Biomedical subjects

M Castelli

Publications and source records attributed to M Castelli.

At least 19 recordsLinked to original sources

PubMed2006

Predictive signs and indicators of aggressiveness and violence: a comparison between a group of adolescents attending an external penal area, a group of prisoners and a group of patients with borderline personality disorder.

AIM: Aggressive and violent behaviours in juveniles and young adults have become increasingly widespread. Most such behaviours have 2 common roots: lack of actual motivation and brutality. The most reliable indicators and predictive signs have been linked to structural personality features (e.g. defensive strategies, impulse control). With this cross-sectional study we wanted to determine specific indicators and predictive signs of violent and aggressive behaviours in these population segments. METHODS: We compared the structural personality features of 3 groups: one with 26 male adolescents with conduct disorder (F91.8), one with 29 male patients with borderline personality disorder (F60.31) and one with 34 male prisoners with antisocial personality disorder (F60.2). The test battery included: the ''Structured clinical interview for DSM-IV axis II disorders'' (for the recruitment of adult groups); the ''Indicators of aggressive conduct'' and the ''Profile of mood states'' (for the recruitment of the adolescent group); the ''Defense mechanisms inventory'' (DMI). RESULTS: The predominant defensive strategies and starting emotional backgrounds differed significantly among the groups. A profile of low emotional response was found to support aggressiveness, while a profile of aggressiveness and violence was associated with clinically significant impulsivity. CONCLUSIONS: Several indicators and clinical predictors of aggressiveness and violence, as well as high-risk-profiles, may be determined using these instruments.

Adolescent↗

PubMed2005

Ruthenium red-mediated suppression of Bcl-2 loss and Ca(2+) release initiated by photodamage to the endoplasmic reticulum: scavenging of reactive oxygen species.

The photosensitizer 9-capronyloxytetrakis (methoxyethyl) porphycene localizes predominantly in the endoplasmic reticulum (ER) and, to a lesser extent, in mitochondria of murine leukemia L1210 cells. Subsequent irradiation results in the loss of ER > mitochondrial Bcl-2 and an apoptotic response. Although an increase in cytosolic Ca(2+) was observed after irradiation, apoptosis was not inhibited by either the presence of the calcium chelator BAPTA or by the mitochondrial uniporter inhibitor ruthenium amino binuclear complex (Ru360). Moreover, neither reagent prevented the loss of Bcl-2. Ruthenium red (RR) devoid of Ru360 prevented Bcl-2 loss, release of Ca(2+) from the ER and the initiation of apoptosis. Since RR was significantly more sensitive than Ru360 to oxidation by singlet oxygen, we attribute the protective effect of RR to the quenching of reactive oxygen species. Although cytosolic and (to a lesser extent) mitochondrial Ca(2+) levels were elevated after photodynamic therapy, these changes were apparently insufficient to contribute to the development of apoptosis.

Animals↗

PubMed2004

Spontaneous low cerebrospinal pressure: a mini review.

Spontaneous intracranial hypotension (SIH) is a syndrome of low cerebrospinal fluid (CSF) pressure characterised by postural headaches in patients without any history of dural puncture or penetrating trauma. Described by Schaltenbrand in 1938, SIH is thought to result from an occult CSF leak resulting in decreased CSF volume and, consequently, in low CSF pressure. Magnetic resonance imaging of the head and spine has improved the diagnosis of the syndrome showing peculiar radiographic abnormalities including diffuse pachymeningeal enhancement, subdural fluid collections and downward displacement of the cerebral structures. Treatment of SIH headache should start with conservative, non-invasive therapies while epidural blood patch has emerged as the treatment of choice for those symptomatic patients who have failed medical noninvasive approaches.

Cerebrospinal Fluid Pressure↗

PubMed2004

A mechanism for the proapoptotic activity of ursodeoxycholic acid: effects on Bcl-2 conformation.

Ursodeoxycholic acid (UDCA), a relatively nontoxic bile acid, enhanced the apoptotic response of tumor cells to both photosensitizers that cause photodamage to Bcl-2 and to the nonpeptidic Bcl-2/Bcl-x(L) antagonist HA14-1. The latter agent binds to the surface pocket formed by the BH1, BH2 and BH3 domains of Bcl-2 and Bcl-x(L). Fluorescence polarization studies indicated that affinity of HA14-1 for Bcl-2 was enhanced in the presence of UDCA. Moreover, Bcl-2 photodamage was promoted by UDCA using a photosensitizing agent with affinity for the endoplasmic reticulum, a site of Bcl-2 localization. Fluorescence resonance energy transfer (FRET) studies revealed that the proximity of Bcl-2 to a hydrophobic photosensitizing agent embedded in liposomes was enhanced by UDCA. Since photodamage will occur only if a protein is in close contact with a photosensitizing agent, we propose that these findings support the hypothesis that UDCA causes a conformational change in Bcl-2, promoting HA14-1 binding and enhancing affinity for certain membrane-bound photosensitizers.

Animals↗

PubMed2003

Gastrointestinal stromal tumors of the stomach. A ten-year surgical experience.

Gastrointestinal stromal tumors show an increasing incidence. Immunohistochemistry is mandatory to make differential diagnosis with other mesenchimal tumors. We retrospectively reviewed 15 primary stomach GISTs operated during the last decade. Gastroscopy, Ultrasonography and CT scan were employed to obtain the diagnosis. Tumor size ranged from 1.5 to 30 cm in diameter. Treatment consisted of curative surgical resection without sistematic lymph node dissection. A wedge resection was sufficient in 8 cases. In 2 patients a distal subtotal gastrectomy was required and in 1 a total enlarged gastrectomy with pancreaticosplenectomy was performed. 4 GISTs were incidentally discovered and removed during surgical procedures for other gastrointestinal malignancies. In 4 cases a laparoscopic wedge resection was possible. In all cases postoperative course was uneventful. No adjuvant treatment was administered. Concerning the follow-up, two patients died for local and distant relapse while 13 are still alive (most of them operated during the last three years). GISTs show a very unpredictable clinical course and curative surgery is the only potential effective curative treatment.

Adult↗

PubMed2002

Sentinel node in gastric cancer surgery.

Sentinel Node (SN) biopsy studies have been recently applied to gastric cancer. In this series, 40 selected patients operated for gastric adenocarcinoma located in the lesser curvature and/or anterior wall of the body and antrum, underwent an intraoperative dye lymphography. The lymphatic ducts and nodes were visualized and a SN was evidenced in all cases. This was removed and a frozen section examined. In all cases a radical D2-3 gastrectomy was performed and histology, molecular biology, RT-PCR research of micrometastases (CEA-mRNA), were determined on the specimens. Correlations between T and histological status of SN and regional nodes were done. In 16 cases the SN was negative and all the resected regional nodes were negative too. In 15 cases the SN node was positive and other nodes in other stations were found to be positive as well. In 2 cases the SN was negative but other nodes, in the same stations and in others, were positive (false negative = 5%). In 7 cases the SN was the only node in which metastases occurred, 3 demonstrated by conventional histology and 4 detected by RT-PCR. In these 7 cases the SN was the only involved node out of all resected nodes, thus demonstrating to be the real first node along the lymphatic routes from the tumour. This experience seems to confirm the existence of a Sentinel Node and that each gastric adenocarcinoma has its own lymphatic basin in which metastasis can occur. Although a prudent attitude towards the indications resulting from these observations is required, in selected cases a controlled and tailored lymphoadenectomy could be adopted.

Humans↗

PubMed2001

Evidence that bcl-2 is the target of three photosensitizers that induce a rapid apoptotic response.

We originally proposed that the subcellular target for one class of photosensitizing agents was the mitochondrion. This classification was based on effects that occur within minutes of irradiation of photosensitized cells: rapid loss of the mitochondrial membrane potential (delta psi m), release of cytochrome c into the cytosol and activation of caspase-3. These effects were followed by the appearance of an apoptotic morphology within 30-90 min. Fluorescence localization studies on three sensitizers initially classified as 'mitochondrial' revealed that these agents bind to a variety of intracellular membranes. The earliest detectable effect of photodamage is the selective loss of the antiapoptotic protein bcl-2 leaving the proapoptotic protein bax undamaged. Bcl-2 photodamage can be detected directly after irradiation of cells at 10 degrees C. Subsequent warming of cultures to 37 degrees C results in loss of delta psi m, release of cytochrome c and activation of caspase-3. The latter appears to amplify the other two effects. Based on results reported here we propose that the apoptotic response to these photosensitizers is derived from selective photodamage to the antiapoptotic protein bcl-2 while leaving the proapoptotic protein bax unaffected.

Animals↗

PubMed2001

Antiviral and antiproliferative activity in vitro of some new benzimidazole derivatives.

The antiviral and antiproliferative activity of new compounds having n-benzenesulphony 1-2 (2 or 3-pyridylethyl) benzimidazole as a base structure were studied in vitro. Their antitumour activity against human chronic myeloid leukaemia cells was evaluated and compared with that of equimolar doses of daunorubicin. Only compound 7a, with the presence of both the pyridyl moiety bound at the ethylenic bridge in C-2 of benzimidazole and the nitro-group in the benzene ring, displays a selective antiproliferative effect against certain leukaemia cells and a good antiviral activity especially towards the Coxsackie B5 virus. However, it should be noted that, in the case of hydroxybenzyl-benzimidazole, resistance also builds up to compound 7a, the Coxsackie B5 virus developing resistance to it after about ten runs. Cytotoxicity tests show that many of these substances are well tolerated by the VERO cells. The mechanism of action is still unclear.

Animals↗

PubMed2001

Serum cytokeratins determination in differentiated thyroid carcinoma.

To assess the potential value of cytokeratins (CK) 8,18,19 as tumor markers for thyroid diseases, a study was performed comparing serum CK 8,18,19 levels in patients affected from thyroid carcinoma, adenoma, other benign thyroid diseases and healthy volunteers as controls. One hundred cases (65 patients and 35 controls) were examined. Thirty patients had thyroid carcinoma (18 papillary--PTC, 8 follicular--FTC, 4 medullary--MTC), 19 non-toxic goiter, 10 thyroid adenoma, 6 chronic thyroiditis and 35 healthy volunteers as controls. These controls were matched by age and sex. The mean value of CK in benign thyroid diseases (46.1 U/L) was significantly higher (p<0.02) than that in healthy controls (29.6 U/L). The mean value of CK in carcinomas (68.1 U/L) was significantly higher than that in healthy controls (p<0.01) and benign thyroid diseases patients (p<0.05). The positive rate of CK in thyroid carcinomas was 28.1%, while in benign thyroid diseases was 17.8%. The CK sensitivity for thyroid carcinomas was 28.1%, with a specificity of 80% and accuracy of 70.4%. In PTC patients the mean CK value was not significantly higher than in the benign diseases' group and in healthy subjects. No evident correlation between CK levels and tumor mass was found. In FTC patients the mean value was significantly higher than in the benign diseases' group and in healthy subjects. Large tumors showed the highest levels, while small tumor values were similar to the control ones. In MTC patients the mean value was significantly higher than in the benign diseases' group and in healthy subjects, with the highest peaks in large tumors and metastatic tumors. The detection of increased values in thyroid carcinomas with high metastatic potential (FTC and MTC) seems to confirm the role of these antigens in predicting the malignancy's degree of the neoplasm. These findings, if confirmed in larger series, could play an important role in assessing the CK 8,18,19 serum level as a real prognostic factor. Further repeated serum determinations after total thyroidectomy might indicate the role of CK 8,18,19 as serum markers predicting the risk of metastases.

Adenocarcinoma, Follicular↗

PubMed2000

Synthesis and antiproliferative activity of some benzimidazole-4,7-dione derivatives.

A series of benzimidazole-4,7-diones bearing at the 2-position the thiomethyl group or the 2-pyridyl moiety has been synthesized and tested in vitro on three tumor cell lines. Two of them show a very good antiproliferative effect. Compounds 1 and 2d are more active or equiactive, respectively, than MMC against human lymphoblastic leukemia. Both compounds exhibit high activity on human non-Hodgkin lymphoma. Compound 1 is non toxic at all the concentrations used in the antiproliferative assay and 2d is toxic only at high concentration.

Antibiotics, Antineoplastic↗

PubMed2000

Low-grade left varicocele in patients over 30 years old:the effect of spermatic vein ligation on fertility.

OBJECTIVES: To evaluate the effect of spermatic vein ligation in patients over 30 years old and with low-grade left varicocele, and thus help to establish whether such patients might benefit from surgery. PATIENTS AND METHODS: A randomized study was conducted on 68 infertile patients (30-38 years old) with evidence of sperm abnormalities and who had low-grade varicocele (grade I according to Hirsch), comparing left spermatic vein ligation with no treatment. The outcome was assessed by standard sperm analysis and eventual paternity. RESULTS: There was no improvement in sperm quality in either of the groups one year after surgery, and no significant difference in paternity. CONCLUSIONS: Left spermatic vein ligation for low-grade varicocele in patients more than 30 years old cannot be recommended.

Adult↗

PubMed2000

Cytotoxicity and probable mechanism of action of sulphimidazole.

Sulphimidazole (1-methyl-2((4-aminophenyl)-sulphonyl)-amino-5-nitroimidazole) is a new compound in which a p-aminobenzenesulphonamide radical has been attached at position 2 of the 5-nitroimidazole ring. It possesses a useful spectrum of activity in vitro against various anaerobic microorganisms and its action against aerobic and facultative bacteria is synergically enhanced in association with trimethoprim. In the present study, we determined the cytotoxicity in vitro of sulphimidazole and trimethoprim, both alone and in combination, and analysed the viability of Vero cells and the protein content of their cell lysate in the presence of increasing concentrations of these drugs. Also, in order to verify the hypothesis that the action of sulphimidazole against aerobic and facultative bacteria is mediated by the sulphonamide component of the molecule, while that against anaerobic bacteria depends on the action of the nitro group of the 5-nitroimidazole ring, we studied the mechanism of action of the new compound both indirectly, by means of microbiological techniques, and directly, by determining its oxidoreduction potential with respect to that of metronidazole. The results show that sulphimidazole is only slightly toxic in vitro for Vero cells, either alone or in association with trimethoprim, and that the combination of the two functional groups in a single molecule not only maintains its structure-activity relationship intact but also broadens its antibacterial spectrum.

Animals↗

PubMed1999

Correlation between high intake of glycyrrhizin and myolysis of the papillary muscles: an experimental in vivo study.

The ingestion of large quantities of glycyrrhizin, whether as a drug or a sweetener, is known, in susceptible subjects, to induce a syndrome similar to hypermineralcorticoidism, with bouts of hypertension, hypokaliaemia and rabdomyolysis, sometimes associated with severe renal failure and hypokaliaemia-induced arrythmias. Glycyrrhizin is also known to isomerize into the glycyrrhetic (or glycyrrhetinic) acids 18alpha- and 18beta-. In previous works, we reported that these metabolites cause bouts of hypertension and reduction in diuresis at low doses in the rat. In particular, the alpha isomer causes significant elimination of the calcium ion in the urine. The present findings confirm that 18alpha-glycyrrhetic acid is more toxic than either glycyrrhizin or the beta isomer. Histopathological study of tissue samples taken from rats treated with the alpha isomer also reveal selective damage to the myocardium with oedema, myolysis, apoptosis and blistering of the sarcoplasm. These effects begin to appear in the course of subchronic treatment, they manifest themselves in acute treatment and correlate closely with the electrocardiographic changes recorded in rats acutely treated with 18alpha-glycyrrhetic acid.

Animals↗

PubMed1998

Synthesis and antiproliferative activity of some N-sulphonated-2-substituted benzimidazoles and imidazo[4,5-b]pyridines.

Some N-sulphonated-2-substituted benzimidazoles and imidazo[4,5-b]-pyridines were synthesized and tested in vitro for antiviral and antiproliferative activity. None of the compounds had antiviral properties. However, three of them inhibited the proliferation of leukaemia and lymphoma cell lines at micromolar concentrations. The maximum potency of antiproliferative activity is correlated with the presence of an ethylenic spacer between the two heterocycles.

Antineoplastic Agents↗

PubMed1998

Unlike tenascin-X, tenascin-C is highly up-regulated in pig cutaneous and underlying muscle tissue developing fibrosis after necrosis induced by very high-dose gamma radiation.

Fibrosis is characterized by proliferation of fibroblasts and deposition of extracellular matrix (ECM). As alterations in the composition of ECM may account for its chronic extension, we studied the expression of the tenascin-C (TN-C) and tenascin-X (TN-X) ECM glycoproteins in our pig model of the effects of accidental exposures to radiation, in which cutaneous and muscle fibrosis developed after the induction of necrosis after a high single dose (160 Gy at the skin surface) of gamma rays. We found that, in the healed fibrotic dermis and underlying muscle fibrosis, the amount of TN-C mRNA was increased up to 18- and 39-fold, respectively, compared to normal dermis, whereas the level of TN-X mRNA remained almost unchanged. In analyses by Western blotting, the two main TN-C isoforms of 235-240 and 190-200 kDa increased up to 45- and 105-fold in fibrotic tissues, respectively. The large isoform was expressed more strongly than the smaller, although in healed fibrotic scar tissues their ratio was lower in protein than in RNA. Compared to unirradiated skin, an immunohistological study revealed stronger TN-C staining at the dermo-epidermal junction and in areas of remodeling in healed skin. An intense extracellular staining was observed around myofibroblasts in muscle fibrosis. Therefore, the gene encoding TN-C is highly up-regulated in fibrotic tissues, and mechanisms regulating the levels of TN-C variants occur at both the RNA and protein levels. Each isoform might play a distinct role in the chronic activation of fibrosis by differentially regulating mechanisms like cell adhesion, migration or proliferation.

Alternative Splicing↗

PubMed1998

Gastric cancer. Clinico-biological updating and analysis of 400 operated cases.

Gastric cancer is a rather common disease worldwide. In Italy it still accounts for 15,000 deaths annually. A sharp drop in the incidence rate of Lauren's intestinal histotype has been reported, whereas the frequency of the diffuse histotype is relatively steady. If the histogenesis of the latter is still somewhat obscure, the intestinal type confirms the sequence: atrophic gastritis--intestinal metaplasia--dysplasia--neoplasia. These different stages of development can nowadays be singled out through a series of indicators, the most reliable of which are the pepsinogen I/pepsinogen II ratio, the presence of sulphomucins and Lewis antigens in the gastric juices and NOR (Nucleolar Organizer Regions), cell ploidy and oncogenes determination. The genes involved in the neoplastic transformation are mostly oncosuppressors, the most frequent alterations being those relative to the APC gene, p53 and c-myc. In addition to the by now indispensable pathological staging of the disease, the modern prognostic factors are arising great interest: the most significant are the immunohistochemical examination of the peritoneal washing, and cell ploidy. Surgery is still the only potentially curative treatment: the earlier surgery is performed in the course of disease, the greatest the curative potential. The Authors' experience, which includes 400 operated cases with complete follow-up records, is here reported. The resectability rate turned out to be 84%, overall operative mortality was 6.5% with that due to surgical causes along being 3.7%. Overall survival at 5 years was 36%, while that of the curative operations 47%. Good results were obtained with the association surgery + intraoperative radiotherapy which resulted in a significant decrease in local recurrences of the disease.

Adenocarcinoma↗

PubMed1998

Synthesis, antiviral and antiproliferative activity of some N-benzenesulphonyl-2(2- or 3-pyridylethyl)-benzimidazoles.

Some N-benzenesulphonyl-2(2- or 3-pyridylethyl)-benzimidazoles were synthesized and tested in vitro for antiproliferative and antiviral activity. Only one compound displayed a degree of antiproliferative activity against chronic myeloid leukaemia cells. However, a number of them exerted an antiviral effect at micromolar concentrations. The antiproliferative activity and the maximum potency of antiviral activity correlate with the presence of both the 2-pyridyl moiety bound at the ethylenic bridge in C-2 of benzimidazole and the nitro group in the benzene ring.

Animals↗

PubMed1997

Fine-needle aspiration of 697 palpable breast lesions with histopathologic correlation.

BACKGROUND: Fine-needle aspiration breast biopsy has been used increasingly as an alternative to excisional biopsy. The purpose of this study is to evaluate the accuracy of fine-needle aspiration with histopathologic confirmation. METHODS: A retrospective study was performed using a computer database over a 5-year period. All women who had had fine-needle aspiration breast biopsy with histopathologic confirmation of the diagnosis were included. Fine-needle aspirations were interpreted as malignant, suspicious, or benign. Histopathologic diagnosis included core-needle biopsy, open excisional biopsy, or mastectomy specimen. RESULTS: A total of 697 patients fulfilled the criteria. Only 5 (0.7%) of the specimens were inadequate for study. There were 401 total malignant fine-needle aspiration diagnoses, with only 3 false-positive specimens. All three were ductal hyperplasia, one from a previously radiated breast. There were 125 suspicious readings; 84 of these were malignant and 41 were false-suspicious specimens. Most of the false-suspicious lesions were fibrocystic disease. Of the 166 lesions interpreted as benign, there were 13 false-negative specimens. The test had a 97% sensitivity, 78% specificity, 92% positive predictive value, and 92% negative predictive value. CONCLUSIONS: Fine-needle aspiration is a sensitive test that can be useful as an adjunct in the diagnosis of breast cancer. "Malignant" and "benign" interpretations are highly predictive but must be used only in the context of other diagnostic modalities. "Suspicious" lesions require further investigation.

Biopsy, Needle↗