Intra-crystalline protein diagenesis (IcPD) in Patella vulgata. Part II: Breakdown and temperature sensitivity.

Artificial diagenesis of the intra-crystalline proteins isolated from Patella vulgata was induced by isothermal heating at 140 °C, 110 °C and 80 °C. Protein breakdown was quantified for multiple amino acids, measuring the extent of peptide bond hydrolysis, amino acid racemisation and decomposition. The patterns of diagenesis are complex; therefore the kinetic parameters of the main reactions were estimated by two different methods: 1) a well-established approach based on fitting mathematical expressions to the experimental data, e.g. first-order rate equations for hydrolysis and power-transformed first-order rate equations for racemisation; and 2) an alternative model-free approach, which was developed by estimating a "scaling" factor for the independent variable (time) which produces the best alignment of the experimental data. This method allows the calculation of the relative reaction rates for the different temperatures of isothermal heating. High-temperature data were compared with the extent of degradation detected in sub-fossil Patella specimens of known age, and we evaluated the ability of kinetic experiments to mimic diagenesis at burial temperature. The results highlighted a difference between patterns of degradation at low and high temperature and therefore we recommend caution for the extrapolation of protein breakdown rates to low burial temperatures for geochronological purposes when relying solely on kinetic data.

Intra-crystalline protein diagenesis (IcPD) in Patella vulgata. Part I: Isolation and testing of the closed system.

This study successfully isolates a fraction of intra-crystalline proteins from shells of the marine gastropod Patella vulgata and assesses the suitability of these proteins for IcPD (Intra-crystalline Protein Diagenesis) geochronology. We discuss the mineralogical composition of this gastropod, investigated for the first time by X-ray diffraction mapping, and use the results to inform our sampling strategy. The potential of the calcitic rim and of a bulk sample (containing both apex and rim) of the shell to act as stable repositories for the intra-crystalline proteins during diagenesis is examined. The composition and the diagenetic behaviour of the intra-crystalline proteins isolated from different locations within the shell are compared, highlighting the necessity of targeting consistent sampling positions. We induced artificial diagenesis of both intra-crystalline and whole-shell proteins by conducting high-temperature experiments in hydrous environment; this allowed us to quantify the loss of amino acids by leaching and therefore evaluate the open- or closed-system behaviour of the different fractions of proteins. The results obtained provide further confirmation that patterns of diagenesis vary according to the protein sequence, structure, and location within or outside the intra-crystalline fraction. As Patella is frequently found in the fossil record, both in archaeological and geological contexts, the application of IcPD geochronology to this biomineral opens up the possibility to obtain reliable age information from a range of sites in different areas of the world.

Hepatocellular carcinoma complicating primary sclerosing cholangitis in Crohn's disease. A case report.

The prevalence of primary sclerosing cholangitis (PSC) in Crohn's disease (CD) patients is up to 8.5%. Although cholangiocarcinoma may complicate long-standing PSC in one third of the cases if follow-up is extended long enough, hepatocellular carcinoma (HCC) is a rare complication of PSC. The concomitant presence of PSC, HCC and CD have been reported sporadically. We discuss here a case of association of these three conditions.

Efficacy and safety of oral beclomethasone dipropionate for ileal or ileal-right colon Crohn's disease of mild-to-moderate activity or in remission: Retrospective study.

Although conventional glucocorticosteroids are the main treatments for active Crohn's disease, several problems are associated with steroid dependence and steroid-related adverse events. To assess the efficacy and safety of oral beclomethasone dipropionate (BDP) coated tablets in adults with mild-to-moderate Crohn's disease. Thirty-four patients (age 18-70years) with a diagnosis of Crohn's disease confirmed by conventional criteria (barium enema, clinical criteria, colonoscopy, histology) were retrospectively evaluated in the study. All subjects received a treatment schedule with BDP 5-10mg/day for 24weeks. BDP significantly (p=0.005) reduced mean Crohn's Disease Activity Index (CDAI) score from 169.6 at baseline to 123.2 after 24weeks. Clinical success was evident at 24weeks in 66.7% of patients with initial active disease, and remission was maintained at week 24 in 93.8% of patients with remission at baseline. Overall, female non-smokers had the best response to treatment. BDP was well tolerated and the only adverse events observed were nausea (n=1), facial erythema (n=1) and one patient with raised fasting blood glucose level. These results clearly suggest that oral BDP coated tablets are effective and safe for treatment of mild-to-moderate Crohn's disease of ileal or ileal-right colonic localisation.

Association between Crohn's disease and Conn's syndrome. A report of two cases.

The natural history of Crohn's disease (CD) is characterised by periods of remission followed by phases of flares. Persistent or intractable diarrhoea may be associated with ileal disease or arise following ileal resection, resulting in potassium depletion. Medical therapy with steroids presents troublesome side-effects (e.g. hypertension). Conn's syndrome, caused by unilateral aldosterone-producing adenoma, is characterised by clinical features including hypokalaemia and hypertension. Thus, CD and Conn's syndrome may have an overlap of manifestations, and up to now, the simultaneous occurrence of these conditions has not been described. We report here 2 cases of association between CD and Conn's syndrome.

Influence of a lipase inhibitor on gastric sensitivity and accommodation to an orally ingested meal.

BACKGROUND: Intraduodenal administration of lipids, through lipid digestion and release of cholecystokinin (CCK), induces viscero-visceral reflexes that affect gastric tone and sensitivity. It is unclear whether the same mechanisms control gastric function after an orally ingested meal. AIM: To evaluate the effect of orlistat, a selective lipase inhibitor, on gastric response to an orally administered meal. METHODS: Eighteen healthy volunteers participated in this study. They were treated for 5 days with orlistat (120 mg) or placebo t.d.s. in a double-blind randomized crossover design. During treatment, all subjects underwent a gastric barostat study, measurement of plasma CCK levels and a satiety drinking test. RESULTS: Although CCK plasma levels were significantly decreased, pre-treatment with orlistat failed to affect gastric compliance (72 +/- 6 mL/mm Hg and 64 +/- 6 mL/mm Hg, NS), gastric sensitivity (discomfort threshold 12.2 +/- 0.6 mm Hg vs. 10.9 +/- 0.6 mm Hg above minimal distending pressure, NS) or gastric accommodation (172 +/- 41 mL vs. 206 +/- 49 mL, NS) to an orally ingested meal. Furthermore, orlistat pre-treatment had no significant effect on the amount of calories ingested during a satiety drinking test (1329 +/- 88 kcal vs. 1217 +/- 115 kcal, NS). CONCLUSION: Administration of a lipase inhibitor does not affect gastric compliance, sensitivity to distension and accommodation to an orally ingested meal, and does not influence meal-induced satiety.

Laboratory evaluation of the patient with liver disease.

Because the liver performs multiple functions, no single laboratory test or battery of tests is sufficient to provide a complete estimate of the function of the liver in every clinical situation. A broad array of biochemical tests are used to assess the many functions of the liver and to evaluate patients with suspected or established liver disease. These tests are referred to collectively as "liver function tests" (LFTs). LFTs are used to screen people for the presence of liver disease, suggest the underlying cause, estimate the severity, assess prognosis, and monitor the efficacy of therapy. Abnormal LFTs may be the first indication of sub clinical liver disease and may thereby guide further diagnostic evaluation. After the existence of hepatic dysfunction is recognized, the specific pattern of liver test abnormalities may suggest the category of the underlying liver disease, such hepatitis, biliary obstructions, or infiltrative liver disease. The value of screening healthy, asymptomatic persons for liver disease with the use of LFTs is controversial and may not be cost-effective. If screening is performed a panel of tests (e.g., AST, alkaline phosphatase, bilirubin, albumin) is preferable to using a single test because of superior sensitivity and specificity for liver disease and lower cost than the sum of individually performed tests.

Causes and treatment of functional dyspepsia.

Functional dyspepsia is a clinical syndrome defined by upper abdominal symptoms without identifiable cause by conventional diagnostic means. Recent studies have established that functional dyspepsia is a heterogeneous disorder in which different pathophysiologic disturbances underlie different symptom profiles. Delayed gastric emptying is associated with postprandial fullness, nausea, and vomiting; impaired accommodation is associated with early satiety and weight loss; and hypersensitivity to gastric distention is associated with epigastric pain, belching, and weight loss. The pathogenesis of functional dyspepsia is unknown but may be postinfectious in a subgroup of patients. The role of psychological disturbances and of duodenal hypersensitivity requires further study. Treatment of the underlying pathophysiologic abnormality seems logical, but options for pharmacotherapy are limited to acid suppression, prokinetic drugs, and antidepressants. Psychotherapy can be considered for refractory patients. Several novel drug therapies are under evaluation.

Safety and efficacy of azathioprine in the maintenance of ciclosporin-induced remission of ulcerative colitis.

BACKGROUND: It has been shown that azathioprine prolongs the response to ciclosporin of steroid-refractory ulcerative colitis, but no specific data are available concerning its toxicity in this indication. AIM AND METHODS: The charts of 21 patients with steroid-refractory ulcerative colitis who received azathioprine overlapping with a successful ciclosporin course were reviewed for the onset of toxicity. The controls consisted of 48 initial responders to steroids who received azathioprine for steroid-dependence or resistance/toxicity. RESULTS: Two of the 21 patients were withdrawn because of hypersensitivity to azathioprine. The remaining 19 were treated for a median of 18 months together with a median daily steroid dose of 35 mg (10-75 mg) to be tapered off. Toxicity (31%) included leukopenia alone (two cases), cholestasis alone (one case), cholestasis and increased amylase (one case), increased amylase alone (one case), and cutaneous infection (one case). The frequency of withdrawal was 21%. The mean daily steroid doses were reduced from 38 mg to 3.8 mg in the study cohort, and from 25 mg to 8 mg in the controls, among whom toxicity (27%) included four cases each of leukopenia and increased amylase, two cases each of alteration of liver enzymes and infection, and one case of gastric intolerance. Ten of the 48 controls (20%) were withdrawn from the study. CONCLUSION: Azathioprine is as effective and safe in the maintenance of the response of patients with steroid-refractory ulcerative colitis to ciclosporin as it is in the treatment of those who respond to steroids.

Abdominal pain and bowel dysfunction: diagnostic role of intestinal ultrasound.

BACKGROUND: Abdominal pain and irregular bowel habits are common among young people. Irritable bowel syndrome is frequent in the general population and has important economic and social costs. Inflammatory bowel diseases are chronic processes with an acute or indolent onset in young people. Differential clinical diagnosis between irritable bowel syndrome and inflammatory bowel disease can be difficult since symptoms and signs are often non-specific. OBJECTIVE: To evaluate the role of intestinal ultrasound, a non-invasive, simple and cheap diagnostic tool, in the differentiation between organic and functional bowel diseases. METHODS: Abdominal and intestinal ultrasound examinations were performed on 313 consecutive outpatients presenting with abdominal pain and irregular bowel habits lasting more than 3 months. These patients had no symptoms or signs indicative of organic disorders and no previous diagnosis of organic disease. An intestinal wall thickness of more than 7 mm was considered diagnostic for inflammatory bowel disease. Subsequently, we compared the ultrasound results with diagnoses obtained following the traditional criteria (radiological and endoscopic examinations). RESULTS: Intestinal ultrasound for the diagnosis of inflammatory bowel disease showed 74% sensitivity, 98% specificity, a positive predictive value of 92% and a negative predictive value of 92%. CONCLUSIONS: In our experience, intestinal ultrasound seems important as a first diagnostic tool in young patients without clear symptoms or signs of organic diseases, and can be used as an indication that subsequent invasive tests are required.

[Abdominal pain and bowel dysfunction: diagnostic flow-chart could be simplified?]. / Dolore addominale e alterazione dell'alvo: è possibile semplificare l'iter diagnostico?

BACKGROUND: The aim of the study was to evaluate the diagnostic role of Kruis score and intestinal ultrasound in young patients with abdominal pain and bowel dysfunction. METHODS: Prospective, double blind, case-control study in 297 consecutive patients with Crohn's disease and irritable bowel syndrome (from 1993 to 1995). INCLUSION CRITERIA: abdominal pain, bowel dysfunction without clear symptoms or signs of organic disease. The final diagnosis is obtained with usual diagnostic criteria and confirmed by at least 2 years of follow-up. Intestinal ultrasound is considered diagnostic of Crohn's disease if bowel wall thickness is = or > 7 mm; the Kruis score is diagnostic for irritable bowel syndrome if = or > 44. RESULTS: To diagnose Crohn's disease, intestinal ultrasound and Kruis score respectively showed sensitivity of 84 and 97%, specificity of 98 and 50%, positive predictive value of 91 and 33%, negative predictive value of 96 and 98%, efficacy of 95 and 60%. Both exams suggest the same diagnosis in 55% of patients with a correct diagnosis of 97%. CONCLUSIONS: The intestinal ultrasound and the Kruis score can be a good diagnostic association in young patients with abdominal pain and bowel dysfunction but without clear symptoms or signs of organic disease. If their diagnostic conclusions are the same (55%), they have a low probability of diagnostic error (3%). If they show a different diagnostic hypothesis, other markers of disease, for example ASCA, can be used.

A six-week clinical tooth whitening study of a new calculus-inhibiting dentifrice formulation.

This six-week double-blind clinical study compared the toothwhitening effects of a new calculus-inhibiting dentifrice containing pyrophosphate, tripolyphosphate and copolymer in a 0.243 sodium fluoride/silica base (Test Dentifrice) with two commercially available dentifrices: Aquafresh Whitening Toothpaste with Fluoride and Crest Regular Fluoride Toothpaste. After a baseline examination for extrinsic tooth stain, qualifying adult males and females from Manchester, United Kingdom and from Mississauga, Ontario, Canada were randomly assigned into three test groups. Each group was balanced for gender, tobacco habits and levels of tooth stain. Subjects were to brush their teeth twice daily with a soft-bristled toothbrush using the assigned toothpaste. One-hundred and twenty-eight (128) subjects complied with instructions and completed the trial. Subjects using the Test Dentifrice exhibited statistically less stain area and less stain intensity than did either the Aquafresh or Crest groups. Crest Regular Fluoride toothpaste was statistically less effective than Aquafresh Whitening toothpaste in removing stain. Results in this trial support the conclusion that a new dentifrice formulation containing pyrophosphate, tripolyphosphate and a copolymer, in a 0.243% sodium fluoride/silica base, effectively removes extrinsic tooth stain.

A six-week clinical efficacy study of a new dentifrice for the removal of extrinsic tooth stain.

The objective of this double-blind clinical study was to investigate the tooth whitening efficacy of a new dentifrice (Colgate Tartar Control Plus Whitening Fluoride Toothpaste) for the removal of extrinsic tooth stain, through a comparison with two commercially available dentifrices, Aquafresh Whitening Toothpaste with Fluoride, and Crest Regular Fluoride Toothpaste. Following a baseline examination for extrinsic tooth stain area and intensity, qualifying adult male and female subjects from the Mississauga, Ontario, Canada area were randomized into three treatment groups which were balanced for age, gender, and level of extrinsic tooth stain. Subjects were instructed to brush their teeth twice daily (morning and evening) for one minute with their assigned dentifrice using a soft-bristled toothbrush. Examinations for extrinsic tooth stain were repeated after six weeks' use of the study dentifrices. One hundred twenty-two (122) subjects complied with the protocol and completed the entire study. At the six-week examination, subjects assigned to the Colgate Tartar Control Plus Whitening treatment group and subjects assigned to the Aquafresh Whitening treatment group exhibited statistically lower levels (p < 0.0001) of extrinsic tooth stain area and intensity than did those subjects assigned to the Crest Regular Fluoride treatment group. Further, subjects assigned to the Colgate Tartar Control Plus Whitening treatment group exhibited significantly lower levels of extrinsic tooth stain area and intensity than did those assigned to the Aquafresh Whitening treatment group (p < 0.0001).

Management of duodenal ulcer disease in the era of H. pylori.

BACKGROUND: Today it is expected that the great majority of patients with duodenal ulcer (DU) respond to H. pylori eradication treatment without DU recurrence. The aim of the research is to identify patients who need a different therapeutic approach and the best management of their disease. METHODS: We examined retrospectively the medical history of 474 patients (326 males, mean age 61 years), followed up in 5 years in the outpatients department of a third level GI Center. From our research, 5 subgroups of patients emerged: 1) 63.5% carrying H. pylori infection, with successful eradication treatment and without DU recurrence; 2) 4% failing 3 courses of H.pylori eradication treatment; 3) 11% with DU lacking evidence of H. pylori infection or relapsing after verified eradication; 4) 8% being treated with NSAIDs; 5) 13% with DU complicated by hemorrhage or perforation. RESULTS: 23% of patients with DU need long-term therapy after H. pylori eradication treatment. Concerning this, the percentage of ulcerous recurrences in patients receiving anti-H2 therapy is 18.5%, but decreases considerably to 2% when PPI were used. CONCLUSIONS: Although representing the mainstay of DU therapy, H. pylori eradication treatment may not abolish all issue in DU management. Actually, of DU patients referred to a third level GI Center, 23% need a different therapeutic approach, which results from a thorough analysis of the medical history of the patient.

Effects of adenosine receptor agonists on renal function in anaesthetized rats.

OBJECTIVES: To investigate the effects of the interaction between adenosine receptors and renal nerves on urinary sodium excretion and glomerular filtration rate. METHODS AND DESIGN: The effects on water and sodium excretion and glomerular filtration rate of A1 [2-chloro-N6-cyclopentyl-adenosine (CCPA)] and A2 [2-hesinyl-5'-N-ethyl-carboxamido-adenosine (2HE-NECA)] adenosine agonists were studied in anaesthetized rats with one kidney surgically denervated. Arterial blood pressure, heart rate and rate of urine flow from each kidney were continuously recorded; inulin clearance was used as an index of glomerular filtration rate. The experiments were performed with three groups of rats, into which, after a control period of 20 min, CCPA, 2HE-NECA or vehicle was infused for two subsequent 20 min periods. RESULT: During infusion of CCPA, the slight decrease in arterial pressure was associated with a transient decrease in glomerular filtration rate and marked long-lasting decreases in heart rate, water and sodium excretion and fractional sodium excretion. The response of the innervated kidney was similar to the response of the denervated kidney. Infusion of 2HE-NECA caused decreases in arterial pressure, glomerular filtration rate and excretion of water and sodium associated with an increase in heart rate. The reduction of water and sodium excretion from the innervated kidney was larger than that from the denervated kidney. CONCLUSIONS: Activation both of A1 and of A2 receptor causes a reduction in urinary water and sodium excretion. The renal response to activation of A2 receptors is enhanced by the presence of renal nerves, whereas the response to activation of A1 receptors is not influenced by renal nerves.