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Biomedical subjects

M Moretti

Publications and source records attributed to M Moretti.

At least 19 recordsLinked to original sources

A functional alpha-bungarotoxin receptor is present in chick cerebellum: purification and characterization.

It has recently been demonstrated that alpha-bungarotoxin receptors, which behave as functional nicotinic receptors, are present in chick CNS. In this paper, we report the purification and characterization of a functional alpha-bungarotoxin receptor from chick cerebellum, a nervous tissue in which a clear inhibition of induced nicotine effects has been reported in vivo. This receptor contains at least three subunits of apparent mol. wt 52,000, 57,000 and 67,000. The use of monoclonal antibodies specific for the alpha 7 subunit demonstrated that 75% of the molecules present in our purified preparation belong to the alpha 7 subtype and that this antibody labels the 57,000 band in western blot, thus indicating that this is the toxin binding subunit. Reconstruction experiments in planar lipid bilayers show that this alpha-bungarotoxin receptor forms a cation selective channel whose opening is blocked by d-tubocurarine. Binding experiments on immobilized receptors over an alpha-bungarotoxin-Sepharose affinity column show that the ligand binding subunit is present in vivo in two copies per receptor. Immunological, pharmacological and functional experiments show that this purified receptor is very similar, but not identical, to the previously characterized chick optic lobe receptor, thus indicating the heterogeneity of these alpha-bungarotoxin receptors in the CNS.

Animals

Umbilical artery and uteroplacental velocimetry in pregnancies complicated by idiopathic low birthweight centile.

Umbilical artery and uteroplacental Doppler flow velocity waveforms were studied in 35 pregnancies complicated by idiopathic low birthweight centile. Thirty fetuses (86%) were below the 5th centile birthweight for gestation. Fifteen (43%) had an abnormal umbilical artery systolic to diastolic ratio. Uteroplacental waveforms were recorded in 29 of the 35 pregnancies and five (17%) showed an abnormal systolic to diastolic ratio. Abnormal uteroplacental systolic to diastolic ratios were associated with a significantly earlier gestational age at delivery and significantly more cesarean sections for fetal distress compared with normal uteroplacental systolic to diastolic ratios (p less than or equal to 0.01). The absence of umbilical artery end-diastolic frequencies was associated with a significantly earlier gestational age at delivery compared with the presence of umbilical artery end-diastolic frequencies (p less than 0.005). No differences in pregnancy outcome were observed comparing normal with abnormal amniotic fluid volume assessment. These findings suggest that Doppler studies may be useful in estimating the risk of adverse perinatal outcome for small for gestational age fetuses with no identifiable cause.

Blood Flow Velocity

Influence of acid-secretion blockers on gastric and hepatic alcohol dehydrogenase in rat.

The effects of Cimetidine, Ranitidine, and Omeprazole on gastric and hepatic alcohol-dehydrogenase (ADH) activity was studied in rat. Two apparent values for Km were found for gastric ADH (220 mmol l-1 and 1043 mmol l-1 respectively) and one for hepatic ADH (0.54 mmol l-1). Cimetidine was shown to exert an uncompetitive inhibition of low Km gastric ADH with a Ki of 0.167 mmol l-1 and a competitive inhibition of high Km gastric ADH with a Ki 2.3 mmol l-1. Ranitidine was found to present non-competitive inhibition only on low Km gastric ADH with a Ki of 12 mmol l-1. Omeprazole affects only low Km gastric ADH with a Ki of 5.6 mmol l-1 and presents a linear-mixed type of inhibition. Hepatic ADH was shown to be competitively inhibited only by Cimetidine with a Ki of 6.0 mmol l-1 whereas no inhibition for either Ranitidine and Omeprazole was observed. These results confirm the inhibitory action of Cimetidine on both gastric and hepatic ADH; Ranitidine and Omeprazole show minor effects on ADHS activity and probably on first-pass metabolism.

Alcohol Dehydrogenase

Purification and characterization of an alpha-bungarotoxin receptor that forms a functional nicotinic channel.

Neither the structure nor the function of alpha-bungarotoxin (alpha Bgtx) binding molecules in the nervous system have yet been completely defined, although it is known that some of these molecules are related to cation channels and some are not. Using an improved method of affinity chromatography, we have isolated a toxin binding molecule from chicken optic lobe that contains at least three subunits with apparent Mr values of 52,000, 57,000, and 67,000. The Mr 57,000 subunit binds alpha Bgtx and seems to be present in two copies per receptor. The receptor is recognized by antibodies raised against the alpha Bgtx receptors of human neuroblastoma cells, fetal calf muscle, and chicken optic lobe but not by antibodies raised against Torpedo acetylcholine receptor, the serum of myasthenic patients, or monoclonal antibody, 35. 125I-labeled alpha Bgtx binding to the isolated receptor is blocked, with the same potency, by nicotinic agonists and antagonists, such as nicotine, neuronal bungarotoxin and, d-tubocurarine. When reconstituted in a planar lipid bilayer, the purified alpha Bgtx receptor forms cationic channels with a conductance of 50 pS. These channels are activated in a dose-dependent manner by carbamylcholine and blocked by d-tubocurarine.

Animals

Determinants of perinatal outcome in pregnancy-induced hypertension with absence of umbilical artery end-diastolic frequencies.

Forty-three pregnancies that were complicated by pregnancy-induced hypertension and either absence of umbilical artery end-diastolic frequencies (n = 32) or reversal of umbilical artery end-diastolic frequencies (n = 11) were reviewed. The incidence of perinatal mortality and morbidity was similar for the two Doppler patterns. Perinatal survival was highly dependent on the gestational age when hypertension first appeared. Presentation at greater than or equal to 30 weeks' gestation was associated with a perinatal survival rate of 86%. Presentation at less than 30 weeks' gestation was associated with a perinatal survival rate of 38% (p less than 0.005). Pregnancy-induced hypertension that presented before 30 weeks was more often associated with a 5-minute Apgar score less than 7 (p less than 0.005) and a nonreactive nonstress test (p less than 0.05) compared with pregnancy-induced hypertension that presented at or beyond 30 weeks. For pregnancies that presented before 30 weeks, the only difference between perinatal survivors (n = 11) and perinatal deaths (n = 18) was a higher incidence of birth weight at or below the 10th percentile among deaths (p = 0.02).

Diastole

Patterns of dyspepsia in patients with no clinical evidence of organic diseases.

We studied 2000 dyspeptic patients with no obvious signs of organic disease at their first examination, in order to (1) verify how many diagnoses of idiopathic dyspepsia had really been made after exhaustive diagnostic procedures and (2) evaluate the diagnostic power of the symptoms in distinguishing organic from idiopathic dyspepsia. This latter was considered only when no structural abnormalities were found. In all the other cases, a distinction was made between "related" and "associated" organic dyspepsia according to whether or not there was a certain relationship between the abnormalities and the dyspeptic symptoms. The patients were referred to us as follows: (1) spontaneously, (2) sent by physicians collaborating with us, (3) referred to our open access endoscopic service. The results show the frequency of idiopathic dyspepsia was 26%, whereas associated structural abnormalities were present in 45.4%. Obvious organic causes of dyspepsia were seen in 28.6% (24% benign and 4.6% malignant diseases). When considered separately, no symptom alone allows a correct diagnosis. The simultaneous evaluation of the symptoms with linear discriminant analysis distinguishes between idiopathic and organic dyspeptic patients in about 70% of the cases. A higher discrimination percentage in about 70% of the cases. A higher discrimination percentage could probably be obtained using a wider range of clinical parameters and/or a more complex statistical analysis of the interrelationships which exist between the clinical symptoms and the final diagnosis.

Adolescent

Antimony and glass pH electrodes can be used interchangeably in 24-hour studies of gastric acidity.

Antimony and glass pH electrodes show almost identical experimental errors in continuously measuring buffer solutions at constant temperature over 24 hr. These errors are lower than the nominal quantization error of the instruments and are not properly described by the 24-hr drift determination. The addition of food particles to the solutions can induce severe reading artifacts. The longer response time reported in vitro of antimony electrodes when moving from pH 1 to pH 7 (3.4 sec vs 0.8 sec with glass electrodes) is irrelevant during in vivo pH-metry studies, because we found that the greatest absolute difference between raw fast acquired (4-6 sec) consecutive pH readings of two commonly used devices was 0.7 pH units in circadian profiles obtained from 413 subjects with various clinical conditions. In our in vivo studies, gastric acidity was monitored continuously with two side-by-side minielectrodes, which were variously combined (antimony-glass, A-G; antimony-antimony A1-A2; glass-glass, G1-G2) and applied on groups of 27 subjects matched for clinical condition. The 24-hr pH means and the 24-hr [H+] means calculated from the acidity profiles obtained with the three electrode combinations, lie on the identity line in each group. Using the Bland-Altman technique for assessing measurement agreement, the differences between the 24-hr pH means and the 24-hr [H+] means obtained with the three combined systems are similar (P = .903 and P = 0.824, respectively) and their 95% confidence limits are comprised within the range (+/-) of the reading error of the measuring systems (namely, +/- 0.3 pH units and +/- 12 mmol/liter in terms of [H+]).(ABSTRACT TRUNCATED AT 250 WORDS)

Antimony

Effects of erdosteine on sputum biochemical and rheologic properties: pharmacokinetics in chronic obstructive lung disease.

Erdosteine is a new thioderivative endowed with mucokinetic, mucolytic, and free-radical-scavenging properties. This study evaluated (in a double-blind design vs. placebo) its efficacy on biochemical and rheologic properties of sputum and on some indices of respiratory function in chronic patients with chronic bronchitis (10 per group), while receiving basic treatment with a controlled-release theophylline preparation. The pharmacokinetics of erdosteine and theophylline were also studied. We found that a 2 week treatment with erdosteine (300 mg 3 times daily) was able to reduce significantly (p less than 0.05) the sputum apparent viscosity, fucose content, and macromolecular dry weight (MDW) with no statistically significant influence on sputum elasticity, DNA, albumin, total proteins, total IgA, lactoferrin, and lysozyme content. The treatment caused a significant increase in the following ratios: total IgA/albumin, lactoferrin/albumin, and lysozyme/albumin. The pharmacokinetics of erdosteine, its metabolites, and theophylline were the same after 1 or 14 days of treatment, evidence both of absence of an enzymatic induction and of an accumulation process. Further confirmation that there was no interference between erdosteine and theophylline was obtained from the data available on the group of patients receiving only theophylline, since its plasma levels and related pharmacokinetic parameters were identical to those obtained in patients receiving both drugs. In conclusion, 2 weeks of therapy with erdosteine reduced the marker of mucus glycoproteins (fucose) in patients with chronic bronchitis but did not interfere with the pharmacokinetics of xanthine derivatives. We also suggest that the significant increment in the IgA/albumin ratio might be related to a sum of other local effects such as reduction of the inflammatory process and enhancement of the humoral defense mechanism.

Bronchitis

A protocol for managing severe preeclampsia in the second trimester.

One hundred nine patients with severe preeclampsia in the second trimester were studied. Pregnancy termination was recommended for those with gestational age less than or equal to 24 weeks (n = 25), whereas expectant management with aggressive maternal and fetal monitoring was recommended for those with gestational age greater than 24 but less than or equal to 27 weeks (n = 84). Ten of the 25 women in the early pregnancy group accepted termination and 15 elected to continue the pregnancy. The overall perinatal survival in the latter 15 patients was 6.7%, and maternal complications developed in six patients. Thirty of the 84 patients in the late second-trimester group had immediate delivery, and 54 had expectant management. The average length of pregnancy prolongation in the expectant group was 13.2 days (range, 4 to 28 days). Compared with the immediate delivery group, the expectant management group had significantly higher perinatal survival (76.4% versus 35%), significantly higher birth weights (880 versus 709 gm), and a lower incidence of neonatal complications. There were no differences between the two groups with regard to maternal complications. Expectant management with aggressive monitoring of maternal and fetal status at a perinatal center improves perinatal outcome in patients with severe preeclampsia with gestational age greater than 24 but less than or equal to 27 weeks.

Clinical Protocols

The effect of mode of delivery on the perinatal outcome in fetuses with abdominal wall defects.

A descriptive study of 125 infants with abdominal wall defects was undertaken to determine the effect of mode of delivery on outcome. Fifty-six infants had gastroschisis and 69 had omphalocele. Overall, there were no differences between the omphalocele and the gastroschisis groups in either cesarean section rate (22% vs 26%) or prematurity rate (26% vs 30%). However, the omphalocele group had a significantly higher infant death rate (22% vs 7%, p less than 0.001), a significantly higher incidence of associated major congenital anomalies (29% vs 5%, p less than 0.001), and a higher incidence of long-term infant morbidity (14.5% vs 8.9%). Within either group there was no significant difference between vaginal and cesarean delivery regarding either infant mortality, acute or long-term infant outcome, or frequency of associated major anomalies. We conclude that vaginal delivery of infants with abdominal wall defects does not adversely affect infant outcome.

Abdominal Muscles

Non-A, non-B hepatitis and anti-HCV antibodies in dialysis patients.

To define the prevalence of non-A, non-B hepatitis, antibodies to HCV were detected in 193 patients on renal replacement therapy (52 transplant and 141 hemodialysis patients) and in 50 staff members of a Nephrology Department. Unequivocal seroconversion was documented in 5 transplant (9.6%) and in 26 dialysis patients (18.4%). In the dialysis population, the prevalence of anti-HCV antibodies was evaluated in patients grouped according to the number of blood transfusions and to the different sections of dialytic treatment. The most striking findings were the marked differences in the prevalence of anti-HCV antibodies among patients treated in different sections (from 0% to 70%), and the presence of a significant increase in alanine-amino-transferase (ALT) concentrations in 14 anti-HCV negative patients. The results suggest that the diffusion of non-A, non-B hepatitis is mainly transfusion-related, with the possibility of significant environmental diffusion related to the violation of infection-control measures. The current immunoassay is probably unable to detect the actual frequency of the infection.

Adult