Risk and Protective Factors for Gastrointestinal Symptoms associated with Antibiotic Treatment in Children: A Population Study

Bau, Mario,Moretti, Alex,Bertoni, Elisabetta,Vazzoler, Valentino,Luini, Chiara,Agosti, Massimo,Salvatore, Silvia The Korean Society of Pediatric Gastroenterology 2020 Pediatric gastroenterology, hepatology & nutrition Vol.23 No.1

Purpose: Gastrointestinal symptoms are often related to antibiotic treatment. Their incidence, risk and protective conditions in children are not well defined and represent the aims of this study. Methods: We prospectively enrolled inpatient children submitted to antibiotic treatment. Indication, type, dose and duration of treatment, probiotic supplementation and gastrointestinal symptoms were recorded at recruitment, after two and four weeks. Antibiotic-associated diarrhea (AAD) was defined as the presence of at least 3 loose/liquid stools within 14 days from antibiotic onset. Results: AAD occurred in 59/289 (20.4%) of patients, with increased risk in children younger than 3 years (relative risk [RR]=4.25), in lower respiratory (RR=2.11) and urinary infections (RR=3.67), intravenous administration (RR=1.81) and previous AAD episodes (RR=1.87). Abdominal pain occurred in 27/289 (9.3%), particularly in children >6 years (RR=4.15), with previous abdominal pain (RR=7.2) or constipation (RR=4.06). Constipation was recorded in 23/289 (8.0%), with increased risk in children having surgery (RR=2.56) or previous constipation (RR=7.38). Probiotic supplementation significantly reduced AAD (RR=0.30) and abdominal pain (RR=0.36). Lactobacillus rhamnosus GG (LGG) and L. reuteri significantly reduced AAD (RR=0.37 and 0.35) and abdominal pain (RR=0.37 and 0.24). Conclusion: AAD occurred in 20.4% of children, with increased risk at younger age, lower respiratory and urinary tract infections, intravenous treatment and previous AAD. LGG and L. reuteri reduced both AAD and associated abdominal pain.

Risk and Protective Factors for Gastrointestinal Symptoms associated with Antibiotic Treatment in Children: A Population Study

Mario Baù,Alex Moretti,Elisabetta Bertoni,Valentino Vazzoler,Chiara Luini,Massimo Agosti,Silvia Salvatore 대한소아소화기영양학회 2020 Pediatric gastroenterology, hepatology & nutrition Vol.23 No.1

Purpose: Gastrointestinal symptoms are often related to antibiotic treatment. Their incidence, risk and protective conditions in children are not well defined and represent the aims of this study. Methods: We prospectively enrolled inpatient children submitted to antibiotic treatment. Indication, type, dose and duration of treatment, probiotic supplementation and gastrointestinal symptoms were recorded at recruitment, after two and four weeks. Antibiotic-associated diarrhea (AAD) was defined as the presence of at least 3 loose/liquid stools within 14 days from antibiotic onset. Results: AAD occurred in 59/289 (20.4%) of patients, with increased risk in children younger than 3 years (relative risk [RR]=4.25), in lower respiratory (RR=2.11) and urinary infections (RR=3.67), intravenous administration (RR=1.81) and previous AAD episodes (RR=1.87). Abdominal pain occurred in 27/289 (9.3%), particularly in children >6 years (RR=4.15), with previous abdominal pain (RR=7.2) or constipation (RR=4.06). Constipation was recorded in 23/289 (8.0%), with increased risk in children having surgery (RR=2.56) or previous constipation (RR=7.38). Probiotic supplementation significantly reduced AAD (RR=0.30) and abdominal pain (RR=0.36). Lactobacillus rhamnosus GG (LGG) and L. reuteri significantly reduced AAD (RR=0.37 and 0.35) and abdominal pain (RR=0.37 and 0.24). Conclusion: AAD occurred in 20.4% of children, with increased risk at younger age, lower respiratory and urinary tract infections, intravenous treatment and previous AAD. LGG and L. reuteri reduced both AAD and associated abdominal pain.

Protective Effects of Probiotic Lactobacillus rhamnosus IMC501 in Mice Treated with PhIP

( Luca Dominici ),( Milena Villarini ),( Francesca Trotta ),( Ermanno Federici ),( Giovanni Cenci ),( Massimo Moretti ) 한국미생물 · 생명공학회 2014 Journal of microbiology and biotechnology Vol.24 No.3

The aim of the present study was to investigate the antigenotoxic properties of the probiotic Lactobacillus rhamnosus IMC501; DNA damage was induced by one representative food mutagen, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). Mice were treated orally with suspensions of lactobacilli for 10 days before administration of food mutagen. During the treatment, the abundance of lactobacilli in feces, as assessed by qPCR analysis, increased, whereas β-glucuronidase and N-acetyl-β-glucosaminidase activities decreased. The extent of DNA damage was measured in colon and liver cells by comet assay. In colonocytes, diet supplementation with IMC501 resulted in a significant inhibition of DNA damage induced by PhIP. The results obtained in this in vitro study suggest that Lactobacillus rhamnosus IMC501 used as a dietary supplement can provide a useful integration of antimutagen food components of the normal diet, which are generally lower than the protective level.

High Efficacy and Safety of Flat-Dose Ribavirin Plus Sofosbuvir/Daclatasvir in Genotype 3 Cirrhotic Patients

Adriano Pellicelli,Vincenzo Messina,Valerio Giannelli,Marco Distefano,Valeria Pace Palitti,Pascal Vignally,Pierluigi Tarquini,Antonio Izzi,Alessandra Moretti,Sergio Babudieri,Serena Dell’Isola,Massimo 거트앤리버 소화기연관학회협의회 2020 Gut and Liver Vol.14 No.3

Background/Aims: Patients with genotype 3 hepatitis C virus (G3-HCV) cirrhosis are very difficult to treat compared to patients with other HCV genotypes. The optimal treatment duration and drug regimen associated with ribavirin (RBV) remain unclear. To evaluate the efficacy and safety of daclatasvir (DCV)/sofosbuvir (SOF) plus a flat dose of 800 mg RBV (flat dose) compared to DCV/SOF without RBV or DCV/SOF plus an RBV dose based on body weight (weight-based) in G3-HCV patients with compensated or decompensated cirrhosis. Methods: We analyzed data for 233 G3 cirrhotic patients. Of these, 70 (30%), 87(37%) and 76 (33%) received SOF/DCV, SOF/DCV/RBV flat dose, and SOF/DCV/RBV weight-based dose, respectively. Treatment duration was 24 weeks. Sustained virological response (SVR) was evaluated at week 12 posttreatment (SVR12). Results: Overall, SVR12 was achieved in 220 out of 233 patients (94.4%). The SVR12 rate was lower in the DCV/SOF group than in the DCV/SOF/RBV flat-dose group and the DCV/SOF/RBV weight-based group (87.1% vs 97.7% and 97.4%, respectively, p=0.007). A higher incidence of anemia occurred in the DCV/SOF/RBV weight-based group compared to those in the other two groups (p<0.007). Conclusions: We found that the DCV/SOF/RBV flat-dose regimen is an effective treatment in terms of efficacy and safety in patients with G3-HCV compensated or decompensated cirrhosis. Therefore, antiviral regimens without RBV should be restricted only to naïve patients with G3-HCV compensated cirrhosis who have a clear contraindication for RBV.

In vitro toxicological assessment of PhSeZnCl in human liver cells

di Vito Raffaella,Levorato Sara,Fatigoni Cristina,Acito Mattia,Sancineto Luca,Traina Giovanna,Villarini Milena,Santi Claudio,Moretti Massimo 한국독성학회 2023 Toxicological Research Vol.39 No.1

Phenylselenenylzinc chloride (PhSeZnCl) is an air-stable selenolate, easily synthesizable through oxidative insertion of elemental zinc into the Se-halogen bond of the commercially available phenylselenyl chloride. PhSeZnCl was shown to possess a marked GPx-like activity both in NMR and in vitro tests, and to effectively react with cellular thiols, and was supposed for a potential use in the chemotherapy of drug-resistant cancers. However, activity of PhSeZnCl in hepatic cells has never been tested before now. In this in vitro approach, we evaluated the cytotoxic, genotoxic, and apoptotic activities, as well as the effects on cell cycle of PhSeZnCl in two preclinical hepatic models, namely HepG2 and HepaRG cells. Results showed that cell viability of HepG2 and HepaRG cells decreased in a dose-dependent manner, with a more marked effect in HepG2 tumour cells. Moreover, treatment with 50 μg/mL PhSeZnCl caused an increase of primary DNA damage (4 h) and a statistically significant increase of HepG2 cells arrested in G2/ M phase. In addition, it altered mitochondrial membrane potential and induced chromosomal DNA fragmentation (24 h). In HepaRG cells, PhSeZnCl was able to determine a cell cycle-independent induction of apoptosis. Particularly, 50 μg/mL induced mitochondrial membrane depolarization after 24 h and apoptosis after 4 h treatment. Futhermore, all PhSeZnCl concentrations tested determined a significant increase of apoptotic cells after 24 h. Apoptosis was also highlighted by the detection of active Caspase-3 by Western Blot analysis after 24 h exposure. In conclusion, this first toxicological assessment provides new insights into the biological activity of PhSeZnCl in preclinical hepatic models that will be useful in future safety assessment investigation of this compound as a potential pharmaceutical.