Luca Santoro

Lactobacillus acidophilus protects tight junctions from aspirin damage in HT-29 cells

Background/Aims: Non-steroidal anti-inflammatory drugs cause enterocyte damage inducing an increase of intestinal permeability. Tight junctions are the key structures in the permeability of the intestinal mucosa. ZO-1 is a tight junction associated protein considered a good marker of their integrity. It has been suggested that probiotics could play a protective role in the intestinal barrier function. We determined, in vitro, whether the heat-killed Lactobacillus acidophilus strain LB (LaLB) with its spent culture supernatant protects tight junctions of HT-29 cells from aspirin (ASA) damage. Methods: HT-29 cells were treated with ASA alone or ASA and LaLB with its spent culture supernatant together. Morphological alterations of tight junctions were evaluated by immunofluorescence using an anti-ZO-1 antibody. Moreover, a semiquantitative assay for ZO-1 was performed by Western blot. Results: Immunofluorescence analysis showed a fragmented and granulous ZO-1 staining, after ASA treatment. Using both ASA and LaLB with its spent culture supernatant together, we found a fine continuous linear web at cell-cell contacts similarly to control. Western blot revealed that ASA inhibited ZO-1 expression and LaLB with its spent culture supernatant counteracted this effect. Conclusions: This pilot study shows, for the first time, the protective effect of LaLB with its spent culture supernatant on tight junctions from ASA damage. These results suggest that probiotics could play a role in the prevention of ASA-induced alterations of intestinal permeability.

Probiotic treatment increases salivary counts of lactobacilli: a double-blind, randomized, controlled study.

Background/Aims: Lactobacilli are used in the prevention and treatment of several diseases, but they are also known to play a role in the pathogenesis of dental caries. The aim of our study was to evaluate whether the oral administration of lactobacilli could change the salivary counts of these bacteria compared with placebo. Moreover, lactobacilli were administered in liquid and in capsule form to determine the role of direct contact with the oral cavity. Methods: Thirty-five healthy volunteers were randomized into three groups to receive lactobacilli and/or placebo for 45 days: group A (n = 14) received probiotics in capsules and placebo in liquid form; group B (n = 16) took liquid probiotics and placebo in capsules, and group C (n = 5) used placebo in both liquid and capsule form. Streptococcus mutans populations served as control. The salivary counts of lactobacilli and S. mutans were measured semi-quantitatively using the CRT® bacteria kit. Results: Compared with placebo, the oral administration of probiotics, both in capsules and in liquid form, significantly increases salivary counts of lactobacilli (p = 0.005 and p = 0.02, respectively). S. mutans populations were not significantly modified. Conclusions: The increased salivary counts of lactobacilli may indicate the need to closely monitor the dental health of patients undergoing long-term probiotics treatment, even when this treatment is administrated in a form that avoids direct contact with the oral cavity.

Temporal evolution and functional outcome of no reflow: sustained and spontaneously reversible patterns following successful coronary recanalisation.

Objective: To identify in humans the temporal patterns of no reflow and their functional implications. Methods: 24 patients with first acute myocardial infarction and successful coronary recanalisation by recombinant tissue-type plasminogen activator (n = 15) or primary percutaneous transluminal coronary angioplasty (n = 9) were studied by myocardial contrast echocardiography within 24 hours of recanalisation and at one month’s follow up. Myocardial contrast echocardiography was performed by intermittent harmonic power Doppler and intravenous Levovist. The regional contrast score index (CSI) was calculated within dysfunctioning myocardium. Videointensity was measured (dB) within risk and control areas and their ratio was calculated. Results: In 8 patients reflow was observed at 24 hours and persisted at one month. Conversely in 16 patients areas of no reflow were detectable at 24 hours. At one month, no reflow was spontaneously reversible in 9 patients (mean (SD) CSI and videointensity ratio improved from 2.5 (0.5) to 1.4 (0.6) and from 0.6 (0.1) to 0.7 (0.1), respectively; p < 0.05) and was sustained in the remaining 7 patients (CSI and videointensity ratio remained unchanged from 2.6 (0.6) to 2.6 (0.5) and from 0.5 (0.2) to 0.5 (0.2), respectively; NS). Left ventricular function improved significantly in patients with reflow and reversible no reflow. Volumes were enlarged only in patients with sustained no reflow. Conclusions: No reflow detected at 24 hours may be sustained or spontaneously reversible at one month. Such reversibility of the phenomenon is associated with preserved left ventricular volumes and function. Clarification of the mechanisms of delayed reversibility may lead to tailored treatment of no reflow even in the subacute phase of myocardial infarction.

A novel mutation in SACS gene in a family from southern Italy

A form of autosomal recessive spastic ataxia (ARSACS) has been described in the Charlevoix and Saguenay regions of Quebec. So far a frameshift and a nonsense mutation have been identified in the SACS gene. The authors report a new mutation (1859insC), leading to a frameshift with a premature termination of the gene product sacsin, in two sisters from consanguineous parents. The phenotype is similar to previously described patients with ARSACS.

Autoimmune enteropathy in children and adults.

Autoimmune enteropathy is a rare disorder characterized by severe and protracted diarrhea, weight loss from malabsorption and immune-mediated damage to the intestinal mucosa, generally occurring in infants and young children, although some cases of adult onset have been reported in the literature. Pathogenetic mechanisms involve immunological disorders, in which the presence of antienterocyte autoantibodies, although detected since first description, seems now to be secondary. As occurs frequently in autoimmunity, subjects with autoimmune enteropathy may be affected by other autoimmune disorders, sometimes leading to particular forms, i.e. the IPEX syndrome and the APECED syndrome. The prognosis of autoimmune enteropathy patients depends on the severity of digestive symptoms (including fecal output), on the severity and extension of histological lesions along the gastrointestinal apparatus, and on the presence of extra-intestinal involvement. Management of autoimmune enteropathy patients is based on nutritional support and adequate hydration to ensure optimal growth and development, together with immunosuppressive therapy. Recently, biological agents have been introduced, with apparent beneficial effects.

Clinical trial: the effects of a probiotic mixture on non-steroidal anti-inflammatory drug enteropathy – a randomized, double-blind, cross-over, placebo-controlled study

Aliment Pharmacol Ther 2010; 32: 209–214

Effect of exogenous |[beta]|-galactosidase in patients with lactose malabsorption and intolerance: a crossover double-blind placebo-controlled study

Objective:To evaluate the efficacy of the addition to milk, 5 min and 10 h before its consumption, of a lactase obtained from Kluyveromyces lactis in lactose malabsorbers with intolerance.Design:Double-blind, placebo-controlled, crossover study.Setting:University Hospital.Subjects:In total, 11 male and 19 female (aged from 18 to 65 y, mean age 43.3 y) lactose malabsorbers with intolerance participated.Interventions:Each patient underwent three H2 breath tests, in a random order. We used 400 ml of cows semiskimmed milk as substrate and a β-galactosidase obtained from K. lactis. The test A was carried out adding to the milk the enzyme (3000 UI), 10 h before its consumption; the test B was performed adding the β-galactosidase (6000 UI) 5 min before milk ingestion and the test C was made using placebo. We evaluated the maximum breath H2 concentration, the cumulative H2 excretion and a clinical score based on intolerance symptoms (bloating, abdominal pain, flatulence and diarrhoea).Results:Our study showed a significant reduction of the mean maximum H2 concentration after both test A (12.07±7.8 p.p.m.) and test B (13.97±7.99 p.p.m.) compared with test C (51.46±16.12 p.p.m.) (ANOVA F=54.33, P<0.001). Similarly, there was a significant reduction of the mean cumulative H2 excretion after both test A (1428±1156 p.p.m.) and test B (1761±966 p.p.m.) compared with test C (5795±2707 p.p.m.) (ANOVA F=31.46, P<0.001). We also observed a significant reduction of the mean clinical score after both test A (0.36±0.55) and test B (0.96±0.85) compared with test C (3.7±0.79) (ANOVA F=106.81, P<0.001). Moreover, with regard to the mean clinical score, there was a significant reduction after test A with respect to test B (Bonferronis P=0.03).Conclusions:Our study shows that in lactose malabsorbers with intolerance, the lactase obtained from K. lactis can represent a valid therapeutic strategy, with objective and subjective efficacy and without side effects.

Ataxia with oculomotor apraxia type 1 in Southern Italy: late onset and variable phenotype.

Ataxia with oculomotor apraxia type 1 (AOA1) is an autosomal recessive disorder characterized by early-onset cerebellar ataxia, oculomotor apraxia, and peripheral neuropathy. The causative gene (APTX) has been recently identified in Portuguese and Japanese kindreds. Three patients with AOA1 were identified in an APTX mutation screening on 28 Southern Italian patients with progressive ataxia and peripheral neuropathy. A novel homozygous missense mutation (H201Q) was found in one patient and a Japanese missense mutation (P206L) in two. AOA1 clinical heterogeneity and onset later than previously described are shown.

THE EFFECTS OF A PROBIOTIC MIXTURE ON NSAID ENTEROPATHY: A RANDOMIZED, DOUBLE-BLIND, CROSS-OVER, PLACEBO-CONTROLLED STUDY.

Aliment Pharmacol Ther 2010; 32: 209–214

Low-dose lactose in drugs neither increases breath hydrogen excretion nor causes gastrointestinal symptoms

Background Despite the reported tolerance to a low dose of lactose, many lactose malabsorbers follow a rigorous lactose‐free diet also avoiding lactose‐containing drugs. Up to now, only a few case reports have described the onset of gastrointestinal symptoms in lactose malabsorbers following the ingestion of these drugs. It has been suggested that capsules/tablets contain no more than 400 mg of lactose.