Mechanisms of antidiarrhoeal effects by diosmectite in human intestinal cells

Rotavirus (RV) induces diarrhoea through a sequence of enterotoxic and cytotoxic effects. The former are NSP4-dependent, induce calcium-dependent chloride secretion and involve oxidative stress. Diosmectite (DS) is a natural clay that has been recommended as an active therapy for diarrhoea, but the mechanism of its effect is not clear. Electrical parameters may be used to measure the direct enterotoxic and cytotoxic effects in polar epithelial intestinal cells. To investigate the effects of DS on RV-induced enterotoxic and cytotoxic damage. Caco-2 cells were used as a model of RV infection to evaluate chloride secretion, epithelial integrity, oxidative stress and viral infectivity in Ussing chambers

Isolated liver transplantation for treatment of liver failure secondary to intestinal failure

Intestinal Failure is a permanent loss of digestive and absorptive functions as a consequence of short bowel syndrome and/or other primary intestinal conditions. Patients with intestinal failure (IF) require long term parenteral nutrition to survive. The only alternative to parenteral nutrition is intestinal transplantation which still entails high mortality. Children with intestinal failure on parenteral nutrition may develop liver failure (LF), as a consequence of central line infections and other conditions. In children with both irreversible IF and LF a combined transplantation is generally considered. Despite low survival rate, combined liver/intestine transplantation is associated to better intestinal graft survival and lower incidence and severity of rejection compared to isolated small bowel transplantation. Recently, isolated liver transplantation was proposed in children with IF and LF. This procedure may have a higher survival probability compared to isolated intestinal transplant, it may allow progressive weaning from PN in children in whom the remnant intestine has the potential for adaptation and offer a timely solution in children for whom intestinal graft is not immediately available. This innovative approach may prove a better option compared to combined transplantation in both the short and long ter

Chronic diarrhoea in children.

Chronic diarrhoea in children shows an age related spectrum. In infants and young children a major role is related to persistent intestinal infections, intolerance to specific nutrients such as cow's milk protein, and toddler's diarrhoea. In older children and adolescents, inflammatory bowel diseases are strongly increasing and nonspecific diarrhoea is also frequent. Coeliac disease is a major cause of diarrhoea throughout childhood. In neonates, congenital diarrhoea is a rare but severe syndrome that includes several highly complex diseases. In children, diagnosis should be based on noninvasive techniques. Endoscopy should be decided based on clinical criteria, but also driven by noninvasive tests to assess the digestive absorptive functions and intestinal inflammation. A stepwise approach may reduce the need of endoscopy, also in the light of its relatively limited diagnostic yield compared to adult patients. Treatment of chronic diarrhoea in children is also substantially different from what is generally done in adults and includes a major role for nutritional interventions. Therefore chronic diarrhoea in children is a complex age-specific disorder that requires an age-specific management that is in many aspects distinct from that in adults

Probiotics as prevention and treatment for diarrhea

PURPOSE OF REVIEW: To critically appraise evidence on probiotic use for prevention and treatment of diarrhea in children and adults. RECENT FINDINGS: Several randomized controlled trials and meta-analyses suggested that probiotics are effective in primary and secondary prevention of gastroenteritis and its treatment. Selected Lactobacillus strains had a modest, although significant effect in primary prevention. Saccharomyces boulardii was effective in antibiotic-associated and in Clostridium difficile diarrhea. There is evidence that it might prevent diarrhea in day-care centers. Lactobacillus rhamnosus GG was associated with reduced diarrheal duration and severity, more evident in case of childhood Rotavirus diarrhea. Similar, although weaker, evidence was obtained with S. boulardii. Both strains are included in evidence-based recommendations for gastroenteritis management in children. Data on other Lactobacillus strains are preliminary. Probiotic efficacy was related to cause, early administration and bacterial load, and their mechanisms were associated with antiinfectious action in the intestine or, indirectly, to modulation of innate and adaptive immunity. SUMMARY: Probiotics have gained a role as adjunctive treatment of infantile gastroenteritis together with rehydration. Their efficacy is less convincing in adults, but promising in antibiotic-associated diarrhea. However, evidence of efficacy is limited to a few strains

Early-Life Intestine Microbiota and Lung Health in Children

The gastrointestinal microbiota plays a critical role in nutritional, metabolic, and immune functions in infants and young children and has implications for future lung health status. Understanding the role of intestinal dysbiosis in chronic lung disease progression will provide opportunities to design early interventions to improve the course of the disease. Gut microbiota is established within the first 1 to 3 years of life and remains relatively stable throughout the life span. In this review, we report the recent development in research in gut-lung axis, with focus on the effects of targeting microbiota of infants and children at risk of or with progressive lung diseases. The basic concept is to exploit this approach in critical window to achieve the best results in the control of future health

Dolutegravir-based anti-retroviral therapy is effective and safe in HIV-infected paediatric patients

BACKGROUND: Treatment of HIV infection in adolescents is challenging due to long duration of therapy and poor adherence. Recently, the integrase strand transfer inhibitor dolutegravir (DTG) has been approved for the use in adolescents with HIV, but evidence in clinical practice is very limited. METHODS: We describe six cases of HIV-infected children/adolescents successfully treated with DTG-based regimen. Data relative to children/adolescents managed at the Referral Center for Pediatric HIV/AIDS of the University of Naples were reviewed. Patients were tested before introduction of DTG, after 1 month and every 3 months in the first 2 years to assess virologic and immunological response, tolerance and development of side effects. Families were asked to report any suspected adverse events. RESULTS: Six patients (2 male, median age 17 years, range 12-18) were started on DTG-based anti-retroviral regimen due to low adherence to anti-retroviral treatment (ART), multiple drug resistance mutations, or development of ART-related side effects. Within 4-8 weeks after DTG treatment onset, a complete viral suppression and a concomitant increase of CD4+ cell count was observed. Four patients showed a persistent suppression after 2 years of follow-up, and 2 patients at about 1 year. One month after the introduction of DTG, the patient enrolled because of severe dyslipidaemia and hyper-transaminasemia showed a complete normalization of laboratory values. During follow-up (median 24 months, range 9-24) no adverse events were reported and most patients demonstrated a good adherence to treatment. CONCLUSIONS: DTG-based treatments demonstrated efficacy and good safety profile in adolescents. All patients demonstrated a rapid virologic and immunological response within 4-8 weeks, with good adherence and absence of side effects

Lactoferrin induces concentration-dependent functional modulation of intestinal proliferation and differentiation

Human milk stimulates intestinal development through the effects of various moieties. Lactoferrin (LF) is a glycoprotein of human milk whose concentration is highest in colostrum decreasing in mature milk. LF promotes enterocyte growth in intestinal cell lines. We tested the hypothesis that LF induces a distinct effect on enterocyte proliferation and differentiation, depending on its concentration. We examined the dose-related effects by human-native LF (N-LF) in Caco-2 (human colon adenocarcinoma) cells. At high concentrations, N-LF stimulated cell proliferation in immature Caco-2 cells, as judged by 3H-thymidine incorporation. In contrast, sucrase and lactase activities were increased at low but not high LF concentrations and their mRNA were also increased, indicating a transcriptional effect. Because iron binds specific LF sites, we compared the potency of N-LF and iron-saturated LF (I-LF) and found the native form more potent. Finally, we tested the effects by bovine LF (bLF) in the same system and found the latter more potent than the human isoform in inducing cell growth and lactase expression. These results suggest that LF directly induces enterocyte growth and proliferation, depending on its concentration, thereby regulating the earlyx postnatal intestinal development. bLF could be added to infant formula as a growth factor in selected intestinal disease