Specific dyspeptic symptoms are associated with poor response to therapy in patients with gastroesophageal reflux disease.

INTRODUCTION: In patients with gastroesophageal reflux disease (GORD), co-existence of functional dyspepsia (FD) is known to be associated with poor response to proton pump inhibitors (PPIs), but the contribution of specific dyspepsia symptoms has not yet been systematically investigated. OBJECTIVE: We aimed to characterize the impact of dyspepsia symptoms on response to PPIs in patients with GORD. METHODS: The enrolled subjects were consecutive patients with a diagnosis of GORD. All patients underwent a 24 hour pH-impedance test, while on PPI therapy. Patients were divided into two groups, refractory and responders, according to the persistence of GORD symptoms. A standardized questionnaire for FD was also administered to assess presence of dyspepsia symptoms. RESULTS: In the subgroup of refractory patients FD was more prevalent than in responders, with post-prandial fullness, nausea, vomiting, early satiation and epigastric pain being significantly prevalent in refractory GORD patients. In the multivariate analysis only early satiation and vomiting were significantly associated with poor response to PPIs. CONCLUSION: Co-existence of FD is associated with refractory GORD. We showed that only early satiation and vomiting are risk factors for poor response to therapy with PPIs. Our findings suggest that symptoms of early satiation and vomiting would help to identify the subset of PPI-refractory GORD patients.

The effect of top-layer chemistry on the formation of supported lipid bilayers on polyelectrolyte multilayers: primary versus quaternary amines.

The influence of the surface chemistry of polyelectrolyte multilayers (PEMs) on the formation of lipid bilayers is studied here for PEMs with either polyallylamine hydrochloride (PAH) or polydiallyldimethylammonium chloride (PDADMAC) as a polycation as a top layer, and polystyrene sulfonate (PSS) as a polyanion. Small unilamellar vesicles (SUVs) composed of phosphatidyl choline and phosphatidyl serine at a 50 : 50 molar ratio are deposited on top of the PEM films. The assembly of the SUVs into bilayers is studied via a quartz crystal microbalance with dissipation (QCM-D) and fluorescence recovery after photobleaching (FRAP). SUV deposition on PDADMAC/PSS results in vesicle adsorption while on PAH/PSS under the same conditions a bilayer is formed mainly due to weak interactions between the quaternary amines of PDADMAC. FRAP measurements confirm that SUVs are not fused on top of PDADMAC/PSS. The effect of phosphate ions, in solution, on the formation of lipid bilayers is also analysed. X-ray photoelectron spectroscopy shows the complexation of phosphate salts to the primary amines of PAH and no interaction with the quaternary amines of PDADMAC. ζ-potential measurements show a potential close to 0 for the PAH/PSS multilayers in PBS while PDADMAC/PSS displays a potential of 25 mV. A model is presented for the formation of lipid bilayers on PAH/PSS PEMs taking into account the role of phosphate ions in decreasing the electrostatic interactions between SUVs and PEMs and the formation of hydrogen bonds between the phospholipids and the primary amines of PAH.

Exercise training and music therapy in elderly with depressive syndrome: a pilot study.

OBJECTIVE: Recent studies have thrown doubt on the true effectiveness of anti-depressants in light and moderate depression. The aim of this study is to evaluate the impact of physical training and music therapy on a sample group of subjects affected by light to moderate depression versus subjects treated with pharmacological therapy only. DESIGN AND SETTING: Randomized controlled study. Patients were randomized into two groups. Subjects in the pharmacotherapy group received a therapy with antidepressant drugs; the exercise/music therapy group was assigned to receive physical exercise training combined with listening to music. The effects of interventions were assessed by differences in changes in mood state between the two groups. MAIN OUTCOME MEASURES: Medically eligible patients were screened with the Hamilton Anxiety Scale and with the Geriatric Depression Scale. We used plasmatic cytokine dosage as a stress marker. RESULTS: We recruited 24 subjects (mean age: 75.5 ± 7.4, 11 M/13 F). In the pharmacotherapy group there was a significant improvement in anxiety only (p<0.05) at 6-months. In the exercise/music therapy was a reduction in anxiety and in depression at 3-months and at 6-months (p<0.05). We noted an average reduction of the level of TNF-a from 57.67 (± 39.37) pg/ml to 35.80 (± 26.18) pg/ml. CONCLUSIONS: Our training may potentially play a role in the treatment of subjects with mild to moderate depression. Further research should be carried out to obtain more evidence on effects of physical training and music therapy in depressed subjects.

[Effect of AChE and BuChE inhibition by rivastigmin in a group of old-old elderly patients with cerebrovascular impairment (SIVD type)]. / Effecto dell'inibizione AChE e BuChE tramite rivastigmina in un gruppo di soggetti geriatrici old-old affetti da demenza vascolare (SIVD-type).

AIM: Vascular dementia (VaD) is defined as a loss of cognitive function resulting from ischemic, hypoperfusive, or hemorrhagic brain lesions due to cerebrovascular disease or cardiovascular pathology. The main types of VaD are: Small Vessel Disease Dementia (sVAD), Large vessel disease dementia, hypoperfusive-ischemic dementia and hemorragic dementia. The sVAD is divided into two main categories: subcortical ischemic vascular dementia (SIVD) and cortical dementia. Currently, no drugs are approved for the treatment of VaD. This study aimed to determine whether rivastigmine, a second generation cholinesterase inhibitor with selectivity for the CNS, with capacity to inhibit both acetylcholinesterase (AChE) and butyryl-cholinesterase (BuChE), slows the rate of cognitive decline associated with VaD. METHODS: Study subjects were 27 male and 43 female outpatients aged 80.03±6.53 years, with Mini-Mental State Examination (MMSE) score ranging batween 22 and 12, affected by VaD. They were included in the study if they were undergoing pharmacological treatment with acetylsalicylic acid 100 mg for at least six months. Patients were divided into two groups: one group was treated with ASA 100 mg and rivastigmine patch 9.5 mg (Rivastigmine group), the other just with ASA 100 mg (ASA group). All patients were followed for 6 months, with a first evaluation (T0) and a second examination after six mounths of treatment (T1). RESULTS: Statistically data proved as the Rivastigmine group showed constant values at MMSE, compared with patients of the ASA group who experienced decline of their cognitive performances. The same result was found in CDR, ADL, GDS and NPI scales. It is remarkable to underline as Rivastigmine-treated patients had a mean improvement in GDS scales, in comparison with patients of the ASA group who showed a worsening of mood. CONCLUSION: Rivastigmine-therapy improves cognitive performance in elderly with SIVD.

Hypovitaminosis D: which oral supplement therapy?

OBJECTIVES: the possible therapeutic role of vitamin D in different kind of diseases explains the growing interest in this vitamin due to its pleiotropic effects. This short report shows preliminary results of prevalence of hypovitaminosis D in a group of patients and proposes a oral supplement therapy effective in correcting hypovitaminosis in a short time, without side effects. METHODS: 243 patients (aged 26-93; 67 males) were enrolled at this study. We evaluated plasma levels of 25-hydroxyvitamin D [25(OH)D] with the following cut-off values: <10 ng/ml or <0-25 nmol/L (deficient), 10-30 ng/ml or 25-75 nmol/L 30-50 (insufficient) and > 30 ng/ml or > 50 nmol/L (normal). The first 73 patients with hypovitaminosis D received at baseline 25,000 IU (Cholecalciferol) per os twice a month (Tp.A). The next patients (Tp.B) at baseline received a loading dose of 50,000 IU once a week for 8 weeks, followed by a maintenance dose of 25,000 IU twice a month. RESULTS: hypovitaminosis D is a widespread condition (i.e., 82.3%) not only in elderly (75.6% of 75 patients aged <65 yrs and 86.5% of 168 subjects aged >65 yrs). Preliminary results at 6 months show that Tp.B is more effective in correcting hypovitaminosis D (baseline 14.4 ± 5.3 ng/ml; 24 wk 43.3 ± 14.7 ng/ml; p<0.0001). CONCLUSION: hypovitaminosis D is an important public health problem. We believe it is important to quickly achieve normal Vit. D plasma values in order to produce pleiotropic effects.

Role of cardiovascular risk factors (CRF) in the patients with mild cognitive impairment (MCI).

Few therapeutic options are available nowadays to improve the prognosis of patients with Alzheimer's disease (AD). There are rather several evidences in literature that controlling vascular risk factors may be an effective intervention for modifying the course of this disease. The aim of our study was to investigate the role of CRF in 50 patients with MCI according to Petersens's criteria, and to evaluate their influence on cognitive and behavioral features of the disease and on the development of dementia. Statistical analysis of the data showed that the 60% of the patients with MCI and CRF developed dementia, while 40% maintained the same cognitive conditions at the end of the study. Only 32% of the subjects without cardiovascular comorbidities developed dementia. The results of the study suggest that CRF play a key role in cognitive decline of patients with MCI. Patients with MCI and CRF showed not only worse cognitive performances, but also behavioral disorders, depression and functional disability. Patients with CRF had higher conversion rate to AD than the other group, with a mean disease-free period 3 months shorter than the control group.

Effect of beta-glucan, inositol and digestive enzymes in GI symptoms of patients with IBS.

BACKGROUND: Irritable bowel syndrome (IBS) is a very common functional gastrointestinal (GI). Diagnosis of IBS is based on the fulfilment of the Rome III criteria. Common GI symptoms are lower abdominal pain, bloating and disturbed defecation, such as urgent diarrhoea and/or episodes of chronic constipation. Many agents have been employed in the management of IBS, although only few have been demonstrated to show a relevant efficacy. AIM: To evaluate the effectiveness of the administration of a mixture of beta-glucan, inositol and digestive enzymes (Biointo) in improving GI symptoms in patients affected by IBS. PATIENTS AND METHODS: 50 IBS patients (20 males, 30 females; mean age 51 +/- 19) were treated with Biointo (group A) while another group consisting of 40 IBS patients (15 males, 25 females; mean age 50 +/- 18) did not receive any therapy (group B). RESULTS: Biointol administration improved significantly bloating, flatulence and abdominal pain, with a slight increasing of urgency for bowel movements. On the contrary, Biointol did not show any significant effect on the other IBS symptoms. CONCLUSIONS: Currently, only few agents used in the management of IBS have been proven to be effective. Biointol administration has shown to improve some IBS symptoms, such as bloating, flatulence and abdominal pain, all connected to the presence of gas inside the intestinal lumen.

Gastrointestinal regulation of food intake: do gut motility, enteric nerves and entero-hormones play together?

The gastrointestinal system can be considered the gateway for food entry in our body. Rather than being a passive player, it is now clear that gut strongly influence the feeding behavior and contribute to maintain energy balance with different signals. The aim of this review is to summarize the current knowledge about the role of gastrointestinal tract in the control of food intake, by focusing on the interplay existing between the enteric nervous system and gastrointestinal hormones and their ability to modulate digestive motility and sensitivity. Also the latest advances about the contribution of gut microbiota and gastrointestinal taste receptors are described. From the reported data it clearly emerges that gut hormones together with nervous signals likely contribute to the regulation of energy balance and modulate food intake through the control of digestive motility and sensations. The close linkage among gastrointestinal hormones, the gut and the central nervous systems appears very intriguing and has induced the development of a new field of research: the gastroendocrinology.

Long-term antibody persistence and immune memory to hepatitis B virus in adult celiac patients vaccinated as adolescents.

Aim of this study was to investigate the anti-HBs antibody persistence and immune memory to hepatitis B virus in adult celiacs vaccinated as adolescents and the effect of a booster administration in non-protected individuals. Eleven years after primary vaccination, the proportion of vaccinees with titres ≥ 10 mIU/ml and antibody geometric mean concentrations (GMCs) were lower among celiac patients than among controls (68.6% vs 91.7%, p<0.01; GMCs 29.38 mIU/ml vs 250.6 mIU/ml, p<0.001). Participants with anti-HBs below 10 mIU/ml received a booster dose and were retested 2 weeks later to assess the anamnestic response. Post-booster anti-HBs levels were still <10 mIU/ml in 71.4% celiacs and 25% controls (p<0.01). Our findings indicate that the prevalence of seroprotective levels of anti-HBs detected eleven years after primary immunization as well as the frequency of response to a booster dose of vaccine are lower in celiac patients compared to healthy controls.

The quality of sleep in patients with coeliac disease.

BACKGROUND: Coeliac disease is a chronic disease with a various clinical presentation, including anxiety and depression. AIM: To investigate the quality of sleep in coeliac disease. METHODS: The participants were coeliacs at diagnosis; coeliacs on a gluten-free diet at follow-up and healthy volunteers. Participants completed the Pittsburgh Sleep Quality Index (PSQI), SF36, Zung and Fatigue scales and State-Trait Anxiety Inventory (STAI). RESULTS: The PSQI score was higher in coeliacs at diagnosis and in a gluten-free diet than in healthy volunteers (P < 0.001). A gluten-free diet did not improve the PSQI score (P = 0.245) in coeliac disease. The other test scores were similar between coeliacs at diagnosis and those on a gluten-free diet, whereas significant differences were found between coeliacs and volunteers. PSQI score was inversely associated with the quality of the physical (r = -0.327, P = 0.002) and mental (r = -0.455, P < 0.001) component scores. The sleep quality scores were related to depression (r = 0.633, P < 0.001), fatigue (r = 0.377, P < 0.001), state anxiety (r = 0.484, P < 0.001) and trait anxiety (r = 0.467, P < 0.001). CONCLUSIONS: Sleep disorders are common in coeliac disease not only at diagnosis but also during treatment with a gluten-free diet. Sleep disorders are related to depression, anxiety and fatigue, and inversely related to quality of life scale scores.

Oxidative-stress-mediated arterial dysfunction in patients with peripheral arterial disease.

AIMS: To investigate the existence of a relationship among flow-mediated dilation (FMD), nitric oxide (NO), and oxidative stress in patients with peripheral arterial disease (PAD), and to assess if the administration of an antioxidant was able to improve arterial dilatation. METHODS AND RESULTS: We performed a cross-sectional study comparing FMD, 8-Hydroxy-2-deoxy-2-deoxyguanosine (8-OHdG), a marker of oxidative stress, and nitrite/nitrate (NOx) serum levels in a population of 25 PAD patients and 40 controls. In the second part of the study, 21 PAD patients were randomly allocated to a treatment sequence of 7 days of i.v. infusion of placebo or 6 g/day propionyl-L-carnitine (PLC) in a cross-over design. Compared with controls, patients with PAD had enhanced 8-OHdG serum levels (2.4 +/- 1.2 vs. 4.24 +/- 3.11 ng/mL; P < 0.001), reduced NOx (17.02 +/- 6.11 vs. 11.28 +/- 6.02 microM; P < 0.001), and lowered FMD (10.34 +/- 2.14 vs. 6.69 +/- 2.95; P < 0.001). PLC infusion was associated with an increase of FMD [from 6.6 +/- 0.6 to 11.1 +/- 1.2% (mean +/- SE), P = 0.004] and NOx (from 14.5 +/- 1.4 to 17.1 +/- 1.2 microM; +18%, P = 0.012) and a decrease of 8-OHdG (from 3.62 +/- 0.37 to 2.64 +/- 0.32 ng/mL; -27%, P < 0.001). No changes were observed after placebo treatment. CONCLUSION: This study shows that in PAD patients, oxidative stress is implicated in determining reduced FMD.

Cetirizine, a second-generation H1 antagonist, modulates Rantes and MCP-1 levels in allergic rhinitis.

Chemokines and their receptors are involved in several allergic diseases. We measured RANTES and MCP-1 levels in sera of allergic rhinitis patients, and also we evaluated the effect of cetrizine, a second-generation H1 antagonist, on these chemoattractant proteins. 15 subjects were studied (10 males and 5 females; mean age: 26.7 years). They were suffering from perennial or seasonal allergic rhinitis induced by Dermatophagoides pteronyssinus (8 patients) or by grasses (7 patients). RANTES and MCP-1 serum levels were detected with an enzyme immunoassay before and after two weeks of treatment with 10 mg of cetirizine daily, and again after two weeks of washout. Baseline serum levels of RANTES and MCP-1 chemokines were significantly higher (p < 0.02 and p = 0.007, respectively) in allergic patients than in the healthy control group. Cetirizine resulted in a significant decrease in RANTES (p < 0.02) and MCP-1 (p = 0.003) versus baseline values. There is an increase in RANTES and MCP-1 in allergic rhinitis, which is counteracted by cetirizine.

Mast cell activation in acquired chronic urticaria-angioedema.

Mast cells play a central role in the pathogenesis of many allergic disorders. They can be activated in different ways. The present study was focused to evaluate the role of mast cells in acquired chronic urticaria-angioedema induced by gastroesophageal reflux. Tryptase, an important marker of mast cell activation, was detected with UniCap Tryptase Fluoroenzymeimmunoassay (Pharmacia & Upjohn AB, Uppsala, Sweden). Eight subjects were studied: four males and four females, aged between 29 and 71 years (mean age: 45 yrs.), suffering from acquired chronic urticaria-angioedema. Results were compared with the results of seven healthy control subjects. Moreover, data were compared with those of 13 subjects (10 males and 3 females, mean age: 24.7 years) suffering from allergic rhinitis. In acquired chronic urticaria-angioedema, serum tryptase levels (mean +/- S.D.: 9.6 +/- 4.3 microg/l) were significantly higher (P < 0.007) than those of the controls (mean +/- S.D.: 3.0 +/- 1.2 microg/l) and higher also than in allergic rhinitis (mean +/- S.D.: 6.1 +/- 2.4 microg/l, P < 0.03). The results underline the central role of mast cells in the inflammation of acquired chronic urticaria-angioedema.

Serum tryptase in allergic rhinitis: effect of cetirizine treatment.

Activated mast cells release a large range of potent mediators of allergic inflammation, including proteases. The tryptase serum levels were evaluated in 13 subjects suffering from allergic perennial rhinitis. Moreover the effects of cetirizine treatment on serum tryptase were studied using the UniCap™ tryptase fluoroenzymeimmunoassay. In allergic patients the serum tryptase values (M±SD: 6.1 ± 2.4 μg/L) were significantly (p < 0.02) higher than the values detected in controls (3.0 ± 1.2 μg/L). In allergic rhinitis, after antihistamine treatment, tryptase values (4.4 ± 1.8 μg/L) decreased significantly (p < 0.001). After two weeks from the cetirizine stop, the tryptase levels increased again (5.5 ± 2.6 μg/l). The results demonstrate that mast cells are constantly activated in perennial allergic rhinitis. The antihistamine treatment is effective in reducing the tryptase release from mast cells, but the mechanism of action of cetirizine is still to understand.

Serum tryptase in allergic rhinitis: effect of cetirizine and fluticasone propionate treatment.

PURPOSE: A specific reaction against several kinds of inhalant allergens characterizes allergic rhinitis. Mast cells play a crucial role in the allergic inflammation releasing histamine and other mediators. Tryptase is considered to be a specific marker of mast cell activation. This study was devoted to evaluate the serum tryptase in allergic rhinitis and to evaluate the effect of cetirizine and fluticasone propionate on mast cell activation. 13 subjects, suffering from perennial allergic rhinitis induced by Dermatophagoides pteronyssinus, were studied. MATERIALS AND METHODS: Tryptase serum levels were detected by the fluoroenzymeimmunoassay (Pharmacia & Upjohn AB, Uppsala, Sweden). Blood samples were taken four times: before starting the study, after two weeks of 10 mg cetirizine treatment once a day, after two weeks of wash-out, and again after 15 days of 100 micrograms intranasal fluticasone propionate therapy twice a day. RESULTS: In allergic rhinitis, the basal values of serum tryptase (M +/- SD: 6.1 +/- 2.4 micrograms/l) were significantly higher than in controls (M +/- SD: 3.0 +/- 1.2 micrograms/l). After the antihistamine treatment, tryptase values (M +/- SD: 4.4 +/- 1.8 micrograms/l) decreased significantly (p < 0.001). After the stop of antihistamine treatment, tryptase levels increased (M +/- SD: 5.5 +/- 2.6 micrograms/l, p < 0.001). After the topical corticosteroid treatment, tryptase values decreased again significantly (M +/- SD: 4.5 +/- 3.1 micrograms/l, p < 0.04). CONCLUSIONS: All these data seem to confirm the effective action of cetirizine and fluticasone propionate on tryptase serum levels. While the action of corticosteroid is well known, the action of cetirizine is still to define, considering the recent reports on anti-inflammatory effect of the second generation of H1 receptor antagonists. Further studies are necessary to understand if the pharmacological effect on tryptase is a specific one of cetirizine, or if it is common to other anti-H1 molecules.

Gastric asthma: an unrecognized disease with an unsuspected frequency.

Bronchial asthma is a disease that has been recognized for centuries, which is influenced mainly by genetic and environmental factors. The current interest of bronchial asthma is focused to ascertain the causes and the mechanisms that induce bronchoconstriction. Recently, abnormalities of the esophageal and gastric tracts have become important related areas for research. In predisposed individuals, these abnormalities can trigger or worsen the particular syndrome better known as "gastric asthma." In bronchial asthma the disorder of gastroesophageal reflux (GER) occurs more often than would be expected by chance. The neurogenic mechanism is considered to be the main cause of bronchoconstriction. The diagnosis of gastric asthma is particularly difficult and it should be considered also when GER is less evident or not recognized. In asthmatic patients the recognition of gastric abnormalities is very relevant for therapeutic problems also when GER is in a subclinical stage. In fact, many drugs used in the treatment of bronchial asthma can promote or enhance GER and subsequently they can worsen the symptoms of gastric asthma.

Hepatitis C virus: a high risk factor for a second primary malignancy besides hepatocellular carcinoma. Fact or fiction?

PURPOSE: Second primary malignancies occur more and more often. But the hepatocellular carcinoma (HCC) linked to a second primary cancer is not frequent. MATERIALS AND METHODS: A retrospective study focused on a second primary cancer was performed in 37 patients with HCC, aged between 46 and 81 years, 27 males and 10 females. RESULTS: 5 out of them (13.5%), 3 males and 2 females, developed a second primary neoplasm before or after HCC. In 3 cases the second malignancy was a carcinoma of the kidney, of the breast, and the prostate. The fourth patient had a Hodgkin's lymphoma before HCC. The last and most unlucky case, besides HCC, had a basal cell carcinoma, a colorectal cancer, and a bladder carcinoma. The common data of these 5 patients were the presence of anti-HCV antibodies and the positivity of the HCV RNA polymerase reaction. One patient was also HBV positive. CONCLUSION: Considering that a large number of virus has been found linked to human cancers, our results brought us to hypothesize that HCV could have played an important role not only in the development of HCC but of the second primary malignancy too. This is likely favoured by constitutional or acquired biological and molecular alterations. Tumor suppressor genes alterations have been reported to be frequently linked to cancers of kidney and breast, of colorectal and skin, of prostate, and lymphoemopoietic tissue. Now just these organs are involved in our patients in addition to the liver. Our results, if confirmed, are of a relevant interest, considering that world-wide HCC is constantly increasing for the spreading of the virus risk-factors.