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E Silvestri

Publications and source records attributed to E Silvestri.

At least 19 recordsLinked to original sources
PubMed2005

Thyroid-hormone effects on putative biochemical pathways involved in UCP3 activation in rat skeletal muscle mitochondria.

In vitro, uncoupling protein 3 (UCP3)-mediated uncoupling requires cofactors [e.g., superoxides, coenzyme Q (CoQ) and fatty acids (FA)] or their derivatives, but it is not yet clear whether or how such activators interact with each other under given physiological or pathophysiological conditions. Since triiodothyronine (T3) stimulates lipid metabolism, UCP3 expression and mitochondrial uncoupling, we examined its effects on some biochemical pathways that may underlie UCP3-mediated uncoupling. T3-treated rats (Hyper) showed increased mitochondrial lipid-oxidation rates, increased expression and activity of enzymes involved in lipid handling and increased mitochondrial superoxide production and CoQ levels. Despite the higher mitochondrial superoxide production in Hyper, euthyroid and hyperthyroid mitochondria showed no differences in proton-conductance when FA were chelated by bovine serum albumin. However, mitochondria from Hyper showed a palmitoyl-carnitine-induced and GDP-inhibited increased proton-conductance in the presence of carboxyatractylate. We suggest that T3 stimulates the UCP3 activity in vivo by affecting the complex network of biochemical pathways underlying the UCP3 activation.

Animals↗
PubMed2005

Thyroid hormones as molecular determinants of thermogenesis.

Thyroid hormones (TH) are major modulators of energy metabolism and thermogenesis. It is generally believed that 3,5,3'-triiodo-l-thyronine (T3) is the only active form of TH, and that most of its effects are mediated by nuclear T3 receptors, which chiefly affect the transcription of target genes. Some of these genes encode for the proteins involved in energy metabolism. However, a growing volume of evidence now indicates that other iodothyronines may be biologically active. Several mechanisms have been proposed to explain the calorigenic effect of TH, but none has received universal acceptance. Cold acclimation/exposure and altered nutritional status are physiological conditions in which a modulation of energy expenditure is particularly important. TH seem to be deeply involved in this modulation, and this article will review some aspects of their possible influence in these conditions.

Adipose Tissue, Brown↗
PubMed2003

Novel and recurrent mutations in the integrin beta 4 subunit gene causing lethal junctional epidermolysis bullosa with pyloric atresia.

In this study we examined two unrelated patients affected with the lethal variant of junctional epidermolysis bullosa with pyloric atresia (PA-JEB) who were found to carry mutations in the integrin beta4 subunit gene (ITGB4). Although in both patients Northern blot analysis showed only a 50% reduction in the level of ITGB4 transcript, a complete lack (patient 1) or a strong reduction (patient 2) of beta4 immunoreactivity was observed in the skin. Using immunoprecipitation analysis, integrin beta4 could not be visualized in patient 1 cells while a markedly reduced amount (approximately 20%) of normal sized beta4 chains was detected in patient 2. These data suggested the presence of ITGB4 mutations that interfere with both mRNA and protein stability. Using molecular analysis, patient 1 was shown to be a compound heterozygous for a single amino acid deletion (deltaN318) and a not yet identified mutation that induces a very rapid decay of the encoded mRNA transcript. Patient 2 was, instead, a compound heterozygous for a novel 4-bp tandem duplication (4298-4299ins4) and a previously described missense mutation (R252C). Our data support the notion that PA-JEB lethal phenotypes associated with a markedly decreased/absent alpha6beta4 expression can be due not only to the presence of null alleles, but also to specific mutations leading to protein instability and/or altered function.

Epidermolysis Bullosa↗
PubMed2003

Power Doppler analysis of tendon vascularization.

Forty-nine patients with tendonitis (patellar in 16, quadriceps in two, Achilles in 12, rotator cuff disease in 19) and 47 patients with tenosynovitis (acute tenosynovitis in 25, stenosing tenosynovitis in 22) underwent ultrasound (US) and Power Doppler (PD)-US examination. Spectral analysis of flow signals was performed in all patients. Ten patients (six with tendonitis, four with tenosynovitis) were rewired after medical therapy. Six healthy volunteers were also examined for control purposes. Three different patterns of flow distribution were found in patients with tendonitis and active tenosynovitis. The vessels of tendons without tendon sheaths began with great peduncles at the level of the peritendinous soft tissues and were then distributed inside the tendon (pattern I). A clear peritendinous hypervascular pattern was found in all active tenosynovitis, but no vessels were found inside the tendons (pattern II). In some cases of intratendinous or partial lesions PD-US revealed some vessels located near or inside the lesion (pattern II). On spectral analysis these vessels corresponded to arteries with a low resistance index or small venules. PD-US revealed a significant reduction of flow signals in patients rewired after medical therapy. No pathological flow signals were found either in patients with stenosing tenosynovitis or in the control group. PD-US gives us an in vivo confirmation of tendon vascularity. Spectral analysis adds further information to gray-scale US.

Adolescent↗
PubMed2002

Skeletal muscle mitochondrial free-fatty-acid content and membrane potential sensitivity in different thyroid states: involvement of uncoupling protein-3 and adenine nucleotide translocase.

The effect of triiodothyronine (T3) on mitochondrial efficiency could be related to an increase in the concentrations of some proteins, such as uncoupling proteins (UCPs). Free fatty acids (FFA) seem to be a cofactor essential for the uncoupling activity of UCP3. In this paper, we report that the hypothyroidism-hyperthyroidism transition is accompanied by increases: (i) in the endogenous levels of mitochondrial FFA and (ii) in the sensitivity to FFA shown by the mitochondrial respiration rate and membrane potential, which correlated with the level of UCP3 protein. The level of the mRNA for adenine-nucleotide translocase-1 (ANT) was not affected by the thyroid state, while the ANT contribution to FFA-induced changes in mitochondrial uncoupling was low in the hypothyroid and euthyroid states but became more relevant in the hyperthyroid state at the highest concentration of FFA.

Adenine Nucleotide Translocator 1↗
PubMed2002

c-FLIP efficiently rescues TRAF-2-/- cells from TNF-induced apoptosis.

For the past 20 years, it has been known that preparations of Tumor Necrosis Factor alpha (TNF) fail to induce apoptosis due to cytoprotective responses that render cells resistant to its cytotoxic activity. Here we show that TRAF-2-/- embryonic fibroblasts express reduced levels of the anti-apoptotic molecule c-FLIP due to extensive degradation of the protein. Reconstitution of TRAF-2-/- EF with c-FLIP is sufficient for resistance to TNF toxicity. Our results strengthen the role of c-FLIP in protecting cells from the cytotoxic effect of TNF and have implication for the treatment of inflammatory and proliferative disorders.

Animals↗
PubMed2001

Uncoupling protein-3 is a molecular determinant for the regulation of resting metabolic rate by thyroid hormone.

Thyroid hormones increase energy expenditure, partly by reducing metabolic efficiency. The control of specific genes at the transcriptional level is thought to be the major molecular mechanism. However, both the number and the identity of the thyroid hormone-controlled genes remain unknown, as do their relative contributions. Uncoupling protein-3, a recently identified member of the mitochondrial transporter superfamily and one that is predominantly expressed in skeletal muscle, has the potential to be a molecular determinant for thyroid thermogenesis. However, changes in mitochondrial proton conductance and resting metabolic rate after physiologically mediated changes in uncoupling protein-3 levels have not been described. Here, in a study on hypothyroid rats given a single injection of T(3), we describe a strict correlation in terms of time course between the induced increase in uncoupling protein-3 expression (at mRNA and protein levels) and decrease in mitochondrial respiratory efficiency, on the one hand, and the increase in resting metabolic rate, on the other. First, we describe our finding that uncoupling protein-3 is present and regulated by T(3) only in metabolically relevant tissues (such as skeletal muscle and heart). Second, we follow the time course (at 0, 6, 12, 24, 48, 65, 96, and 144 h) of both uncoupling protein-3 mRNA levels and mitochondrial uncoupling protein-3 density in gastrocnemius muscle and heart. In both tissues, the maximal (12-fold) increase in uncoupling protein-3 density was reached at 65 h. The resting metabolic rate [lO(2)(kg(0.75))(-1)h(-1)] showed the same time course, and at 65 h the increase vs. time zero was 45% (1.316 +/- 0.026 vs. 0.940 +/- 0.007; P < 0.001). At the same time point, gastrocnemius muscle mitochondria showed a significantly higher nonphosphorylating respiration rate (nanoatoms of oxygen per min/mg protein; increase vs. time zero, 40%; 118 +/- 4 vs. 85 +/- 9; P < 0.05), whereas the membrane potential decreased by 8% (168 +/- 2 vs. 182 +/- 4; P < 0.05). These data are diagnostic of mitochondrial uncoupling. The results reported here provide the first direct in vivo evidence that uncoupling protein-3 has the potential to act as a molecular determinant in the regulation of resting metabolic rate by T(3).

Animals↗
PubMed2000

An appraisal of magnetic resonance imaging of the wrist in rheumatoid arthritis.

OBJECTIVES: To evaluate the role of magnetic resonance imaging (MRI) in the diagnosis, staging, and follow-up of the rheumatoid wrist. METHODS: A Medline search was performed to identify all publications from the years 1985 to 1999 concerning MRI of the wrist in patients with rheumatoid arthritis (RA). Additional papers were retrieved by scanning the references to the Medline-listed articles. Details of the MRI technique, as well as clinical data, were analyzed and compared. RESULTS: A total of 55 papers were identified. There were considerable variations in imaging sequence, section type, and slice thickness. Erosions and synovitis were the conditions that mostly profited from the adoption of MRI. Although the visualization of erosions was better detailed with MRI than with conventional radiography, erosions were only rarely related to clinical and laboratory parameters. Another advantage was that synovitis imaging, which can be enhanced by contrast agents, was amenable to quantitation. The extent of the synovial surface and the rate of contrast enhancement in a series of consecutive, rapidly acquired images were the most common measures. CONCLUSIONS: MRI of the rheumatoid wrist is a useful technique to ascertain the criteria for diagnosis and progression of RA, and to monitor the effects of treatment. Implementation of a standardized protocol could further increase its value.

Ankylosis↗
PubMed1999

Changes in bioimpedance analysis after stable refeeding of undernourished anorexic patients.

OBJECTIVE: To evaluate bioimpedance analysis (BIA) parameters in patients with anorexia nervosa when undernourished and then after stable refeeding. DESIGN: Follow-up study. SUBJECTS: Thirteen patients with anorexia nervosa who were studied when undernourished (body weight (Wt): 36.9+/-5.6kg, body mass index (BMI): 14.8+/-1.8kg/m2) and after stable refeeding (Wt: 52.9+/-7.1kg, BMI: 21.2+/-2.3 kg/m2) compared to 25 well-nourished control women (Wt: 53.7+/-4.9 kg, BMI: 21.1+/-1.3 kg/m2). MEASUREMENTS: Impedance and phase angle were determined for the whole body (13 patients) and separately for arms and legs (10 patients). RESULTS: Bioimpedance index (height2/impedance) and phase angle were lower in the undernourished group. Whole-body impedance declined (median, min-max) by 45, 1-151 Ohm after refeeding; the variations of bioimpedance index (BI-Index) were weakly correlated (P < 0.10) with BMI changes. Limb phase angles increased with refeeding, but only changes in whole-body phase angle were correlated (P < 0.025) with the corresponding variations of Wt or BMI. CONCLUSION: Whole-body phase angle increased after weight recovery of anorexic patients, suggesting the occurence of modifications in the extracellular-to-intracellular water ratio. These changes were proportional to the increase in BMI and Wt.

Adolescent↗
PubMed1998

The anterior tilt of the acromion: radiographic evaluation and correlation with shoulder diseases.

The aim of this study was to test whether the anterior tilt of the acromion can be objectively evaluated on lateral radiographs, and whether there is a relation between this anatomical feature and the most common shoulder diseases. Lateral radiographs of 15 dried scapulas were performed in neutral position and with 5 degrees of caudal, cranial, anterior and posterior angulations. Two hundred and forty-three shoulders, both asymptomatic and affected by chronic and post-traumatic impingement, calcific tendinitis and instability, were examined by conventional radiography. The presence of rotator-cuff tears was investigated by sonography. A method was elaborated to obtain reproducible lateral radiographs and to determine the acromial tilt angle. Inter- and intraobserver and inter- and intraoperator variations in measurements were evaluated. Variations in tube angulation produced changes in tilt-angle values on dried scapulas. The average tilt angle for the chronic impingement and the instability groups were significantly different from the post-traumatic, calcific tendinitis and control groups. Rotator-cuff tears were significantly more frequent in the chronic impingement group and related to a more acute tilt angle. The inter- and intraobserver variability coefficients were 0.95 and 0.98, whereas the inter- and intraoperator variability coefficients were 0.94 and 0.96, respectively. Conventional radiography using fluoroscopy for positioning is a well-reproducible method for the evaluation of acromial tilt. There is a significant difference in tilt-angle values between some groups of subjects examined, but the lack of specificity limits the clinical importance of such measurement.

Acromion↗
PubMed1997

US imaging and color Doppler in patients undergoing inhibitory therapy with calcitriol for secondary hyperparathyroidism.

The aim of this study was to evaluate the changes in volume, structure, and flow pattern of parathyroid glands in uremic patients with secondary hyperparathyroidism treated with long-term intravenous calcitriol (CTL) therapy. Ultrasonography was used to follow-up volume changes occurring in 18 enlarged glands in 11 patients during an 18-month period; in 6 of these cases, 11 glands were followed-up also with color-Doppler to monitor variations in flow pattern. Vascularization was classified using three grades: grade 0 = no color signal; grade I = vessels covering less than 50 % of glandular cross-sectional area; grade II = vascular signals covering more than 50 % of glandular cross-sectional area. No significant changes in volume were demonstrated during the 18 months of follow-up. On the contrary, significant decrease in flow was observed with almost complete disappearance of color-Doppler signals. This finding related well with the observed decrease in parathormone blood levels. Lack of volume changes during medical therapy demonstrates the inability of US alone to monitor the effect of this treatment on the parathyroid glands. Conversely, the observed intraglandular flow reduction indicates the possibility to use color Doppler to monitor the effects of CLT in uremic hemodialyzed patients with secondary hyperparathyroidism. This imaging procedure can be proposed for follow-up of the response of the parathyroid glands to therapy.

Blood Flow Velocity↗
PubMed1995

Normal prostate gland: examination with color Doppler US.

PURPOSE: To evaluate the vascular anatomy of the prostate gland with transrectal color Doppler ultrasound (US). MATERIALS AND METHODS: Thirty-five normal prostate glands were studied. Imaging findings were interpreted on the basis of findings from previous anatomic studies. RESULTS: Distribution of flow signals within the gland was differentiated into two parenchymal groups of arteries, urethral and capsular. The urethral group entered the prostate at the bladder neck and sent forth branches to supply the periurethral zone and the inner portion of the gland. The capsular group coursed along the anterolateral surface of the prostate and sent forth perforating branches to the outer portion of the gland. Intraprostatic venous signals were seen mainly within the periurethral zone. CONCLUSION: Transrectal color Doppler US can depict the vascular anatomy of the prostate gland. Knowledge of the normal vascular appearance of the gland should aid in the differentiation of normal from abnormal findings.

Adult↗
PubMed1995

Echotexture of peripheral nerves: correlation between US and histologic findings and criteria to differentiate tendons.

PURPOSE: To correlate the histologic structure and echotexture of peripheral nerves and verify if ultrasound (US) findings can be used to differentiate nerve from tendon. MATERIALS AND METHODS: In an in vitro study, the echotexture of normal peripheral nerves was correlated with the histologic findings. In an in vivo study, US was used to differentiate median nerve from flexor pollicis longus tendon in healthy volunteers (12 male and eight female subjects 7-68 years of age; mean age, 35 years). RESULTS: US examination of the peripheral nerve specimens showed hypoechoic areas separated by hyperechoic bands. The hypoechoic areas corresponded to neuronal fascicles at histologic examination. This fascicular pattern was clear in all median and ulnar nerves, 15 of 20 vagus nerves, and 19 of 20 sciatic nerves in the volunteers but not in recurrent laryngeal nerves. CONCLUSION: Peripheral nerves have a typical US pattern that correlates with histologic structure and facilitates differentiation between nerves and tendons.

Adolescent↗
PubMed1994

Split hand/split foot, syndactyly, urinary tract obstruction, radial, diaphragmatic, and neural tube defects: Czeizel-Losonci syndrome?

We report on a baby girl with absence of the left hemidiaphragm, lumbosacral myelomeningocele, syndactyly with limb deficiencies, and bilateral hydronephrosis. A similar array of malformations was described previously by Czeizel and Losonci [Hum Genet 77:203-204, 1987] in a single family which showed a transmission pattern suggesting autosomal dominant inheritance with variable expressivity. The presence of limb abnormalities and the location of the neural tube defects in these cases suggest that the underlying pathogenesis probably does not involve the same disturbances of midline field development which have been postulated to occur in the schisis association.

Abnormalities, Multiple↗
PubMed1994

Case report: US detection of tendinous metastasis from malignant melanoma.

The introduction of high frequency transducers has considerably improved the application of US in the study of musculo-tendinous diseases. We report a rare case of tendinous metastasis from malignant melanoma. The tumour (high karyokinetic index, Clark level IV) arose 4 years earlier in the dorsal region. The patient was admitted for pain in the left knee. A nodular hypoechoic lesion, 0.8 cm in diameter, poorly marginated, located in the subcutaneous tissue and involving the patellar tendon was identified with ultrasound. Histological examination confirmed the diagnosis.

Adult↗