 women with gestational hypertension at 24-26 weeks. INTERVENTION: Measurements of maternal plasma FII:C activity levels, ultrasonographic biometrical parameters and Doppler velocimetry of maternal uterine arteries. MAIN OUTCOME MEASURE(S): The probability of developing pre-eclampsia was the main outcome of the study and it was computed by combining the FII:C and the mean uterine artery resistance index cut-off points, chosen by receiver operating characteristic (ROC) curve analysis. RESULTS: F-II:C activity levels and mean uterine artery resistance index were significantly (both P < 0.01) higher in women who developed pre-eclampsia. A weak, but significant correlation (r = 0.3, P < 0.05) was found between these two parameters. FII:C activity levels at the cut-off value of 136.5% achieved a sensitivity of 61.1% and a specificity of 71.3%, while mean uterine artery resistance index (RI) at the cut-off value of 0.57 showed a sensitivity of 85.7% and a specificity of 90.2% in predicting the onset of pre-eclampsia. When both FII:C and mean uterine RI were over the cut-off points the positive predictive value was of 89%, with a 100% negative predictive value when both were below the cut-off points. CONCLUSION: F-II:C activity levels and mean uterine artery resistance index determination at mid trimester may improve the prediction of superimposed pre-eclampsia on women with early onset gestational hypertension.

Adult↗

PubMed2004

Simultaneous determination of t,t-muconic, S-phenylmercapturic and S-benzylmercapturic acids in urine by a rapid and sensitive liquid chromatography/electrospray tandem mass spectrometry method.

We describe a rapid and sensitive high-performance liquid chromatography/electrospray tandem mass spectrometry (HPLC/ESI-MS/MS) method for simultaneous determination of the most relevant metabolites of benzene and toluene, t,t-muconic acid (t,t-MA), S-phenylmercapturic acid (S-PMA), and S-benzylmercapturic acid (S-BMA). Urine samples were purified before analysis by solid-phase microextraction (SPE) on SAX cartridges with 50 mg sorbent mass. The developed method fulfils all the standard requirements of precision and accuracy. Calibration curves were linear within the concentration range of the standards (0-80 microg/L(urine) for t,t-MA, and 0-25 microg/L(urine) for S-PMA and S-BMA), and had correlation coefficients > or =0.997. Limits of detection were 6.0 microg/L for t,t-MA, 0.3 microg/L for S-PMA, and 0.4 microg/L for S-BMA. The method was used to determine t,t-MA, S-PMA and S-BMA levels in urine of 31 gasoline-station workers, with personal monitoring data obtained from radial symmetry passive diffusive samplers. In the context of mean work-shift exposures of 75.9 microg/m(3) (range 9.4-220.2) for benzene and 331.9 microg/m(3) (78.2-932.1) for toluene, metabolite concentrations in end-of-shift urine samples ranged from 23.5-275.3 microg/g(creatinine) for t,t-MA, non-detectable to 0.9 microg/g(creatinine) for S-PMA, and 3.8-74.8 microg/g(creatinine) for S-BMA. No significant correlation was found between the environmental concentrations and urinary metabolites (p > 0.05 for all cases); the ratios of benzene metabolites could be influenced by exposure levels and co-exposure to xylenes and toluene. The high throughput of this procedure should facilitate exploration of the metabolic effects of benzene-related co-exposure to toluene and alkylbenzenes in large populations of subjects exposed to gasoline.

Acetylcysteine↗

PubMed2003

The search for thrombophilic gene mutations in women with gestational hypertension does not help in predicting poor pregnancy outcome.

OBJECTIVE: To evaluate whether genetic thrombophilic mutations, biochemical and biophysical indices help to predict pregnancy outcome in women with gestational hypertension. DESIGN AND METHODS: A group of 59 women with gestational hypertension were prospectively tested between 24 and 26 weeks of gestation for: (i) DNA analysis to search for gene mutations of Factor V Leiden, prothrombin, methylenetetrahydrofolate reductase and plasminogen activator inhibitor type 1 (PAI-I) polymorphism; (ii) maternal serum concentrations of homocysteine and PAI-1, activated protein resistance and Factor II:C activity levels; (iii) mean uterine arterial resistance index (RI) by Doppler velocimetry; and (iv) history of hypertensive disorders in relatives (the mother and/or the father). Pregnancy outcome was evaluated, and considered 'poor' when patients developed severe pre-eclampsia, haemolysis-elevated liver enzymes-low platelets (HELLP) syndrome, fetal growth restriction (FGR), thromboembolic complications and disseminated intravascular coagulopathy (DIC). RESULTS: Eighteen women had a poor pregnancy outcome (11 with severe pre-eclampsia, of whom two had superimposed FGR; three with full HELLP syndrome, of whom one had DIC; four with FGR) and delivered, by emergency Caesarean section, neonates with a significantly lower mean gestational age (P < 0.0001) and birthweight (P < 0.0001). History of hypertensive disorders was significantly (P < 0.001) more common in the women group with poor (11 of 18) than normal (10 of 41) outcome. In addition, patients with a poor pregnancy outcome did not have a higher incidence of gene polymorphisms incidence, but significantly (P < 0.01) higher Factor II:C activity levels and significantly (P < 0.0001) higher mean uterine arterial RI than women with normal pregnancy outcome. CONCLUSIONS: Only Factor II:C activity levels, uterine arterial Doppler and a history of familial hypertension are useful in predicting poor pregnancy outcome in gestational hypertension.

Adult↗

PubMed2002

Ursodeoxycholic acid (UDCA) prevents DCA effects on male mouse liver via up-regulation of CYP [correction of CXP] and preservation of BSEP activities.

To investigate whether ursodeoxycholic acid (UDCA) can prevent metabolic impairment induced by deoxycholic acid (DCA), we evaluated the effects of these bile acids on murine CYP enzymes and the relationship with canalicular bile salt export pump (Bsep) expression. In Swiss Albino CD1 mice, UDCA and DCA were injected intraperitoneally either singly, concurrently, or sequentially (UDCA 1 hour before DCA) at equimolar 24.4 mg/kg body weight (BW) doses. CYP content, NADPH-CYP-c-reductase, and individual mixed function oxidases (MFO) were measured 24 hours later. Modulations were observed mainly in males: whereas DCA decreased MFO activities to various isoenzymes with respect to controls (up to 43%, CYP1A2-linked activity), UDCA boosted them (up to 6-fold, testosterone 16 beta-hydroxylase); concurrent administration of UDCA and DCA provided a preventive effect, enhancing MFO activity with respect to single administration of DCA by up to 4.4-fold in the CYP3A1/2 and CYP2B1/2 (6 beta-hydroxylase) and by 2.1-fold in the CYP2E1 (p-nitrophenol hydroxylase). In males (but not females), sequential administration (UDCA then DCA) produced a rather similar protective pattern, but the extent of recovery was generally smaller. Western immunoblotting results for the most affected isoenzymes (CYP3A1/2 and CYP2E1) and Bsep confirmed that UDCA can both prevent and reduce the CYP-dependent MFO inactivation and Bsep down-regulation caused by DCA. These findings may shed further light on the mechanisms responsible for UDCA's protective role in the treatment of cholestatic liver disease.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMedDate not supplied

[Acquired factor VIII hemophilia in a geriatric patient].

Acquired hemophilia is a rare coagulopathy in adults, associated with bleeding complications. Although the etiology of this disorder remains obscure, an autoimmune mechanism produces the development of autoantibodies against factor VIII. About half of cases are associated with other conditions, mainly post-partum, underlying cancer, autoimmune disease. An 81-year-old male was admitted to the hospital with extensive hematomas (neck, chest, arms and lower limbs). There was no family or personal history of congenital bleeding diathesis. He had chronic bronchitis and cerebrovascular disease; no drugs had been used during the month prior to noted symptoms. Laboratory parameters revealed: hemoglobin 10.9 g%, normal platelet count and white blood cells, prolonged activated partial thromboplastin time (98 s), with normal prothrombin time and fibrinogen concentration. An activated partial thromboplastin time mixing study did not show any correction, suggesting a coagulation inhibitor. Lupus anticoagulant and anticardiolipin antibodies were negative. Biochemical, immunological tests and tumor markers were normal. Thoracic and abdominal computed tomographic scan did not reveal pathological images or hematomas. Analysis of clotting factors revealed decreased factor VIII (< 2%) and elevated factor VIII inhibitor (55 Bethesda units). Idiopathic acquired hemophilia diagnosis was made. Red blood cell transfusion and human factor VIII (2000 U/day for 7 days) infusion were initiated, intravenously with methylprednisolone. A progressive improvement in clinical conditions and laboratory parameters was observed. After 18 days the patient was discharged and treated with prednisone. At follow-up control the clinical conditions and laboratory parameters were normal.

Aged, 80 and over↗

PubMedDate not supplied

[Occupational exposure to antineoplastic drugs in a hospital setting: biological and environmental monitoring].

OBJECTIVE: To estimate the occupational exposure of hospital personnel handling antineoplastics drugs using a highly sensitive and specific analitycal method in biological and environmental samples. DESIGN: To develop analitycal methods for the biological and environmental monitoring of more than one substance. SETTING: Five departments of the Policlinico Sant'Orsola-Malpighi (Bologna, Italy) involved in the preparation and administration of antineoplastic drugs. PARTICIPANTS: 50 nurses handling antineoplastics drugs. MAIN OUTCOME MEASURES: Evaluation of the occupational exposure of hospital personnel handling and administering anticancer drug cocktails. RESULTS: 19 of 50 subjects were positive to biological monitoring. Three were positive for MTX only, 11 for CP only and 5 subjects were positive for both. Urinary MTX levels ranged from 0.3 to 2.0 ppb, CP ranged fom 0.06 to 10.0 ppb. Wipe tests showed a higher contamination on the hoods working tray (where drugs are prepared), suggesting that the organization layout can affect the surface contamination level. Samples from each department resulted positive for at least one of three drugs. CONCLUSIONS: The analytical methods developed allow sensitive and specific determination of indicators of internal and external dose. Biological monitoring is of primary importance for assessing the real espoxure of hospital personnel during the preparation and administration of the drugs. Environmental monitoring stresses the importance to observe the Guidelines for standard operating procedures and the importance of protective disposables to reduce exposure and the associated health risk.

Antineoplastic Agents↗