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M Casati

Publications and source records attributed to M Casati.

At least 19 recordsLinked to original sources
PubMed2006

Improvements in CVD diamond properties for radiotherapy dosimetry.

The goal of this work was to compare the behaviour of a chemical vapour deposited (CVD) diamond sample, grown at the University of Florence using a local procedure, with that of a commercial CVD diamond. The comparison was performed exposing both systems to 25 MV photons and measuring the current response during irradiation. Properties of dosimetric interest such as stability of response, dose rate dependence and rise time were investigated. After a preliminary study, which evidenced better performances of the commercial device with respect to the local CVD diamond, the latter was irradiated with a high fluence of fast neutrons. As a result of the neutron treatment, the quality of the CVD home-made diamond has been improved to match with that of the commercial dosemeter.

Diamond↗
PubMed2006

Pretreatment verification of IMRT absolute dose distributions using a commercial a-Si EPID.

A commercial amorphous silicon electronic portal imaging device (EPID) has been studied to investigate its potential in the field of pretreatment verifications of step and shoot, intensity modulated radiation therapy (IMRT), 6 MV photon beams. The EPID was calibrated to measure absolute exit dose in a water-equivalent phantom at patient level, following an experimental approach, which does not require sophisticated calculation algorithms. The procedure presented was specifically intended to replace the time-consuming in-phantom film dosimetry. The dosimetric response was characterized on the central axis in terms of stability, linearity, and pulse repetition frequency dependence. The a-Si EPID demonstrated a good linearity with dose (within 2% from 1 monitor unit), which represent a prerequisite for the application in IMRT. A series of measurements, in which phantom thickness, air gap between the phantom and the EPID, field size and position of measurement of dose in the phantom (entrance or exit) varied, was performed to find the optimal calibration conditions, for which the field size dependence is minimized. In these conditions (20 cm phantom thickness, 56 cm air gap, exit dose measured at the isocenter), the introduction of a filter for the low-energy scattered radiation allowed us to define a universal calibration factor, independent of field size. The off-axis extension of the dose calibration was performed by applying a radial correction for the beam profile, distorted due to the standard flood field calibration of the device. For the acquisition of IMRT fields, it was necessary to employ home-made software and a specific procedure. This method was applied for the measurement of the dose distributions for 15 clinical IMRT fields. The agreement between the dose distributions, quantified by the gamma index, was found, on average, in 97.6% and 98.3% of the analyzed points for EPID versus TPS and for EPID versus FILM, respectively, thus suggesting a great potential of this EPID for IMRT dosimetric applications.

Body Burden↗
PubMed2002

Activity of GH/IGF-1 axis in burn patients: comparison with normal subjects and patients with GH deficiency.

The aim of this study was to clarify the activity of GH/IGF-1 axis as well as the variations of nutritional parameters following a thermal injury in man. To this goal, in 22 patients with burn [BURN, age (mean+/-SE): 46.5+/-3.4 yr, BMI: 25.0+/-0.8 kg/m2, % burn surface area: 26.0+/-3.0%, ROI score: 0.22+/-0.1] we evaluated IGF-1, IGF binding protein (IGFBP-3), GH, GH binding protein (GHBP), pre-albumin (pre-A), albumin (A) and transferrin (TRA) levels on days 1, 3, 7, 14 and 28 after intensive care unit (ICU) admission. IGF-1, IGFBP-3, GH and GHBP levels were also assayed basally in 29 normal subjects (Ns) (Ns, age: 47.5+/-2.8 yr, BMI: 22.0+/-1.4 kg/m2) and in 34 panhypopituitary patients with severe GH deficiency (GHD, age: 42.7+/-2.5 yr, BMI: 25.6+/-0.8 kg/m2). On ICU day 1, IGF-1 and IGFBP-3 in BURN were higher than those in GHD (p<0.05 for both, respectively) and lower than those in Ns (p<0.05) while GH levels in BURN did not differ from those in Ns and higher than GHD (p<0.01). In BURN, IGF-I and IGFBP-3 levels showed a progressive decline (p<0.05) with nadir on day 14, when they overlapped those in GHD, and then an increase on day 28, though persisting lower than in Ns, while GH levels did not vary during ICU stay. IGF-I levels were associated neither to burn extension nor to ROI score. On ICU day 1 pre-A, A and TRA levels were similar to those in Ns, but underwent a progressive decrease with nadir on day 7 (p<0.001) for pre-A and TRA, and later, on day 14 (p<0.05) for A; pre-A and TRA but not A showed a rebound increase (p<0.01) on day 14, though persistingly lower than in Ns. In conclusion, our present data firstly show the time course variation of IGF-I levels in burn patients as function of nutritional and hormonal variables. It has to be emphasized that in the most critical phase after burn injuries, IGF-1 levels are as low as in hypopituitary patients with severe GHD. The physiological basis which leads to the impairment of this endogenous anabolic drive in this phase is, however, not clear yet.

Adult↗
PubMed2000

Determination of MAG-camptothecin, a new polymer-bound camptothecin derivative, and free camptothecin in dog plasma by HPLC with fluorimetric detection.

A high throughput. selective and sensitive high-performance liquid chromatographic (HPLC) method for the determination of a water-soluble polymer-bound Camptothecin conjugate (MAG-CPT) and Camptothecin (CPT) in dog plasma has been developed and validated. The method involved the analysis of free and total CPT (free + polymer-bound). Free CPT (intact lactone plus carboxylate) was extracted from acidified plasma using Oasis SPE material in 96-well plates. For the assay of the total CPT, plasma proteins were first precipitated with methanol in a 96-well plate containing a 10-microm melt blown polypropylene membrane. The methanolic supernatant was separated and collected into a second 96-well plate by simply applying vacuum to the plate. After hydrolysis at pH 9.8 for 18 h and re-acidification, samples were injected directly from the collection plate onto the HPLC system. MAG-CPT concentration was then calculated by subtraction of free from total CPT. The LLOQs of the method were 1.17 ng/ml for free CPT and 103.10 ng/ml (as CPT equivalent) for MAG-CPT using 0.1 and 0.05 ml of plasma, respectively. Linearity, precision, accuracy and recovery of the method were evaluated. The stability of MAG-CPT in plasma alone and after its stabilisation was carefully evaluated. No interference from blank dog, mouse and human plasma was observed. The suitability of the method for in vivo samples was assessed by the analysis of samples obtained from dogs that had received a single and 5-day repeated dose of MAG-CPT.

Acrylamides↗
PubMed1997

Determination of turosteride, a new inhibitor of 5 alpha-reductase, in human plasma by high-performance liquid chromatography with ultraviolet detection.

A sensitive and specific HPLC method for the determination of turosteride in human plasma was developed and validated. Turosteride was extracted from plasma with diethyl ether. Further purifications of the fraction extracted were performed sequentially by solid-phase extraction using a CN cartridge and by liquid-liquid partition between n-hexane and acetonitrile. Finally the acetonitrile solution containing the test compound was evaporated to dryness and the residue dissolved in the mobile phase, then injected onto the HPLC system. The chromatographic separation was performed isocratically by a reversed-phase column filled with ODS using a water-acetonitrile-methanol mixture. The eluate was monitored at 210 nm. No peak interfering with that of turosteride was observed when blank human plasma was assayed. Linearity was obtained in the turosteride concentration range of 5-1000 ng/ml plasma. Six calibration curves in plasma prepared and run on six different days showed correlation coefficients higher than 0.99 and good reproducibility of the slope (C.V. = 4.3%). The intra-day precision, evaluated at three concentrations (in the low, mid and high range of the standard curve) and expressed as C.V., ranged from 0.81 to 13.25%. The inter-day precision evaluated at the same concentrations was better than 10.7%. The inter-day accuracy evaluated in the same samples and expressed as the ratio of found/added amount of turosteride ranged from 97.66 to 98.38%. The limit of quantitation was 5 ng/ml plasma. The HPLC method described was successfully employed for the determination of turosteride in plasma samples obtained during a phase I clinical trial with the test compound.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed1997

Interleukin-12 in early or advanced cancer patients.

Interleukin-2 (IL-2) and interleukin-12 (IL-12) may represent the most important antitumour cytokines in human neoplasms. IL-2 blood levels decrease in advanced solid malignancies, but currently there are no data on IL-12 secretion in cancer patients. This study was performed to obtain preliminary data about IL-12 secretion in patients with solid malignant tumours, either in relation to the extension of disease, or to other cytokines, including IL-2, IL-6 and IL-10. The study included 40 solid cancer patients, 24 of whom showed distant organ metastases. Cytokine serum levels were measured by an enzyme immunoassay of blood samples collected during the morning. No patient had abnormally low levels of IL-12, but the levels were high in 14/14 (35%) patients. Mean levels of IL-12 were significantly higher in metastatic patients compared with non-metastatic patients (P < 0.05). Moreover, metastatic patients with high blood concentrations of IL-12 showed significantly lower levels of IL-10 than metastatic patients with normal IL-12 values, while no difference was seen in IL-2 mean concentrations. IL-6 mean levels were lower in metastatic patients with increased IL-12 levels, but this was non-significant. This preliminary study shows that advanced solid cancers are not characterised by a diminished secretion of IL-12, but rather IL-12 levels tend to be abnormally high in metastatic cancer patients.

Adult↗
PubMed1996

Involvement of CYP2D6 but not CYP2C19 in nicergoline metabolism in humans.

1. Nicergoline, an ergot derivative previously used as a vasodilator, has gained a new indication in treating the symptoms of senile dementia. 2. Nicergoline is rapidly hydrolysed to an alcohol derivative, 1-methyl-10-alpha-methoxy-9,10-dihydrolysergol (MMDL), which is further N-demethylated to form 10-alpha-methoxy-9,10-dihydrolysergol (MDL). A few individuals display aberrant metabolism of this drug, as shown by their diminished capacity to form the MDL metabolite. The aim of this study was to determine whether defective nicergoline metabolism is associated with the debrisoquine and/or the S-mephenytoin hydroxylation polymorphisms. 3. After a single, oral 30 mg dose of nicergoline, the plasma concentrations of its two metabolites were studied in 15 subjects, divided into three groups with respect to their debrisoquine and S-mephenytoin hydroxylation phenotypes. 4. The pharmacokinetic parameters of MMDL and MDL were similar in the ten subjects who were extensive metabolisers of debrisoquine (five of whom were poor metabolisers of S-mephenytoin) (mean MMDL Cmax 59 nmol l-1 and AUC (0, th) 144 nmol l-1h, mean MDL Cmax 183 nmol l-1 and AUC 2627 nmol l-1h) but were markedly different from the five subjects who were poor metabolisers of debrisoquine (mean MMDL Cmax 356 nmol l-1 and AUC 10512 nmol l-1h, MDL concentrations below limit of quantitation). 5. We conclude that the formation of MDL from MMDL in the metabolism of nicergoline is catalysed to a major extent by CYP2D6 and that the observed interindividual variation in the metabolic pattern of the drug is related to the debrisoquine hydroxylation polymorphism.

Adult↗
PubMed1995

Crystal structure of reduced bovine erythrocyte superoxide dismutase at 1.9 A resolution.

Cu,Zn superoxide dismutase was investigated crystallographically in the reduced form. Co-ordinate errors were estimated by comparing two independently refined models, based on two different data sets. This gave a detailed error estimation as opposed to the standard sigma A and Luzzati plots, which estimate only the overall error. The high quality of the final model, obtained after scaling together the two data sets, combined with the error estimates allowed a detailed analysis of the protein and solvent structures. An automatic procedure for building and refining solvent structure was tested and found to give reproducible results. Contrary to results obtained from spectroscopic studies, the co-ordination of the metal ions in the catalytic site is preserved in the crystal structure of the reduced enzyme, as compared with the crystal structure of the oxidised form. Analysis of the solvent reveals a well-defined chain of closely packed, hydrogen-bonded water molecules filling the active site groove. This structural feature could serve as a hydrogen bond relay for efficient delivery of protons to the active centre. Analysis of electron density suggests that Glu119 is covalently modified. The modification, if originated in vivo, could have a role in the catalytic mechanism and could affect the overall electrostatic field in the active site. There are significant differences between the active sites of the two crystallographically independent monomers. They are explained in terms of local differences in the crystal environment.

Amino Acid Sequence↗
PubMed1995

Treatment of autonomous thyroid nodules: value of percutaneous ethanol injection.

OBJECTIVE: Percutaneous injection of alcohol was recently proposed as an alternative to surgical and radioiodine treatments of autonomous thyroid nodules. The purpose of this study was to determine the value of this procedure and to define its limitations and indications when used for this purpose. MATERIALS AND METHODS: Thirty-one patients with autonomous thyroid nodules underwent a cycle of treatment with percutaneous injection of ethanol in multiple sessions (three to seven) on alternate days depending on the diffusion of the ethanol in the nodule. Fifteen patients were hyperthyroid, and 16 were euthyroid but had inhibited secretion of thyrotropin. The treatment results were evaluated by thyroid scintigraphy and sonography, by triiodothyronine, thyroxine, and thyrotropin assays, and by a thyrotropin-releasing hormone stimulation test 6 months after the end of treatment. Baseline scintigraphy demonstrated exclusive radionuclide uptake in the nodule in 29 patients and partial uptake in the extranodular tissue in two. The volume of the nodules ranged from 0.8 to 34.0 ml (mean +/- SD, 11.8 +/- 8.8 ml). Patients were monitored clinically for 24 hr after each session of ethanol injection to evaluate complications. Fifteen patients underwent a second cycle of ethanol injection when the results 6 months after the first cycle were unsatisfactory. The mean +/- SD follow-up was done at 26.9 +/- 12.3 months. RESULTS: Scintigraphy showed recovery of extranodular uptake of radionuclide in 72% of patients with nodules less than 13 ml in volume (maximum diameter [mean +/- SD], 2.7 +/- 0.7 cm; range, 1.4-4.0 cm) after one cycle of treatment and in 83% after two cycles. Among subjects with larger nodules, radionuclide uptake returned to normal in 9% after one cycle of treatment and in 9% after two cycles. For hyperthyroid patients, levels of thyroid hormones returned to normal in 69% after one cycle and in 77% after two cycles, and levels of thyrotropin returned to normal in 38% after one cycle and in 69% after two cycles; normal levels of thyrotropin were achieved in 93% of the euthyroid patients after one cycle of treatment and in 100% of these patients after two cycles. Symptoms resolved in 73% of the hyperthyroid subjects after the first cycle of treatment and in 93% of these subjects after the second. No important complications were observed; the most common side effects were acute pain at the injection site, referred pain, fever, transient dysphonia (< 12 hr), local hematoma, palpitations, and sinus tachycardia. CONCLUSION: Our results show that percutaneous injection of ethanol is appropriate therapy for autonomous thyroid nodules less than 13 ml in volume. The treatment should be considered successful when levels of thyroid hormones and thyrotropin return to normal. Nodule size appears to be the most important determinant of the success of the treatment. No complications that required termination of the treatment occurred.

Adult↗
PubMed1989

Ovarian and cervical thyroid struma. A case report.

A case of associated ovarian and cervical thyroid struma in a 24-year old female, is reported. The patient was affected by a right thyroid cold nodule which at fine needle aspiration biopsy showed the cytological pattern of benign follicular adenoma; as the nodule was increasing after one year of suppressive therapy, the patient was selected for surgery. At admission during routine physical examination a previously undetected left pelvic mass was discovered: at laparotomy it proved to be a cystic tumor consisting of benign thyroid tissue at the level of left ovary. Histology confirmed the diagnosis of follicular adenoma of the right thyroid nodule after right lobectomy. Albeit cases of thyroid tissue in the ovary have been reported, true struma ovarii is a rare occurrence. A concomitant hyperthyroidism is seen in only 1/4 of cases and the patients can be divided into three groups: hyperthyroid, ascitic and asymptomatic: our patient was in the asymptomatic group.

Adenoma↗
PubMed1985

Plasmid pFCE4: a new system of Escherichia coli expression-modification vectors.

Two versatile expression-modification vectors were obtained by inserting the origin of replication (ori) of phage f1 into the expression vector pOTS. The resulting plasmids produce large amounts of coding or noncoding ssDNA (depending on ori orientation in pFCE4+ and pFCE4-) and excrete it into the medium as virus-like particles following infection with phage f1. These features make them suitable for dideoxy chain termination sequencing, oligonucleotide directed mutagenesis and gene expression without further manipulations. The human IFN alpha-2 gene, lacking the codon for the first amino acid, cysteine, was efficiently expressed by these vectors.

Base Sequence↗
PubMed1980

Immunogenetic and population genetic analyses of Iberian cattle.

Blood samples were collected from more than 100 animals in each of 2 Spanish cattle breeds (Retinto and De Lidia), 2 Portuguese breeds (Alentejana and Mertolenga), and American Longhorn cattle. All samples for the 4 Iberian breeds were tested for 20 polymorphic systems; American Longhorn were tested for 19 of the 20. For each breed an average inbreeding coefficient was estimated by a comparison of the observed and expected heterozygosity at 7 or 8 codominant systems tested. All breeds had positive values but only 3 breeds had estimates of inbreeding that were statistically significantly different from 0: De Lidia with f = 0.17, Retinto with f = 0.08 and Mertolenga with f = 0.05. The De Lidia breed especially may be suffering from inbreeding depression since this high value is greater than expected if all of the animals were progeny of half-sib matings. Genetic distances were calculated from the gene frequency data on these 5 breeds plus 9 other European breeds. Analyses of these distances show a closely related group of the 4 Iberian breeds and American Longhorn, confirming the close relationships among the Iberian breeds and the Iberian, probably Portuguese, origin of American Longhorn cattle.

Alleles↗
PubMedDate not supplied

Growth hormone binding protein activity in obese children.

We evaluated growth hormone binding protein (GHBP) activity in a group of obese children (12 boys and 12 girls, age 3.1-14.7 years, BMI 21.1-33.3, 11 prepubertal and 13 early pubertal) and in 26 age-matched normal weight children (14 boys and 12 girls, age 2.1-16.0 years, BMI 14.2-21.4, 18 prepubertal and 8 early pubertal). All children were of normal stature. GHBP activity was significantly higher in the obese (39.1 +/- 1.1%) than in the control children (28.3 +/- 1.0%, p < 0.0001). Mean serum GHBP was not different between boys and girls or between prepubertal and pubertal subjects. A positive correlation was found between BMI and GHBP levels only in the normal weight children (r = 0.425, p < 0.05). Baseline insulin concentrations in the obese children were 97.6 +/- 7.9 pmol/l (normal values, 45.0 +/- 18.6 pmol/l), and the mean insulin AUC following OGTT in the obese was 811.3 +/- 160.7 pmol/l (normal values, 373.1 +/- 150.1 pmol/l). Serum GHBP activity in the obese was not correlated with baseline serum insulin concentrations or with the insulin AUC following OGTT. In conclusion, we found that obese children have elevated GHBP activity, and speculate that this phenomenon may serve to compensate for their reduced GH secretion and accelerated GH clearance.

Adolescent↗