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ABSTRACT: AIM: To develop an integrated approach for monitoring gastrointestinal motility and inflammation state suitable for application in long-term spaceflights. METHODS: Breath tests based on the oral administration of (13)C-labeled or hydrogen-producing substrates followed by the detection of their metabolites ((13)CO2 or H2) in breath were used to measure gastrointestinal motility parameters during the 520-d spaceflight ground simulation within the MARS-500 Project. In particular, the gastric emptying rates of solid and liquid contents were evaluated by (13)C-octanoic acid and (13)C-acetate breath tests, respectively, whereas the orocecal transit time was assessed by an inulin H2-breath test, which was performed simultaneously with the (13)C-octanoic acid breath test. A ready-to-eat, standardized pre-packaged muffin containing 100 mg of (13)C-octanoic acid was used in the (13)C-octanoic acid breath test to avoid the extemporaneous preparation of solid meals. In addition, a cassette-type lateral flow immunoassay was employed to detect fecal calprotectin, a biomarker of intestinal inflammation. Because no items could be introduced into the simulator during the experiment, all materials and instrumentation required for test performance during the entire mission simulation had to be provided at the beginning of the experiment. RESULTS: The experiments planned during the simulation of a manned flight to Mars could be successfully performed by the crewmembers without any external assistance. No evident alterations (i.e., increasing or decreasing trends) in the gastric emptying rates were detected using the (13)C-breath tests during the mission simulation, as the gastric emptying half-times were in the range of those reported for healthy subjects. In contrast to the (13)C-breath tests, the results of the inulin H2-breath test were difficult to interpret because of the high variability of the H2 concentration in the breath samples, even within the same subject. This variability suggested that the H2-breath test was strongly affected by external factors, which may have been related to the diet of the crewmembers or to environmental conditions (e.g., the accumulation of hydrogen in the simulator microenvironment). At least in closed microenvironments such as the MARS-500 simulator, (13)C-breath tests should therefore be preferred to H2-breath tests. Finally, the fecal calprotectin test showed significant alterations during the mission simulation: all of the crewmembers were negative for the test at the beginning of the simulation but showed various degrees of positivity in at least one of the subsequent tests, thus indicating the onset of an intestinal inflammation. CONCLUSION: Breath tests, especially those (13)C-based, proved suitable for monitoring gastrointestinal motility in the 520-d isolation experiment within MARS-500 project and can be applied in long-term spaceflights.
World Journal of Gastroenterology 04/2013; 19(14):2208-2216. · 2.47 Impact Factor
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ABSTRACT: A non-invasive test for oro-ileal transit time (OITT) evaluation was developed, based on the measurement of tauroursodeoxycholic acid (TUDCA) oral fluid concentration profile after its oral administration. Exploiting the fact that TUDCA is actively absorbed only in the ileum, OITT is measured as the time corresponding to TUDCA maximum oral fluid concentration (tmax). To measure oral fluid TUDCA concentration in a point-of-care setting, an ultrasensitive portable immunosensor was developed, based on a competitive chemiluminescent enzyme immunoassay (CL-EIA), using immobilized anti-TUDCA antibody and an ursodeoxycholic acid (UDCA)-peroxidase conjugate as tracer, detected by enhanced chemiluminescence employing a portable charge-coupled device (CCD)-based device. The test was validated in 24 healthy subjects before and after treatment with Loperamide, a drug that increases OITT. The developed CL-EIA was accurate and precise, with a LLOQ of 50pmolL(-1). The measured OITT for healthy subjects (291±50min) was fairly well correlated with OITT values obtained by measuring TUDCA in serum (r=0.89). An increased OITT was observed in all the studied subjects after Loperamide treatment. The CL immunosensor can be employed directly in gastroenterology and paediatric units and it can thus represent a new non-invasive simple test for OITT evaluation in a point-of-care setting, with improved diagnostic utility.
Journal of pharmaceutical and biomedical analysis 03/2013; 81-82C:1-7. · 2.45 Impact Factor
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ABSTRACT: Simple, rapid and highly sensitive assays, possibly allowing on-site analysis, are required in the security and forensic fields or to obtain early signs of environmental pollution. Several bioanalytical methods and biosensors based on portable devices have been developed for this purpose. Among them, Lateral Flow ImmunoAssays (LFIAs) offer the advantages of rapidity and ease of use and, thanks to the high specificity of antigen-antibody binding, allow greatly simplifying and reducing sample pre-analytical treatments. However, LFIAs usually employ colloidal gold or latex beads as labels and they rely on the formation of colored bands visible by the naked eye. With this assay format, only qualitative or semi-quantitative information can be obtained and low sensitivity is achieved. Recently, the use of enzyme-catalyzed chemiluminescence detection in LFIA has been proposed to overcome these problems. In this work, we describe the development of a quantitative CL-LFIA assay for the detection of 2,4,6-trinitrotoluene (TNT) in real samples. Thanks to the use of a portable imaging device for CL signal measurement based on a thermoelectrically cooled CCD camera, the analysis could be performed directly on-field. A limit of detection of 0.2 μg mL(-1) TNT was obtained, which is five times lower than that obtained with a previously described colloidal gold-based LFIA developed employing the same immunoreagents. The dynamic range of the assay extended up to 5 μg mL(-1) TNT and recoveries ranging from 97% to 111% were obtained in the analysis of real samples (post blast residues obtained from controlled explosion).
Analytica chimica acta 04/2012; 721:167-72. · 4.31 Impact Factor
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ABSTRACT: A compact portable chemiluminescent biosensor for simple, rapid, and ultrasensitive on-site quantification of fumonisins (fumonisin B1+fumonisin B2) in maize has been developed. The biosensor integrates a competitive lateral flow immunoassay based on enzyme-catalyzed chemiluminescence detection and a highly sensitive portable charge-coupled device (CCD) camera, employed in a contact imaging configuration. The use of chemiluminescence detection allowed accurate and objective analyte quantification, rather than qualitative or semi-quantitative information usually obtained employing conventional lateral flow immunoassays based on colloidal gold labeling. A limit of detection of 2.5 μgL(-1) for fumonisins was achieved, with an analytical working range of 2.5-500 μgL(-1) (corresponding to 25-5000 μgkg(-1) in maize flour samples, according to the extraction procedure). Total assay time was 25 min, including sample preparation. A simple and convenient extraction procedure, performed by suspending the sample in a buffered solution and rapidly heating to eliminate endogenous peroxidase enzyme activity was employed for maize flour samples analysis, obtaining recoveries in the range 90-115%, when compared with LC-MS/MS analysis. The chemiluminescence immunochromatography-based biosensor is a rapid, low cost portable test suitable for point-of-use applications.
Biosensors & bioelectronics 12/2011; 32(1):283-7. · 5.43 Impact Factor
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Marco Montagnani,
Matvey Tsivian,
Flavia Neri,
Ido Ben Zvi,
Irina Mantovani,
Paolo Nanni,
Marco Benevento, Patrizia Simoni,
Antonella Marangoni,
Milena Pariali,
Romana Fato,
Christian Bergamini,
Serena Leoni,
Francesco Azzaroli,
Giuseppe Mazzella,
Bruno Nardo,
Enrico Roda,
Rita Aldini
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ABSTRACT: Due to the importance of intestinal transport in pharmacological studies and the emerging role of intestinal signaling activity in the gut-liver axis, we have developed a new method to investigate intestinal transport and liver signaling using cell and serum free mesenteric perfusion system in the rat. The method regarding bile acid active absorption was validated, then, the portal venous content was examined for fibroblast growth factor 15(FGF15), a putative signaling protein produced by the ileal enterocytes following bile acid absorption. After isolation and cannulation of the relevant vessels (abdominal aorta and portal vein), the abdominal aorta and the terminal ileum were infused with respectively Krebs-Ringer solution and tauroursodeoxycholate (TUDCA) and the absorption was assessed by its recovery in the portal vein. After immunoblot, liquid chromatography and mass spectrometry analysis were performed both on gel bands digestion products and on portal outflow samples in order to evaluate if negligible amounts of FGF15 were present in the portal circulation. TUDCA absorption was efficient, intestinal morphology and oxygen consumption were normal. Despite accurate analysis, we could not find FGF15. Our method proved to be reliable for studying the active bile acid absorption. It is also suitable to identify molecules produced by enterocytes and transferred to the portal circulation in response to absorption of different substances such as nutrients or drugs. Since FGF15 was not recovered we suggest the possibilities that this protein is produced in very little amounts, poorly transferred outside the cell, or that it is extremely unstable and rapidly degraded.
Medicinal chemistry (Shāriqah (United Arab Emirates)) 05/2011; 7(4):257-64. · 1.64 Impact Factor
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ABSTRACT: A simple and versatile analytical device designed to perform, even simultaneously, different types of bioassays has been developed and optimized. A transparent microfluidics-based reaction chip, where analytes were quantitatively detected by means of biospecific reactions and chemiluminescence detection, was placed in contact with a thermoelectrically cooled CCD sensor through a fiber optic taper. Such a lensless contact imaging configuration combined adequate spatial resolution and high light collection efficiency within a small size portable device. The miniaturization of the reaction chamber ensured short analysis times (in the minutes range), while the use of chemiluminescence detection provided wide signal dynamic range and high detectability, down to attomole levels of protein and femtomole levels of nucleic acid analytes. A model hybrid panel test was realized by combining an enzyme assay for alkaline phosphatase activity, a nucleic acid hybridization assay for Parvovirus B19 DNA, and an immunoassay for horseradish peroxidase as a model antigen. The successful simultaneous quantification of the three targets demonstrated that a range of analytes, from enzymes to antigens, antibodies, and nucleic acids, can be measured in a single run, thus enabling the realization of a complete, personalized diagnostic panel test for early diagnosis of a given disease and patient follow-up.
Analytical Chemistry 03/2011; 83(8):3178-85. · 5.86 Impact Factor
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ABSTRACT: Exocrine pancreatic dysfunction has been reported in humans in the convalescent period after acute pancreatitis, but the data are scarce and conflicting. This study aimed to prospectively assess the exocrine pancreatic function in patients with acute pancreatitis at the time of their refeeding.
Fecal elastase-1 was determined on the day of refeeding in all consecutive acute pancreatitis patients with their first episode of the disease. They were 75 patients including 60 (80.0%) patients with mild acute pancreatitis and 15 (20.0%) patients with severe acute pancreatitis. Etiologically 61 patients (81.3%) had biliary disease, 1 (1.3%) had alcoholic disease and 3 (4.0%) had hypertriglyceridemia. No causes of acute pancreatitis were found in the remaining 10 patients (13.3%). The mean (+/-SD) refeeding time after the attack of acute pancreatitis was 11.2+/-10.2 days.
Pathological values of fecal elastase-1 were found in 9 of the 75 patients (12.0%): 7 (9.3%) patients with mild pancreatitis and 2 (2.7%) patients with severe pancreatitis (P=1.000). The frequency of the pathological values of fecal elastase-1 was significantly different from that of various etiologies of the disease (P=0.030). It was significantly lower in patients with biliary pancreatitis (9.8%; P=0.035) than in one patient with alcoholic pancreatitis (P=0.126), one patient with hypertriglyceridemia-induced pancreatitis (33.3%; P=0.708), and one patient with idiopathic pancreatitis (10.0%; P=0.227). Pathological fecal elastase-1 was not significantly related to sex, age or day of refeeding.
Exocrine pancreatic function should be routinely assessed in patients with acute pancreatitis at the time of refeeding in order to supplement their diet with pancreatic extracts.
Hepatobiliary & pancreatic diseases international: HBPD INT 07/2009; 8(3):316-9. · 1.08 Impact Factor
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ABSTRACT: In this work, the biospecific recognition antigen-antibody reaction was implemented in gravitational field-flow fractionation (GrFFF), a flow-assisted separation technique for micron-sized particles, in order to realize a hybrid immunomodulated GrFFF system in which two different principles are combined to achieve highly versatile fractionation. Micron-sized polystyrene beads coated with horseradish peroxidase (HRP) were used as a model sample, and anti-HRP antibodies were immobilized on the accumulation wall of the GrFFF channel. Ultrasensitive chemiluminescence imaging was employed to visualize the beads during elution and to optimize experimental conditions. The same principle was then applied to real biological samples composed by Yersinia enterocolitica and Escherichia coli cells. Results show the possibility to modify the elution of selected sample components and even to retain them into the channel. The hybrid immunomodulated GrFFF system is a step towards the development of a module that could be integrated in a lab-on-a-chip-based point-of-care testing device which includes sample pre-analytical cleanup and analysis.
Analytical and Bioanalytical Chemistry 04/2009; 394(4):953-61. · 3.78 Impact Factor
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ABSTRACT: OBJECTIVES: Little is known about the natural history and pathogenesis of small gallbladder polyps (<10 mm, usually of the cholesterol type), particularly in Western populations. It is unclear if these polyps and gallstones represent different aspects of the same disease. The aim of this study was to characterize the natural history and pathogenesis of small gallbladder polyps.
The American Journal of Gastroenterology 02/2009; 104(3):624-629. · 7.28 Impact Factor
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ABSTRACT: Little is known about the natural history and pathogenesis of small gallbladder polyps (<10 mm, usually of the cholesterol type), particularly in Western populations. It is unclear if these polyps and gallstones represent different aspects of the same disease. The aim of this study was to characterize the natural history and pathogenesis of small gallbladder polyps.
Fifty-six Caucasian patients with small gallbladder polyps, 30 matched gallstone patients, and 30 controls were enrolled in this 5-year prospective study. Patients underwent a symptomatic questionnaire, abdominal ultrasonography, and ultrasonographic evaluation of gallbladder motility at baseline and yearly intervals for 5 years. Cholesterol saturation index, cholesterol crystals in bile, and apolipoprotein E genotype were also determined.
Most patients with polyps (mean size: 5.3 mm) were men (61%), asymptomatic, and had multiple polyps (57%). Polyps did not change in 91% of patients during follow-up. No subject experienced biliary pain or underwent cholecystectomy; four developed gallstones. Cholesterol saturation index was higher in patients with polyps or gallstones than in controls (P<0.05). Cholesterol crystals were more frequent in patients with polyps than in controls (P<0.0001) but less common than in gallstone patients (P<0.0001). Polyps and gallstones were associated with nonapolipoprotein E4 phenotypes.
The natural history of small gallbladder polyps was benign, as no patient developed specific symptoms and/or morphological changes in polyps. Consequently, a "wait and see" policy is advisable in these patients. Polyps have some pathogenetic mechanisms in common with gallstones, but few patients developed gallstones.
The American Journal of Gastroenterology 02/2009; 104(3):624-9. · 7.28 Impact Factor
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ABSTRACT: Among the various studies of pancreatic function in the elderly published so far, none have dealt with subjects over 90 years of age. The aim of this study was to examine pancreatic function in healthy individuals over 90 years old.
Sixty-eight healthy noninstitutionalized elderly persons, aged 91-104 years, with a mean age of 95 years, and 63 younger controls were studied. Pancreatic function was studied by determining fecal elastase 1 concentration. In addition to this test, we also measured serum amylase, pancreatic isoamylase and lipase in 53 of the 68 elderly subjects.
All but 1 of the 68 elderly subjects had normal elastase 1 values; the one who did not had a value slightly below normal. No significant difference with controls was found. Serum pancreatic enzymes were normal in almost all of the 53 elderly studied; 3 had a mild elevation only of amylase and 1 had a persistent elevation of amylase, pancreatic isoamylase and lipase.
In subjects over 90 years of age, exocrine pancreatic function continues to be normal; if an impairment occurs, it is mild and not significant for digestion of food. In addition, serum pancreatic enzymes remain within normal limits in the vast majority of cases.
Pancreatology 02/2009; 9(3):240-4. · 1.99 Impact Factor
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ABSTRACT: The treatment of Inflammatory Bowel Diseases (IBDs) requires a relative high therapeutic daily dose of mesalazine and thus, the drug formulation need to be well tolerate and safe.
A new pH-dependent controlled release 5-ASA microgranule formulation in 1.2 g sachets has been developed. The plasma levels of both the active principle 5-ASA and the main metabolite N-Acetyl-5-ASA, after oral administration of the new formulation or after an equimolar dose of three separated enteric coated 400 mg tablets administered in the same time (Pentacol® 400, SOFAR, Milan, ITALY), were measured with a validated high performance liquid chromatography-tandem mass spectrometry method. C<sub>max</sub>, t<sub>max</sub> and AUC values were considered as primary variables and the drug safety was the secondary one.
The plasma 5-ASA concentration appearance was faster after microgranule administration ( tmax of 8.1 hours) than after the reference tablets assumption (tmax of 10.6 hours). The Cmax and AUC values were similar for both formulations and the kinetic of plasma disappearance of the test formulation was slight faster. The intersubject variability was lower after administration of the microgranules with a %CV of 17.5% vs 40.4% for the tablets (n=23), due to a more controlled homogeneous drug release from the granule format. The N-Acetyl-5-ASA metabolite presents a similar plasma profile of the 5-ASA for both formulations. The use of microgranulesis safe and will allow to reduce the daily dosages, by improving the patients compliance also in presence of difficulty to swallow large tablets.
Journal of Bioequivalence & Bioavailability. 01/2009;
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ABSTRACT: We measured fecal elastase-1 (FE1) levels in 34 preterm newborns (15 small-for-gestational-age and 19 appropriate-for-gestational-age) during the first 2 months of life and evaluated whether they were correlated with nitrogen loss in stools. FE1 increased over time, and values were similar in both groups of newborns. Fecal nitrogen was significantly higher in small-for-gestational-age infants. There was no correlation between FE1 levels and fecal nitrogen excretion. Pancreatic proteolytic function was efficient at an early stage in enterally fed preterm newborns. Despite the similar FE1 values, fecal nitrogen loss was significantly higher in small-for-gestational-age preterm infants than in appropriate-for-gestational-age preterm infants.
Journal of pediatric gastroenterology and nutrition 11/2008; 47(4):517-21. · 2.18 Impact Factor
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ABSTRACT: A new HPLC method for the determination of 5-aminosalicylic acid (5-ASA) and N-acetyl-5-aminosalicylic acid (N-Ac-5-ASA) in human plasma was developed and validated. Plasma samples were analyzed after protein precipitation with methanol and the two analytes were separated using a C18 column with a mobile phase composed of 17.5 mmol/L acetic acid (pH 3.3):acetonitrile=85:15 (v/v) at 0.2 mL/min flow rate. 4-ASA and N-Ac-4-ASA were used as internal standards. Selective detection was performed by tandem mass spectrometry with electrospray source, operating in negative ionization mode and in multiple reaction monitoring acquisition (m/z 152-->108 for 5-ASA; m/z 194-->150 and 194-->107 for N-Ac-5-ASA). The limit of quantification (LOQ) was 50 ng/mL for both analytes (0.2 ng injected) and matrix-matched standard curves showed linearity up to 4000 ng/mL. In the entire analytical range the within- and between-batch precision (R.S.D.%) values were respectively < or = 6.3% and < or = 11% for 5-ASA and < or = 8.0% and < or = 10% for N-Ac-5-ASA. For both analytes the within- and between-batch accuracy (bias%) values ranged respectively from -8.4% to 7.9% and from -7.9% to 8.0%. The overall recoveries (n=6) at three tested concentration levels (i.e. 100, 1000 and 4000 ng/mL) were respectively >90% for 5-ASA and >95% for N-Ac-5-ASA (R.S.D.% < or = 10%). The method was applied to evaluate the pharmacokinetic of 5-ASA after a single oral dose administration of this compound (1200 mg) to 24 healthy volunteers. The mean maximum concentration levels were 680 ng/mL for 5-ASA and 1240 ng/mL for N-Ac-5-ASA and the kinetic profiles were in agreement with previous studies.
Journal of Chromatography B 09/2008; 872(1-2):99-106. · 2.89 Impact Factor
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ABSTRACT: Despite the controversies surrounding genetically modified organisms (GMOs), the production of GM crops is increasing, especially in developing countries. Thanks to new technologies involving genetic engineering and unprecedented access to genomic resources, the next decade will certainly see exponential growth in GMO production. Indeed, EU regulations based on the precautionary principle require any food containing more than 0.9% GM content to be labeled as such. The implementation of these regulations necessitates sampling protocols, the availability of certified reference materials and analytical methodologies that allow the accurate determination of the content of GMOs. In order to qualify for the validation process, a method should fulfil some criteria, defined as "acceptance criteria" by the European Network of GMO Laboratories (ENGL). Several methods have recently been developed for GMO detection and quantitation, mostly based on polymerase chain reaction (PCR) technology. PCR (including its different formats, e.g., double competitive PCR and real-time PCR) remains the technique of choice, thanks to its ability to detect even small amounts of transgenes in raw materials and processed foods. Other approaches relying on DNA detection are based on quartz crystal microbalance piezoelectric biosensors, dry reagent dipstick-type sensors and surface plasmon resonance sensors. The application of visible/near-infrared (vis/NIR) spectroscopy or mass spectrometry combined with chemometrics techniques has also been envisaged as a powerful GMO detection tool. Furthermore, in order to cope with the multiplicity of GMOs released onto the market, the new challenge is the development of routine detection systems for the simultaneous detection of numerous GMOs, including unknown GMOs.
Analytical and Bioanalytical Chemistry 07/2008; 392(3):355-67. · 3.78 Impact Factor
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ABSTRACT: A one-step triplex-polymerase chain reaction (PCR)-based assay was developed to discriminate between three tuna species, Thunnus albacares, Thunnus obesus, and Katsuwonus pelamis, even in highly processed food samples such as canned or cooked tuna. Diagnostic nucleotides were identified by direct sequencing and alignment of part of the mitochondrial cytochrome b gene of 30 authenticated exemplars, which allowed us to evaluate intraspecific variation and the genetic distance between three tuna species. The assay relies on a one-step triplex-PCR reaction in which in a single tube species-specific amplification products are generated only in the presence of the correct template nucleic acid and the species of origin of the DNA is indicated by the distinctive size of the PCR product. The identification of tuna species can be performed with a good accuracy, low cost, and with potential automation for large-scale high-throughput screenings in small in-house laboratories.
Journal of Agricultural and Food Chemistry 10/2007; 55(19):7638-47. · 2.82 Impact Factor
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ABSTRACT: A simple and rapid multiplexed sandwich chemiluminescent enzyme immunoassay has been developed for the simultaneous detection of Escherichia coli O157:H7, Yersinia enterocolitica, Salmonella typhimurium, and Listeria monocytogenes. To achieve the multiplexed detection of the four pathogens, a new polystyrene 96 well microtiter plate format has been designed, in which each main well contains four subwells in the bottom. The monoclonal antibodies specific for each bacteria were separately immobilized in each subwell. When the samples were added to the main wells, the bacteria able to specifically bind to the corresponding monoclonal antibody were captured in one of the four subwells. Subsequently, a mixture of peroxidase-labeled polyclonal antibodies against the four bacteria was added and the peroxidase activity of the bound polyclonal labeled antibodies in each well was measured by an enhanced luminol-based chemiluminescent cocktail using a low-light charge-coupled imaging device. The assay was simple and fast, and the limit of quantification was in the order of 104-105 CFU/mL for all bacterial species. The accuracy of the method, evaluated by comparison of the results with a conventional culturing methodology, was satisfactory, with recovery values ranging from 90 to 120%. This method can be used as a screening test to evaluate the presence of these pathogen bacteria in different foodstuffs.
Journal of Agricultural and Food Chemistry 07/2007; 55(13):4933-9. · 2.82 Impact Factor
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ABSTRACT: Ursodeoxycholic acid (UDCA), previously used for cholesterol gallstone dissolution, is currently considered the first choice therapy for many forms of cholestatic syndromes. Many mechanisms and sites of action have been proposed for UDCA, but definitive data are still missing regarding the key points of its efficacy and optimal dosage in order to achieve a sustained clinical effect. Among the suggested mechanisms of action of UDCA, changes in bile acid pool composition, hepatocyte membrane protection, immunomodulatory effects and bicarbonate-rich hypercholeresis have been extensively studied. However, recent evidence indicate that UDCA is a potent intracellular signalling agent that counterbalances impaired biliary secretion, inhibits hepatocyte apoptosis and protects injured cholangiocytes against toxic effects of bile acids. It is clear that the relative contribution of these mechanisms to the anticholestatic action of UDCA depends on the type and stage of the liver injury. Available clinical evidence suggest that UDCA treatment has to be initiated as early as possible and that higher doses could be more efficacious in inducing and maintaining clinical remission of cholestatic diseases. The future availability of UDCA derivatives will possibly enhance the chances to effectively treat chronic cholestatic diseases.
Current Clinical Pharmacology 06/2007; 2(2):155-77.
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ABSTRACT: To develop a new formulation with hydroxy propyl methyl cellulose and Shellac coating for extended and selective delivery of butyrate in the ileo-caecal region and colon.
One-gram sodium butyrate coated tablets containing 13C-butyrate were orally administered to 12 healthy subjects and 12 Crohn's disease patients and the rate of 13C-butyrate absorption was evaluated by 13CO2 breath test analysis for eight hours. Tauroursodeoxycholic acid (500 mg) was co-administered as a biomarker of oro-ileal transit time to determine also the site of release and absorption of butyrate by the time of its serum maximum concentration.
The coated formulation delayed the 13C-butyrate release by 2-3 h with respect to the uncoated tablets. Sodium butyrate was delivered in the intestine of all subjects and a more variable transit time was found in Crohn's disease patients than in healthy subjects. The variability of the peak 13CO2 in the kinetic release of butyrate was explained by the inter-subject variability in transit time. However, the coating chosen ensured an efficient release of the active compound even in patients with a short transit time.
Simultaneous evaluation of breath 13CO2 and tauroursodeoxycholic acid concentration-time curves has shown that the new oral formulation consistently releases sodium butyrate in the ileo-cecal region and colon both in healthy subjects and Crohn's disease patients with variable intestinal transit time. This formulation may be of therapeutic value in inflammatory bowel disease patients due to the appropriate release of the active compound.
World Journal of Gastroenterology 03/2007; 13(7):1079-84. · 2.47 Impact Factor
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ABSTRACT: The presence of endocrine-disrupting compounds in influent and effluent water samples from four waste water treatment plants located in Italy was studied. The estrogen-like activity of the water samples was measured using a chemiluminescent recombinant yeast assay which is based on genetically engineered yeast cells that express the human estrogen receptor. This receptor, once activated, elicits the expression of the reporter gene lac-Z and, consequently, the production of beta-galactosidase, which is then measured by chemiluminescence. To control and minimize sample matrix effects, an external control based on a modified yeast strain stably expressing beta-galactosidase was developed and also used in the assay. Rapid and sensitive chemiluminescent enzyme immunoassays were also developed and validated for the quantification of 17beta-estradiol, estrone, and estriol in waste water samples. Results from both methods were compared with a reference high-performance liquid chromatography and electrospray ionization tandem mass spectrometry (HPLC ESI-MS-MS) method developed for the quantification of natural estrogens. The recombinant yeast assay revealed a significant estrogenic activity in the influent samples, ranging from 80 to 400 pmol/L 17beta-estradiol equivalents (EEQ), which was reduced by 70-95% in the effluent samples. The yeast assay also showed a systematic 20-30% overestimation of estrogenic activity relative to the HPLC ESI-MS-MS method, suggesting the presence of other compounds in the samples with estrogenic activity. The chemiluminescent enzyme immunoassays showed the presence of estrogens in the influent samples (mean concentrations: 350-450 pmol/L for estrone, 5-100 pmol/L for 17beta-estradiol, 25-300 pmol/L for estriol), with significantly lower concentrations detected in the respective effluent samples. The waste water treatment was able to reduce natural estrogen concentrations by 40-95%, although a high variability was observed. The enzyme immunoassay data correlated well with data obtained by the HPLC ESI-MS-MS method. Although the recombinant yeast assay represents a useful tool for a first-level screening of estrogenic activity due to its simplicity and high analytical throughput, sample matrix effects observed in waste water of industrial origin were found to strongly affect the yeast cells response, even when properly corrected for using the external control, thereby limiting its use to urban waste water. Its integration with chemiluminescent enzyme immunoassays would improve its performance by reducing false negative results, thereby enabling its use in extensive studies monitoring for the presence of endocrine-disrupting compounds in urban treatment plant effluents.
Analytical and Bioanalytical Chemistry 07/2006; 385(4):742-52. · 3.78 Impact Factor
