Freezing-induced self-assembly of amphiphilic molecules.

The self-assembly of amphiphilic molecules usually takes place in a liquid phase, near room temperature. Here, using small angle X-ray scattering (SAXS) experiments performed in real time, we show that freezing of aqueous solutions of copolymer amphiphilic molecules can induce self-assembly below 0 °C.

[Asbestos-related diseases in former asbestos-cement workers in Senigallia]. / Le patologie asbesto-correlate degli ex addetti alla produzione di manufatti in cemento amianto a Senigallia.

BACKGROUND: A factory that produced asbestos-cement products, using chrysotile, amosite and crocidolite in very low percentages, cement and water, operated in Senigallia from 1948 to 1984. Workers and residents still living in Senigallia are 238. OBJECTIVES: The need for an organic response to requests by former workers for protection of health and recognition of occupational diseases induced the Prevention and Safety at the Workplace Service in Senigallia/Area Vasta 2 to implement a programme of health surveillance. METHODS: In 2010 a health surveillance programme was initiated that involved 158 subjects, 58 women and 100 men. The average age of men was 75 years and 70 for women. The time elapsed between first exposure and participation in the programme was on average 50 years (SD 7.49). The average number of years of exposure to asbestos fibres was 17 (SD 10.36). The programme included counselling activities, especially as regards cessation of smoking, and first and second level health checks. RESULTS: The health surveillance programme enabled us to diagnose pleural plaques and pleural thickening in 81% of the subjects and various degrees of interstitial abnormalities in 49.4%. The high percentage of asbestos-related diseases was connected mainly with the long latency of the population under study and the higher diagnostic sensitivity of low dose chest CT scan applied to these diseases. CONCLUSIONS: In our experience, in order to optimize the benefits of a health surveillance programme of former workers exposed to asbestos, it will be advisable to define parameters of access to the programme for individual subjects in relation to life expectancy, clinical conditions, time elapsed since first exposure, time of cessation of exposure. Such parameters, together with any risk factors, will influence the diagnostic process.

Waist circumference correlates with liver fibrosis in children with non-alcoholic steatohepatitis.

OBJECTIVE: Waist circumference is widely accepted as a risk factor for cardiovascular disease and metabolic syndrome. Non-alcoholic fatty liver disease (NAFLD) is a feature of the metabolic syndrome. A contribution of metabolic syndrome, and especially of waist circumference, to liver fibrosis in children with NAFLD is strongly suspected. DESIGN: Cross-sectional study. SETTING: Department of Hepatogastroenterology and Nutrition, Paediatric Hospital "Bambino Gesù", Rome, Italy. PATIENTS: 197 consecutive Caucasian children with NAFLD (136 males and 61 females) aged 3-19 years. MAIN OUTCOME MEASURES: Multivariable logistic regression models were used to examine the contribution of gender, age, body mass index (BMI) and metabolic syndrome components (waist circumference, high-density lipoprotein (HDL)-cholesterol, triglycerides, blood pressure and glucose) to the odds of liver fibrosis as detected by liver biopsy. RESULTS: 92% of the children had BMI > or = 85(th) percentile and 84% had a waist > or = 90(th) percentile for gender and age. Ten per cent of the children had metabolic syndrome and 67% had liver fibrosis, mostly of low degree. At multivariable analysis, waist was the only metabolic syndrome component to be associated with liver fibrosis. This was seen both when the components of the metabolic syndrome were coded as dichotomous (odds ratio (OR) = 2.40; 95% confidence interval (CI), 1.04 to 5.54) and continuous (OR = 2.07; 95% CI, 1.43 to 2.98 for a 5 cm increase). In the latter case, age was also associated with the outcome (OR = 0.70; 95% CI, 0.55 to 0.89 for a 1 year increase). CONCLUSIONS: Abdominal rather than generalised obesity contributes to liver fibrosis in children with NAFLD. Waist is also the only component of the metabolic syndrome to be associated with fibrosis in these children. Therefore, the presence of abdominal obesity is an additional criterion for the selection of children and adolescents who should undergo extensive investigation, including liver biopsy.

Metabolic syndrome and liver histology in paediatric non-alcoholic steatohepatitis.

OBJECTIVE: Our aim was to estimate prevalence of metabolic syndrome (MS), obesity and comorbidities in a cohort of 120 children (3-18 years) with biopsy-proven non-alcoholic fatty liver disease (NAFLD) or non-alcoholic steatohepatitis (NASH) and to evaluate correlations between clinical or biochemical variables and liver histology. RESEARCH METHODS AND PROCEDURES: MS was diagnosed according to the adapted National Cholesterol Education Program criteria. Homeostatic model assessment of insulin resistance (HOMA-IR), quantitative insulin-sensitivity check index (QUICKI); and ISI composite, insulin secretion (insulin response at 30 min after a glucose load; HOMA-beta cell; insulinogenic index) were all estimated. BMI z-score and total body fat (dual-energy X-ray absorptiometry) were evaluated as indexes of obesity. RESULTS: MS was diagnosed in 66% of children. About 92% had weight above the 85th percentile, of which 42% were obese with weight above 97th percentile. Prevalence of hypertriglyceridaemia was 63%, low HDL cholesterol 45%, hypertension 40% and impaired glucose tolerance 10%. Levels of aminotransferases were higher as the number of comorbidities increased, the highest values being found in subjects with MS (P< or =0.05). Prevalence of a grade of steatosis > or =2 (P=0.05) and fibrosis (P< or =0.01) was higher in subjects with MS. Histology was associated significantly with higher values of a number of clinical and biochemical parameters (steatosis > or =2 with BMI z-score (P=0.04), fasting insulin (P=0.02), HOMA-IR (P=0.03), beta-cell secretion (P=0.04); necroinflammation with BMI z-score (P=0.007), glucose (P< or =0.0001), cholesterol (P< or =0.04) and white blood cells (P=0.025); fibrosis with body weight (P=0.05), BMI z-score (P=0.03), cholesterol (P=0.05), triglycerides (P=0.05), fasting insulin (P< or =0.0001) and mean values of the hormone at the OGTT (P=0.03), HOMA-IR (P< or =0.0001)). CONCLUSION: Presence of MS or clinical and biochemical variables associated with the syndrome seems to be strictly related to histological features of NASH in paediatric fatty liver disease. Thus, routinely liver biopsy should be encouraged in these children.

Escherichia coli Nissle 1917 restores epithelial permeability alterations induced by irritable bowel syndrome mediators.

BACKGROUND: Intestinal permeability is altered in a subgroup of irritable bowel syndrome (IBS) patients and may contribute to symptom development. The aim of this study was to evaluate the in vitro effect of the probiotic Escherichia coli Nissle 1917 (EcN) on Caco-2 permeability alterations induced by mediators released by IBS mucosal biopsies compared to asymptomatic controls (AC). METHODS: Caco-2 cells were used as an in vitro model of intestinal permeability. Seven AC and 28 well-phenotyped IBS (9 IBS-D, 8 IBS-C, and 11 IBS-M) patients were enrolled. Mucosal mediators spontaneously released (SUP) by IBS and AC biopsies were collected. Two concentrations of EcN (108 and 106 ) were applied to Caco-2 with or without SUP or SLIGRL (a protease-activated receptor-2 activating peptide), tumor necrosis factor-α, and interferon-γ. Paracellular permeability was assessed by evaluating the flow of sulfonic-acid conjugated to fluorescein through Caco-2 monolayer. KEY RESULTS: EcN 108 significantly reinforced Caco-2 monolayer compared to cells incubated with medium alone. IBS SUP induced a significant increase in paracellular permeability compared to AC SUP, independently of IBS bowel habit. EcN 108 induced a significant recovery of permeability rate compared to IBS SUP. Permeability increase induced by IBS SUP significantly correlated with severity and frequency of abdominal pain and abdominal distension. The co-incubation of EcN and IBS SUP abolished the above significant correlations. CONCLUSIONS AND INFERENCES: EcN reinforces the integrity of Caco-2 monolayer and reverts the increase of permeability induced by mediators released by IBS biopsies. Future studies should investigate EcN therapeutic potentials in IBS.

The inflammation-sensitive protein alpha 1-anti-chymotrypsin neutralizes fibrillar aggregation and cytotoxicity of the beta-amyloid peptide more effectively than alpha 1-antitrypsin.

OBJECTIVES: A neuroinflammatory process, triggered by amyloid-beta (Abeta)-peptide, is thought to play a central role in the neurodegenerative process leading to Alzheimer's disease (AD). Abeta(25-35) retains the functionality of Abeta(42) and was employed to investigate the effects of inflammation-sensitive proteins (ISPs) alpha1-antichymotrypsin (A1ACT) and alpha1-antitrypsin (A1AT) on fibrillar aggregation and cytotoxicity. DESIGN AND METHODS: Inhibitory concentrations of the ISPs were determined in an established human red blood cell lysis model of Abeta-cytotoxicity. For studies of Abeta-fibrillar aggregation CSF levels of A1ACT (0.041 microM)/A1AT (0.11 microM) were incubated with Congo Red dye 25 microM+Abeta(25-35) 10 microM noting the formation of visible aggregates and spectrophotometric changes over 24 h. RESULTS: A1ACT at CSF reported levels inhibited fibrillar aggregation and cytotoxicity while A1AT at CSF reported levels failed to cause a similar inhibition. CONCLUSIONS: A1ACT neutralizes fibrillar aggregation and cytotoxicity of Abeta-peptide more effectively than A1AT. Both proteins are known to be co-deposited with Abeta within senile plaques of AD brains.

Effect of vitamin E on aminotransferase levels and insulin resistance in children with non-alcoholic fatty liver disease.

BACKGROUND: Few data are available on the effect of antioxidants in paediatric non-alcoholic fatty liver disease (NAFLD). AIM: To compare the effect of a nutritional programme alone or combined with alpha-tocopherol and ascorbic acid on alanine aminotransferase (ALT) levels, and insulin resistance (IR) in biopsy-proven NAFLD children. METHODS: IN a 12-month double-blind placebo study, 90 patients were prescribed a balanced calorie diet (25-30 cal/kg/d), physical exercise, and placebo (group A) or alpha-tocopherol 600 IU/day plus ascorbic acid 500 mg/day (group B). IR was estimated by the homeostasis model assessment (HOMA-IR). RESULTS: At month 12, ALT (32.67 +/- 8.09 vs. 32.18 +/- 11.39 IU/L; P = NS), HOMA-IR (1.52 +/- 0.66 vs. 1.84 +/- 0.95 IU/L; P = NS), and weight loss (32% vs. 35% of excessive body weight; P = NS) did not differ between the two arms. Among subjects who lost >or=20% of their excessive weight, ALT and body weight percentage changes were significantly related (r(o) = 0.260; P = 0.03). In subjects, who lost more than 1.0 kg, HOMA-IR significantly decreased (2.20 +/- 0.21 to 1.57 +/- 0.13 in group A (P

Intensive weekly chemotherapy for advanced gastric cancer using fluorouracil, cisplatin, epi-doxorubicin, 6S-leucovorin, glutathione, and filgrastim: a report from the Italian Group for the Study of Digestive Tract Cancer.

PURPOSE: A multiinstitutional trial was performed to confirm the clinical activity, in terms of response rate and toxicity (primary objectives) and duration of responses and survival (secondary objectives), of an intensive weekly regimen in advanced gastric cancer. PATIENTS AND METHODS: Patients with measurable unresectable and/or metastatic gastric carcinoma received 1-day per week administration of cisplatin (CDDP) 40 mg/m2, fluorouracil (5FU) 500 mg/m2, epi-doxorubicin (epi-ADR) 35 mg/m2, 6S-stereoisomer of leucovorin 250 mg/m2, and glutathione 1.5 g/m2. On the other days, filgrastim was administered by subcutaneous injection at a dose of 5 mg/kg. One cycle of therapy consisted of eight 1-week treatments. Patients who showed a response or stable disease received a further 6 weeks of therapy. RESULTS: Of 105 enrolled patients, 11 had locally advanced unresectable disease only; 33 had primary nonresected and metastatic disease; 48 had metastatic disease and primary tumor resected; 10 had locoregional recurrence and metastatic disease; and three had locoregional recurrence only. After one cycle, 18 complete responses (CRs) and 47 partial responses (PRs) were achieved, for an overall response rate of 62% (95% confidence interval [CI], 53% to 71%). Twenty patients had stable disease and 20 progressed on therapy. The median survival duration of all 105 patients was 11 months, with 1- and 2-year survival rates of 42% and 5%, respectively. World Health Organization (WHO) grade III to IV toxicity, in terms of anemia, neutropenia, thrombocytopenia, and mucositis, was experienced by 40 patients (38%). There were no treatment-related deaths. CONCLUSION: These data support the results of the pilot study and confirmed the high activity of the regimen, with acceptable toxicity. This schedule deserves evaluation in the adjuvant setting.

Interferon treatment in children with chronic hepatitis C: long-lasting remission in responders, and risk for disease progression in non-responders.

BACKGROUND AND AIM: Large interferon-based therapeutic trials are still lacking in children with hepatitis C and the long-term safety and efficacy of interferon is unknown. This study describes the outcome of hepatitis C in 43 children enrolled in an open-label interferon trial, and were followed up to 66 months after stopping treatment. PATIENTS AND METHODS: All patients received interferon alfa2a (5MU/m(2)) thrice weekly for 6 months; children with genotype 1b received 3MU/m(2) thrice weekly for 6 additional months. RESULTS: Nine children discontinued interferon for adverse events and three were not compliant to treatment. Eight (19%, intention to treat analysis), including 2/20 (10%) with genotype 1b and 6/12 (50%) with genotypes 2 or 3, were sustained responders 12 months after stopping therapy. During further follow-up (mean+/-S.D.: 44.7+/-14.6 months), response was maintained; two non-responders cleared viremia, while a young boy progressed to cirrhosis. CONCLUSIONS: Small sample size and therapy withdrawal are the major limitations in the interpretation of our results. Nevertheless, our data, suggesting that response to interferon in children with hepatitis C is genotype-related and stable, agree with the results of large studies in adults. The outcome in non-responders was variable, including persistence of viremia and mild-moderate cytolysis (most cases), progression to cirrhosis, or eventual sustained viremia clearance.

High dosage alpha-interferon for treatment of children and young adults with chronic hepatitis C disease.

BACKGROUND: There are limited data on the use of high interferon (IFN) dosage for treatment of children and young adults with hepatitis C virus infection and in those affected by thalassemia major (TM). OBJECTIVES: To assess the response of children and young adults with chronic hepatitis C disease, including those affected by TM, to high dose natural alpha-interferon (IFN-alpha). To evaluate the effect of iron overload in response to high dose IFN-alpha in young chronic hepatitis C virus thalassemia patients. METHODS: We conducted a therapeutic trial of natural IFN-alpha, using 10 million units/m2 three times a week for 6 months in 14 chronic hepatitis C patients ages 5 to 28 years; 7 also had TM. The follow-up period lasted 12 months. RESULTS: Ten patients (73%) showed normal or nearly normal alanine aminotransferase values at the end of follow-up (biochemical response), but only five (35%) were negative for serum hepatitis C virus-RNA (complete responders). Four of the patients (57%) with TM were sustained complete responders. No correlation was found between the initial serum concentration of ferritin and response to IFN therapy. Patients infected with genotype 1b showed a poor response although high dose of natural IFN was used. CONCLUSIONS: These results indicate that IFN-alpha can be used in children and young patients with chronic hepatitis C disease as well as in those affected by TM. Treatment with high dosage natural IFN-alpha in children and young adults with hepatitis C infection does not appear to be more effective than dosages previously used.

Gemcitabine in pre-treated advanced renal carcinoma: a feasibility study.

Eigtheen patients affected by metastatic renal cell carcinoma, 16 which were assesable, were treated with 1 g/m2 of Gemcitabine (GCB) on days 1, 8 and 15 of a 28-day treatment cycle up to a maximun of ten cycles. All patients in neoplastic progression were treated with chemo- and immunotherapy (5 FU, IL-2, IFN alpha d 13-cis-retinoic acid.) Out of the 16 assessable patients, 5/16 (31%) showed overall response (ICR, 4 PR), 5 (31%) stable disease (SD) and 6 (38%) progression of disease (PD). Toxicity was limited to WHO grades I only, primarily hematological.

Nerve-sparing surgery in rectal cancer: feasibility and functional results.

Traditional rectal cancer surgery has been burdened with a high rate of sexual and urinary dysfunctions due to intraoperative injury or the cutting of the sympathetic and/or parasympathetic nerves. The experience acquired in the last ten years with total mesorectal excisions has permitted the use of the "nerve-sparing" technique. The present study regards 239 patients from two surgical centres, most of whom underwent sphincter-saving radical surgery between 1994 and 1998 with the above mentioned technique for resectable colon cancer. Details regarding the technique were recorded in the last 58 patients, in order to examine the severity of the surgical damage. The subgroup with the longest follow-up, which included 36 patients, was diagnostically evaluated by a surgeon, psychologist, urologist and neurologist to analyze the risk of sexual and urinary dysfunctions. A complete nerve-sparing was performed in 86.3% of the cases. The parasympathetic nerve trunks were those most often damaged because of perineural tumor spreading. Partial to complete sexual impotence was observed in 44% of the patients and surprisingly, preoperative dysfunctions were detected by means of the multidisciplinary approach in one third of these patients. Therefore, only 30.5% of the patients presented with strictly postoperative sexual impotency, above all, those who had undergone high-dose preoperative chemoradiation for T3 or T4 middle to low rectal cancer. A prospective study was initiated to evaluate the genitourinary dysfunctions after rectal cancer surgery in all of the clinical phases by means of a multidisciplinary approach aimed at functional recovery and improved quality of life.

Prevalence of liver complications in pediatric patients on home parenteral nutrition: indications for intestinal or combined liver-intestinal transplantation.

Parenteral nutrition (PN) is the only treatment for patients affected by chronic intestinal failure (CIF). Home parenteral nutrition (HPN) programs are started when patients need prolonged PN. Unfortunately, many patients on prolonged PN develop liver disease (LD). The aim of our study was to assess the prevalence of LD in our series of patients on HPN. We reviewed our records of patients discharged from the hospital on HPN for CIF. HPN was started when one parent was fully trained in the use of this treatment and if the social and familial home environment was reliable. All patients received total PN by a central venous catheter. All patients with abnormal AST, ALT, ALK, gammaGT, and bilirubin values for more than 3 months were considered affected by PN-related LD. Thirty-six patients (23 of whom were boys and 13 girls) were discharged on HPN. During the study period, for CIF, 16 were affected by short bowel syndrome (SBS), of whom 6 had ultra-short bowel; 16 with functional intestinal failure, and 4 with chronic intestinal pseudobstruction (CIPO). Mean duration of HPN was 2.1 years/patient. Nine of 36 patients (25%) on HPN for CIF showed LD. Seven of the 16 patients (43%) with LD were affected by SBS and 2 (12.5%) patients by functional intestinal failure. No patients with CIPO developed LD. In patients affected by SBS, the onset of LD was very earlier than in patients with ID.

A pilot clinical trial of postoperative intensive weekly chemotherapy using cisplatin, epi-doxorubicin, 5-fluorouracil, 6S-leucovorin, glutathione and filgrastim in patients with resected gastric cancer.

AIMS AND BACKGROUND: The study was performed to assess the feasibility and activity of an intensive chemotherapeutic regimen as adjuvant treatment for patients with resected gastric cancer at high risk of recurrence (pT(2)N(1-2); pT(3-4)N(any) M0). PATIENTS AND METHODS: Starting 21 to 28 days after potentially curative surgery for primary gastric cancer, 25 patients received 8 weekly cycles of cisplatin 40 mg/m2, 5-fluorouracil 500 mg/m2, epidoxorubicin 35 mg/m2, 6S-stereoisomer of leucovorin at a dose of 250 mg/m2, and glutathione at a dose of 1.5 g/m2. From the day after to the day before each cycle of chemotherapy, filgrastim was administered by subcutaneous injection at a dose of 5 microg/kg. RESULTS: After a median follow-up of 33 months, 80% of the patients were alive and disease-free. Five patients had relapsed: three in the liver, one in the peritoneum and one in the lymph nodes. Toxicity was mild: five patients experienced WHO grade III toxicity (three leukopenia, two thrombocytopenia); no toxic deaths occurred. CONCLUSION: Intensive weekly chemotherapy is a feasible postoperative treatment option for patients with resected gastric cancer at high risk of relapse. These data, together with recent results in advanced disease, make this approach of interest for the development of new programs of adjuvant therapy in this setting.

[Changes in the lymphocyte subpopulations in a patient with orthotopic transplant of the liver]. / Variazioni delle sottopopolazioni linfocitarie in un paziente con trapianto ortotopico di fegato.

Earlier experimental studies have shown that the cyclosporin immunosuppressive effect (CsA) can be modulated by drug timing as well as dose. More specifically treatment during the night was constantly associated with a statistically significant improvement in the prevention or delay of allograft rejection. The present study reports on the circadian variations in T-lymphocyte subpopulations in the peripheral blood of a patient given an orthotopic liver allograft and treated with CsA and steroids. In particular, a statistically significant circadian rhythm (p = 0.012) was observed for the T-helper (OKT4) subset with a peak time (acrophase) occurring during the night at 4:27 A.M. In this patient, CsA treatment was, therefore, adapted to the T-helper cycle with the aim of marching CsA blood level variations to that curve. The results suggest that CsA timing can provide a tool for daily dose reduction and then improve the success rate of drug treatment.

[Imaging follow-up of orthotopic ileal neobladders++]. / Follow-up per immagini nelle neovesciche ileali ortotopiche.

In the follow-up for new urinary reservoirs created from the ileum in the orthotopic position, study by imaging plays a fundamental role The routine radiological examinations for monitoring patients with surgically created orthotopic bladders comprise M.R., C.T., urography, cystography and transrectal ultrasonography (U.S.). By means of these examinations, it is possible to evaluate the ureter-neobladder anastomosis, the capacity of the reservoir and the urethra-neobladder junction. Trans rectal U.S. is of particular importance, providing information on the new neck, the critical point of this new type of urinary diversion. 90 patients with new orthotopic ileal neobladder by Studer were examined. The image investigation in these patients subjected to total cystectomy for cancer, with preparation of a new orthotopic ileal neobladder by Studer, was shown to be indispensable in detecting both of disease and the behaviour of the upper urinary tract following these current urinary diversion.

[Post-transfusional AIDS]. / AIDS post trasfusionale.

Two cases of post-transfusional AIDS in two premature babies who received blood of the same seropositive donor, are reported. The risk of the susceptibility to HIV infection of these patients, in relation to the immaturity of immune system and to the transfusional treatment often necessary in premature newborns, is stressed.

[Nerve-sparing cystectomy and ileal bladder substitution]. / Cistectomia nerve-sparing e neovescica ileale di sostituzione.

Nerve-sparing techniques and bladder substitution following radical cystectomy allow today to obviate functional sequelae once registered in this type of surgery. Intraoperative identification of the pelvic plexus, which provides autonomic innervation to the corpora cavernosa, is necessary to preserve sexual function. Ileal orthotopic bladder substitution with preservation of the distal urethral sphincter assures a micturition per urethram and the urinary continence. The Authors report their experience with the Studer and Zingg procedure (ileal orthotopic bladder reservoir) performed in 26 cases. Results, technique, complications, and long-term evaluation are stressed.