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Biomedical subjects

Giulio De Marco

Publications and source records attributed to Giulio De Marco.

12 recordsLinked to original sources
PubMed2007

Cancer rates after year 2000 significantly decrease in children with perinatal HIV infection: a study by the Italian Register for HIV Infection in Children.

PURPOSE: To evaluate the impact of highly active antiretroviral therapy (HAART) on cancer incidence in HIV-infected children throughout a 20-year period. PATIENTS AND METHODS: An observational population study was conducted on 1,190 perinatally HIV-infected children enrolled onto the Italian Register for HIV Infection in Children from 1985 to 2004 and never lost to follow-up (total observation time, 10,037.66 years). Cancer rates were calculated in the pre-HAART (1985 to 1995), early HAART (1996 to 1999), and late HAART (2000 to 2004) periods and compared using Poisson regression adjusted for age. The proportion of HAART-treated children increased from 4.1% in 1996 to 60.4% in 1999 and to 81.5% in 2004. In the same time frame, the proportion of children receiving HAART for at least 2 years increased from 3.1% to 77.0%. RESULTS: Overall, 35 cancers occurred. Cancer rates were 4.49 (95% CI, 2.37 to 6.64), 4.09 (95% CI, 1.68 to 6.50), and 0.76 (95% CI, 0.00 to 1.80) per 1,000 children per year in 1985 to 1995, 1996 to 1999, and 2000 to 2004, respectively. Notably, there was no significant difference comparing the periods from 1985 to 1995 and 1996 to 1999 (P = .081). By contrast, cancer rates were significantly lower in the period from 2000 to 2004 than in 1996 to 1999 (P < .0001). Results were confirmed by separately analyzing data from children observed from birth (P = .418 for 1985 to 1995 v 1996 to 1999; P = .001 for 1996 to 1999 v 2000 to 2004). CONCLUSION: Dramatically reduced cancer rates were observed only in the late HAART period in parallel to the increasing proportion of children receiving HAART therapy.

Antiretroviral Therapy, Highly Active↗
PubMed2006

Growth hormone regulates intestinal ion transport through a modulation of the constitutive nitric oxide synthase-nitric oxide-cAMP pathway.

AIM: Growth hormone (GH) directly interacts with the enterocyte stimulating ion absorption and reducing ion secretion induced by agonists of cAMP. Since nitric oxide (NO) is involved in the regulation of transepithelial ion transport and acts as a second messenger for GH hemodynamic effects, we tested the hypothesis that NO may be involved in the resulting effects of GH on intestinal ion transport. METHODS: Electrical parameters reflecting trans-epithelial ion transport were measured in Caco-2 cell monolayers mounted in Ussing chambers and exposed to GH and cholera toxin (CT) alone or in combination, in the presence or absence of the NO synthase (NOS) inhibitor, Nomega-nitro-L-arginine methyl ester (L-NAME). Similar experiments were conducted to determine cAMP and nitrite/nitrate concentrations. NOS expression was assayed by Western blot analysis. RESULTS: L-NAME causes total abrogation of absorptive and anti-secretory effects by GH on intestinal ion transport. In addition, L-NAME was able to inhibit the GH-effects on intracellular cAMP concentration under basal conditions and in response to CT. GH induced a Ca(2+)-dependent increase of nitrites/nitrates production, indicating the involvement of the constitutive rather than the inducible NOS isoform, which was directly confirmed by Western blot analysis. CONCLUSION: These results suggest that the GH effects on intestinal ion transport, either under basal conditions or in the presence of cAMP-stimulated ion secretion, are mediated at an intracellular level by the activity of cNOS.

Caco-2 Cells↗
PubMed2006

Inhibitory effect of HIV-1 Tat protein on the sodium-D-glucose symporter of human intestinal epithelial cells.

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. alpha-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 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 alpha-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.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed2006

Network approach to the child with primary intestinal failure.

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.

Child↗
PubMed2006

Antiemetics for children with gastroenteritis: off-label but still on in clinical practice.

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.

Acute Disease↗
PubMed2005

Zinc inhibits cholera toxin-induced, but not Escherichia coli heat-stable enterotoxin-induced, ion secretion in human enterocytes.

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 mu mol/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.

Bacterial Toxins↗
PubMed2005

Reduction of inappropriate hospital admissions of children with influenza-like illness through the implementation of specific guidelines: a case-controlled study.

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 specific 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 inappropriate 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 appropriateness. 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.

Adolescent↗
PubMed2004

Microflora in inflammatory bowel diseases: a pediatric perspective.

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.

Animals↗
PubMed2004

Management of gastrointestinal disorders in children with HIV infection.

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.

AIDS-Related Opportunistic Infections↗
PubMed2003

Nitric oxide produced by the enterocyte is involved in the cellular regulation of ion transport.

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.

Biological Transport↗
PubMed2003

Natural history of intestinal failure, investigated through a national network-based approach.

OBJECTIVES: Intestinal failure (IF) is a condition whose treatment requires advanced knowledge and techniques and a multidisciplinary approach. Intestinal failure is the endpoint of many intestinal diseases and may result in full recovery, in life-long parenteral nutrition, or in the death of the child. The aim of this study was to evaluate the natural history of IF in children using a national network of resources. METHODS: Italian centers of pediatric gastroenterology merged in a national network, developing a collaborative management approach for children with IF. A consensus definition of IF was achieved. A database was set up to investigate the cause, epidemiologic factors, and natural history of IF. RESULTS: One hundred nine children were enrolled in 5 years. The cause of IF was: short bowel syndrome (n = 48), disorders of motility (n = 16), structural enterocyte defects (n = 14), multiple food intolerance (n = 10), autoimmune enteropathy (n = 7), and others or unknown (n = 14). The eventual outcome was closely related to the primary cause, ranging from full and permanent intestinal sufficiency in children with multiple food intolerance to high death rate or total dependance upon parenteral nutrition in those with structural enterocyte defects. Intermediate outcomes were observed for the other causes. Four children received intestinal transplantation. CONCLUSIONS: The network approach for IF provides an effective model to optimize resources and to investigate prospectively the natural history of IF. Based on the work on this series, a European network for IF could be an effective model for fulfilling the diagnostic and management needs, including intestinal transplantation.

Adolescent↗