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Vaccination is a key protective factor against COVID-19. Some vaccines have already received emergency authorization from Health Agencies, but growing skepticism and vaccine hesitancy will probably affect COVID-19 vaccination campaigns. In the attempt to shed light on this issue, we conducted an online survey in a population of parents referring to 4 pediatric practices in Naples, Italy in whom we evaluated potential vaccine acceptability in relation to socio-demographic characteristics, perception of personal health and of the impact of COVID-19, and attitudes toward general vaccination practices. Vaccination rates were analyzed also in the corresponding pediatric population. Almost 27% of participants declared they were in favor of vaccinations, and in fact real life vaccination rates in children exceeded the national mean. Only 26.5% of respondents declared they would receive COVID-19 vaccine. Vaccine refusal was attributed to safety concerns in 76% of parents. Specific vaccine attributes further reduced the acceptance rate. Female gender, younger age and lower education level were associated with non-adherence to vaccination. Among extrinsic factors of COVID-19 vaccination, only information from National Health Authorities was significantly associated to vaccine acceptance. The rate of potential COVID-19 vaccine acceptability was very poor in our population of parents. Vaccine hesitancy was mainly due to safety concerns. Demographic and educational factors were correlated to vaccine acceptability. Health education and communication strategies are needed to achieve large-scale vaccine acceptability and finally herd immunity.

Summary Background Ginger is a spice with a long history of use as a traditional remedy for nausea and vomiting. No data on the efficacy of ginger are presently available for children with vomiting associated with acute gastroenteritis (AGE). Aim To test whether ginger can reduce vomiting in children with AGE. Methods Double‐blind, randomised placebo‐controlled trial in outpatients aged 1 to 10 years with AGE‐associated vomiting randomised to ginger or placebo. The primary outcome was the occurrence of ≥1 episode of vomiting after the first dose of treatment. Severity of vomiting and safety were also assessed. Results Seventy‐five children were randomised to the ginger arm and 75 to the placebo arm. Five children in the ginger arm and 4 in the placebo arm refused to participate in the study shortly after randomisation, leaving 70 children in the ginger arm and 71 in the placebo arm (N = 141). At intention‐to‐treat analysis (N = 150), assuming that all children lost to follow‐up had reached the primary outcome, the incidence of the main outcome was 67% (95% CI 56 to 77) in the ginger group and 87% (95% CI 79 to 94) in the placebo group, corresponding to the absolute risk reduction for the ginger versus the placebo group of −20% (95% CI −33% to −7%, P = 0.003), with a number needed to treat of 5 (95% CI 3 to 15). Conclusion Oral administration of ginger is effective and safe at improving vomiting in children with AGE. Trial registration: The trial was registered on https://clinicaltrials.gov/ with the identifier NCT02701491., In a double‐blind, randomised placebo‐controlled trial in pediatric outpatients with acute gastroenteritis (AGE)‐associated vomiting the oral administration of ginger resulted effective and safe at improving vomiting.

Summary Background & aim Fermented foods have been proposed for the prevention of infectious diseases. We evaluated the efficacy of fermented foods in reducing common infectious diseases (CIDs) in children attending daycare. Methods Prospective randomized, double-blind, placebo-controlled trial (registered under Clinical Trials.gov identifier NCT01909128) on healthy children (aged 12–48 months) consuming daily cow's milk (group A) or rice (group B) fermented with Lactobacillus paracasei CBA L74, or placebo (group C) for three months during the winter season. The main study outcome was the proportion of children who experienced at least one CID. All CIDs were diagnosed by family pediatricians. Fecal concentrations of innate (α- and β-defensins and cathelicidin LL-37) and acquired immunity biomarkers (secretory IgA) were also evaluated. Results 377 children (193 males, 51%) with a mean (SD) age of 32 (10) months completed the study: 137 in group A, 118 in group B and 122 in group C. Intention-to-treat analysis showed that the proportion of children who experienced at least one CID was lower in group A (51.8%) and B (65.9%) compared to group C (80.3%). Per-protocol analysis showed that the proportion of children presenting upper respiratory tract infections was lower in group A (48.2%) and group B (58.5%) compared with group C (70.5%). The proportion of children presenting acute gastroenteritis was also lower in group A (13.1%) and group B (19.5%) compared with group C (31.1%). A net increase of all fecal biomarkers of innate and acquired immunity was observed for groups A and B compared to group C. Moreover, there was a negative association between fecal biomarkers and the occurrence of CID. Conclusion Dietary supplementation with cow's milk or rice fermented with L. paracasei CBA L74 prevents CIDs in children attending daycare possibly by means of a stimulation of innate and acquired immunity.

Background: Fermented foods have been proposed to prevent common infectious diseases (CIDs) in children attending day care or preschool. Objectives: To investigate the efficacy of dietary supplementation with cow’s skim milk fermented with the probiotic Lactobacillus paracasei CBA L74 in reducing CIDs in children attending day care or preschool. Methods: Multicenter, randomized, double-blind, placebo-controlled trial on healthy children (aged 12–48 months) consuming daily 7 grams of cow’s skim milk fermented with L. paracasei CBA L74 (group A), or placebo (maltodextrins group B) attending day care or preschool during the winter season. The main outcome was the proportion of children who experienced ≥1 episode of CID during a 3-month follow-up. Fecal biomarkers of innate (α- and β-defensins, cathelicidin) and acquired immunity (secretory IgA) were also monitored. Results: A total of 126 children (71 males, 56%) with a mean (SD) age of 33 (9) months completed the study, 66 in group A and 60 in group B. At intention to treat analysis, the proportion of children presenting ≥1 CID was 60% in group A vs. 83% in group B, corresponding to an absolute risk difference (ARD) of −23% (95% CI: −37% to −9%, p < 0.01). At per-protocol-analysis (PPA), the proportion of children presenting ≥1 CID was 18% in group A vs. 40% in group B, corresponding to an absolute risk difference (ARD) of −22% (95% CI: −37% to −6%, p < 0.01). PPA showed that the proportion of children presenting ≥1 acute gastroenteritis (AGE) was significantly lower in group A (18% vs. 40%, p < 0.05). The ARD for the occurrence of ≥1 AGE was −22% (95% CI: −37% to −6%, p < 0.01) in group A. Similar findings were obtained at PPA regarding the proportion of Nutrients 2017, 9, 669; doi:10.3390/nu9070669 www.mdpi.com/journal/nutrients Nutrients 2017, 9, 669 2 of 15 children presenting ≥1 upper respiratory tract infection (URTI), which was significantly lower in group A (51% vs. 74%, p < 0.05), corresponding to an ARD of −23% (95% CI: −40% to −7%, p < 0.01). Significant changes in innate and acquired immunity biomarkers were observed only in subjects in group A. Conclusions: Dietary supplementation with cow’s skim milk fermented with L. paracasei CBA L74 is an efficient strategy in preventing CIDs in children.

Guanylin receptor guanylate cyclase (GC-C) peaks in neonatal intestine and is involved in either enterocyte proliferation or chloride secretion. The latter is more potent when GC-C activator guanylin, or its analog Escherichia coli heat-stable enterotoxin (ST), is added to the mucosal rather than serosal side of intestinal monolayers. By using Ussing chambers, we investigated transepithelial ion transport and enterocyte proliferation and their mechanisms in response to the addition of guanylin or ST to the mucosal or serosal side of Caco-2 monolayers and in ileal specimens from neonates. GC-C activation showed a polar pattern of the effects. GC-C mucosal activation resulted in a potent cGMP-chloride secretion activation and in a marginal enterocyte proliferation. Conversely, serosal GC-C activation induced a potent enterocyte proliferation, through MAP kinase ERK 1/2. Finally, the inhibition of ERK1/2 enhanced the Isc increase in response to serosal but not to mucosal ST stimulation, indicating that ERK1/2 also acts as a brake of chloride secretion. These data suggest that the guanylin/GC-C system plays a key role in early postnatal intestinal adaptation exploiting the polar structure of enterocyte.

Objective: Oral rehydration solution remains the mainstay of acute gastroenteritis therapy. The aim of this study was to investigate the acceptability of a new zinc-containing hypotonic super-oral rehydration solution (ORS) in a gel formulation and its efficacy in reducing the duration and severity of diarrhea in children. Methods: This was a randomized-controlled trial of children (5-36 months of age) observed for diarrhea lasting less than 24 h. Children were randomized to receive standard hypotonic ORS (group 1) or a gel hypotonic super-ORS containing zinc (group 2). The main study outcome was ORS intake in the first 24 h. ORS intake at 4 h, rate of diarrhea resolution at 72 h of treatment, total duration and severity of diarrhea, hospitalization, and adverse effects were also evaluated. Results: Eighty-three children were enrolled (group 1: 40; group 2: 43). The amount of ORS consumed at 24 h was significantly higher in group 2 than in group 1. A similar result was observed at 4 h. The number of children who refused ORS (

BACKGROUND Serum α-L-fucosidase activity is considered a marker of hepatocellular carcinoma. To the authors' knowledge, its clinical usefulness in the early detection of hepatocellular carcinoma in the follow-up of cirrhotic patients has not been reported previously. METHODS The authors prospectively studied serum α-L-fucosidase activity, in addition to α-fetoprotein and ultrasonography, in a regular screening of 132 cirrhotic patients during an 8-year follow-up. RESULTS At enrollment, 120 patients had low α-L-fucosidase activity (below the cutoff value) and 12 had high activity. All patients had serum α-fetoprotein levels below the cutoff value. During the follow-up, hepatocellular carcinoma was detected in 19 patients, 16 with α-L-fucosidase activity below the cutoff value at enrollment and 3 with activity above it. In 7 of those 16 patients with carcinoma and low enzyme activity, the enzyme activity showed a significant increase 6-9 months before there was ultrasonographic evidence of a focal lesion, and by the time of diagnosis it had risen above the cutoff value in all of them; in only 3 of the 7 patients was the increase in α-L-fucosidase activity associated with an increase in α-fetoprotein. In another 4 of the 19 patients with carcinoma, only α-fetoprotein increased. CONCLUSIONS Serum α-L-fucosidase activity is useful in the early detection of hepatocellular carcinoma. The data from this study suggest that cirrhotic patients who have a marked increase in serum α-L-fucosidase levels during follow-up should be closely monitored for signs of hepatocellular carcinoma development. Cancer 1998;83:2468-2474. © 1998 American Cancer Society.

To evaluate the efficacy of a hypotonic oral rehydration solution (ORS) containing zinc and prebiotics for treatment of acute diarrhea in children.We conducted a single-blind, prospective, controlled trial including children (age range, 3-36 months) with acute diarrhea randomly assigned to standard hypotonic ORS (group 1) or to new hypotonic ORS containing zinc and prebiotics (group 2). The main outcome was the rate of resolution of diarrhea at 72 hours.A total of 60 children in group 1 (34 male; mean age, 18.58 months; 95% CI, 15.5-21.6) and 59 in group 2 (36 male; mean age, 19.26 months; 95% CI, 15.9-22.6) completed the study protocol. The rate of diarrhea resolution at 72 hours was higher in group 2 (50% versus 72.9%, P = .010). Total ORS intake in the first 24 hours was higher in group 2 (50 mL/kg; 95% CI, 41-59 versus 22 mL/kg; 95% CI, 17-29; P.001). The mean number of missed working days by the parents of children in group 2 was lower (0.39; 95% CI, 0.08-0.70 versus 1.45; 95% CI 1.02-1.88; P.001). Fewer patients in group 2 needed adjunctive drugs for the treatment of diarrhea 6/59 versus 19/60, P = .004. No adverse events were observed in either of the two groups.The addition of zinc and prebiotics to ORS limits diarrhea duration in children.

The mechanisms of diarrhea due to rotavirus infection in humans are not fully understood; no specific therapy is available, but orally administered human serum immunoglobulins are effective in blocking stool output. We aimed to investigate the effect of rotavirus on ion transport and the role of NSP4 in human-derived enterocytes, and to test the efficacy of human serum immunoglobulin in a model of rotavirus infection. Soon after infection, rotavirus induces active chloride secretion in enterocytes. This effect is evident before viral replication leads to cell damage and correlates with NSP4 production. Inhibition of NSP4 prevents the early secretory phase but not cell damage. Incubation with human serum immunoglobulin blocks both ion secretion and cell damage. Rotavirus exerts an early NSP4-dependent ion secretion and subsequent tissue damage. The combined enterotoxic and cytotoxic effects may be responsible for the increased severity of diarrhea due to rotavirus infection, and both are counteracted by human serum immunoglobulin.

Objective To compare the efficacy of five probiotic preparations recommended to parents in the treatment of acute diarrhoea in children. Design Randomised controlled clinical trial in collaboration with family paediatricians over 12 months. Setting Primary care. Participants Children aged 3-36 months visiting a family paediatrician for acute diarrhoea. Intervention Children's parents were randomly assigned to receive written instructions to purchase a specific probiotic product: oral rehydration solution (control group); Lactobacillus rhamnosus strain GG; Saccharomyces boulardii; Bacillus clausii; mix of L delbrueckii var bulgaricus, Streptococcus thermophilus, L acidophilus, and Bifidobacterium bifidum; or Enterococcus faecium SF68. Main outcome measures Primary outcomes were duration of diarrhoea and daily number and consistency of stools. Secondary outcomes were duration of vomiting and fever and rate of admission to hospital. Safety and tolerance were also recorded. Results 571 children were allocated to intervention. Median duration of diarrhoea was significantly shorter (P

Summary Background & aims Probiotics reduce intestinal inflammation in children with cystic fibrosis (CF). We want to determine the effects of Lactobacillus GG (LGG) on pulmonary exacerbations in CF. Methods A prospective, randomized, placebo-controlled, cross-over study was performed. Nineteen children received LGG for 6 months and then shifted to oral rehydration solution (ORS) for 6 months. In parallel nineteen received ORS and then shifted to LGG. Main outcome parameters were: incidence of pulmonary exacerbations and of hospital admissions, forced expiratory volume (FEV 1 ), and modifications of body weight. Results Patients treated with LGG showed a reduction of pulmonary exacerbations (Median 1 vs. 2 , range 4 vs. 4, median difference 1, CI 95% 0.5–1.5; p =0.0035) and of hospital admissions (Median 0 vs. 1, range 3 vs. 2, median difference 1, CI95% 1.0–1.5; p =0.001) compared to patients treated with ORS. LGG resulted in a greater increase in FEV 1 (3.6%±5.2 vs. 0.9%±5; p =0.02) and body weight (1.5kg±1.8 vs. 0.7kg±1.8; p =0.02). Conclusions LGG reduces pulmonary exacerbations and hospital admissions in patients with CF. These suggest that probiotics may delay respiratory impairment and that a relationship exists between intestinal and pulmonary inflammation.

Intestinal failure (IF) is a rare condition resulting from short gut and other heterogeneous intestinal diseases. Major centers in Italy merged in a national network to build common diagnostic and management approaches and to investigate the natural history of IF. Gastroenterological reference centers with specific expertise in intestinal morphology, diagnosis of autoimmune conditions, intestinal microbiology and parenteral nutrition were identified to act as consultants to the network. These centers of expertise provided specific diagnostic approaches while ensuring high technical standards. The approach allowed each center to learn from a larger cohort of patient samples. A database was set up to investigate etiology, epidemiology and natural history of IF. A common diagnostic algorithm for intractable diarrhea was designed. This process was largely based on electronic communication among centers and specimen shipping. Etiologic diagnosis was obtained in almost all cases of IF secondary to severe protracted diarrhea. The study of the natural history of IF showed a close association between etiology of IF and its outcome. The natural history of IF also provided the starting point for specific therapeutic approaches to its complications such as parenteral nutrition-associated cholestasis and catheter-related sepsis. The network approach to IF provides an effective model to optimize resources and prospectively investigate the natural history of IF, essential steps to design interventions, including intestinal transplantation and improve the outcome of IF.

Objective: The pathophysiology of HIV-1-related intestinal dysfunction is largely unknown. We previously found that the transactivator factor peptide (Tat) produced by HIV-1 induces ion secretion and inhibits cell proliferation in human enterocytes. Because sugar malabsorption is a frequent feature in AIDS patients, we evaluated whether Tat inhibits intestinal glucose absorption. Design and methods: We measured Na + -D-glucose symporter (SGLT-1) activity and determined its phenotypic expression in Caco-2 cells, in the presence and absence of Tat, in uptake experiments using a non-metabolized radiolabelled glucose analogue, and by western blot analysis, respectively. α-Tubulin staining was used to study the effects exerted by Tat on cell structure. Results: Tat dose dependently inhibited glucose uptake by human enterocytes. This effect was prevented by anti-Tat polyclonal antibodies and by L-type Ca 2+ channels agonist Bay K8644. Western blot analysis of cellular lysates and brush-border membrane preparations showed that Tat induced SGLT-1 missorting. Tat also caused a dramatic decrease in α-tubulin staining, which indicates dysruption of the cytoskeleton organization. Conclusions: Tat acutely impairs intestinal glucose absorption through SGLT-1 missorting. This result indicates that Tat is directly involved in AIDS-associated intestinal dysfunction.

Antiemetics are not included for treatment of vomiting associated with acute gastroenteritis (AGE) in children by standard guidelines. We performed a survey to determine antiemetic prescribing rates by Italian pediatricians. A structured questionnaire was distributed at a pediatric national conference. The majority of responders reported prescribing antiemetics for pediatric gastroenteritis. Although there is insufficient evidence to justify their use, the use of antiemetics is widely present among pediatricians. © 2006 Lippincott Williams & Wilkins.

Background. In an attempt to reduce the burden of influenza-like illness (ILI) on health resources, the Italian Ministry of Health released clinical practice guidelines (CPGs) on ILI management that include spe- cific indications for the admission of children to the hospital. The aim of this study was to evaluate whether application of these CPGs reduced the rate of inappro- priate hospital admissions. Methods. In the first phase, 2 independent observers recorded the number and clinical condition of children presenting with ILI to the emergency department (ED) of a large urban pediatric hospital and the main reasons for hospital admission. The latter were compared with the CPG indications for hospital admission to evaluate ap- propriateness. One year later (phase 2), we recorded the number of children with ILI admitted to the hospital by pediatricians trained in a 3-hour course on CPGs and by "untrained" control pediatricians. Results. In phase 1 of the study, 854 children accessed the ED; 318 (37.2%) had ILI. Of the latter, 26.2% were admitted to the hospital, and 33.7% of admissions were inappropriate according to CPG criteria. In phase 2, 16% of the children with ILI were admitted by CPG-trained pediatricians and 25.8% by control pediatricians. The number of inappropriate hospital admissions was higher among control than among CPG-trained pediatricians. Conclusions. ILI in children is associated with a high rate of inappropriate hospital admissions. Training of ED pediatricians in the application of a specific CPG may result in a substantial decrease of the admission rate and of inappropriate admissions. Pediatrics 2005; 116:e506-e511. URL: www.pediatrics.org/cgi/doi/10.1542/ peds.2005-0053; influenza-like illness, inappropriate ad- mission, guideline, children.

We previously detected specific binding activity of Escherichia coli heat-stable enterotoxin (ST), the guanylin exogenous ligand, in rat colonic basolateral membranes. Because guanylin circulates in the bloodstream, we tested the hypothesis that it modulates intestinal ion transport by acting on the serosal side of intestinal cells. The effects of the mucosal and serosal addition of ST and guanylin on ion transport were investigated in the rat proximal colon and in Caco-2 cells in Ussing chambers, by monitoring short-circuit current (Isc). cGMP concentration was measured in Caco-2 cells by RIA. Mucosal ST addition induced an increase in Isc in rat proximal colon consistent with anion secretion. Serosal addition induced the same effects but to a lesser extent. The electrical effects observed in Caco-2 cells paralleled those observed in rat proximal colon. A pattern similar to the electrical response was observed with cGMP concentration. Guanylin addition to either side of Caco-2 cells induced the same effects as ST, although to a lesser extent. In all conditions, the electrical effect disappeared in the absence of chloride. ST directly interacts with basolateral receptors in the large intestine inducing chloride secretion through an increase of cGMP. However, the serosal effects are less pronounced compared with those observed with mucosal addition. Guanylin shows the same pattern, suggesting that it plays a role in the regulation of ion transport in the colon, but the relative importance of serosally mediated secretion remains to be determined.

Background. Because zinc deficiency in malnourished children is associated with severe diarrhea, use of zinc supplementation has been proposed as an adjunct to oral rehydration. However, the effects of zinc on enterocyte ion transport are largely unknown. The objective of the present study was to investigate the effects of zinc on transepithelial ion transport under basal conditions and under conditions of enterotoxin-induced ion secretion. Methods. Ion transport was investigated by monitoring electrical parameters in human intestinal Caco-2 cells that were mounted in Ussing chambers and exposed to increasing concentrations of zinc, both in the absence and presence of either cholera toxin (CT) or Escherichia coli heat-stable enterotoxin (ST). Intracellular cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) concentrations were also determined. Results. The addition of zinc to the luminal or basolateral side of enterocytes induced a chloride-dependent, dose-related decrease in short-circuit current, indicating ion absorption. It also resulted in a substantial reduction in CT-induced ion secretion and in cAMP concentration. E. coli ST–induced ion secretion and cGMP concentration were not affected. Ion absorption peaked at 35 mmol/L zinc, whereas excess zinc load induced active ion secretion. Conclusions. By causing a decrease in cAMP concentration, zinc directly promotes ion absorption and substantially reduces CT-induced, but not E. coli ST–induced, ion secretion. Worldwide, infectious diarrhea is still associated with high morbidity and mortality in persons of pediatric ages. The death rate has been estimated to be as high as 2.5 million children every year, with almost all deaths occurring in malnourished children in developing countries. Besides rotavirus, the major causal agents of diarrhea are Vibrio cholerae and enterotoxigenic Escherichia coli [1]. Cholera toxin (CT) and E. coli heat-labile enterotoxin (LT) induce secretory diarrhea by causing an increase in cAMP concentration, whereas E. coli heat-stable enterotoxin (ST) does so by activating the guanylate cyclase/cGMP system [2]. The use of oral rehydration solution (ORS) for treatment of diarrhea has become widespread and has resulted in reduced

Several lines of evidence link inflammatory bowel diseases to modifications of intestinal microflora. Epidemiologic and clinical data suggest a triggering role for select agents in ulcerative colitis and in Crohn disease. Experimental evidence indicates that intestinal microorganisms are needed for developing intestinal inflammation in IL-10 knockout mice, and this is associated with an increased number of adherent clostridia and a decrease of lactobacilli and bifidobacteria. It may be hypothesized that a host-agent-specific relationship leads to an abnormal immune response, which may be genetically driven in select inflammatory bowel diseases. However, different from adults, the pattern of intestinal microflora undergoes profound changes during the early stage of life, contributing to the development of the immune system. A close relationship exists between microbiologic and immunologic imprinting. The microbiologic imprinting in neonates may be modified using bacterial probiotics that colonize the intestine, modify the immune response, and decrease the risk for atopy. Probiotics may decrease the recurrences of inflammatory bowel diseases. Preliminary evidence of intestinal antiinflammatory effects has been detected in children with cystic fibrosis. Overall these data provide the rationale to investigate the interaction between intestinal microflora and the local and general immune response in children with, or at risk for, inflammatory bowel diseases. This approach may be a key for understanding the pathophysiology of intestinal inflammation and may disclose novel strategies to educate better the immune system, particularly during its developmental stage.

A double scenario characterizes the epidemiology of HIV infection in children. In countries where highly active antiretroviral therapy (HAART) is available, the pattern of HIV infection is evolving into that of a chronic disease, for which control strictly depends on patients' adherence to treatment. In developing countries with no or limited access to HAART, AIDS is rapidly expanding and is loaded with a high fatality ratio, due to the combined effects of malnutrition and opportunistic infections. The digestive tract is a target of the disease in both settings. Opportunistic infections play a major role in children with severe immune impairment, with Cryptosporidium parvum being the leading agent of severe diarrhea. Several therapeutic approaches are effective in reducing fecal output, but the eradication of the parasite is rarely obtained. Other opportunistic infections may induce severe and protracted diarrhea, including atypical mycobacteria and cytomegalovirus. Diagnosis of diarrhea should be individually tailored based on presenting symptoms and risk factors. A stepwise approach is effective in limiting patient discomfort and minimizing the costs of investigations, starting with microbiologic investigation and proceeding with endoscopy and histology. Aggressive treatment of infectious diarrhea is required in severely immunocompromised children. However, antiretroviral therapy prevents the development of severe cryptosporidiosis. The liver and pancreas are also target organs in HIV infection, although functional failure is rare. The digestive-absorptive functions are impaired, with steatorrhea, nutrient malabsorption, and increased permeability occurring in 20-70% of children. Intestinal dysfunction contributes to growth failure and further immune derangement, leading to wasting, the terminal stage of AIDS. Nutritional management is crucial in HIV-infected children and is based on aggressive nutritional rehabilitation through enteral or parenteral routes and micronutrient supplementation.HIV may play a direct enteropathogenic role and is implicated in both diarrhea and intestinal dysfunction. This explains the efficacy of antiretroviral therapy in inducing remission of diarrhea and restoring intestinal function. Gastrointestinal side effects of antiretroviral drugs are increasingly observed; they are often mild and transient. Severe reactions are rare but require the withdrawal of drugs. In conclusion, severe enteric infections and intestinal dysfunction characterize the intestinal involvement of HIV infection. This is more common in, but not limited to, children who do not receive effective antiretroviral therapy. Diagnostic approaches include microbiologic and morphologic examinations and assessment of digestive processes, but immunologic and virologic data should be also carefully considered. Treatment is based upon specific anti-infectious drugs, antiretroviral therapy, and nutritional rehabilitation.

The role of nitric oxide (NO) in the intestinal basal ion transport and under conditions of enterotoxin-induced ion secretion is controversial. Namely it is not clear whether NO enhances or counteracts intestinal ion secretion and whether the effects on transport result from a direct interaction with the enterocyte. The cell origin of NO is also unclear. We have tested the hypothesis that NO produced by the enterocyte directly regulates ion transport processes either in basal condition or in response to cholera toxin-induced secretion. Electrical variables reflecting transepithelial ion transport were measured in Caco-2 cell monolayers mounted in Ussing chambers exposed to the NO synthase inhibitor Nomega-nitro-l-arginine methyl ester, in the presence or absence of cholera toxin. cAMP concentrations were also measured. NO release was determined by nitrite-nitrate concentration. NO synthase activities were assayed by Western blot analysis. Nomega-nitro-l-arginine methyl ester had a secretory effect, as judged by increased basal short-circuit current and cAMP concentration. It also increased cholera toxin-induced electrical response and cAMP production. Either cholera toxin or the cAMP analog 8-bromo-cAMP induced a rapidly progressive and Ca2+-dependent increase in NO concentration, suggesting a homeostatic up-regulation of the constitutive form of NO synthase. Western blot analysis showed an increase in constitutive NO synthase enzyme isoform. These results indicate that the enterocyte regulates its own ion transport processes, either in basal condition or in the presence of active secretion, through the activation of a constitutive NO synthase-NO pathway, functioning as a braking force of cAMP-induced ion secretion.

Celiac disease is an exemplary model of T cell-mediated pathology. Therefore, therapeutic approaches that target T cells may successfully control this disease. CTLA-4 immunoglobulin (CTLA-4Ig) can inhibit T-cell activation by blocking the engagement of CD28. We took advantage of this tool to define the pathogenic role of gliadin-specific T cells in the induction of celiac disease.Duodenal biopsy specimens from 7 treated celiac patients were challenged in vitro with gliadin and CTLA-4Ig or CD40-Ig. After 24 hours, the biopsy specimens were analyzed for the presence of characteristic modifications induced by gliadin challenge.CTLA-4Ig down-regulated the expression of CD25, intercellular adhesion molecule 1, interleukin 2, and interferon gamma (stained lamina propria mononuclear cells/mm2; P0.05) induced by gliadin challenge, caused apoptosis of gliadin-specific T cells (apoptotic T cells/mm2; P0.05), and inhibited the production of antiendomysial antibody (P0.01). However, it did not control intraepithelial T-cell migration (P = NS) and Fas expression by enterocytes. Conversely, CD40-Ig only controlled production of antiendomysial antibody.In an organ culture model, CTLA-4Ig controls many but not all of the immunologic features of celiac disease.

Cystic fibrosis (CF) is a single-gene disease caused by mutations in the CFTR gene, which result in disrupted chloride secretions with inspissated mucous secretions by exocrine glands. Nick-end labelling was used to assess DNA fragmentation in 14 CF and 24 control duodenal samples, and in two CF and two control lung tissues. In CF small intestine median 46% (range: 30–82) villus enterocytes show DNA fragmentation (vs. 3% (range: 1–7) in controls P