Search PubMed⌕ Search

Biomedical subjects

C Betti

Publications and source records attributed to C Betti.

At least 19 recordsLinked to original sources

Evaluation of DNA damage in leukocytes of ex-smokers by single cell gel electrophoresis.

Single cell gel electrophoresis (SCGE), or comet assay, appears to be a promising tool to estimate DNA damage at the single cell level and it provides information on the presence of damage among individual cells. A follow-up study of 90 smokers who ceased smoking was undertaken to determine the possible decrease of DNA damage in their leukocytes. Before beginning the trial, volunteers smoked on average 26.1 +/- 8.4 cigarettes/day. Comet length did not correlate with the number of cigarettes/day or with the condensate tar content. At the end of the study, 28 volunteers had abandoned the trial, 40 volunteers relapsed into smoking at different times, but with a reduced number of cigarettes/day, whereas 22 fully succeeded in smoking cessation. Throughout the 5 sampling times, a great variability of comet length at individual level was found. However, after 1 year of follow-up, comet length means were found to be significantly shorter (p < 0.0001) in those volunteers who completely quit smoking compared to those who relapsed into smoking (27.2 +/- 1.6 vs. 31.9 +/- 5.1 microns, respectively), irrespective of the amount of cigarettes previously smoked. No effect of age or sex was found. Six months later, these results were confirmed by a further study carried out on a reduced sample of volunteers. The present data strongly suggest that, in spite of the great variability observed, 1 year of smoking cessation is associated with a significant reduction of DNA damage in circulating leukocytes.

Adult↗

Comparative studies by comet test and SCE analysis in human lymphocytes from 200 healthy subjects.

The comet test (single cell gel electrophoresis, SCGE) appears to be a promising tool to estimate DNA damage at the single cell level and it provides information on the presence of damage among individual cells. Previously, we analyzed the degree of DNA damage in peripheral human lymphocytes from 100 healthy subjects living in Pisa (Italy) taking into account age, gender and smoking habit, and we also reported some results aiming at the assessment of the comet test (Betti el al., 1994). In addition, SCE analysis was carried out in order to compare the two endpoints. Because of the interesting results obtained, the present study was extended to 200 individuals, and data analyzed included information concerning number of cigarettes smoked a day, tar/cigarette and job. Data obtained confirmed that the SCGE is more sensitive than SCE in revealing smoking habit effects but comet induction did not seem to be related to the amount of cigarette tar inhaled. Moreover, sampling time was found to play a greater role in the comet assay as compared to SCE. Job position did not significantly influence SCE mean/subject or comet length mean/subject.

Adolescent↗

Upper gastrointestinal motor abnormalities in children with active celiac disease.

Although from the clinical point of view a GI motor disorder can be suspected in celiac disease, objective evidence for this is still lacking. We therefore conducted a study on children with active celiac disease to detect possible GI motor abnormalities in this disease. Fourteen children (age range, 1-13 years) were studied; they underwent fasting and fed manometric recordings in the gastroduodenojejunal area. Four patients were restudied after a 6-month gluten-free diet. Data were compared with those obtained in eight control children. As compared with controls, celiac disease patients showed a shorter duration of activity fronts (p < 0.01) and a significant (p < 0.01) reduction of the postprandial antral motility index; furthermore, > 90% of the patients displayed marked fasting and/or fed motor abnormalities, suggesting a neuropathic disorder. Interestingly, gut dysmotilities disappeared in the four subjects reassessed after the gluten-free diet. It is concluded that celiac disease frequently affects the motor behavior of the gut and that its effects may be reversed by appropriate diet.

Adolescent↗

Microgel electrophoresis assay (comet test) and SCE analysis in human lymphocytes from 100 normal subjects.

Microscopic examination of individual human lymphocytes embedded in agarose, subjected to electrophoresis and stained with a fluorescent DNA-binding dye, provides a novel way of measuring DNA damage as extent of migration of DNA fragments, mainly single-strand breaks. With this relatively simple method, DNA damage arising as a consequence of smoking, age and other factors was examined in peripheral human lymphocytes from 100 healthy individuals living in Pisa (Italy). The extent of DNA migration was found to be significantly increased by smoking. It is noteworthy that the effect of smoking was more significant in men than in women and that DNA migration was similar in the young and in the older people. SCE analysis did not reveal any significant effect of smoking, sex or age in the same population, suggesting a higher responsiveness of the comet test to DNA-damaging agents.

Adolescent↗

Anorectal manometric abnormalities and colonic propulsive impairment in patients with severe chronic idiopathic constipation.

Idiopathic chronic constipation is a frequent and disabling symptom, but its pathophysiological grounds are still poorly understood. In particular, there is little knowledge about the relationships between distal (anorectal area) and proximal (colonic area) motor abnormalities in this condition, especially concerning high-amplitude propagated colonic activity. For this purpose, we studied 25 patients complaining of severe idiopathic constipation and categorized them as normal- or slow-transit constipation according to colonic transit time. Twenty-five age-matched controls were also studied. Investigations included standard anorectal motility testing and prolonged (24-hr) colonic motility studies. Analysis of results showed that both groups of constipated patients displayed significantly different (P < 0.05) minimum relaxation volumes of the internal anal sphincter, defecatory sensation thresholds, and maximum rectal tolerable volumes with respect to controls. Patients with normal-transit constipation also showed lower internal anal sphincter pressure with respect to slow-transit constipation and controls (P < 0.001 and P < 0.02, respectively). The daily number of high-amplitude propagated contractions (mass movements) as well as their amplitude and duration, was significantly reduced in both subgroups of constipated patients (P < 0.02 vs controls). We conclude that (1) in normal-transit constipation, motor abnormalities are not limited to the anorectal area; (2) patients with slow-transit constipation probably have a severe neuropathic rectal defect; (3) prolonged colonic motility studies may highlight further the functional abnormalities in constipated subjects; and (4) an approach taking into account proximal and distal colon motor abnormalities might be useful to understand pathophysiological grounds of chronic constipation and lead to better therapeutic approaches.

Adolescent↗

Abnormal gastrointestinal motility in patients with celiac sprue.

No study to date has objectively investigated whether the motor behavior of the small bowel is abnormal in celiac sprue. The purpose of this study was to systematically address this topic by means of intraluminal pressure recordings in a series of such patients. Sixteen subjects (nine adults, seven children, age range 2-69 years) with celiac sprue were recruited and studied while untreated. Manometric examination was carried out for 6 hr during fasting and 3 hr after a meal. Adult celiac patients displayed a significantly (mean +/- SEM) greater frequency of migrating motor complexes in comparison to controls during fasting (4.44 +/- 1.6 vs 2.45 +/- 0.20, P < 0.01), whereas no differences were found in the pediatric group with respect to this variable. Fasting motor abnormalities, chiefly represented by discrete clustered contractions, giant jejunal contractions, and bursts of nonpropagated contractions, were discovered in a high percentage in both groups of celiac subjects (89% in adults and 44% in children, respectively). Similar abnormalities were observed in the postprandial period, especially in adults. In conclusion, patients with celiac sprue frequently display discrete gastrointestinal motor abnormalities, which though perhaps nonspecific may account for several symptoms complained of by such patients.

Adult↗

Micronucleus test and metaphase analyses in mice exposed to known and suspected spindle poisons.

Micronucleus (Mn) and metaphase chromosome analyses were performed in mouse bone marrow cells with two known and eight suspected mitotic spindle poisons. Polychromatic (PCEs) and normochromatic (NCEs) erythrocytes were scored for presence of Mn, while structural (CAs) and numerical chromosome aberrations (NCAs), i.e. hyperploid cells, were evaluated by metaphase analysis. CAs were scored in first, and NCAs in the second metaphases, identified by BrdUrd differential staining. Hydroquinone induced Mn, NCAs and CAs; colchicine, vinblastine and, to a lesser extent, chloral hydrate, diazepam and econazole induced both Mn and NCAs; cadmium chloride and thimerosal induced Mn and CAs, while pyrimethamine and thiabendazole induced Mn only. The proposed stepwise protocol allowed satisfactory statistical evaluation of the effects induced with a reduction in the number of animals killed. An acceptable agreement was found between induction of Mn and NCAs, suggesting a possible use of the Mn test for revealing compounds with aneugenic properties.

Animals↗

Effect of erythromycin administration on upper gastrointestinal motility in scleroderma patients.

BACKGROUND: Gastrointestinal involvement is frequent in patients with scleroderma. Erythromycin, a macrolide antibiotic, has been shown to accelerate gastric emptying in normal subjects and diabetic patients. The present study investigated the effects of acute erythromycin administration on gastric and gallbladder motility in patients with scleroderma and gastrointestinal involvement. METHODS: Twelve scleroderma patients and 14 healthy subjects were investigated. Each subject was investigated on 4 different days. Gastric and gallbladder emptying and gastric motility were determined by sonography and manometry, and the effect of 2 mg/kg/h erythromycin in fasted patients or after semisolid meal evaluated. RESULTS: The half-time of gastric emptying in response to semisolid meal was 121.3 +/- 14.0 min (SE) in scleroderma patients and 45.7 +/- 10.4 min in healthy subjects (P < 0.01). The peak of gallbladder emptying occurred later in scleroderma patients (95.0 +/- 5.0 min) than in healthy subjects (45.0 +/- 8.0 min) (P < 0.01). Erythromycin stimulated gastric and gallbladder motility in fasted subjects, as shown by manometry and sonography, and accelerated gastric and gallbladder emptying when administered immediately before the meal (P < 0.01). CONCLUSIONS: Erythromycin accelerates gastric and gallbladder emptying in scleroderma patients and might be helpful in the treatment of gastrointestinal motor abnormalities in these patients.

Adult↗

Comparative studies on cytotoxic and genotoxic effects of two organic mercury compounds in lymphocytes and gastric mucosa cells of Sprague-Dawley rats.

Human lymphocytes (HL) as well as lymphocytes (RL), hepatocytes (RH), and gastric mucosa cells (GM) of Sprague-Dawley rats were treated in vitro for 1 h with methylmercury chloride (MMC, 0.5-4 micrograms/ml) and dimethylmercury (DMM, 5-40 micrograms/ml). The cytotoxicity of the two organic mercury compounds was assessed by dye exclusion, and the extent of induced DNA fragmentation was measured with a single-cell microgel electrophoresis assay. Both MMC and DMM induced DNA damage and cytotoxicity in a dose-related manner in HL, RL, and GM. MMC was more effective in causing a significant increase in median DNA migration than DMM at doses yielding approximately the same degree of cytotoxicity. In rat hepatocytes the MMC-induced DNA damage was, however, lower than in the other cells. An analysis of repair kinetics following exposure to 2 micrograms/ml MMC was carried out in human lymphocytes obtained from an adult male donor. The bulk of DNA repair occurred 90 min after in vitro exposure, and it was about complete by 120 min following cessation of exposure. Finally, in order to have a basis for extrapolating to the human situation, in vivo studies were performed with Sprague-Dawley rats, also assessing the DNA damage and cytotoxicity in the lymphocytes and gastric mucosa cells. These in vivo results after oral exposure may be directly compared to the in vitro data obtained in the same cells.

Adult↗

Impaired colonic motor response to cholinergic stimulation in patients with severe chronic idiopathic (slow transit type) constipation.

Chronic idiopathic constipation, especially the slow transit type, is a troubling problem often afflicting young women. The pathophysiological basis for this entity is unknown, although a defective cholinergic innervation has been postulated. We tested the hypothesis that cholinergic colonic innervation is deranged in this condition by studying colonic motor activity after strong cholinergic stimulation with edrophonium chloride in 14 women complaining of slow transit constipation. Unlike healthy subjects, constipated patients showed minimal or no response to edrophonium injection. It is concluded that in slow transit constipation there is an important alteration of colonic cholinergic activity and that edrophonium chloride may represent a useful test drug for colonic pathophysiological investigations.

Adult↗

Liquid holding effects on methylmercury genotoxicity in human lymphocytes.

Methylmercury chloride (MMC) treatment of resting (G0) human lymphocytes resulted in the formation of chromosome and chromatid aberrations. This treatment also induced aneuploidy in second metaphases, suggesting that MMC produces stable damage involved in chromosome segregation errors. The storage of treated cells (liquid holding for 48 h before cell proliferation) did not result in an important recovery from induced cell toxicity or chromosome damage. Therefore, MMC seems to be an X-ray-like agent, able to produce long-lasting damages giving rise to both structural and numerical chromosome abnormalities.

Aneuploidy↗

Genotoxic activity of methyl mercury chloride and dimethyl mercury in human lymphocytes.

The genotoxicity of methyl mercury chloride (MMC, 0-25 x 10(-6) M) and dimethyl mercury (DMM, 0-434 x 10(-6) M) was evaluated by chromosome metaphase analysis in human lymphocytes treated in vitro for 24 h. Structural (CA) and numerical (AN) chromosomal aberrations were scored for the assessment of induced genotoxic effects, while the variation in mitotic index (MI) was considered a monitor for induced cellular toxicity. MMC induced CA and AN in a dose-related manner at doses exceeding 0.6 x 10(-6) M, and the proportion of cells with CA was constantly and significantly higher than that of cells with AN. DMM was able to induce both effects as well, although to a lesser extent than MMC, CA and AN being induced at doses exceeding 43.4 x 10(-6) M and 1.73 x 10(-6) M, respectively. MMC was 6-fold more effective in inducing CA than DMM at equivalent toxic doses. On the other hand, no significant difference was observed between the two compounds in inducing AN. Therefore MMC was much more clastogenic than DMM, whereas mitotic spindle disturbances appeared to be almost equally induced by both compounds.

Adult↗

Impaired colonic motor response to eating in patients with slow-transit constipation.

Because little is known about the pathophysiological mechanisms responsible for chronic idiopathic constipation, we studied colon motor response to eating, one of the most physiological and reproducible stimuli, in a clinically homogeneous group of severely constipated subjects. Fifteen patients (14 women, one man) with slow transit constipation (average duration of symptoms 18 +/- 2 yr) entered the study. After colonoscopic positioning of a manometric probe, 2-h basal and 3-h postprandial (1000 kcal standard mixed meal) recordings were obtained. Comparison of tracings with those of 29 healthy volunteers showed that motor response to eating was decreased in constipated subjects. Patients' response was characterized by a shorter duration of contractile activity in all three colon segments studied, after ingestion of the meal, and significantly less high-amplitude propagated contractions (7% vs. 45%). We conclude that several mechanisms are involved in the pathophysiology of colon contractile motor function of patients with chronic idiopathic constipation.

Adult↗

Extensive investigation on colonic motility with pharmacological testing is useful for selecting surgical options in patients with inertia colica.

Three women with idiopathic severe chronic constipation and inertia colica, who failed to respond to medical treatment, were extensively investigated for gut motor function, especially that of the colon. Twenty-four-hour manometric recordings disclosed that motility was severely reduced throughout the entire colon and response to eating was minimal. One of the patients also was tested for esophageal, gastric, and small bowel motor activity, which gave normal results. Edrophonium chloride stimulation (10 mg iv) provoked no increase in colonic contractile activity in any patient. On these grounds, the patients were submitted to surgical intervention (total colectomy with ileorectal anastomosis two, and left hemicolectomy the other) with fairly good results at follow-up. These results indicate the wisdom of carrying out extensive functional investigations in severely constipated patients before surgery is contemplated.

Colon↗

Effects of parenteral diclofenac sodium on upper gastrointestinal motility after food in man.

In experimental animal models nonsteroidal anti-inflammatory drugs may influence gastrointestinal motility, but as evidence is lacking in man. The effect of diclofenac sodium 75 mg i.m. on the motor response of the upper gastrointestinal tract to food has been studied by manometry in 9 healthy volunteers. Diclofenac had no effect on the motor activity of the stomach, duodenum, or jejunum after a 605 kcal meal.

Adult↗

Edrophonium chloride for testing colonic contractile activity in man.

The effects of cholinergic stimulation on the entire human colon are at present relatively unknown. For this reason, we evaluated the influence of a short-lived anticholinesterase agent, edrophonium chloride, on proximal and distal colonic contractile activity in man. Eight healthy volunteers of both sexes were studied with a multi-lumen manometric probe positioned with the aid of a colonoscope. Recordings were then obtained 30 minutes pre- and post-drug administration. Edrophonium chloride (10 mg intravenous) significantly stimulated both proximal and distal colonic contractile activity, and the maximum increase was observed within 10 minutes following injection, although some differences were observed between colonic segments in response to the drug. No important side effects were complained of after edrophonium. Due to the potent stimulatory property on colonic smooth muscle, to its short duration of action, and to the paucity of side effects, it is concluded that edrophonium chloride may be useful as a stimulating substance during manometric investigations of the human colon.

Adult↗

Prolonged (24-hour) manometric recording of rectal contractile activity in patients with slow transient constipation.

A periodic motor activity, named the rectal motor complex, has been recently described in the healthy human rectum. We studied the rectal contractile activity for 24 h by a low compliance manometric system in a group of 10 women with slow transit constipation. Analysis of the 24-hour manometric recordings showed that these subjects: (1) had overall scarce rectal motility; (2) display few rectal motor complexes (average, 3.3 +/- 1.3/subject/24 h) which are irregularly distributed over time, and (3) respond weakly to ingestion of a standard meal (average duration of the motor response 19 +/- 6 min). The observations suggest that an underlying neuropathic process may be involved in the pathogenesis of the impaired rectal motility in patients with slow transit constipation.

Adult↗