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Biomedical subjects

M Frigerio

Publications and source records attributed to M Frigerio.

At least 55 records · Page 3Linked to original sources

Synthesis and pharmacological evaluation of enantiomerically pure 4-deoxy-4-fluoromuscarines.

Four isomers of [(4-fluoro-5-methyl-tetrahydrofuran-2-yl)methyl]trimethylammonium iodide (4-deoxy-4-fluoro-muscarines) were prepared in enantiomerically and diastereomerically pure form from (S)-(-)-methyl 4-methylphenyl sulfoxide, ethyl fluoroacetate, and allyl bromide. Their absolute configurations were assigned by 1H NMR analyses. The four optically pure compounds were tested in vitro on guinea pig and their muscarinic potency was evaluated at M3 (ileum and bladder) and M2 (heart) muscarinic receptor subtypes. Compound 1a, the most potent isomer of the series, was also tested in vivo on pithed rat and its muscarinic activity at the M1 receptor subtype was compared with that of muscarine. Moreover, affinity and relative efficacy were calculated in vitro for this compound at M2 (heart force and rate) and M3 (ileum and bladder) receptors in order to investigate muscarinic receptor heterogeneity. The 4-deoxy-4-fluoromuscarines display a similar trend of potency as the corresponding muscarines and compound 1a shows differences in the affinity constants among the studied tissues. Replacement of a hydroxyl group for a fluorine atom in the 4 position of muscarine produces 1 order of magnitude increase in affinity for cardiac M2 muscarinic receptors controlling rate, while the affinity at cardiac M2 muscarinic receptors controlling force is unchanged, opening the possibility of a further classification of cardiac muscarinic receptors.

Animals↗

Usefulness of color Doppler in the diagnosis of ventricular septal rupture after myocardial infarction.

Ten consecutive patients with ventricular septal rupture complicating acute myocardial infarction were studied by means of Doppler echocardiography (including two-dimensional, conventional and color Doppler techniques) and bedside right heart catheterization using a Swan-Ganz catheter. One patient died before an operation could be performed. Seven critically ill patients underwent emergency cardiac surgery without preoperative cardiac catheterization, while in two patients it was also possible to undertake coronary angiography before surgery. Two-dimensional echocardiography diagnosed post-infarction ventricular septal rupture in 6 out of 10 patients. Color Doppler revealed the presence and the location of septal rupture in all 10 patients. The color Doppler diagnosis was confirmed either by surgery or necropsy. The estimates of pulmonary artery pressure, obtained by color Doppler-guided continuous wave Doppler beam, were very close to those measured by simultaneous right heart catheterization. In 3 patients, patch leakage occurred 3 days, 15 days and 1 year after the operation. Two-dimensional echocardiography revealed the patch leakage in only one of 3 patients while its location was visualized by color Doppler in all 3 patients. In one patient the color Doppler diagnosis was confirmed at necropsy. In the remaining 2 patients, a small left-to-right shunt was demonstrated by radionuclide studies. Color Doppler echocardiography is a highly sensitive and rapid technique in the diagnosis of postinfarction ventricular septal rupture. In critically ill patients it offers relevant information and may obviate the need for any invasive preoperate investigation.

Aged↗

[Echocardiographic evaluation of mitral valve calcification].

Preoperative assessment of calcifications is important in order to choose the correct surgical approach for mitral valve disease. To test the accuracy of echocardiography (ECHO) in the semiquantitative analysis of mitral valve (MV) calcifications we preoperatively echo-studied 66 patients, who were to undergo MV replacement of rheumatic disease. Echocardiograms were performed using a standardized method, recorded on videotape and analyzed by two independent observers. Areas of calcification were identified as dense conglomerate echoes which were brighter than those of adjacent internal structures. After removal, the MVs were evaluated by means of inspection (I), direct radiography (X-ray) and quantitative calcium extraction--EDTA spectrophotometry--(QCa). In the three methods ECHO, I and X-ray, MV calcifications were graded as absent (group 1), mild (group 2) nodular (group 3) and diffuse (group 4). Using the chi square test, no significant differences were found between the three methods, or between ECHO and X-ray, or between ECHO and I, while I grading was slightly lower than X-ray grading (P less than 0.002). Using variance analysis, no significant differences were found in QCa in the three methods within group 1 and 4, whereas significant differences were present within group 2 (P less than 0.002) and group 3 (P less than 0.001), due to the lower sensitivity of I. On the base of the observed distribution of QCa in the removed MVs, the following QCa values: a) less than 20 mg, b) 20-80 mg, c) greater than 80 mg, were considered as the selection criteria for a) absent or mild, b) nodular and c) diffuse calcifications respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Activation of a ribosomal protein S6 kinase during the 4-dimethylaminoazobenzene-induced rat hepatocarcinogenesis.

During the induction of 4-dimethylaminoazobenzene (DAB) hepatocarcinogenesis there was a progressive increase in the activity of a kinase which specifically phosphorylated S6 ribosomal protein in vitro. Liver tumour tissue (hepatocellular carcinoma and cholangioma) showed maximal activation of this kinase and elevated levels of S6 phosphorylation. Control rats fed with the same diet containing no dye showed a gradual decline of this activity, with low or lacking phosphorylation at the end of the experimental regimen, suggesting close correlation between tumor cell growth and phosphorylation of this ribosomal protein, under these conditions.

Animals↗

Heat shock, protein synthesis and ribosomal protein S6 phosphorylation in vitro in Yoshida AH 130 ascites hepatoma cells.

An activated 40S ribosomal protein S6 kinase has been demonstrated previously in cytosolic extracts from proliferating as well as resting cells of a very undifferentiated rat ascites hepatoma cell line (Yoshida AH 130), grown in vivo (Cell Biol. Int. Rep., 1986, 10, 821-831). In the present report we present evidence of unmodified activity of this kinase and S6 phosphorylation in vitro in cells submitted to a physiological stress such as a sublethal temperature elevation (heat shock: 42 degrees C for 2 h). The heat treatment causes a progressive decline in the number of active ribosomes and of L-35S methionine incorporation into total protein, suggesting drastically decreased synthesis of cellular proteins under these conditions. Cells recovering from heat shock show the induced synthesis of a protein with an apparent Mr of 50 kDa. Spontaneous high expression of heat shock proteins (HSP 70, 89, 100), without heat shock, occurs in these tumor cells.

Animals↗

Protein synthesis, ribosomal protein S6 phosphorylation in vitro and the effects of amiloride: SDS gel electrophoresis studies in the Yoshida ascites tumor (AH 130) grown in vivo.

Cell-free cytosolic extracts from the Yoshida (AH 130) rat ascites hepatoma cell line, grown in vivo, showed high ribosomal protein S6 kinase activity in vitro, as measured by transfer of 32P to exogenous 40S rat liver ribosomal subunits, in both exponential growing and stationary phase cells. A significant decrease of protein synthesis (3H-leucine incorporation into total cell protein) was found to occur in cells reaching the stationary phase of growth, suggesting that S6 phosphorylation was not tightly coupled to the rate of the intraperitoneal cell growth and of protein synthesis in these tumor cells. When the cell-free cytosolic extracts were prepared from cells exposed to amiloride, at concentrations that inhibit the Na+/H+ exchange, a decrease of S6 kinase activity was observed only in exponential growing cells, suggesting the possibility of coupling of the Na+/H+ exchange with phosphorylation of intracellular proteins in these tumor cells. Actually, stationary phase cells showed unchanged S6 kinase activity under the same conditions, possibly due to the extremely low Na+/H+ exchange activity, previously demonstrated (Cell Biol. Int. Rep., 1985, 9, 1017-1025). The present experiments support the hypothesis that the regulation of protein synthesis is not tightly coupled to phosphorylation-dephosphorylation cycles, at least of ribosomal protein S6, in cells characterized by a rather uncontrolled growth such as the Yoshida (AH 130) rat ascites hepatoma. In this connection, an elevated degree of protein phosphorylation, such as that of the ribosomal protein S6, could be a general phenomenon of neoplastic transformation.

Amiloride↗

[In-hospital and long-term prognosis in acute myocardial infarction. Comparative longitudinal study of 2 patient groups].

The in-hospital mortality, the causes of death, the actuarial survival curves were compared in two subsequent groups of patients admitted to our CCU for acute myocardial infarction: the first (group A) includes 791 pts, admitted from september '67 to december '72, the second (group B) includes 542 pts admitted from january '78 to june '80. The in-hospital mortality was significantly reduced in group B (A: 186/791, 23.5%; B: 72/542, 13,3%, p less than 0.01). This could be due to a reduction of the number of deaths for cardiogenic shock (A: 71/791, 9%; B: 30/542, 5.6%; p less than 0.01) and to reduction in the mortality rate for pulmonary oedema (from 6% to 1.5%, p less than 0.01), although the frequency of pulmonary oedema was the same during the two periods (A: 205 pts, 26%; B/156 pts 29%). We did not observe any significant difference in the long-term prognosis (54 months: A 79.3%, B 71.5%). The actuarial survival curves overlapped after the 1st semester after discharge. The most frequent cause of death during follow-up was a new myocardial infarction. None in the group A and only 3% in the group B were referred to the surgeon for coronary artery bypass grafting. We conclude that, in spite of a significant reduction of the in-hospital mortality, possibly related to the evolution in diagnosis and management of the disease, the long-term survival was not improved in a non-surgically treated population with myocardial infarction.

Adult↗

Argentine hemorrhagic fever: early diagnosis by immunofluorescence.

A procedure that allows to ascertain a diagnosis of Argentine Hemorrhagic Fever (AHF) as early as 24-48 hours after onset of symptoms is described. An immunofluorescent (IF) test on round cells of urinary sediment was employed. The procedure was assayed on 31 patients with febrile syndrome during epidemic peaks of 1975-1976. It was positive in 19 and negative in 12 cases. The 19 positive cases were confirmed AHF by clinical follow up and serology. From 12 negative cases, 8 belonged to other etiologies and 2 were confirmed AHF. The usefulness of the procedure for early diagnosis is emphasized.

Antigens, Viral↗

[Lead poisoning in the newborn and infants: an epidemiological study in an area of Northern Italy].

OBJECTIVE: Lead crosses the placenta and can cause permanent neurological impairment by prenatal poisoning. Blood lead levels higher than 10 mcgr/dl in children age 1 to 2 years may be toxic. In 1991 the CDC (Centers for Disease Control and Prevention) published "Preventing Lead Poisoning in Young Children" with the new guidelines defining the value of 10 mcgr/dl as the security limit. Since no blood lead levels in childhood have been collected in Italy this study reports blood lead levels in newborns and 4 month old infants in the Piemonte Region. DESIGN: The study was carried out on a random sample of 55 mother-infant couples attending the Mauriziano Hospital in Turin. The cohort was divided into urban versus rural residence. In every subject attending the study lead, ALA-d and Zn-PP were measured on venous blood specimens in three different moments. RESULTS: Even though our study refers to a small population our data were reassuring. The mean lead values found in the cohort in the three different stages were all below 10 mcgr/dl. ALA-d and Zn-PP resulted also in normal ranges. No statistical difference emerged between urban and rural coming subjects. CONCLUSIONS: In consideration of the results obtained we cannot confirm the necessity of a general screening programme for lead poisoning in our population. We assert the utility of a selective screening on the basis of a questionnaire as already experimented in some states of the U.S.A.

Adult↗