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81.
Dr. Carlo Clerici Giorgio Gentili Enrico Boschetti Carla Santucci Aaron Garzon Aburbeh Benedetto Natalini Roberto Pellicciari Antonio Morelli 《Digestive diseases and sciences》1994,39(12):2601-2606
In an attempt to obtain site-specific delivery of 5-ASA in the intestinal tract, we have determined the extent of absorption and metabolism of a number of novel 5-ASA derivatives, namely, (N-l-glutamyl)-amino-2-salicylic acid (1), (N-l-aspartyl)-amino-2-salicylic-acid (2), 5-aminosalicyl-l-proline-l-leucine (3), and 5-(N-l-glutamyl)-aminosalicyl-l-proline-l-leucine (4), which are selectively cleaved by intestinal brush border aminopeptidase A and carboxypeptidases. These novel prodrugs, 5-ASA, and sulfasalazine were administered to adult Fisher rats (N=30) and to animals that had undergone prior colostomy (N=30). Urine and feces were collected at timed intervals for 48 hr and the metabolites, 5-ASA, andN-acetyl-5-ASA were measured by high-performance liquid chromatography. The absorption and metabolism of all compounds were essentially identical in colostomized and normal animals. 5-ASA exhibited a rapid proximal intestinal absorption as evidenced by the high cumulative urinary excretion (>65%) and low fecal excretion. Sulfasalazine, as expected, exhibited a lower urinary recovery (<35%) and higher fecal excretion of 5-ASA and its metabolite. The novel glutamate and aspartate derivatives (1 and2) behaved similarly to sulfasalazine, while administration of the proline-leucine derivative (3) resulted in urinary and fecal recovery values intermediate with respect to those observed with 5-ASA and sulfasalazine. 5-(N-l-Glutamyl)-aminosalicyl-l-proline-l-leucine yielded the highest fecal recovery of 5-ASA and itsN-acetyl derivative, indicating a more efficient delivery to the distal bowel. Amino acid derivatives of 5-ASA appear to be potentially useful prodrugs for the site-specific delivery of 5-ASA to different regions of the intestinal tract.We acknowledge the Depha Team for financial support and Dr. Kenneth D.R. Setchell for discussions. 相似文献
82.
Morelli S Gurgo Di Castelmenardo AM Conti F Sgreccia A Alessandri C Bernardo ML Valesini G 《Rheumatology international》2000,19(6):209-212
Wegener's granulomatosis (WG) is a systemic necrotizing vasculitis, which could potentially affect any organ system. However,
there have only been a few reports on cardiac involvement. We described the echocardiographic findings in nine patients affected
by WG. A complete M-mode, two-dimensional, Doppler and color-Doppler transthoracic echocardiogram was performed in nine patients
(seven females and two males) affected by WG. In each patient, cardiac abnormality, for example, valvular damage, left ventricular
global systolic dysfunction, or pericardial effusion, was detected. In particular, heart valve disease was found in eight
patients, and in three cases, aortic valve insufficiency, which was severe enough to require surgical valve replacement, was
observed. Cardiac involvement in patients with WG is common. In particular, there is a high frequency of aortic valve abnormalities.
Thus, an echocardiographic study should be routinely performed.
Received: 21 October 1999 / Accepted: 28 April 2000 相似文献
83.
F.W. Guglielmi C. Panella A. Buda G. Budillon L. Caregaro C. Clerici D. Conte A. Federico G. Gasbarrini A. Guglielmi C. Loguercio A. Losco D. Martines S. Mazzuoli M. Merli G. Mingrone A. Morelli G. Nardone G. Zoli A. Francavilla 《Digestive and liver disease》2005,37(9):681-688
BACKGROUND AND AIMS: A total of 334 stable, compensated cirrhotic patients admitted to 10 Italian Gastroenterology Units were included in a prospective study to evaluate nutritional state and energy balance in liver cirrhosis. MATERIALS AND METHODS: Nutritional state and calorie intake were examined in the total population, while adequacy of calorie intake versus measured total energy expenditure was evaluated in a comparable subpopulation and in 40 matched controls, by computing the energy balance. RESULTS: Our data demonstrated that: (i) malnutrition was present in 25% of the total patients and significantly correlated with the Child's group (A=16%; B=25%; C=44%); (ii) the type of malnutrition is influenced by mBEE: normometabolic patients exhibit a significant (p<0.005) reduction of mid-arm fat area while both hypermetabolic and hypometabolic patients show a significant (p<0.005) decline in kg of free fat mass; (iii) normometabolic and hypometabolic patients have a negative energy balance, due to a high level of physical activity (127+/-14 kJ) in the first group and a reduced energy intake/kg body weight (102+/-12 kJ) in the second; (iv) hypermetabolic patients have a positive energy balance due to decreased daily physical activity/kg body weight (108+/-28 kJ); (v) malnourished and normometabolic patients eat a significantly (p<0.05) reduced percentage of protein whereas malnourished and hypermetabolic patients eat a significantly increased percentage of fat (p<0.05). CONCLUSION: Although multivariate regression analysis confirms that the Child-Pugh's score is a better independent predictor of malnutrition, the measure of REE, TEE, calorie intake and energy balance need to be routinely performed in cirrhotic patients, in order to recognise hypermetabolic and hypometabolic patients (approximately 30%) in whom the nutritional and metabolic parameters are indispensable as a basis for designing and prescribing personalised nutritional strategies that can treat muscle malnutrition and thus improve the morbidity and mortality rates. 相似文献
84.
In vivo effect of human granulocyte-macrophage colony-stimulating factor on megakaryocytopoiesis. 总被引:1,自引:0,他引:1
M Aglietta C Monzeglio F Sanavio F Aprá S Morelli A Stacchini W Piacibello F Bussolino G Bagnara G Zauli 《Blood》1991,77(6):1191-1194
The effect of granulocyte-macrophage colony-stimulating factor (GM-CSF) on megakaryocytopoiesis and platelet production was investigated in patients with normal hematopoiesis. Three findings indicated that GM-CSF plays a role in megakaryocytopoiesis. During treatment with GM-CSF (recombinant mammalian, glycosylated; Sandoz/Schering-Plough, 5.5 micrograms protein/kg/d, subcutaneously for 3 days) the percentage of megakaryocyte progenitors (megakaryocyte colony forming unit [CFU-Mk]) in S phase (evaluated by the suicide technique with high 3H-Tdr doses) increased from 31% +/- 16% to 88% +/- 11%; and the maturation profile of megakaryocytes was modified, with a relative increase in more immature stage I-III forms. Moreover, by autoradiography (after incubation of marrow cells with 125I-labeled GM-CSF) specific GM-CSF receptors were detectable on megakaryocytes. Nevertheless, the proliferative stimulus induced on the progenitors was not accompanied by enhanced platelet production (by contrast with the marked granulomonocytosis). It may be suggested that other cytokines are involved in the regulation of the intermediate and terminal stages of megakaryocytopoiesis in vivo and that their intervention is an essential prerequisite to turn the GM-CSF-induced proliferative stimulus into enhanced platelet production. 相似文献
85.
Does offering human immunodeficiency virus testing at the time of blood donation reduce transfusion transmission risk and increase disclosure counseling? Results of a randomized controlled trial,São Paulo,Brazil
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86.
Istomin V Sade E Grossman Z Rudich H Sofer O Hassin D 《European Journal of Internal Medicine》2004,15(8):531-533
In the course of 6 years, 23 otherwise healthy patients with acute febrile illness and leukopenia were diagnosed as having acute parvovirus B19 infection. Five of these patients had agranulocytosis associated with acute parvovirus B19 infection and one had chronic agranulocytosis due to persistent parvovirus B19 infection. The diagnosis was made after positive anti-parvovirus B19 IgM antibodies were found in all of the patients and viral DNA was detected by PCR in four patients. Neutropenia and agranulocytosis appear to be much more frequently associated with parvovirus B19 infection than previously reported. 相似文献
87.
Fracanzani AL Valenti L Bugianesi E Andreoletti M Colli A Vanni E Bertelli C Fatta E Bignamini D Marchesini G Fargion S 《Hepatology (Baltimore, Md.)》2008,48(3):792-798
It is uncertain whether patients with nonalcoholic fatty liver disease (NAFLD) and normal alanine aminotransferase (ALT) have a milder disease and should undergo liver biopsy. We reviewed the histological data of 458 Italian patients with NAFLD in whom liver biopsy was indicated by altered liver enzymes (395 cases, 86%), or persistently elevated ferritin or long-lasting severe steatosis (63 cases). Factors associated with nonalcoholic steatohepatitis (NASH) and fibrosis >/= 2 were identified by multivariate analysis. Patients with normal ALT were significantly older, had lower body mass index, fasting triglycerides, insulin resistance according to homeostasis model assessment (HOMA-IR), ALT, and gamma-glutamyltransferase, but a higher prevalence of hypertension. NASH was diagnosed in 59% and 74% of the patients with normal and increased ALT, respectively (P = 0.01). In the overall series of patients, NASH was independently predicted by ALT (odds ratio [OR], 1.11; 95% confidence interval [CI], 1.04-1.19 per 10-IU/mL increase) and diabetes (OR, 1.5; 95% CI, 1.1-2.0). The same variables were selected in patients with increased ALT, whereas in those with normal ALT, HOMA-IR and ALT were independent predictors. Severe fibrosis was independently predicted by serum ferritin (OR, 1.04; 95% CI, 1.001-1.08 per 50-ng/mL increase), ALT (OR, 1.07; 95% CI, 1.02-1.14), and diabetes (OR, 1.8; 95% CI, 1.4-2.3) in the overall series, serum ferritin and diabetes in those with increased ALT, and only HOMA-IR (OR, 1.97; 95% CI, 1.2-3.7) in patients with normal ALT. CONCLUSION: Normal ALT is not a valuable criterion to exclude patients from liver biopsy. Alterations in glucose metabolism and insulin resistance in subjects with normal ALT should also be considered in the selection of NAFLD cases for histological assessment of disease severity and progression. 相似文献
88.
89.
Ester Chai Kheng Yeoh Ling Choo Lim Siok Bian Ng Kok Yang Tan C. Rajasoorya 《Endocrine pathology》2014,25(3):302-306
The cribriform morular variant of papillary thyroid carcinoma (CMV-PTC) is a rare morphologic entity that is associated with familial adenomatous polyposis (FAP). We report a case of a young lady with an incidentally discovered right-sided neck nodule on ultrasonography with a diagnosis of CMV-PTC confirmed on thyroidectomy and review the literature associated with the clinical presentation, imaging characteristics, pathological findings and the association with FAP. 相似文献