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Biomedical subjects

Michele Di Stefano

Publications and source records attributed to Michele Di Stefano.

13 recordsLinked to original sources

The effect of oral alpha-galactosidase on intestinal gas production and gas-related symptoms.

Bloating, abdominal distention, and flatulence represent very frequent complaints in functional disorders but their pathophysiology and treatment are largely unknown. Patients frequently associate these symptoms with excessive intestinal gas and the reduction of gas production may represent an effective strategy. The aim was to evaluate the effect of alpha-galactosidase administration, in a randomized double-blind placebo-controlled protocol, on intestinal gas production and gas-related symptoms after a challenge test meal in healthy volunteers. Eight healthy volunteers ingested 300 or 1200 GalU of alpha-galactosidase or placebo during a test meal containing 420 g of cooked beans. Breath hydrogen excretion and occurrence of bloating, abdominal pain, discomfort, flatulence, and diarrhea were measured for 8 hr. The administration of 1200 GalU of alpha-galactosidase induced a significant reduction of both breath hydrogen excretion and severity of flatulence. A reduction in severity was apparent for all considered symptoms, but both 300 and 1200 GalU induced a significant reduction in the total symptom score. Alpha-galactosidase reduced gas production following a meal rich in fermentable carbohydrates and may be helpful in patients with gas-related symptoms.

Adult↗

Role of colonic fermentation in the perception of colonic distention in irritable bowel syndrome and functional bloating.

BACKGROUND & AIMS: Bloating represents a frequent gastrointestinal symptom, but the pathophysiologic mechanism responsible for its onset is still largely unknown. Patients very frequently attribute the sensation of bloating to the presence of excessive bowel gas, but not all patients with gas-related symptoms exhibit increased intestinal production of gas. It is therefore possible that other still unrecognized mechanisms might contribute to its pathophysiology. Our aim was to evaluate whether a subgroup of patients affected by functional abdominal bloating presents hypersensitivity to colonic fermentation. METHODS: Sixty patients affected by functional gastrointestinal disorders (11 functional bloating, 36 constipation-predominant, and 13 diarrhea-predominant irritable bowel syndrome) and moderate to severe bloating took part in the study. Twenty sex- and age-matched healthy volunteers were enrolled as a control group. All the subjects underwent a preliminary evaluation of breath hydrogen excretion after oral lactulose. Then, on a separate day, an evaluation of sensitivity thresholds at rectal level was performed with a barostat before and after the induction of colonic fermentation with oral lactulose. A control test with electrolyte solution was also performed. RESULTS: Both breath hydrogen excretion and mouth-to-cecum transit time did not differ between the 4 groups studied. Neither electrolyte solution nor lactulose modified sensitivity thresholds in healthy volunteers. In low hydrogen producers, basal perception and discomfort thresholds were similar to high hydrogen producers, but after lactulose both perception and discomfort thresholds were significantly reduced only in low hydrogen producers. CONCLUSIONS: A subgroup of patients with functional gastrointestinal disorders and moderate to severe bloating might have hypersensitivity to products of colonic fermentation.

Adult↗

Characterization of GE82832, a peptide inhibitor of translocation interacting with bacterial 30S ribosomal subunits.

GE82832, a secondary metabolite produced by Streptosporangium cinnabarinum (strain GE82832), has been identified as a translational inhibitor by in vitro screening of a library of natural products. Secondary functional tests specific for individual steps of the translational pathway demonstrated that translocation is the specific target of GE82832. Chemical probing in situ demonstrated that this antibiotic protects bases A1324 and A1333 and exposes C1336 of 16S rRNA, thereby indicating that its binding site is located on the head of the 30S ribosomal subunit. The ribosomal location of GE82832, near ribosomal protein S13 and G1338, two elements of the small subunit that are part of or close to the B1a intrasubunit bridge, suggests that translocation inhibition results from an altered dynamics of 30S-50S ribosomal subunit interaction.

Actinomycetales↗

Treatment of functional bowel disorders: is there room for antibiotics?

Small bowel bacterial overgrowth is a syndrome associated with a broad range of predisposing conditions, characterized by the presence of pathological amounts or types of bacteria at the level of the small bowel, clinically evident with a spectrum of symptoms such as diarrhea, flatulence, abdominal pain and bloating. Some of these symptoms are very common complaints in patients suffering from functional bowel disorders (FBDs). Although the pathophysiological mechanisms responsible for FBDs are certainly multifactorial and not yet completely understood, several pieces of evidence suggest that an increased metabolic activity of intestinal bacteria is responsible for gas-related intestinal symptoms in a large subgroup of patients. In addition, byproducts of colonic fermentation might be able to trigger symptoms in those patients displaying visceral hypersensitivity. Targeting enteric bacteria with antibiotics therefore represents a logical approach to FBDs. Although systemic antimicrobials have been mostly used in the past, the availability of poorly absorbed antibiotics like rifaximin, being safe and effective, has represented a step forward in the treatment of this challenging clinical condition.

Anti-Bacterial Agents↗

Neostigmine-induced postprandial phasic contractility in the proximal stomach and dyspepsia-like symptoms in healthy volunteers.

BACKGROUND AND AIMS: In a subset of functional dyspepsia patients, we have recently described the association between unsuppressed postprandial phasic contractions of the proximal stomach and a specific symptom pattern. To better elucidate the role of phasic contractility of the proximal stomach in symptom generation, we aimed at inducing this motility pattern in healthy volunteers and we carefully monitored symptom onset. PATIENTS AND METHODS: Eleven healthy volunteers underwent gastric barostat on two separate days. Gastric tone and phasic contractility were evaluated for a 90-minute period. In particular, after 30 min of basal recording, a caloric liquid meal and neostigmine 0.5 mg IV or saline in a double-blind, randomized, crossover protocol were administered. During the measurement, severity of 9 dyspeptic symptoms was evaluated on a visual analog scale. Computer-aided baseline reconstruction allowed us to quantify phasic contractions as a motility index (MI), reflecting the area between signal and baseline normalized over time. Perception of contractions after placebo or neostigmine was evaluated. Moreover, we tested for influence of gastric tone and phasic contractility on symptoms. RESULTS: After neostigmine, gastric accommodation was not different than after placebo (225 +/- 36 vs 206 +/- 76 mL, P= NS). During the first 30-min postprandial period, the MI was significantly higher after neostigmine than after placebo (26.4 +/- 3 vs 21.4 +/- 3, P < 0.001), confirming the induction of unsuppressed postprandial phasic contractions. The postprandial total symptom score was significantly higher after neostigmine compared to saline; several individual postprandial symptom scores were also significantly higher after neostigmine-compared placebo. After neostigmine, a higher percentage of postprandial contractions was perceived compared to placebo. CONCLUSIONS: Unsuppressed postprandial phasic contractility of the proximal stomach is a mechanism potentially involved in the pathogenesis of dyspeptic symptoms.

Adult↗

Patients with headache and functional dyspepsia present meal-induced hypersensitivity of the stomach.

Headache is a frequent feature of functional gastrointestinal disorders but there is no data on the responsible pathophysiological mechanism. The aim of this study was to verify whether alteration of post-prandial gastric tone or sensitivity might explain this association. Fourteen patients affected by functional dyspepsia (7 migraine without aura) and 7 healthy volunteers (HV) underwent gastric tone measurement in fasting condition and after the administration of a liquid meal by barostat. Gastric volume (GV) and accommodation were calculated as difference between mean post-prandial and mean fasting volume. Mean postprandial GV increase and fasting perception and discomfort threshold (DTh) were similar among the 3 groups. DTh after meal was lower in dyspeptic headache patients than in HV and dyspeptic without headache patients. Patients with migraine and functional dyspepsia may be characterised by meal-induced hypersensitivity of the stomach.

Adult↗

Bones in coeliac disease: diagnosis and treatment.

Coeliac disease predisposes to metabolic osteopathy. The entity of bone loss is higher in patients with malabsorption at diagnosis but it is also present in asymptomatic or poorly symptomatic patients, occurring in roughly half of them. Calcium malabsorption and the release of proinflammatory cytokines, activating osteoclasts, represent the main mechanisms responsible for bone derangement. In coeliacs, the presence of an increased fracture risk was recently questioned and its importance on clinical grounds was reconsidered, in view of the fact that gluten-free diet generally improves bone mass and, consequently, reduces fracture risk. However, gluten-free diet rarely normalizes bone mass and the co-administration of mineral active drugs may be useful in a subgroup of coeliacs.

Bone Density↗

Treatment of small intestine bacterial overgrowth and related symptoms by rifaximin.

The treatment of small intestine bacterial overgrowth should address different aims: the removal of the predisposing condition, guarantee of adequate nutritional support to reintegrate both caloric and vitamin requirements and, obviously, suppression of the contaminating bacterial flora, which represents the major goal. The polymicrobic nature of contaminating flora suggests the administration of wide-spectrum antibiotics, but until now there has been no conclusive information on the most effective therapeutic approach. In this paper, the efficacy of the different therapeutic approaches used is reviewed.

Anti-Bacterial Agents↗

Fermentation of endogenous substrates is responsible for increased fasting breath hydrogen levels in celiac disease.

Fasting breath hydrogen (FBH) levels are frequently increased in celiac disease (CD). In this study we sought to determine whether the unknown source of the fermented substrates is endogenous glycoproteins shed or exuded through the damaged mucosa. To test the role of nonabsorbable exogenous substrates, we subjected 39 untreated and 23 treated CD patients and 37 healthy volunteers to the H(2) breath test after administration of lactulose after both an unrestricted and a restricted pretest meal. To test the relevance of endogenous substrates, we measured breath H(2) excretion during a 9-hour fast and after the administration of lactulose solution. To determine whether the luminal content of CD patients contains an increased amount of fermentable substrates, we incubated samples of jejunal juice from 7 untreated CD patients, 6 healthy volunteers, and 6 dyspeptic patients in vitro with a fecal homogenate obtained from a healthy H(2)-producer volunteer and measured the cumulative H(2) production. Untreated CD patients showed higher FBH levels than did treated patients and healthy volunteers. Only in untreated CD did FBH levels show no difference if a restricted or an unrestricted dinner was eaten the evening before the test. Nine-hour FBH levels were significantly higher in untreated CD than in healthy volunteers, whereas no difference was found after administration of lactulose. In vitro H(2) production was significantly higher in untreated CD patients than in controls. Increased FBH levels in CD do not depend on fermentation of malabsorbed exogenous substrates; endogenous substrates are increased in the lumens of CD patients and may be responsible for increased FBH levels.

Adult↗

Hydrogen breath test in the diagnosis of lactose malabsorption: accuracy of new versus conventional criteria.

Increased hydrogen excretion in the breath after carbohydrate ingestion, an expression of carbohydrate malabsorption, represents the pathophysiologic basis of the hydrogen breath test, a simple, noninvasive, reproducible test for the diagnosis of this condition. Few data are available concerning the breath hydrogen response that most accurately identifies carbohydrate malabsorption. In this article we report our application for the first time in clinical practice of 2 recently described, more accurate criteria for the diagnosis of lactose malabsorption (ie, breath hydrogen excretion value > 6 parts per million (ppm) 6 hours after carbohydrate load and a sum greater than 15 ppm for the breath hydrogen values obtained 5, 6, and 7 hours after carbohydrate load). On 3 separate days, we subjected 84 consecutive patients with functional or organic gastrointestinal disease to measurement of hydrogen excretion in the breath after the administration of lactose to test for lactose malabsorption; after the administration of lactulose as a means of ruling out false-negative results resulting from hydrogen-nonproducer status; and after the administration of a nonabsorbable electrolyte solution as a means of ruling out false-positive results caused by the mixing of intestinal content and release of preformed hydrogen trapped in the feces. According to the conventional criterion, 51% of the subjects proved to be lactose malabsorbers. Positive results were obtained with the use of the 6th-hour criterion in 76% of patients, and positive results were found in 80% when the sum of the excretion at hours 5, 6, and 7 was used as the criterion (P < .05 for both comparisons). Ten of 21 and 11 of 25, respectively, showed intolerance symptoms. It was therefore possible for us to diagnose lactose malabsorption in 24% and 27% of patients, respectively, who tested negative according to the conventional criterion. The conventional criterion must be abandoned and these new criteria adopted.

Adult↗

Mixing of the intestinal content and variations of fermentation capacity do not affect the results of hydrogen breath test.

OBJECTIVE: Although the hydrogen (H(2)) breath test has been in use for many years for diagnosis of sugar malabsorption, research is still underway to improve its diagnostic accuracy. In this study, we investigated whether possible confusing factors caused by the ingestion of the test solution itself (such as the delivery to the colon of other fermentable substrates pre-existing in the small bowel lumen, the release of preformed H(2) trapped in the feces, or differences in the fermenting capacity of the colonic bacteria) may interfere with the increase of breath H(2) concentration, an expression of malabsorption of the test substrate. METHODS: In 25 patients with untreated celiac disease and 23 sex- and age-matched healthy volunteers, breath H(2) excretion was measured after ingestion of a 250-ml solution containing sorbitol, a poorly absorbed alcohol sugar. On 2 other separate days, 12 randomly selected subjects in each group underwent breath H(2) excretion measurement after ingestion of 250 ml of a sugar free, nonabsorbable electrolyte solution and 250 ml of a solution containing lactulose, a nonabsorbable disaccharide. RESULTS: After sorbitol ingestion, celiac disease patients showed a significantly higher breath H(2) excretion than did healthy volunteers. Otherwise, breath H(2) responses to electrolyte solution and lactulose showed no difference between the two groups of subjects. CONCLUSIONS: In a group of patients with sugar malabsorption, increased breath H(2) excretion does reflect malabsorption. The washout or the mixing of the intestinal content or intergroup difference of fermenting activity of the colonic bacteria do not represent interfering factors and do not modify the accuracy of the H(2) breath test in day-to-day clinical practice.

Adult↗

Lactose malabsorption and intolerance and peak bone mass.

BACKGROUND & AIMS: Lactose malabsorption per se is not associated with alterations of bone mineral density (BMD) or calcium intake, but when intolerance symptoms are present a lower calcium intake and reduction of BMD values are evident. The purpose of this study was to evaluate whether lactose intolerance interferes with the achievement of an adequate peak bone mass in young adults. METHODS: Of 103 enrolled healthy subjects, 55 proved to be lactose malabsorbers with H(2) breath test after lactose administration, and 29 of them experienced intolerance symptoms (diarrhea, abdominal pain, bloating, flatulence). Lumbar and femoral BMD by dual-energy X-ray absorptiometry was measured, and calcium intake and biochemical indices of bone and mineral metabolism were evaluated. RESULTS: Lumbar and femoral BMD, calcium intake, and mineral metabolism did not differ between malabsorbers and absorbers, although among malabsorbers, intolerant subjects showed significant alterations of all these parameters in comparison with tolerant subjects. A strict correlation was evident between BMD values and both severity of symptoms and calcium intake and between calcium intake and severity of symptoms. CONCLUSIONS: Lactose intolerance prevents the achievement of an adequate peak bone mass and may, therefore, predispose to severe osteoporosis.

Absorptiometry, Photon↗