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Biomedical subjects

M Castelli

Publications and source records attributed to M Castelli.

At least 127 records · Page 7Linked to original sources

Anti-p53 and anti-heat shock proteins antibodies in patients with malignant or pre-malignant lesions of the oral cavity.

BACKGROUND: Evaluation of circulating anti-p53 antibodies is an easy-to-perform, widely employed, procedure to assess the p53 status in cancer patients. MATERIALS AND METHODS: Levels of circulating anti-p53 antibodies in patients affected either by oral SCC or by pre- malignant oral lesions were assayed using a commercial ELISA kit. Autoantibody titers to Hsp60 and Hsp72 were determined by conventional ELISA. RESULTS: Anti-p53 antibodies were detected in 3 out of 16 SCC-bearing patients (18.7%) and in 9 out of 13 patients suffering from pre-malignant oral lesions (69.2%). High titers of anti-Hsp60 autoantibodies were detected in 3 out of 29 patients (10.3%), while in all patients anti-Hsp72 titers were in the normal range. CONCLUSION: The presence of anti-p53 antibodies in both SCC-bearing patients and in patients with pre-malignant lesions support the notion that p53 gene mutation is an early event in oral tumorigenesis and suggest that this assay could be useful for diagnostic screening of pre-neoplastic lesions at high risk of recurrence and/or transition towards overt malignancy.

Adult↗

The effect of nizatidine on neuromuscular transmission.

The effect of the H2-receptor antagonist, nizatidine, on neuromuscular transmission was investigated using sciatic nerve-gastrocnemius muscle preparations of rat in vivo. Nizatidine, administered by i.v. injection, potentiates the neuromuscular blockade induced by d-tubocurarine, pancuronium and the aminoglycoside antibiotic, kanamycin. Moreover, the drug alone is capable of producing a blockade on preparations stimulated at high frequency. The neuromuscular blockade induced by nizatidine is reversed by 4-aminopyridine but not by dimaprit.

4-Aminopyridine↗

Variations of telomerase activity in cultured mouse fibroblasts upon proliferation of polyomavirus.

Telomerase plays a central role in various biological phenomena such as cell differentiation and proliferation, apoptosis, malignant transformation and virus infection, for instance HIV and papillomavirus. In addition, it has recently been shown that, in human fibroblasts transformed by monkey polyomavirus SV40, telomeres became stabilized as a consequence of telomerase activation. However, no information exists on the effects of acute infection by murine polyomavirus on the telomeres maintenance and telomerase activity in the host cell. In this paper we report on a differential activity of telomerase in productively infected cells. The results showed a decreased activity of the enzyme as assessed by the TRAP assay. The decrease had already occurred at a non-lytic time of infection and was observed both after infection and naked DNA transfection. Therefore nuclear decapsidation is not involved in the determination of the phenomenon that is attributed to the proliferation of the virus.

Animals↗

Microbiological assay-trienzyme procedure for total folates in cereals and cereal foods: collaborative study.

In 1996, U.S. Food and Drug Administration regulations mandated the fortification of enriched cereal-grain products with folic acid, thereby emphasizing the need for validated methods for total folates in foods, particularly cereal products. The AOAC Official Methods (944.12, 960.46) currently used for the analysis of folate in foods for compliance purposes are microbiological methods. When the fortification regulations were finalized, no Official AOAC or Approved AACC methods for folate in cereal-grain products were in place. The AOAC Official Method (992.05) for folic acid in infant formula does not incorporate important improvements in the extraction procedure and was not considered suitable for the analysis of folates in foods in general. A microbiological assay protocol using a trienzyme extraction procedure was prepared and submitted for comments to 40 laboratories with recognized experience in folate analysis. On the basis of comments, the method was revised to have the conjugase (gamma-glutamyl-carboxy-peptidase) treatment follow a protease treatment, to include the use of cryoprotected inoculum, and to include the spectroscopic standardization of the standard and optional use of microtiter plates. Thirteen laboratories participated in a collaborative study of 10 required and 10 optional cereal-grain products, including flour, bread, cookies, baking mixes, and ready-to-eat breakfast cereals. The majority of the participating laboratories performed the assay by the standard test tube method; others used the microtiter plate modification for endpoint quantitation with equal success. For the required products, the relative standard deviation between laboratories (RSD(R)) ranged from 7.4 to 21.6% for 8 fortified (or enriched) products compared with expected (Horwitz equation-based) values of 11-20%. RSD(R) values were higher (22.7-52.9%) for 2 unfortified cereal-grain products. For the optional products, the RSD(R) ranged from 1.8 to 11.2% for 8 fortified products. RSD(R) values were higher (27.9-28.7%) for 2 unfortified cereal-grain products. Based on the results of the collaborative study, the microbiological assay with trienzyme extraction is recommended for adoption as Official First Action.

Automation↗

Presence and incidence of DNA sequences of human polyomaviruses BKV and JCV in colorectal tumor tissues.

The human polyomaviruses JCV and BKV are widespread within population, as shown by serological studies. However, exposure to these viruses does not seem to have pathological consequences in immunocompetent individuals, while in immunocompromised or immunosuppressed patients, polyomaviruses can be activated, giving rise to serious pathologies. Viral DNA sequences were also found in cells from a number of human tumors of mesothelial origin, suggesting that activation of BKV and JCV, taking place in genetically predisposed and/or in immunodepressed individuals, might be involved in the mechanisms of tumor transformation. In this study, samples obtained from 18 patients with colon rectal carcinoma were probed for the presence of JCV and BKV by three different techniques: Southern blot, PCR and in situ hybridization. Our results demonstrate that viral DNA sequences were present in 16 out of the 18 cases considered (88.9%). In the large majority of cases, viruses were detected both in the tumor mass and in the surrounding healthy tissues. Lymphocytes in the investigated areas were also found to be infected by polyomaviruses. These data indicate, for the first time, a possible involvement of polyomaviruses in the pathogenesis of tumors of endothelial origin, like the human colon rectal carcinoma.

Adenocarcinoma↗

The diimide drug PIPER has a cytotoxic dose-dependent effect in vitro and inhibits telomere elongation in HELA cells.

It is known that, in vitro, PIPER (N,N'-bis [2-(1-piperidino)ethyl]-3,4,9,10-tetracarboxylic diimide) induces the formation of the Hoogsteen quadruplex structure in telomere DNA, thus inhibiting the polymerisation of telomeric repeats. Since the action of PIPER in vivo has been scarcely investigated, this study was addressed to gain some insight into the effects of this drug on cultured HeLa cells. Vital staining with erythrosine, performed on cells exposed to different PIPER concentrations (from 1 to 50 microM), showed that the drug exerts a dose-dependent cytotoxic effect, clearly evident after a short-term (24 h) treatment. This early cytotoxic effect of PIPER on cultured HeLa cells was confirmed by a spectrophotometric/colorimetric method employing methylthiazoletetrazolium (Mossmann assay). Hematoxylin/eosin staining of cells treated with PIPER for 24 h showed a nuclear condensation and a cytoplasmic vacuolisation, very pronounced at higher drug concentrations. These pictures suggest that PIPER-induced cell death might be of the apoptotic type. Finally, the anti-telomerase activity of PIPER was monitored by TRAP assay, performed on HeLa cell nuclear extracts treated with increasing drug concentrations. It was found that some inhibition of telomerase is apparent even at low concentrations, while at the highest concentration the enzyme is completely inhibited. These results indicate that the cytotoxic power of PIPER is possibly related to its antitelomeric effect.

Dose-Response Relationship, Drug↗

Clinical and biological features of an intranodal palisaded myofibroblastoma.

Intranodal palisaded myofibroblastoma (IPM) is a rare benign tumor of the lymph nodes probably arising from smooth muscle-like cells. The tumor is characterized by intranodal proliferation of spindle cells. Neoplastic spindle-cell proliferation is most often of metastatic repetition which is very important in the recognition of IPM, because it may be mistaken for metastasis or other tumors such as Kaposi's sarcoma. We report a novel case of IPM that confirms the myofibroblastic differentiation of the tumor. The onset of IPM has been associated with Epstein-Barr virus (EBV). In addition, recently reported cases of IPM have been seen with cyclin 1 overexpression and also with human herpes virus (HHV)-8 and EBV DNA sequences. In our case, there was no evidence of HHV-8 and EBV DNA sequences and we were not able to find cyclin 1 overexpression.

Female↗

The bactericidal effect on Pseudomonas strains of adriamycin associated with quinolones.

The in vitro antibacterial activity of quinolone compounds was assessed on strains of Pseudomonas aeruginosa isolated from clinical infections. The bactericidal effect of quinolones was high and their respective antibacterial properties with adriamycin remained unimpaired on strains both sensitive and resistant to betalactam and aminoglycoside antibiotics. The cytotoxic effect of the combination of adriamycin and quinolones was determined in cultured P388 leukemia cells: no interference with the cytotoxic activity of adriamycin was observed.

Ciprofloxacin↗

Bactericidal and cytotoxic effect of combination of norfloxacin and 5-fluorouracil.

Using the agar dilution technique, we examined the in vitro antibacterial activity of 5-fluorouracil and norfloxacin alone and in association against several bacterial strains. When administered in association, the two drugs did not antagonize each other in tests carried out on strains both sensitive and resistant to penicillins, cephalosporins, aminoglycosides, tetracyclines; furthermore their respective antibacterial properties remained largely unimpaired. The cytotoxic activity and the antitumoral effect of a combination of 5-fluorouracil and norfloxacin was determined in cultured tumor cells, and in mice bearing Ehrlich ascites carcinoma. No significant interference with the cytotoxic activity and antitumoral activity of 5-fluorouracil was observed.

Animals↗

Reduction of anthracycline cardiotoxicity by amrinone and sulmazole.

In attempts to alleviate or prevent anthracycline toxicity, we have recently reported that amrinone and sulmazole markedly reduce the negative inotropic effect of adriamycin and 4-epiadriamycin in isolated spontaneously beating guinea pig atria in normodynamic or hypodynamic conditions. Amrinone and sulmazole are non catecholamine, non glycoside agents with inotropic properties. The present study reports the effects of adriamycin and 4-epiadriamycin (100 micrograms/ml) on electrically driven isolated guinea pig left atrium in normodynamic or hypodynamic conditions. Exposure for 60' to the two drugs caused a depression of contractile force and of maximal rate of contractile force (df/dt). The cardiac depressant effect of adriamycin as shown previously on spontaneously beating atria does not differ from that of 4-epiadriamycin. The negative effects of the two antitumor drugs are antagonized by amrinone (200 micrograms/ml) and sulmazole (100 micrograms/ml).

Amrinone↗

ACTH-(1-24) antagonizes the cholestatic and constipating effects of morphine.

In guinea-pigs and rats, ACTH-(1-24), i.m. injected in a dose-range of 10-150 micrograms/kg, dose-dependently antagonized the cholestatic effect of morphine (15 mg/kg i.m.). In guinea-pigs, however, the effect of morphine (66 +/- 7.7% bile flow) was only partially antagonized even by the highest dose of ACTH-(1-24) (89.21 +/- 3.4%), while in rats it was completely prevented by the dose of 75 micrograms/kg of ACTH. In morphine-dependent rats, ACTH-(1-24), injected i.p. at doses of 50, 100 and 150 micrograms/kg, dose-dependently increased the number of fecal pellets during the first 3 hr after treatment. These results show that ACTH antagonizes morphine in vivo at the biliary and intestinal level, and further support the idea that ACTH-MSH peptides are physiological antagonists of opioids.

Animals↗

Endoscopic brush cytology and biopsy in the diagnosis of cancer of the upper gastrointestinal tract.

Brush cytology and biopsy under direct vision was performed on 250 patients. Of the 44 proven cases with cancers of the upper gastrointestinal tract, brush cytology yielded positive results in 88.6%, and multiple mucosal biopsies yielded positive results in 93.2%. With the combined technique the results increased to 95.4%. False-negative results were due to large tumors with necrotic surfaces or to infiltrative tumors at the cardioesophageal junction. There was one false positive with brush cytology and none with biopsy. Four cases of early gastric cancer were diagnosed with the combined technique.

Biopsy↗

Comparative effects of alfuzosin versus Serenoa repens in the treatment of symptomatic benign prostatic hyperplasia.

OBJECTIVES: Sixty-three patients suffering from benign prostatic hyperplasia (BPH) entered a double-blind, comparative, parallel-groups study lasting 3 weeks, carried out to compare the efficacy and safety of alfuzosin 2.5 mg tid (n = 32) vs serenoa repens 160 mg bid (n = 31) in BPH. METHODS: Efficacy was assessed both on clinical symptoms (Boyarsky's scale, visual analogue scale, clinical global impression), urinary flow rates (uroflowmetry) and residual urinary volume (transabdominal ultrasound). Events and reported signs were recorded throughout the entire study. RESULTS: Statistically significant and clinically relevant differences were found between the two treatments in favour of alfuzosin for Boyarsky's total score (decrease from 9.6 +/- 3.0 to 5.9 +/- 3.0, 38.8% for alfuzosin and from 9.3 +/- 2.5 to 6.8 +/- 2.8, 26.9% for serenoa repens) and obstructive score (decrease from 4.9 +/- 2.1 to 3.0 +/- 1.9, 37.8% for alfuzosin; from 4.4 +/- 1.7 to 3.4 +/- 1.8, 23.1% for Serenoa repens; p = 0.01 for both). Clinically relevant differences were found between the two treatments for visual analogue scale and overall clinical impression at the end of the study. Furthermore, the increase in quality of micturition was better with alfuzosin. The proportion of responders (increase on day 21 in peak flow rate of at least 25% relative to the baseline values) was in favour of alfuzosin (71.8% and 48.4% for alfuzosin and Serenoa repens, respectively; p = 0.057). Both treatments were well tolerated. No patient treated with alfuzosin complained of any adverse event at any time during the study. One patient in the Serenoa group complained of mild pruritus which cleared spontaneously. Systolic, diastolic blood pressure and heart rate did not show any clinically relevant change during treatment with alfuzosin. CONCLUSIONS: The findings confirm the efficacy and safety of alfuzosin in symptomatic BPH and indicate the superiority of alfuzosin over Serenoa repens in the treatment of urinary signs and symptoms of BPH.

Adrenergic alpha-Antagonists↗