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Biomedical subjects

A Guarino

Publications and source records attributed to A Guarino.

At least 37 records · Page 2Linked to original sources

Which place for bismuth subsalicylate in the treatment of enteric infections?

ORS has led to improved outcome of acute gastroenteritis in both industrialised and developing countries. In both settings there is an increasing demand for active therapy to reduce the duration of diarrhoea and its complications. Persistent diarrhoea is a major consequence of intestinal infections and is responsible for a high number of deaths in poor countries. Bismuth subsalicylate has been used for treatment of acute diarrhoea, with preliminary promising results. In this issue of Acta Paediatrica, a trial with BSS is essential. However the results were marginal and did not justify a mass scale use of BSS, also because of poor cost efficacy rate.

Acute Disease↗

Neosporosis in water buffalo (Bubalus bubalis) in Southern Italy.

A study was carried on 1377 water buffalo serum samples from 50 farms in southern Italy to test the presence of Neospora caninum antibodies by indirect fluorescence antibody test (IFAT). Rabbit anti-buffalo immunoglobulins conjugated to fluorescein were used in the test. Fluorescence in sera dilutions above 1:200 was considered as indicative of the presence of N. caninum antibodies. The overall prevalence of infection in the animals was 34.6%. The prevalence increased in relation to the age of subjects and most of the herds examined (82%) were found infected. In two farms abortions and neurological signs were reported. No suppurative inflammatory lesions were seen, but few protozoan-like cysts were observed on foetal tissues by histology.

Abortion, Veterinary↗

Recombinant human, active site-blocked factor VIIa reduces infarct size and no-reflow phenomenon in rabbits.

Oxygen free radicals induce de novo synthesis of tissue factor (TF), the initiator of the extrinsic pathway of coagulation, within the coronary vasculature during postischemic reperfusion. In the present study we wanted to assess whether TF expression might cause myocardial injury during postischemic reperfusion. Anesthetized rabbits underwent 30 min of coronary occlusion followed by 5.5 h of reperfusion. At reperfusion the animals received 1) saline (n = 8), 2) human recombinant, active site-blocked activated factor VII (FVIIai, 1 mg/kg, n = 8), or 3) human recombinant activated FVII (FVIIa, 1 mg/kg, n = 8). FVIIai binds to TF as native FVII, but with the active site blocked it inhibits TF procoagulant activity. The area at risk of infarction (AR), the infarct size (IS), and the no-reflow area (NR) were determined at the end of the experiment. FVIIai resulted in a significant reduction in IS and NR with respect to control animals (28.1 +/- 11.3 and 11.1 +/- 6.1% of AR vs. 59.8 +/- 12.8 and 24.4 +/- 2.7% of AR, respectively, P < 0.01), whereas FVIIa resulted in a significant increase in IS and NR to 80.1 +/- 13. 1 and 61.9 +/- 13.8% of AR, respectively (P < 0.01). In conclusion, TF-mediated activation of the extrinsic coagulation pathway makes an important contribution to myocardial injury during postischemic reperfusion.

Amino Acid Chloromethyl Ketones↗

Structural and functional features of modified heat-stable toxins produced by enteropathogenic Klebsiella cells.

Heat-stable enterotoxins (STs) are 18- or 19-amino acid peptides (STa or ST1) produced by enteropathogenic bacteria with small differences in their amino acid sequence and a highly conserved carboxy terminus. All STs contain a core of three disulfide bridges whose integrity is believed to be necessary for full biologic activity. We previously reported that strains of Klebsiella pneumoniae transformed by the plasmid pSLM004 produce a modified toxin not recognized by MAb raised against genuine Escherichia coli ST. Investigation of the chemical structure of the modified toxins revealed that three new toxins were present. These were purified to homogeneity by a series of sequential chromatography on reverse-phase columns using guanylate cyclase to monitor the enterotoxic activity during purification procedures. The sequence of the modified toxins was obtained by a combination of Edman degradation and mass spectrometry, showing that they are proteolytically processed forms of E. coli ST1b. In particular, toxin A-2 lacks the cysteine at position 18 and then is not able to form the disulfide bridge cysteine-10-cysteine-18. All three toxins showed the ability to stimulate guanylate cyclase and to elicit chloride secretion in Caco-2 cell monolayers mounted in Ussing chambers. Toxin A-1 and toxin B demonstrated greatly reduced immunoreactivity whereas toxin A-2 was not recognized at all in the ELISA. It is likely that the three modified toxins were generated by Klebsiella specific proteolytic processing of the original pretoxin. These results have important implications for the diagnosis and prevention of heat-stable toxin-induced diarrhea.

Antibodies, Bacterial↗

[The timing of tracheotomy. Advantages of early timing].

Tracheotomy is widely performed in Intensive Care Units, but no general agreement exists about its correct timing in ventilated patients. Many articles examine the complications of long-term endotracheal intubation and tracheotomy; few data, however, relate these damages and ventilated patients outcome to tracheotomy timing. No universally accepted guidelines exist, but last years clinical practice prefer early tracheotomy, particularly if performed by percutaneous approach. Many authors suggest prospective and randomized clinical trials in order to evaluate tracheotomy performance correct time. At this time decision making must consider risks and benefits related to patient clinical conditions: at this regard some reports seem to advantage early tracheotomy.

Critical Care↗

Ritonavir combination therapy restores intestinal function in children with advanced HIV disease.

OBJECTIVES: To investigate the intestinal absorptive processes in children with HIV infection before and after treatment with combination therapy that includes ritonavir. To test the hypothesis that combination therapy improves intestinal function. DESIGN: Intestinal function tests were performed in 10 children with advanced HIV disease at the enrollment and after 3 and 6 months of therapy with ritonavir combined with two HIV reverse transcriptase inhibitors. HIV viral load and CD4 cell counts were also determined; body weight was monitored. METHODS: The D-xylose absorption test, the steatocrit and the determination of fecal alpha1-antitrypsin concentration were used to evaluate carbohydrate and fat absorption, as well as fecal protein loss. Serum iron levels were measured to indirectly evaluate iron absorption. HIV-1 RNA-polymerase chain reaction (PCR) and immunofluorescence imaging were used to evaluate virologic and immunologic responses. RESULTS: In all, 9 children had carbohydrate malabsorption, 3 steatorrhea, 2 protein loss, and 7 iron deficiency. Most tests produced normal results after 3 months of therapy, and all abnormalities were abolished 6 months after institution of combination therapy. Mean results of each of four absorption tests were significantly changed on combination therapy. Viral load was progressively reduced and CD4 count was increased, with an inverse relationship. An evident shift of body weight pattern toward catch-up growth was observed in all children. CONCLUSIONS: Ritonavir combination therapy results in prompt and sustained restoration of intestinal function, which is associated with reduction in viral load, increase in CD4 counts, and gain in body weight.

Adolescent↗

Exocrine pancreatic function and fat malabsorption in human immunodeficiency virus-infected patients.

BACKGROUND: Nutrients malabsorption frequently occurs in human immunodeficiency virus (HIV)-infected patients, but very few studies have investigated exocrine pancreatic digestive capacity in these patients. We therefore evaluated the frequency of exocrine pancreatic impairment and its eventual relation with fat malabsorption in HIV-infected patients. METHODS: Thirty-five HIV-infected patients (30 male, 5 female: mean age +/- standard deviation, 33.6 +/- 7.2 years) and 51 sex- and age-matched controls without gastroenterologic diseases were studied. In all subjects fecal elastase 1 (EL-1) was assayed, and fecal fat excretion was evaluated with the steatocrit test. RESULTS: Nineteen of 35 (54%) HIV-infected patients showed subnormal EL-1 values, whereas all the controls had normal values; furthermore, EL-1 values were significantly lower in patients than in controls: mean (95% confidence intervals), 207 ( 164-251 ) microg/g versus 312 (291-332) microg/g (P < 0.0001). Increased fecal fat excretion was observed in almost all (25 of 35) HIV-infected patients, and an inverse but not significant correlation was found between fecal EL-1 and steatocrit values. No association was found between reduced fecal EL-1 and the severity of HIV disease or nutritional and immunologic status. Opportunistic infections and drug administration had no influence on EL-1 concentrations in stools. CONCLUSIONS: Reduced exopancreatic function is frequent in HIV-infected patients but does not seem to be a major factor contributing to fat malabsorption.

Adult↗

Adherence to antiretroviral therapy in HIV-infected children in Italy.

Adherence to antiretroviral therapy is a major problem in children with HIV infection, who depend on parents or foster parents for receiving drugs. During an ongoing investigation on intestinal function in children with symptomatic HIV infection who were treated with zidovudine, blood samples were obtained six hours after the administration of zidovudine as reported by the parents and, again, one and six hours after its administration in the hospital, and drug concentration was measured by radioimmunoassay. Both peak and steady state zidovudine levels were within the expected concentration ranges after administration in the hospital. In contrast, they were below the effective concentration in five of the 10 children that reportedly had received the drug at home by the parents. These data directly show poor compliance with antiretroviral therapy in children. Compliance with antiretroviral therapy should be carefully checked in children and strategies are needed to increase full and permanent adherence with antiretroviral therapy by people in charge to administer drugs to HIV-infected children.

Anti-HIV Agents↗

Growth hormone stimulates, through tyrosine kinase, ion transport and proliferation in human intestinal cells.

BACKGROUND: Growth hormone (GH) stimulates intestinal growth and differentiation and promotes water and ion absorption in the rat intestine. Epidermal growth factor has similar effects, which involve tyrosine kinase activity. The effects of growth hormone on ion transport and cell growth and the role of tyrosine kinase in these effects were examined in a human-derived intestinal cell line (Caco-2). METHODS: For transport study, electrical parameters were measured in human intestinal Caco-2 cell monolayers mounted in Ussing chambers. Cell growth was monitored by counting and 3H-thymidine incorporation in the presence and absence of growth hormone. The role of tyrosine kinase was investigated by using its specific inhibitor genistein. RESULTS: The addition of growth hormone induced a rapid, Cl- -dependent, decrease in short-circuit current without affecting tissue conductance, which is consistent with an anion-absorptive effect. Incubation with growth hormone increased cell count by 85% and 3H-thymidine incorporation by 64% versus the count in control specimens. The absorptive and trophic effects of growth hormone were dose-dependent, and the maximum effective concentration was identical for each effect. Genistein blocked the growth hormone effect on ion transport and cell growth. CONCLUSIONS: Growth hormone stimulates ion absorption and cell growth in human enterocytes. Both effects result from a direct growth hormone-enterocyte interaction, and both require tyrosine kinase activity. Growth hormone may have therapeutic potential in intestinal diseases characterized by epithelial atrophy and loss of water and electrolytes.

Caco-2 Cells↗

Severe and protracted diarrhea: results of the 3-year SIGEP multicenter survey. Working Group of the Italian Society of Pediatric Gastroenterology and Hepatology (SIGEP).

BACKGROUND: The spectrum of severe and protracted diarrhea (SPD), previously defined as intractable diarrhea, has changed during the past several decades. Despite recent advances in determining the cause of SPD and in treatment, this syndrome still represents a challenge and is becoming a major problem affecting health care resources. This study was conducted to characterize the epidemiology, spectrum of causes, and the outcome of SPD in Italy in recent years. METHODS: All the SPD cases seen at the major centers of pediatric gastroenterology in Italy during a 3-year period (1993-1996) were recruited in this multicenter, prospective survey. RESULTS: Thirty-two children (26 boys and 6 girls; median age at the onset of SPD, 40 days) were enrolled in this study by 9 of 26 participating centers. Twelve were newly diagnosed cases, with an estimated SPD incidence rate in Italy of 0.64 to 0.92 x 10(-5) infants per year. The most common causes were autoimmune enteropathy (n = 8) and ultrastructural abnormalities of the enterocyte (n = 7), whereas food intolerance and postenteritis syndrome were less frequent (3 and 2 cases, respectively). Two children with autoimmune enteropathy fulfilled the criteria for the X-linked variant of this condition. At the end of the study period, 9 of 31 patients had recovered, 15 still had diarrhea, and 7 had died. CONCLUSIONS: Severe and protracted diarrhea is a rare but challenging problem in Italy. Because parenteral nutrition or intestinal transplantation are the only options in a subset of cases (e.g., ultrastructural abnormalities of the enterocyte), infants with SPD should be referred to specialized centers where advanced diagnostic and therapeutic facilities are available.

Autoimmune Diseases↗

Experimental tracheal transplantation using a cryopreserved aortic allograft.

BACKGROUND: The tracheal reconstruction after wide resections remains a critical surgical problem. Our aim was to replace trachea with a tissue easy to vascularize, which allows a simple reconstruction and does not require an immunosuppressive regimen. MATERIALS AND METHODS: A segment of cryopreserved aorta was used in order to verify its adequacy as tracheal substitute. In phase 1, the thoracic aorta of 10 rabbits was excised, obtaining 20 segments that were cryopreserved. Ten segments were implanted in the omentum of 10 rabbits that were sacrificed on postoperative days 7, 14 and 21, and the grafts were examined histologically. In phase 2, a segment of cryopreserved aorta arranged with a silicone prosthesis was transplanted in 10 rabbits and wrapped with omentum. The animals were sacrificed on postoperative days 7, 14 and 21. RESULTS: In phase 1, the neovascularization of the grafts was present after 7 days, and after 14 days the fibroblasts invaded the lumen of the aorta. In phase 2, 8 rabbits survived and the histologic examination after 7, 14 and 21 days showed neovascularization, the absence of rejection and the proliferation of fibroblasts inside the lumen of the aorta; this growth has been restrained by an endoluminal prosthesis. CONCLUSIONS: Our study demonstrated that replacing the trachea with cryopreserved aorta is technically feasible and does not evoke immunologic reactions. It requires, however, a silicone tube inside the allograft to limit the colonization of fibroblasts.

Animals↗