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Biomedical subjects

M Marchetti

Publications and source records attributed to M Marchetti.

At least 19 recordsLinked to original sources

Blood oxidative status and selectins plasma levels in healthy donors receiving granulocyte-colony stimulating factor.

Recombinant human G-CSF (rHuG-CSF) is used for hematopoietic progenitor cells (HPC) mobilization and collection. Activation of polymorphonuclear leukocytes (PMN) is present during rHuG-CSF treatment and is associated with endothelial cell dysfunction and hypercoagulation. We evaluated whether PMN activation by rHuG-CSF may alter the blood oxidative status and subsequently affect the vascular cell function. Fourteen healthy individuals received rHuG-CSF for HPC harvesting. Blood was drawn before starting rHuG-CSF (T0), on the last day of rHuG-CSF (T1) and 1 week after stopping rHuG-CSF (T2). Levels of CD11b, myeloperoxidase (MPO), hydroperoxides, nitric oxide (NO), and soluble endothelium (sES), leukocyte (sLS), and platelet (sPS) selectins were measured. During rHuG-CSF, CD11b, MPO and hydroperoxides significantly increased, while NO levels significantly decreased, compared with T0. At T2 all these markers returned to baseline values. Significant increments of all selectins were observed during rHuG-CSF. At T2 sES and sEP significantly decreased back to pre-treatment values, whereas sLS remained significantly high. These data show that rHuG-CSF induces a transient inflammatory status characterized by circulating activated PMN, which release reactive oxygen species and intracellular proteases, promoting the onset of an abnormal oxidative status. This process may modify the hemostatic balance towards a pro-thrombotic state.

Adolescent↗

Listeriosis associated with gorgonzola (Italian blue-veined cheese).

We describe a case of listeriosis in Italy associated with the consumption of cheese. Opened samples of two brands of gorgonzola (Italian blue-veined cheese; referred to as brands "B" and "C") were collected from the patient's refrigerator. Unopened samples of the brand suspected to be the source of infection (brand B) were taken from the store where the cheese had been purchased, other local stores, and the production plant. Listeria monocytogenes serotype 1/2b was isolated from the patient and from the opened and unopened cheese samples. The contamination level varied from <100 to 1,200 cfu g(-1). Molecular typing of the isolates, using both randomly amplified polymorphic DNA (RAPD) and pulsed-field gel electrophoresis (PFGE), demonstrated that the isolates from the patient's refrigerator, food stores, and production-plant samples were indistinguishable from the clinical isolate. Molecular typing verified the peristence of closely related L. monocytogenes isolates in the production plant B for 5 months. The results stress the importance of developing a code of hygienic practice for preventing, limiting, and where possible, eliminating this pathogen in processed foods and of educating at-risk persons on foods likely to be contaminated.

Bacterial Typing Techniques↗

Gene structure, localization and role in oxidative stress of methionine sulfoxide reductase A (MSRA) in the monkey retina.

MSRA (EC 1.8.4.6) is a member of the methionine sulfoxide reductase family that can reduce methionine sulfoxide (MetO) in proteins. This repair function has been shown to protect cells against oxidative damage. In this study we have assembled the complete gene structure of msrA and identified the presence of two distinct putative promoters that generate three different transcripts. These transcripts were cloned by 5'RACE and code for three MSRA isoforms with different N-termini. The different forms of MSRA target to distinct intracellular regions. The main MSRA transcript (msrA1) had been previously shown to target the mitochondria. MsrA2 and 3 originate from a second promoter and target the cytosol and nuclei. In the monkey retina msrA message was detected mainly in the macular RPE-choroid region while its activity was measured mainly in the soluble fractions of fractionated neural retina and RPE-choroid. The MSRA protein is found throughout the retina but is especially abundant at the photoreceptor synapses, ganglion and Müller cells. Interestingly, MSRA was not detected in the mitochondria of the photoreceptor inner segments. The RPE in the peripheral retina shows very low levels of expression but the RPE in the macular region is strongly labeled. Targeted silencing of msrA message rendered cultured RPE cells more sensitive to oxidative damage suggesting a role for MSRA in RPE protection against oxidative stress. Collectively these data suggest MSRA may play an important role in protecting macular RPE from oxidative damage.

Amino Acid Sequence↗

Cost-effectiveness of universal pneumococcal vaccination for infants in Italy.

This study aimed at estimating the health and economic outcomes of universal infant vaccination with seven-valent pneumococcal conjugate vaccine (PCV-7) in Italy. A Markov model simulated lifetime evolution of a birth cohort (538,138 children): universal vaccination would avert 769 invasive infections, 18 deaths and 1323 life years. At base-case analysis, universal three-dose vaccination would cost euro 26,449 (95% CI: 1975-62,075) and euro 38,286 (95% CI: 22,164-70,801) per life year-saved in the societal and the NHS perspective, respectively. In the hypothesis of a 5-year long protection period, vaccination would cost euro 32,694 and euro 43,115 per life-year saved. Considering yearly incidence of invasive pneumococcal disease reported for Veneto and Sardinia regions, PCV-7 vaccination would result highly cost-effective determining a cost of euro 10,479 and euro 16,890 per life year-save in the NHS and the societal perspective, respectively.

Adolescent↗

Correlation between dietary polyunsaturated fatty acids and plasma homocysteine concentration in vitamin B6-deficient rats.

BACKGROUND AND AIM: Vitamin B6 as cofactor of Delta6 desaturase is involved in polyunsaturated fatty acid metabolism; moreover, it is a cofactor of the trans-sulfuration pathway of homocysteine. Some studies report that low concentrations of pyridoxine, by increasing homocysteine levels, are associated with coronary artery disease, and carotid and arterial lesions. The aim of this study was to verify whether different dietary amounts of polyunsaturated fatty acids associated with low content of vitamin B6 could modulate homocysteinemia. METHODS AND RESULTS: Thirty-two rats were divided into two groups, one fed a diet with adequate vitamin B6 content the other a diet containing low amount of the same vitamin. Within each group, rats were divided into two subgroups differing in the polyunsaturated fatty acid content of the diet (63 and 33%, respectively). The vitamin B6-deficient diet induced an increase in homocysteine concentration compared to the vitamin B6-normal diet. This increase was tenfold in the subgroup fed high polyunsaturated fatty acid levels and twofold in the other subgroup. The fatty acid composition of liver phospholipids showed a lower arachidonic acid relative molar content and a lower 20:4/18:2 ratio in vitamin B6-deficient groups compared with B6-normal groups. CONCLUSIONS: On the basis of the different biological functions of pyridoxine and considering that some factors closely related to atherosclerosis are vitamin B(6) dependent, adequate pyridoxine availability could be necessary to assure a normal long chain fatty acid metabolism and to reduce the risk linked to hyperhomocysteinemia.

Animals↗

Endometrial cancer: asymptomatic endometrial findings. Characteristics of postmenopausal endometrial cancer.

Endometrial cancer affects patients at every age, however it occurs more frequently in menopause (> 50) and in postmenopause (> 70). The most frequent symptoms are bleeding and vaginal discharge. When hematometra or pyometra is present the patient may feel pain. In some cases endometrial adenocarcinoma is asymptomatic and the diagnosis is casually made during ultrasound examination or by histological examination of a uterus surgically removed for other indications. In these cases the most frequent findings are polyps and abnormally increased thickness of the endometrial mucosa. In postmenopause polyps and abnormal endometrial thickness are usually limited to a small area and surrounded by atrophic mucosa. Higher incidence rates of endometrial cancer were correlated with polyps and an increased number of serous type tumors were identified in the > 65-year age group. Endometrial carcinoma may be estrogen correlated or non-estrogen associated. Patients in postmenopause are often affected by non-estrogen correlated endometrial carcinoma. According to Kurman and other authors the first type of endometrial adenocarcinoma (estrogen correlated) is characterized by low-grade malignancy. On the contrary, non-estrogen correlated neoplasia is more aggressive. In our case series including 102 women aged > 70 years with endometrial carcinoma we found that survival was correlated with stage and grading - early stages were the most frequent and the grade increased with stage. In fact all the patients with relapses had grade 2 or 3 adenocarcinomas. Thirty-one patients > 70 years (30.69%) had a non-endometrioid type of cancer.

Aged↗

Determinants of sit-to-stand capability in the motor impaired elderly.

Among the healthy elderly, sit-to-stand (STS) movement largely depends on: (a) trunk bending momentum, (b) centre of gravity (CG) position before the body rises and (c) lower limb extensor muscle strength. Because determining whether (c) improvement would affect STS capability in the motor impaired elderly (MIE) has been recommended, we studied the relative importance of (a), (b) and (c) in determining a successful fast STS movement comparing the healthy elderly with MIE with orthopaedic disorders studied before and after a rehabilitation program. Force platform was used to measure body's posture and kinematics during a STS test and therefore to assess (a), (b) and maximum vertical velocity (VVpeak), assumed as outcome measurement. Knee extensor maximal isometric voluntary contraction normalized by body mass (nMVC) was an indicator of (c). A multiple regression model was built to predict VVpeak from the three determinants of STS movement. In both groups, the model significantly determined VVpeak, with (a) and (c) being significant predictors of VVpeak and (a) being the major predictor. Rehabilitation was effective in improving nMVC. This process resulted in a change of the relative importance of (a) and (c), strength becoming the major predictor of VVpeak. In conclusion the present study demonstrates that a rehabilitative intervention aimed at increasing strength is effective in improving STS capability in MIE.

Aged↗

CT-guided neurosurgery: preliminary experience.

BACKGROUND: With the possibility of CT systems becoming more handy and sophisticated, intraoperative CT was introduced in a few neurosurgical Centres with better results in lesion removal and surgical outcome. METHOD: At our Institution a mobile CT scanner was recently used for intraoperative evaluation (Philips Tomoscan M). For 27 tumour resections performed with a neuronavigation system, and 23 deep brain electrode positioning examinations, an intraoperative CT was employed. In addition the CT scanner was used in the recovery room for a postoperative control in 198 patients. FINDINGS: Our preliminary experience used for a real time evaluation of the treated patients, permitted to verify an incomplete removal in 23/27 cases. Evaluation of stereotactic electrode position in relation to the planned target was also possible and demonstrated a correct position in 21 cases. INTERPRETATION: Intraoperative CT scan is a useful system that permits to modify neuronavigation planning and is able to give information to the surgeon for better tumour removal, rule out possible hemorrhagic complications, and suitable deep brain electrode positioning.

Adolescent↗

Defibrotide reduces procoagulant activity and increases fibrinolytic properties of endothelial cells.

Defibrotide (DF), a polydeoxyribonucleotide with antithrombotic properties, has recently proven effective in patients with severe hepatic veno-occlusive disease (VOD), a life-threatening complication of high-dose chemo/radiotherapy regimens for stem cell transplantation. To understand the mechanism of its beneficial effect, we studied the impact of DF on the expression of tissue factor (TF) and fibrinolytic proteins (PAI-1 and t-PA) on endothelial cells. The in vitro response to DF of two types of human endothelial cells (ECs) of different origins, that is from macrovascular (HUVEC) and microvascular (HMEC-1 cell line) beds, was evaluated in the presence or absence of a proinflammatory stimulus (ie bacterial endotoxin, LPS). The results show that DF was able to significantly reduce the LPS-induced TF expression by HMEC-1, and less prominently by HUVEC. In addition, DF importantly influenced the fibrinolytic properties of both HMEC-1 and HUVEC. Specifically, it dose-dependently counteracted the LPS-induced increase in PAI-1 levels and decrease in t-PA activity expression. It also significantly incremented t-PA antigen in resting EC. Decreasing the procoagulant activity and increasing the fibrinolytic potential of EC favors an anticoagulant phenotype of the endothelium, which may protect from fibrin deposition and vascular occlusion.

Blood Coagulation Factors↗

Type I allergy to elderberry (Sambucus nigra) is elicited by a 33.2 kDa allergen with significant homology to ribosomal inactivating proteins.

BACKGROUND: Patients suffering from allergic rhinoconjunctivitis and dyspnoea during summer may exhibit these symptoms after contact with flowers or dietary products of the elderberry tree Sambucus nigra. OBJECTIVE: Patients with a history of summer hayfever were tested in a routine setting for sensitization to elderberry. Nine patients having allergic symptoms due to elderberry and specific sensitization were investigated in detail. We studied the responsible allergens in extracts from elderberry pollen, flowers and berries, and investigated cross-reactivity with allergens from birch, grass and mugwort. METHODS: Sera from patients were tested for IgE reactivity to elderberry proteins by one-dimensional (1D) and 2D electrophoresis/immunoblotting. Inhibition studies with defined allergens and elderberry-specific antibodies were used to evaluate cross-reactivity. The main elderberry allergen was purified by gel filtration and reversed-phase HPLC, and subjected to mass spectrometry. The in-gel-digested allergen was analysed by the MS/MS sequence analysis and peptide mapping. The N-terminal sequence of the predominant allergen was analysed. RESULTS: 0.6% of 3668 randomly tested patients showed positive skin prick test and/or RAST to elderberry. IgE in patients' sera detected a predominant allergen of 33.2 kDa in extracts from elderberry pollen, flowers and berries, with an isoelectric point at pH 7.0. Pre-incubation of sera with extracts from birch, mugwort or grass pollen rendered insignificant or no inhibition of IgE binding to blotted elderberry proteins. Specific mouse antisera reacted exclusively with proteins from elderberry. N-terminal sequence analysis, as well as MS/MS spectrometry of the purified elderberry allergen, indicated homology with ribosomal inactivating proteins (RIPs). CONCLUSION: We present evidence that the elderberry plant S. nigra harbours allergenic potency. Independent methodologies argue for a significant homology of the predominant 33.2 kDa elderberry allergen with homology to RIPs. We conclude that this protein is a candidate for a major elderberry allergen with designation Sam n 1.

Allergens↗

The physiological demands of sail pumping in Olympic level windsurfers.

This study investigated the physiological effects of sail pumping (PB)--a manoeuvre often adopted to provide additional propulsion to the board--in Olympic Class Windsurfing, following relaxation of the "no-pumping" rules by the International Federation. Fifteen Olympic-level windsurfers (10 men) from nine different countries volunteered for the study, which was performed during two international Olympic regattas. The measurements were carried out during actual sailing when both PB and not-pumping (NPB) using a portable metabolimeter. Windsurfing, when PB, elicited a dramatic increase in cardiorespiratory responses compared to NPB. Mean (SD) values for oxygen uptake and heart rate during NPB for the men and women were: 19.2 (4.4) and 15.7 (3.3) ml x kg(-1) x min(-1), and 110 (10) and 122 (12) beats x min(-1), respectively, whereas the values in PB were: 48.4 (5.7) and 40.2 (4.2) ml x kg(-1) x min(-1), and 165 (12) and 172 (13) beats x min(-1), respectively. All the PB parameters, with the exception of heart rate (HR), were significantly higher in the men than in the women but no differences were observed between the sexes in NPB with the exception of HR, which was higher in the women. Our results suggest sail pumping is as physically demanding as most aerobic sporting activities. In the context of the need to deal with a highly demanding athletic branch of sailing as part of an Olympic regatta, recommendations are made on how best to make physical and dietary preparations.

Adult↗

Effect of all-trans-retinoic acid on the hypercoagulable state of patients with breast cancer.

To evaluate whether all-trans-retinoic acid (ATRA) is able to modulate the hemostatic system in patients with solid tumors, we studied patients with locally advanced breast cancer who were enrolled in a Phase Ib study of ATRA +/- Tamoxifen (Tam). In this study, two groups of 15 patients/each were treated for 21 days before operation with ATRA at three doses (15, 45, or 75 mg/m(2)/day on alternate days) given alone (group 1) or in combination with Tam (group 2). One additional group received Tam alone. Plasma samples were evaluated for hypercoagulation markers (FVIIa, F1+2, TAT, D-dimer), fibrinolysis proteins (t-PA, PAI-1), and coagulation inhibitors (protein C, AT). At baseline, cancer patients had FVIIa, F1+2, TAT, and PAI-1 significantly greater than control subjects. During treatment, in the patients given ATRA alone, hypercoagulation markers appeared unmodified. Instead, subjects given Tam alone had a significant elevation of FVIIa, F1+2, and TAT versus baseline. However, in the ATRA + Tam groups, hypercoagulation markers were decreased compared with Tam alone. These results suggest that in selected conditions, pre-operative ATRA may modulate the hypercoagulable state of breast cancer patients.

Aged↗

Effects of dopamine and nitric oxide on arterial pressure and renal function in volume expansion.

1. The aim of the present study was to investigate the role of dopamine (DA) in the hypotensive and renal effects of L-arginine during extracellular fluid volume expansion (10% bodyweight). 2. Animals were randomized to non-expanded and expanded groups. Both groups received different treatments: L-arginine (250 mg/kg, i.v.), N(G)-nitro-L-arginine methyl ester (L-NAME; 1 mg/kg, i.v.), haloperidol (3 mg/kg, i.p.) and L-arginine + haloperidol (n = 8). Mean arterial pressure (MAP), diuresis, natriuresis, kaliuresis, glomerular filtration rate, renal plasma flow (RPF) and nitrite and nitrate (NO(x)) excretion were determined. 3. The increase in MAP induced by L-NAME was greater in expanded than in non-expanded rats (42 +/- 3 vs 32 +/- 3 mmHg, respectively; P < 0.01). Administration of haloperidol did not modify the L-arginine hypotensive effect. 4. Blockade of nitric oxide synthase diminished urine flow in non-expanded (4.15 +/- 0.56 vs 0.55 +/- 0.11 microL/min per 100 g; P < 0.01) and expanded animals (24.42 +/- 3.67 vs 17.85 +/- 2.16 microL/min per 100 g; P < 0.01). Diuresis induced by L-arginine was reduced by DA blockade in both non-expanded (17.15 +/- 2.11 vs 6.82 +/- 0.61 microL/min per 100 g; P < 0.01) and expanded animals (44.26 +/- 8.45 vs 25.43 +/- 5.12 microL/min per 100 g; P < 0.01). 5. Sodium excretion decreased with L-NAME treatment in non-expanded (0.22 +/- 0.03 vs 0.06 +/- 0.01 microEq/min per 100 g; P < 0.01) and expanded animals (3.72 +/- 0.70 vs 1.89 +/- 0.23 microEq/min per 100 g; P < 0.01). Natriuresis induced by L-arginine was diminished by haloperidol both in non-expanded (0.94 +/- 0.13 vs 0.43 +/- 0.04 microEq/min per 100 g; P < 0.01) and expanded rats (12.77 +/- 0.05 vs 3.53 +/- 0.75 microEq/min per 100 g; P < 0.01). Changes in kaliuresis changes seen following treatment with L-arginine, L-NAME and L-arginine + haloperidol followed a pattern similar to that observed for sodium excretion in both groups of rats. 6. L-arginine enhanced RPF in non-expanded animals (11.96 +/- 0.81 vs 14.52 +/- 1.05 mL/min per 100 g; P < 0.01). Glomerular filtration rate was increased by extracellular volume expansion (3.08 +/- 0.28 vs 5.42 +/- 0.46 mL/min per 100 g; P < 0.01). 7. The increase in NOx induced by acute volume expansion (0.18 +/- 0.03 vs 0.52 +/- 0.08 nmol/min per 100 g; P < 0.01) was diminished following the administration of haloperidol (0.52 +/- 0.08 vs 0.26 +/- 0.06 nmol/min per 100 g; P < 0.01). 8. Although DA does not participate in the actions of nitric oxide on vascular tone, both systems would play an important role in renal function adaptation during extracellular fluid volume expansion.

Animals↗

Renal calcium phosphate and oxalate deposition in prolonged vitamin B6 deficiency: studies on a rat model of urolithiasis.

OBJECTIVE: To determine the effect on kidney oxalate-salt deposition of a prolonged diet which induced vitamin B6 deficiency in adult rats, as there are reports of the pathogenic involvement of vitamin B6 deficiency in the formation of renal calcium oxalate calculi. MATERIALS AND METHODS: The study comprised 24 6-month-old male albino Wistar rats; 12 were fed with a purified vitamin B6-deficient diet and the others provided with the same diet but supplemented with 6 mg/kg of vitamin B6. After 12 weeks, all rats were killed, and their kidneys fixed in formalin and routinely processed to paraffin for morphological examination; some fragments were fixed in glutaraldehyde and prepared for ultrastructural examination. From each rat consecutive sections of both kidneys were cut and stained with haematoxylin and eosin, periodic-acid Schiff, Sirius red and the Von Kossa method for calcium. Sections were examined in polarized light and by electron microscopy. RESULTS: The histopathological and ultrastructural features of the kidney of vitamin B6-deficient rats were those of tubular-interstitial nephritis, characterized by tubular atrophy, interstitial fibrosis and chronic inflammatory infiltration. Oxalate and phosphate crystals were present in the papillary and parenchymal connective tissue. Ultrastructural features confirmed severe tubular epithelial lesions and the presence of an interstitial and intraepithelial inflammatory infiltrate; there was mild interstitial fibrosis. None of these features were apparent in the kidney of control rats. CONCLUSIONS: Histopathological and ultrastructural data indicate that a prolonged vitamin B6-deficient diet may contribute to the formation and deposition of calcium phosphate and oxalate crystals, which lead to severe damage of the renal parenchyma. This phenomenon may occur not only in growing rats, which have more active protein metabolism and consequently higher vitamin B6 requirements, but also in adult rats.

Animals↗

Ultrasound as a possible screening method in ovarian cancer.

Ultrasound is a diagnostic method suitable for first level screening of ovarian cancer. The results in 4350 patients confirmed that ultrasound examination, both transabdominal and transvaginal, can be considered quite satisfactory because the sensibility was 100%.

Abdomen↗

The role of hysteroscopy in early diagnosis of endometrial cancer.

The aim of this retrospective study was to compare stage, disease-free survival and overall survival in patients suffering from endometrial cancer who underwent hysteroscopy and those who did not. Between January 1, 1990 and June 30, 2001, 181 patients were referred to our Gynaecologic Department for primary endometrial carcinoma; from clinical charts we reviewed the personal and pathological data of all patients. Patients were divided into two groups: those with hysteroscopy (69 patients) and those without (112 patients). Endometrial biopsy was performed at the end of hysteroscopy. We compared symptoms at diagnosis, stage and survival. Hysteroscopy demonstrates a high diagnostic accuracy for endometrial cancer. In our case series we obtained a sensitivity of 93.10%, specificity of 99.96%, positive predictive value of 98.18% and negative predictive value of 99.85%; when hysteroscopy was associated with endometrial biopsy the sensitivity was 96.55% and specificity 100%. In this study we had a significant difference in stage Ia; in the group with hysteroscopy, stage Ia cases were 23.2% while in the group without, stage Ia cases were 15.2%. Survival in stage Ia only was 100% and 91.7%, respectively, at three and five years. In conclusion hysteroscopy was found to have a very important role in the early diagnosis of endometrial cancer, especially when it is limited to the mucosal surface.

Adult↗