Pathogenesis of chronic cluster headache and bouts: role of tryptamine, arginine metabolism and α1-agonists.

The aim of this study was to explore the possible role of tryptamine in the pathogenesis of chronic cluster headache along with that of adrenaline and noradrenaline (α-agonists) together with arginine metabolism in the origin of cluster bouts. Plasma levels of tyramine, tryptamine, serotonin, 5-hydroxyindolacetic acid, noradrenalin, adrenalin and the markers of arginine metabolism such as arginine, homoarginine, citrulline, ADMA and NMMA, were measured in 23 chronic cluster headache patients (10 chronic cluster ab initio and 13 transformed from episodic cluster) and 28 control subjects. The plasma levels of tyramine, tryptamine, noradrenalin and adrenalin were found several times higher in chronic cluster headache patients compared to controls, whereas the plasma levels of arginine, homoarginine and citrulline were significantly lower. No differences were found in the plasma levels of serotonin, 5-hydroxyindolacetic, ADMA and NMMA between chronic cluster headache patients and control subjects. These results provide support for a role of tryptamine in the pathogenesis of chronic cluster headache and, in particular, in the duration of the cluster bouts. In addition, the low levels of the nitric oxide substrates together with the high levels of noradrenalin and adrenalin suggest an activation of endothelial TAAR1 receptors followed by the release of nitric oxide in the circulation that may constitute the final step of the physiopathology of cluster crisis.

Benefit of supplements in functional dyspepsia after treatment of Helicobacter pylori.

AIM: Functional dyspepsia, though benign, leads to deterioration of the quality of life and high costs for healthcare systems. The optimal therapy for functional dyspepsia is still to be defined because of its multifactorial pathogenesis. In an open multicentric study of patients with functional dyspepsia, we prospectively evaluated the benefit of treatment with a food supplement composed of sodium alginate, carbonate calcium, pineapple, papaya, ginger, α-galactosidase and fennel (Perdiges, Bioten Snc, Turin, Italy). METHODS: Ninety-one consecutive patients were included, suffering from functional dyspepsia, who had been previously submitted to therapy to eradicate the infection from Helicobacter pylori (H. pylori) and were waiting to perform the Urea Breath Test (UBT). The primary goal was to establish the percentage of patients who continued to abstain from proton pump inhibitors (PPI) as they waited to carry out the UBT, differentiating between patients who were treated (N.=55) with Perdiges and those who were not (N.=36). Our secondary goal was to document the differences within the 2 groups in terms of symptoms perceived between the start and end of the observation period. The wellness reported, during or in absence of treatment with Perdiges, was evaluated by the use of the VAS scale (Visual Analogical Scale) completed before the start of the treatment and after 30 days. RESULTS: All the patients treated with Perdiges (55/55, 100%) and 31/36 (86.1%) patients who were not (P=0.008) continued to abstain from PPI in the period awaiting the UBT. The VAS scale of those who took Perdiges improved on average by 1.78 points versus a worsening of 0.08 points of those who did not take it (P<0.0001). Furthermore, while among those who took Perdiges there was a statistically significant improvement (P<0.0001) in the VAS scale, between the baseline and the end of treatment, a worsening of 0.08 points (P=0.78) was noticed among the patients who did not take it. CONCLUSION: Perdiges is significantly effective in the period following treatment to eradicate the infection from H. pylori in patients with functional dyspepsia. This allows to reduce the need to use antisecretive drugs. Further randomised studies, with wide ranging case histories, must assess its long-term efficacy.

Magnetic ordering in strong anisotropic ferromagnetic bilayers with dipolar and antiferromagnetic interlayer exchange interactions: Monte Carlo approach.

In this work, multilayer films consisting of two strong-anisotropic ferromagnetic layers antiferromagnetically coupled by a nonmagnetic spacer are studied by Monte Carlo simulations. The system is modeled by an Ising-based Hamiltonian that depends on both the intralayer exchange and dipolar constants and on the interlayer exchange constant (IEC). The ground state of the monolayers (null IEC) corresponds to alternate stripe domains with width h defined by the ratio between the exchange and dipolar constants (δ). The results show that IEC alters the energy balance that controls the stripe domain formation, leading to a ground state characterized by in-plane stripes out-plane antiferromagnetically coupled. When temperature increases two regimes are identified: an IEC-dominated regime where the orientational and positional orders are simultaneously lost in both layers, driving the system to the tetragonal liquid (TL) phase, and a dipolar-dominated one where signs of layers decoupling and the onset of positional disorder are observed. The last could be related with an intermediate nematic phase (NM). From the study of the nonequilibrium dynamics, the phase transitions to TL phase are characterized as continuous and those to the NM one as Kosterlitz-Thouless type. Also, for both layers the critical temperatures are the same and increase with IEC magnitude. Furthermore, the obtained critical exponents depend on the IEC values, which is indicative of a weak universality. For the dipolar-dominated regime, the decoupling between layers is also evidenced by the difference between their critical exponents.

Molecular findings on Helicobacter pylori: update for clinicians.

Helicobacter pylori (H. pylori) is a gram-negative bacterium which is responsible for a wide range of disorders of the stomach, from chronic gastritis to peptic ulcers to gastric cancer which, however, occurs in a lower percentage of subjects. The difference in the clinical course of infection seems to be correlated both to the typical pathogenicity of the bacterium and to factors related to the host. The reasons underlying these observations include differences in bacterial pathogenicity as well as in host susceptibility. Numerous studies published in the last year have provided new insights into H. pylori virulence factors, their interaction with the host and the relative consequences in the pathogenesis. In this review, we have set ourselves the target of summarising the latest progress made in understanding the molecular aspects of H. pylori infection of notable importance for the physician.

Endoscopic banding for esophageal variceal bleeding: technique and patient outcome.

AIM: Endoscopic variceal ligation (EVL) is recommended for the treatment of esophageal variceal bleeding. The aim of this study was to assess the most cost-effective timing of endoscopic follow-up after variceal eradication. METHODS: Cirrhotics with esophageal varices treated between January 2008 and January 2009 until reached variceal obliteration were retrospectively analyzed for technical aspects and for outcomes. RESULTS: Out of 127 patients treated with EVL, 103 were included. Number of sessions to achieve variceal obliteration and number of bands for each session were 2.8±1.3 (range 1-7) and 4.6±1 (range 2-7), respectively. The placement of >5 bands per session was not associated with higher incidence of complications (19.6% vs. 17.8%, P=ns). Esophageal ulcers were observed in 42% of patients when the interbanding interval was <20 days (versus 15% for interval >20 days, P<0.05). Once obliteration was achieved, varices reappeared in 28% of patients; the early appearance of small varices was not associated with bleeding. CONCLUSION: A longer interbanding interval reduces the incidence of procedural-related complications. After variceal obliteration an early endoscopic control is not useful because it does not influence the approach and does not change the patient outcome.

Environmental electroactive consortia as reusable biosensing element for freshwater toxicity monitoring.

The development of tools to monitor water quality is mandatory in a scenario where clean water resources are decreasing. Here, the biosensing capability of an electroactive river sediment consortium was tested towards three model contaminants (glutaraldehyde, nickel(II) and chromium(III)). The proposed biosensor is a small membrane-less single chamber Microbial Fuel Cell (MFC), fabricated by 3D printing. Its semi-continuous mode of operation resulted in long-term current profile stability and reproducibility. A linear trend of response was obtained for glutaraldehyde in a concentration range of 5-1000 ppm. After the recovery of the electroactive consortium activity, the MFC-based biosensors were shown to be sensitive towards Ni(II) and Cr(III), at concentrations above 2 mg L-1. To effectively analyze biosensor response, a novel algorithm was proposed, offering advantages for the realization of energy-saving protocols for MFC-biosensor data transmission. Implementation of the device and method, from laboratory test to real environment, can offer a low cost in situ system for detection of water contaminants.

Clinical and biochemical parameters related to cardiovascular disease after Helicobacter pylori eradication.

AIM: Since the major established risk factors explain the pathogenesis of ischemic heart disease (IHD) in a proportion of cases, it is crucial to search for other causal mechanisms. The possible link between IHD and Helicobacter pylori (H.pylori) infection has been reported. However, the precise mechanism of this potential relationship, by a proinflammatory activity or metabolic disorder, is unclear. In order to investigate this issue, the authors assessed changes in clinical and biochemical parameters related to IHD after bacterial eradication. METHODS: A total of 496 patients (281 males; mean age 59.7+/-2.3) with H.pylori-positive dyspepsia and/or peptic ulcer were studied after cure of the bacterium. H.pylori status was determined by histology or 13C-urea breath testing. Examinations for body mass index, diastolic blood pressure and blood testing (C-reactive protein, fibrinogen, triglycerides, total cholesterol, high-density and low-density lipoprotein cholesterol, fasting glucose) were performed before eradication and annually for up to five years thereafter. For statistical analyses, the Student's t test was performed. RESULTS: HDL-C increased (P=0.02) while C-reactive protein and fibrinogen levels diminished (P<0.0001) significantly. BMI and diastolic blood pressure increased in a significant (P=0.032 and P=0.039 respectively) manner compared to baseline. CONCLUSIONS: H.pylori eradication is associated with modification of some clinical and biochemical parameters related to IHD during a follow-up of five years. There is a need for large interventional randomized studies in order to prove a causal association.

An update on AIDS-related cholangiopathy.

Both hepatic parenchymal and biliary tract diseases are common in patients with human immunodeficiency virus (HIV). In this paper, the authors focus mainly on clinical aspects of acquired immunodeficiency syndrome (AIDS)-related cholangiopathy. Although the etiology is unclear, several opportunistic infections (cytomegalovirus, Cryptosporidium and others) are suspected to cause it. Endoscopic retrograde cholangiopancreatography (ERCP) is the diagnostic gold standard and it offers a therapeutic means to provide symptomatic relief in case of papillary stenosis. The most common ERCP pattern is diffuse sclerosing cholangitis in combination with papillary stenosis. Clinically, the presentation may be variable, although right upper quadrant pain and fever accompanied by an elevated serum alkaline phosphatase (ALP) level are the most common manifestations. Jaundice is unusual suggesting that complete ductal obstruction is rare. While ERCP results and the need of sphincterotomy do not influence the prognosis, antiretroviral therapy is a protective factor and, on the contrary, high ALP level is related to a less favorable outcome. Regarding the possible pathogenic mechanisms through which HIV infection could be involved in AIDS-related cholangiopathy, in vitro experiments have shown that concurrent active HIV replication and Cryptosporidium parvum infection synergistically increase cholangiocyte apoptosis and thus jointly contribute to AIDS-related cholangiopathies.

Evidence of Kosterlitz-Thouless phase transitions in the Ising model with dipolar interactions.

The ferromagnetic bidimensional Ising model with dipolar interactions has been proposed to model ultrathin films with strong out-of-plane anisotropy. The phase diagram presents a rich phenomenology that includes low-temperature phases characterized by stripes of width n (h_{n}) and a high-temperature phase with domains of stripes with mutually perpendicular orientations, named tetragonal liquid (TL). The latter phase can be reached by two possible ways. One of them is the direct transition h_{n} to TL, and the other one is through an intermediate phase with orientational order but short-range positional disorder, named nematic phase (NM). The regions of the phase diagram where these transitions occur, as well as their character, remain an open question and are the object of the present work. In order to clarify this topic, intensive Monte Carlo simulations were performed by employing short-time dynamics as the main tool for studying the phase transition behavior. The dynamic evolution of the orientational order parameter and its moments are measured for selected values of the ratio between the ferromagnetic exchange and dipolar constants, called δ. The obtained results indicate that the intermediate NM phase is present for δ≥2 in narrow ranges of temperatures. Also, the results suggest that both transitions, i.e., h_{n}-NM and NM-TL, have a Kosterlitz-Thouless character. This type of topological transition is observed in continuous bidimensional models and have been proposed for discrete ones, as in the case of the present work.

Potential relationship between Helicobacter pylori and ischemic heart disease: any pathogenic model?

Helicobacter pylori (H.pylori), causal agent of several gastroduodenal diseases, has been involved in diverse aspects of many extragastric manifestations, including ischemic heart disease (IHD). The present paper focuses on the potential pathogenic mechanisms relating H. pylori to IHD. Since H. pylori DNA has been detected in the coronary arteries only in sporadic occasions, and considering that long-term inflammation might raise cytokine levels in the bloodstream, an indirect pathway is more plausible. Moreover, the evidence that some strains of H. pylori induce platelet aggregation supports a role in the acute phase of IHD. In conclusion, because IHD is a multifactorial disease, it is evident that H. pylori is not the only cause. Thus, the definition of H. pylori or other infectious agents as culprits requires a multidisciplinary approach.

Endoscopic ultrasonography in hepatology: focus on portal hypertension.

Portal hypertension (PHT) is more frequently caused by cirrhosis. Increase in portal pressure induces development of collateral circulation with shunting resulting in disturbances such as gastroesophageal varices (GEV). Prevention and therapy of bleeding from GEV are mandatory. Therefore, the diagnosis of PHT represents a crucial step. Endoscopic ultrasound (EUS), with its combination of endoscopic imaging and ultrasonic capabilities, can offer an almost comprehensive evaluation of portal venous system and porto-systemic collateral circulation. The improved endoscopic view of several video-echoendoscopes has filled the gap between EUS and standard video-endoscopy in diagnosing GEV and in assessing endoscopic criteria of bleeding risk. EUS combined with Color-Doppler capabilities are able to provide hemodynamic information. Furthermore, EUS data allow to stratify patients on the basis of PHT severity and first bleeding risk, monitor the results of pharmacologic and/or endoscopic therapy, predict the response to treatment, quantify the risk of variceal recurrence and recurrent bleeding after GEV obliteration and guide or assist EGD therapy. Despite having this amount of information, there is lack of scientific evidence that EUS imaging and EUS-assisted therapy can have a clear-cut clinical impact and affect patients outcome.

Helicobacter pylori eradication: metronidazole or tinidazole? Data from Turin, Italy.

AIM: Triple therapy consisting of a proton pump inhibitor (PPI) and two antibiotics is used as first choice in treating Helicobacter pylori (H. pylori) infection. Since in the North Italian population, metronidazole resistance is less than 40%, this antibiotic would be preferable as first approach. The aim of this randomized study was to assess the efficacy of a metronidazole-based versus a tinidazole-based treatment, in naïve patients with H. pylori infection. METHODS: Diagnosis and eradication of H. pylori infection were assessed by 13C-urea breath test, and by histology when an endoscopic examination was necessary. A total of 171 patients was treated: 91 (47 males, mean age 50+/-3 years) with metronidazole 250 mg q.i.d., amoxicilline 1 gr b.i.d. and PPI standard dose (MAO), and 80 (36 males, mean age 52+/-3.8 years) with tinidazole 500 mg b.i.d., amoxicilline 1 gr b.i.d. and PPI standard dose (TAO) regimen for 7, 10 or 14 days. RESULTS: Three patients suspended MAO treatment due to side effects. H. pylori eradication was obtained as follow indicated. After 7 days, in 23/30 (76.6%) patients in MAO versus 20/27 (74.0%) in TAO regimen. After 10 days, in 20/26 (76.9%) patients in MAO versus 20/26 (76.9%) in TAO regimen. After 14 days, in 25/32 subjects (78.1%) in MAO versus 21/27 (77.7%) in TAO treatment. The differences among durations or between metronidazole-versus tinidazole-based triple therapy were not statistically different. CONCLUSION: Treatment with metronidazole is as effective as that with tinidazole in terms of efficacy. Moreover, duration did not influence efficacy of treatment.

Severe ulcerative colitis: predictors of response and algorithm proposal for rescue therapy.

BACKGROUND: There is no agreeing if rescue therapy can avoid short-term colectomy in patients treated for severe steroid-refractory ulcerative colitis. AIMS: The aim of our study was to identify predictors of response to infliximab and cyclosporine A. METHODS: In this cross-sectional study, 49 patients with severe ulcerative colitis were included. Response to therapy was defined as three or more point reductions in Mayo score after 6 months of treatment and avoidance of colectomy after 1 year. The predictors analysed were gender, age, time from ulcerative colitis diagnosis, months of steroid or/and azathioprine therapy before onset of the severe phase, smoking habits, extension of the disease, laboratory analyses and Mayo score. RESULTS: Patients treated with infliximab showed a statistically significant higher response rate in case of moderate Mayo score (P = 0.04). Ex-smokers had very low chance of response to infliximab (P = 0.03). In the group treated with cyclosporine A, patients with C-reactive protein >3 mg/L had a response rate significantly higher than those with C-reactive protein <3 mg/L (P = 0.03); those with negative C-reactive protein and moderate Mayo score did not responded to therapy, while in the ones with elevated C-reactive protein and/or severe Mayo score, 15 versus 4 responded (P = 0.008). CONCLUSIONS: Our data suggest that cyclosporine A is advisable in ex-smokers. In never smokers or active smokers, infliximab can be prescribed in case of Mayo score ≤10 and/or negative CRP, while cyclosporine A is indicated in case of Mayo score >10 and positive CRP.

Nanoclusters of crystallographically aligned nanoparticles for magnetic thermotherapy: aqueous ferrofluid, agarose phantoms and ex vivo melanoma tumour assessment.

Magnetic hyperthermia is an oncological therapy where magnetic nanostructures, under a radiofrequency field, act as heat transducers increasing tumour temperature and killing cancerous cells. Nanostructure heating efficiency depends both on the field conditions and on the nanostructure properties and mobility inside the tumour. Such nanostructures are often incorrectly bench-marketed in the colloidal state and using field settings far off from the recommended therapeutic values. Here, we prepared nanoclusters composed of iron oxide magnetite nanoparticles crystallographically aligned and their specific absorption rate (SAR) values were calorimetrically determined in physiological fluids, agarose-gel-phantoms and ex vivo tumours extracted from mice challenged with B16-F0 melanoma cells. A portable, multipurpose applicator using medical field settings; 100 kHz and 9.3 kA m-1, was developed and the results were fully analysed in terms of nanoclusters' structural and magnetic properties. A careful evaluation of the nanoclusters' heating capacity in the three milieus clearly indicates that the SAR values of fluid suspensions or agarose-gel-phantoms are not adequate to predict the real tissue temperature increase or the dosage needed to heat a tumour. Our results show that besides nanostructure mobility, perfusion and local thermoregulation, the nanostructure distribution inside the tumour plays a key role in effective heating. A suppression of the magnetic material effective heating efficiency appears in tumour tissue. In fact, dosage had to be increased considerably, from the SAR values predicted from fluid or agarose, to achieve the desired temperature increase. These results represent an important contribution towards the design of more efficient nanostructures and towards the clinical translation of hyperthermia.

Helicobacter pylori and dementia. Which consistency for an association?

Alongside gastroduodenal diseases, Helicobacter pylori (H. pylori) infection has been associated with extradigestive diseases, including dementia. To identify all publications on the association between H. pylori and dementia, a MEDLINE search of all studies published in English from 1965 to 2007 was carried on. Very few investigations were found. Furthermore, studies with sufficient powerful design did not exist; dementia as well as H. pylori infection were defined with a low degree of homogeneity, biases were obvious in the control groups, thus giving room for large variation in the adjustment of potential confounding factors. Future research should be focused on three main issues: 1) prospective population-based studies, aiming to evaluate the consistency of epidemiological data with etiological hypotheses, and to provide the basis to develop and evaluate preventive procedures and public health practice; 2) intervention trials; 3) studies of physiopathology (both in the animal model and humans) to understand the potential biological plausibility of the association between H.pylori and dementia.

Instruments and accessories for diagnostic endoscopic ultrasound (radial scanning and miniprobes).

Endoscopic ultrasound (EUS) is a relatively new technology developed in the early 80's, but introduced into the clinical practice only in the late 80's. Nowadays there is an increase in demand for EUS examinations and services, because this technique is more and more recognized as an important and integral part in the diagnostic and staging algorithm of many gastrointestinal (GI) and nongastrointestinal pathologies. Even if today the EUS panorama enrich itself with a large number of different instruments, mechanical and electronic scopes, radial and linear ones, several types of miniprobes and specialty probes, for diagnostic purposes the dedicated radial scanning instruments remain the more adopted choice while miniprobes can have applications only in niche areas, like superficial GI cancers staging, small subepithelial lesions evaluation or intraductal ultrasound and some technological advances are needed to solve the potential drawbacks of this miniaturized probes. At last the EUS equipment borrowed most of the electronic sophistication from the mainstream ultrasonography, this made the choice of an EUS instrument even more difficult and challenging, but you must consider that there is no right or wrong equipment, there is only the right instrument for that specific clinical need or situation.

Role of endoscopic ultrasound in biliary and unexplained pancreatitis.

In the Western world, gallstone disease accounts for approximately half of the cases of acute pancreatitis. The benefit of therapeutic endoscopic retrograde cholangiopancreatography (ERCP) has been clearly proven for this disease. On the basis of history, laboratory, and noninvasive imaging studies, about 10-30% of patients with acute pancreatitis have no apparent aetiology. This is critical because it limits the optimal therapeutic management and the prevention of recurrence. Endoscopic ultrasound (EUS) has emerged as an important procedure to clarify the aetiology of acute pancreatitis. After extensive investigation that included EUS, 8-20% of episodes remained idiopathic. Moreover, EUS carried minimal risk when compared to ERCP. The present short review attempts to update on the indications for the employment of EUS in the diagnosis of biliary stones as well as in the clarification of aetiology in the case of unexplained pancreatitis.

[Gastroenterology outpatient clinic of the Molinette Hospital (Turin, Italy): the 2003-2006 report]. / Poliambulatori specialistici di gastroenterologia: l'esperienza 2003-2006 dell'Ospedale Molinette di Torino.

AIM: Given the demographic shifts and needs of cost rationalization, it is of high priority to organize health care on the basis of ambulatory outpatients models. The aim of this study was to examine activity at the gastro-hepatology outpatients clinic of the Molinette Hospital. In this facility, the management is based on a work team organization that follows cohorts of patients with specific pathologies. METHODS: All services, consultations and urea breath test (UBT) for the diagnosis of Helicobacter pylori infection, carried out from January 2003 to December 2006, were extrapolated from the computerized system. Consultations were divided into first examination and controls. Furthermore, the destination of the patients after each consultation was considered. RESULTS: During the year 2003, 8 842 consultations and 4 071 UBT were carried out, in the year 2004, 11 342 consultations and 2 409 UBT, in the year 2005, 12 474 consultations and 2 510 UBT, in the year 2006, 12 249 consultations and 2 357 UBT. No further specialistic management was required for 25% of patients, while 2% had been hospitalized in the bed unit, 3% in the short hospitalization unit or the day-hospital. The remaining 70% were included in work teams or monitored thereafter. The comparison with consultations from 1994 shows an increase due to both first examination (+300%) and controls (+83%). CONCLUSIONS: The burden of the requests from the population and primary care structures addressed to the outpatients clinic of gastro-hepatology is relevant. The activity of this facility leads to a low rate of hospitalization as well as of cost reduction.