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Hyperfibrinogenemia is a vascular risk factor influenced by several conditions such as stasis induced by orthostatism. The authors suggest that stasis could also change local fibrinolytic activity. Twenty healthy subjects and 20 patients affected by primary varicose syndrome underwent blood collection from the antecubital vein and from a vein of the lower third of the leg, under baseline conditions, and after a 1 hour orthostatism. Tests for fibrinogenemia, t-PAa and PAI-1a, were carried out. After stasis induced by orthostatism, statistically significant variations of these three parameters were observed in both the control group and the varicose group.

Background. Vascular dementia (VAD) and Alzheimer’s disease (AD) may share common neuropathological mechanisms. Matrix metalloproteinases (MMPs) may induce destruction of the extracellular matrix, neuronal dysfunction, and death. Increased expression of these molecules has been found in a number of neurological diseases, including cerebral ischemia and AD. Expression and activity of MMPs may be genetically influenced by common polymorphisms in the promoter regions of the corresponding genes. The purpose of this study was to evaluate whether functional polymorphisms of MMP genes are associated with dementia. Methods. This is a cross-sectional study including a total of 599 individuals: 193 with VAD, 183 with AD, and 223 controls. Polymorphisms of the MMP-1, MMP-3, and MMP-9 genes were studied. Results. MMP-1 2G2G, MMP-1 1G2G, MMP-3 5A5A, and MMP-9 TT genotypes were significantly and independently associated with VAD (odds ratio [OR] 2.5, 95% confidence interval [CI] 1.4–4.4, OR ¼ 1.7, 95% CI, 1.0–2.7, OR ¼ 2.9, 95% CI, 1.5–5.9, and OR ¼ 6.8, 95% CI, 1.3–35.1, respectively). MMP-1 2G2G and MMP-3 5A5A genotypes were associated with increased risk of AD only in persons who carry the apolipoprotein E (APOE) e4 allele (OR ¼ 6.0, 95% CI, 2.3–15.5, and OR ¼ 14.3, 95% CI, 3.2–63.0, respectively). Interestingly, the odds of VAD and AD was further increased in persons concomitantly carrying more than one MMP gene variation, compared to individuals that only had one high-risk genotype. Conclusions. Our study suggests that MMP gene polymorphisms are associated with VAD and AD, although these results need to be treated with caution until replicated. MMP genotypes may influence the risk of dementia and merit further investigation as potential genetic markers of disease.

Background Tissue homeostasis is guaranteed by stem proliferating reserve, depending on dynamic changes in gene expression. A high plasticity is shown by the haematopoietic stem cells, potential source for liver regeneration. Aim We aimed to evaluate the gene expression modifications induced by human haematopoietic stem cell therapy after liver injury in rats. Subjects Rats were sorted as follows: (A) human-haematopoietic stem cell injection after allyl alcohol liver damage; (B) only haematopoietic stem cell injection; (C) only allyl alcohol injection; and (D) sacrifice without any treatment. Methods Livers, spleens and bone marrows were analysed with flow-cytometry. Livers were also studied by reverse-transcription PCR, histology, immunohistochemistry and microarray analysis; selected genes were confirmed by real-time PCR. Results In subset A, haematopoietic stem cells were selectively recruited by liver, with respect to the group B, and they improved the liver regeneration process compared to group C. As regards microarrays, haematopoietic stem cell infusion upregulates 265 genes and downregulates 149 genes. Differentially regulated genes belong to a broad range of functional pathways, including proliferation, differentiation, adhesion/migration and transcripts related to oval-cell activation. Real-time PCR validated array results. Conclusions Our study confirmed the capacity of haematopoietic stem cells to contribute to liver regeneration. Moreover, microarray analysis led to the identification of genes whose regulation strongly correlates with a more efficient process of liver repair after haematopoietic stem cell injection.

Background Liver regeneration is a heterogeneous phenomenon involving the proliferation of different cell lineages in response to injury. Under a strong positive selection pressure bone marrow derived stem cells may be involved in this process, by making a contribution to both parenchymal restoration and endothelial cell replacement. We investigate bone marrow stem cell migration to the liver in patients undergoing hepatectomy or with acute on chronic liver failure. Methods We enrolled 6 patients submitted to hepatectomy, 6 patients to cholecystectomy and 8 patients with acute decompensation of liver cirrhosis. Mobilization of CD34+ cells was evaluated by cytofluorimetry on peripheral blood samples at different time points; baseline, 1, 3, 7, 15 and 30 days after surgery and at admission, 1, 7 and discharge among patients with acute on chronic liver failure. 10 healthy subjects undergoing blood donation were also enrolled to evaluated the basal value of CD34+ cells. Results White blood cell counts remained in the normal range (4.1–9.8 × 10 9 /L) in all groups throughout the follow-up. In all patients of Groups 1, 2 and 3, circulating CD34+ failed to show statistically significant differences both as the absolute number and as the percentage at any time point compared to healthy controls. Conclusions Bone marrow derived cell mobilization can not be detected after hepatectomy or during an acute decompensation on a cirrhotic liver. Under these circumstances liver regeneration can probably call upon mature hepatocytes and endogenous progenitor cells. The involvement of extrahepatic progenitors if any, is a rare and limited phenomenon.

SUMMARY Background: Few controlled studies assessing choice and duration of antibiotic therapy for small intestinal bacterial overgrowth are available. Aim: To assess efficacy, safety and tolerability of different doses of rifaximin, a broad spectrum non-absorbable antibiotic, for intestinal bacterial overgrowth eradication. Methods: We enrolled 90 consecutive patients affected by small intestinal bacterial overgrowth. The presence of small intestinal bacterial overgrowth was based on the occurrence of a rise of H2 values >12 p.p.m. above the basal value after 50 g glucose ingestion. Patients were randomized in three 7-day treatment groups: rifaximin 600 mg/day (group 1); rifaximin 800 mg/day (group 2) and rifaximin 1200 mg/day (group 3). Glucose breath test was reassessed 1 month after the end of therapy. Compliance to the treatment and incidence of side-effects were also evaluated. Results: No drop-outs were observed in the three groups. Glucose breath test normalization rate was significantly higher in group 3 (60%) with respect to group 1 (17%; P < 0.001) and group 2 (27%, P < 0.01). No significant differences in patient compliance and incidence of side-effects were found among groups. Conclusions: Higher doses of rifaximin lead to a significant gain in terms of therapeutic efficacy in small intestinal bacterial overgrowth eradication without increasing the incidence of side-effects.

Background and Aim Tissue homeostasis and turnover require reserve stem proliferating cells. Several studies performed on immunodeficient animals have suggested a degree of plasticity by the hematopoietic stem cell compartment that may represent source for liver regeneration. We sought to explore the hepatic differentiation potential of hematopoietic stem cells from human cord blood, after toxic liver damage induced by allyl-alcohol in immunocompetent rats. Materials and Methods Wistar rats were divided into groups (A) allyl-alcohol intraperitoneal injection with hematopoietic stem cell intraperitoneal infusion at 1 day and sacrifice 3 days later; (B) stem cell injection and sacrifice 3 days later; (C) allyl-alcohol infusion and sacrifice 4 days later; and (D) sacrifice without any treatment. Livers, spleens, and bone marrows were analysed for human stem cells using flow-cytometry; livers were also tested by histology and immunohistochemistry to study the pattern of hepatic regeneration after damage and human stem cell conversion into hepatocyte-like cells, respectively. Results Flow-cytometry revealed selective recruitment of human hematopoietic stem cells by damaged livers (group A) compared with control group B. In addition, liver damage was reduced in animals treated with stem cells. Immunohistochemistry demonstrated that human stem cells could convert hepatic cells. Conclusions Our study demonstrated that hematopoietic stem cells selectively recruited by injured livers can contribute to hepatic regeneration after acute toxic damage in immunocompetent recipients.

Background and aim Molecular adsorbent recycling system (MARS) treatment is able to remove both hydrosoluble and small- and medium-sized lipophilic toxins. MARS plays an important role in modifying liver failure complications, such as hepatorenal syndrome and hepatic encephalopathy. We sought to evaluate the clinical efficacy and safety of a MARS device in a consecutive series of hepatic failure patients. Materials Twenty patients with acute liver failure, transplantation failure, or acute on chronic liver failure fulfilled the inclusion criteria of total bilirubin ≥10 mg/dL and at least one of the following: hepatic encephalopathy (HE) ≥II grade, hepatorenal syndrome (HRS) for chronic patients or total bilirubin ≥5 mg/dL and HE ≥I grade for acute patients. Results MARS was able to reduce cholestatic parameters and improve neurologic status and renal function parameters in all treated patients. We also observed an improvement in the 3-month survival rate compared to the expected outcome in patients with MELD scores between 20 and 29, as well as 30 and 39. Conclusions Based on these results, we confirm the safety and clinical efficacy of MARS treatment, with the best results in patients with MELD score of 20 to 29. Further studies are necessary to confirm whether this treatment is able to modify patient outcomes and prognosis.

Small intestinal bacterial overgrowth and sugar malabsorption (lactose, fructose, sorbitol) may play a role in irritable bowel syndrome. The lactulose breath test is a reliable and non-invasive test for the diagnosis of small intestinal bacterial overgrowth. The lactose, fructose and sorbitol hydrogen breath tests are widely used to detect specific sugar malabsorption.To assess the extent to which small intestinal bacterial overgrowth may influence the results of hydrogen sugar breath tests in irritable bowel syndrome patients.We enrolled 98 consecutive irritable bowel syndrome patients. All subjects underwent hydrogen lactulose, lactose, fructose and sorbitol hydrogen breath tests. Small intestinal bacterial overgrowth patients were treated with 1-week course of antibiotics. All tests were repeated 1 month after the end of therapy.A positive lactulose breath test was found in 64 of 98 (65%) subjects; these small intestinal bacterial overgrowth patients showed a significantly higher prevalence of positivity to the lactose breath test (P0.05), fructose breath test (P0.01) and sorbitol breath test (P0.01) when compared with the small intestinal bacterial overgrowth-negatives. Small intestinal bacterial overgrowth eradication, as confirmed by negative lactulose breath test, caused a significant reduction in lactose, fructose and sorbitol breath tests positivity (17% vs. 100%, 3% vs. 62%, and 10% vs. 71% respectively: P0.0001).In irritable bowel syndrome patients with small intestinal bacterial overgrowth, sugar breath tests may be falsely abnormal. Eradication of small intestinal bacterial overgrowth normalizes sugar breath tests in the majority of patients. Testing for small intestinal bacterial overgrowth should be performed before other sugar breath tests tests to avoid sugar malabsorption misdiagnosis.

In the last years, a considerable number of studies have been performed on the correlation between Helicobacter pylori infection and ischaemic heart disease. The reason is the supposed role of some chronic infections in the genesis and development of vessel wall injury and atheromatous plaque, as already reported for Chlamydia pneumoniae and herpes viruses. While this association may be theoretically conceivable, it still remains debated from a practical point of view. Epidemiological and animal studies as well as some eradicating trials gave conflicting results, while studies investigating the specific molecular mimicry mechanisms induced by H. pylori strongly support the association. Moreover, none of the studies performed so far did take into account the effect of the genetic susceptibility to develop ischaemic heart disease or to respond to H. pylori infection. In particular, while the exposure to some known risk factor for atherosclerosis should lead to develop ischaemic heart disease, no condition or exposure, either individual or in combination, completely explains the occurrence and the progression of the disease, as many patients develop ischaemic heart disease in the absence of any risk factor. Based on these concepts, can we state that H. pylori infection may cause the same effect in patients with ischaemic heart disease as in healthy subjects? Further studies are needed in order to clarify this issue.

Background. Several studies have demonstrated that bone marrow contains a subpopulation of stem cells capable of participating in the hepatic regenerative process, even if some reports indicate quite a low level of liver repopulation by human stem cells in the normal and transiently injured liver. Aims. In order to overcome the low engraftment levels seen in previous models, we tried the direct intraperitoneal administration of human cord blood stem cells, using a model of hepatic damage induced by allyl alcohol in NOD/SCID mice. Methods. We designed a protocol based on stem cell infusion following liver damage in the absence of irradiation. Flow cytometry, histology, immunohistochemistry and RT-PCR for human hepatic markers were performed to monitor human cell engraftment. Results. Human stem cells were able to transdifferentiate into hepatocytes, to improve liver regeneration after damage and to reduce the mortality rate both in both protocols, even if with qualitative and quantitative differences in the transdifferentiation process. Conclusions. We demonstrated for the first time that the intraperitoneal administration of stem cells can guarantee a rapid liver engraftment. Moreover, the new protocol based on stem cell infusion following liver damage in the absence of irradiation may represent a step forward for the clinical application of stem cell transplantation.

Aims: There is contrasting evidence on the relevance of chronic infection by Helicobacter pylori ( H. pylori ) as a risk factor for stroke. We performed a meta-analysis of case-control studies to assess association of H. pylori infection and more virulent H. pylori strains, bearing the cytotoxin-associated gene-A (CagA) antigen, with different types of stroke. Methods: Outcome measures were: H. pylori and CagA seroprevalence in (1) patients with stroke versus controls, and (2) patients with stroke due to large vessel stroke versus patients with other types of stroke and controls. Results: Seven cross-sectional, case-control studies were included. Odds ratio for individual case-control studies and pooled OR for the association between H. pylori seropositivity and stroke was 1.49 (95% CI 1.24–1.81), for the association between stroke and anti-CagA positivity was 2.23 (95% CI 1.49–3.36). Patients with large vessel stroke had higher odds for H. pylori infection than patients with other types of stroke (odds ratio 1.65; 95% CI 1.12–2.45), and than controls (odds ratio 1.61; 95% CI 1.13–2.32). Conclusions: Association between H. pylori positivity, anti-CagA positivity and stroke is modest and seems higher with stroke due to large vessel disease. This meta-analysis suggests that the role of CagA positive H. pylori strains in different stroke etiologic subclasses should be the target of future prospective investigation.

Summary Background : Hyperhomocysteinaemia is an independent risk factor for atherosclerosis. It is often related to low levels of vitamin B12 and/or folate, enzymatic co-factors of methionine metabolism. Atrophic gastritis, often caused by Helicobacter pylori infection, may impair vitamin absorption. Aim : To assess whether the presence of atrophic gastritis is associated with hyperhomocysteinaemia via deficiency of its vitamin co-factors. Methods : Thirty-one patients with atrophic gastritis were recruited. The control group consisted of 28 patients with non-atrophic gastritis, matched with patients for sex, age and body mass index. The presence and degree of gastric atrophy were assessed by histology. H. pylori infection was assessed by histology/serology. Blood samples were collected for the measurement of homocysteine, vitamin B12 and folates. Results : Multiple logistic regression analysis showed that atrophic gastritis (odds ratio, 5.3; 95% confidence interval, 1.23–25.26; χ2 = 5.2; P = 0.01) and low vitamin B12 (odds ratio, 3.7; 95% confidence interval, 1.03–22.08; χ2 = 3.6; P

Background The radial artery has recently been proposed as an alternative arterial conduit for surgical myocardial revascularization. This study was conceived to evaluate the degree of atherosclerotic involvement of the radial artery in patients with coronary artery disease and the eventual influence of a subtle degree of preoperative atherosclerosis on the midterm results of radial artery grafts. Methods and results The intima-media thickness of the radial artery, common carotid artery, and internal thoracic artery was evaluated in 42 coronary artery disease patients and in 26 control patients. All radial arteries were then used for myocardial revascularization; 30 patients submitted to control angiography after 5 years. The mean intima-media thickness was 0.92 ± 0.22 mm for the common carotid artery, 0.54 ± 0.16 mm for the internal thoracic artery, 0.55 ± 0.11 mm for the radial artery in coronary artery disease patients versus 0.79 ± 0.14 mm, 0.52 ± 0.11 mm, and 0.56 ± 0.09 mm, respectively, in control patients ( P = .001 only for the common carotid artery). No correlation was found between the intima-media thickness of the carotid, internal thoracic, and radial artery. No correlation was found between the preoperative intima-media thickness of the radial artery and the midterm patency and endothelial-mediated vasodilating capacity of radial artery grafts. Conclusion In coronary artery disease patients, radial artery atherosclerotic involvement is more frequent than that of the gold standard internal thoracic artery but still by far less severe than that of the common carotid artery. The early atherosclerotic signs often observed in the radial artery do not seem to have the potential to influence radial artery graft patency and endothelial function.

Apolipoprotein E-knockout (apoE KO) mice have peripheral sensory nerve defects, reduced and delayed response to noxious thermal stimuli, abnormal morphology of unmyelinated fibers, and impaired blood-nerve and blood-brain barriers. In this study, we show that, compared to wild-type mice, peripheral nerves of apoE KO mice have impaired ability to respond to ischemia, as demonstrated by measurement of motor and sensory conduction velocity. In addition, mice lacking apoE exhibit a deficit of reinnervation of ischemic epidermis, evaluated by immunofluorescent staining for the pan-neuronal marker PGP 9.5. Also regional nerve blood flow, measured by laser Doppler, and intraneural angiogenesis after ischemia are significantly compromised in apoE-deficient mice. Finally, upregulation of the angiogenic cytokine vascular endothelial growth factor (VEGF), which physiologically occurs after ischemia in the peripheral nerve of wild-type mice, is severely impaired in apoE KO mice. Among the several neural defects that have already been described in mice lacking apoE, this is the first demonstration that functional recovery to ischemia is impaired in the peripheral nerves of these animals. This deficit is mirrored by the inability of upregulating VEGF and mounting an appropriate intraneural angiogenic response following injury. These findings provide new evidence of possible interdependent relationships between VEGF, angiogenesis, and nerve function and regeneration and may provide new important information on the role of apoE in the nervous system.

Subclinical celiac disease (CD) has been associated with various neurological disorders, the most common being neuropathy and cerebellar ataxia. The aims of the present study were to assess the following: 1) the prevalence of CD in patients affected by migraine; 2) whether there are regional cerebral blood flow abnormalities in migraine patients with CD compared to migraine patients without CD; and 3) the effects of a gluten free diet in migraine patients with CD.A total of 90 patients affected by idiopathic migraine were enrolled, and 236 blood donors were used as controls. Serum IgG antitransglutaminase (TgA) and IgA antiendomysial (EmA) were measured. In positive cases, diagnosis was confirmed endoscopically. A gluten free diet was started in the patients diagnosed with CD, who were followed for 6 months. A single photon emission CT brain study was performed before and after a gluten free diet.Four of 90 (4.4%; 95% CI = 1.2-11.0) migraine patients were found to have CD compared with 0.4% (95% CI = 0.01-2.3) blood donor controls (p0.05). During the 6 months of gluten free diet, one of the four patients had no migraine attacks, and the remaining three patients experienced an improvement in frequency, duration, and intensity of migraine. Single photon emission CT studies showed a regional baseline reduction in brain tracer uptake in all four patients. Such reduction in uptake completely resolved at follow-up.Our results suggest that a significant proportion of patients with migraine may have CD, and that a gluten free diet may lead to a improvement in the migraine in these patients.

Previous studies showed that either the urease activity possessed by H. pylori and the bacterial load may influence the results of the [13C] urea breath test. However, the correlation between urease activity and dyspepsia is unclear. The aim of our study was to evaluate whether the urease activity of the gastroduodenal tract may influence the severity of dyspeptic symptoms. In all, 2520 dyspeptic patients (1109 men, 1411 women; mean age 47 ± 16 years) without gastroesophageal reflux disease, diabetes, vascular disorders, liver and biliary tract diseases, and tumors of the gastrointestinal tract and with a normal appearing abdominal ultrasonography were enrolled. All these patients underwent a [13C] urea breath test and filled out a questionnaire on dyspeptic symptoms. Subjects were divided in five different groups according to delta over baseline (DOB) values (group 1 23.1). The prevalence and intensity of dyspeptic symptoms were compared among groups. In all, 1688 patients (67%, 928 females and 760 males; mean age 48 ± 15 years) were H. pylori-positive. The chi-squared test and analysis of variance showed increase of frequency and intensity of each dyspeptic symptom according to DOB values. In conclusion, Dyspepsia may parallel gastric urease activity. However, whether higher DOB values are related to higher bacterial load or, alternatively, to the presence of particular H. pylori strains able to produce larger amounts of urease is uncertain.

Before harvesting the radial artery for coronary bypasses, investigating forearm vascularization to avoid postoperative ischemia of the hand is mandatory. The study involved 192 consecutive patients, 155 males and 37 females age 39–76 years (mean 56.1). The CW Doppler static and dynamic test was performed to evaluate the patency of the upper limb's arteries and the adequacy of the ulnar supply in the nondominant arm. The use of the radial artery was contraindicated in 14 patients (3 for stenosis of the subclavian artery and 11 for inadequate collateralization). One hundred and four patients were operated on with the radial artery used as a graft; another conduit was used in the remaining 74 patients. The vascularization of the hand was restudied within 10 days in all patients who underwent surgery; in 82 patients, it was studied again at 1 year. The early Doppler control showed a significant increase of blood flow velocities in the ulnar artery, with a flow redistribution in the common digital palmar arteries (decreased in the 1st and slightly increased in the 3rd). The late Doppler control showed superimposable findings. No local ischemic complications were observed after radial artery removal. Three patients showed thumb dysesthesias with no functional damage, probably due to surgical trauma of the radial nerve collateral branches. The authors conclude that a Doppler study is a useful tool to detect patients for radial artery surgical removal and to predict the efficacy of the ulnar supply through the distal anastomosis.

Plasma fibrinogen is one of the main cardiovascular risk factors and its concentration is influenced by several physiological and pathological situations. In this paper the authors measured the fibrinogen levels in 30 subjects (10 healthy subjects and 20 patients affected by primary varicose syndrome of the lower limbs) under baseline conditions and after 1-hour orthostatism. The results of our study demonstrate that the varicose group shows higher fibrinogen values than the control group in all the examined districts (the upper and lower limbs). In the varicose group, fibrinogenemia increases significantly after orthostatism in both the varicose vein and the arm compared with the baseline values. In the control group, fibrinogenemia increases significantly after orthostatism in both the varicose vein and the arm compared with the baseline values, but this increase is not as significant as in the varicose group. Our results, on the one hand, confirm previous observations showing that fibrinogenemia increases in the vascular districts affected by postural stasis; on the other hand, they prove that the level of fibrinogen can also be influenced in districts other than those directly affected by stasis.

Helicobacter pylori (H. pylori) has been recently associated with some organic and functional vascular disorders. In particular, our group found a high prevalence of H. pylori in patients affected by migraine and a significant improvement of migraine symptoms after eradication of the bacterium, during a follow-up period of 6 months. However, seasonal variations may affect clinical manifestations of migraine, thus influencing our previous results. The present study evaluated the effect of H. pylori eradication during a 1-year follow-up period in a population of 148 consecutively enrolled migraine patients. H. pylori infection was assessed by 13C-urea breath test. Infected subjects underwent specific antibiotic treatment in order to eradiate the bactrium. Frequency, intensity and duration of attacks of migraine were assessed during a 1-year follow-up period. 42% of the patients showed H. pylori infection. 82% resulted eradicated. Interestingly, 28% of the patietns reported a disappearance of migraine during the follow-up period. Moreover, a significant decrease of intensity, frequency and duration of the migraine attacks evaluated 2, 4, 6 and 12 months from H. pylori eradication was observed in the remaining patients. The beneficial effects of H. pylori eradication on migraine seem to be confirmed by this prolonged 1-year follow-up study.

Background: One-week triple therapy is currently considered the golden standard against Helicobacter pylori. However, gastrointestinal side-effects are among the major pitfalls in such regimens. Probiotic supplementation might help to prevent or reduce such drug-related manifestations. Aim: To determine whether adding the probiotic Lactobacillus GG to an anti-H. pylori regimen could help to prevent or minimize the gastrointestinal side-effects burden. Methods: Sixty healthy asymptomatic subjects screened positive for H. pylori infection were randomized to 1 week rabeprazole (20 mg b.d.), clarithromycin (500 mg b.d.), tinidazole (500 b.d.) and the probiotic Lactobacillus GG for 14 days or to the same regimen with a placebo preparation. Patients completed validated questionnaires during the week of treatment and during the following 3 weeks, to determine the type and severity of side-effects and an overall judgement of tolerability. Results: Diarrhoea, nausea and taste disturbance were significantly reduced in the Lactobacillus GG supplemented group (relative risk=0.1, 95% CI: 0.1–0.9; relative risk=0.3, 95% CI: 0.1–0.9; relative risk=0.5, 95% CI: 0.2–0.9, respectively). An overall assessment of treatment tolerability showed a significant difference in favour of the Lactobacillus GG supplemented group (P=0.04). Conclusions: Lactobacillus GG supplementation showed a positive impact on H. pylori therapy-related side-effects and on overall treatment tolerability.

Background:Helicobacter pylori, the main cause of gastritis and peptic ulcer, has been associated with idiopathic chronic urticaria (ICU), an immunological skin disorder of unknown origin. Eosinophilic cationic protein (ECP) is a cytotoxic molecule secreted by the activated eosinophils involved in the pathogenesis of ICU. We assessed serum/gastric juice ECP levels and gastric mucosal eosinophil infiltration in ICU patients infected or not with H. pylori and evaluated the modification after bacterium eradication. Methods: 33 patients with ICU and 25 dyspeptic controls underwent upper gastrointestinal endoscopy for histological evaluation and assessment of H. pylori infection. One-week triple therapy was given to H. pylori-positive patients. Serum and gastric juice ECP levels, eosinophil infiltration from gastric mucosal sections and urticaria symptoms were evaluated in all patients at enrolment and 8 weeks after eradication. Results: 19 of 33 (57%) ICU patients and 16 of 25 (64%) controls were found to be infected with H. pylori. Serum ECP was significantly higher in ICU patients compared to controls, regardless of infectious status. Gastric juice ECP and gastric eosinophil infiltration were significantly higher in infected ICU patients when compared both to uninfected ICU patients and controls. H. pylori eradication determined a significant decrease in gastric juice ECP and gastric eosinophil infiltration only in ICU patients. Moreover, a total or partial remission of urticaria symptoms was observed only in ICU patients in whom the bacterium was eradicated. Conclusions: Although H. pylori infection affects gastric juice ECP and eosinophil infiltration of ICU patients, the role of the bacterium in the pathogenesis of this skin disorder still remains uncertain.

Background: One-week triple therapy is currently regarded as the reference of anti-Helicobacter pylori treatment. However, antibiotic-associated gastrointestinal side effects are among the major pitfalls of such regimens. Probiotic supplementation may be regarded as a therapeutic tool to prevent or reduce these troublesome drug-related manifestations. Aim: To determine whether the addition of the probiotic Lactobacillus GG to an anti-H. pylori standard triple therapy could help to prevent or minimize the occurrence of gastrointestinal side effects. Methods: One hundred and twenty healthy asymptomatic subjects screened positive for H. pylori infection and deciding to receive eradication therapy were randomized either to 1-week pantoprazole (40 mg b.i.d.), clarithromycin (500 mg b.i.d.), tinidazole (500 mg b.i.d.) or to the same regimen supplemented with Lactobacillus GG for 14 days. Patients filled in validated questionnaires during follow-up to determine the type and severity of side effects and to judge overall tolerability. Results: Bloating, diarrhea and taste disturbances were the most frequent side effects during the eradication week and were significantly reduced in the Lactobacillus GG-supplemented group (RR = 0.4, CI 0.2–0.8; RR = 0.3, CI 0.1–0.8; RR = 0.3, CI 0.1–0.7, respectively). The same pattern was observed throughout the follow-up period. Overall assessment of treatment tolerability showed a significant trend in favor of the Lactobacillus GG-supplemented group (p = 0.03). Conclusions:Lactobacillus GG supplementation beneficially affects H. pylori therapy-related side effects and overall treatment tolerance.

Ethanol is known to have a deleterious effect on liver ischemia–reperfusion injury, but recent reports suggest that light ethanol consumption may produce a protective effect in several organs. We aimed to investigate effects of different doses of ethanol on liver oxidative injury. Rats were fed with ethanol-containing diets (24, 30, 36, 40% for groups A, B, C, D, respectively). After four weeks, livers were exposed to ischemia–reperfusion. Chemiluminescence was recorded; total lipids, adenosine triphosphate, malondialdehyde, reduced glutathione and lactic dehydrogenase were assessed. In all groups, ischemia resulted in the disappearance of O2 •-, a decrease in glutathione and adenosine triphosphate, and stable malondialdehyde values. During the reperfusion phase, O2 •- production, malondialdehyde and lactic dehydrogenase increased, reaching significantly higher values in groups C and D and significantly lower values in group B. The effect of ethanol on ischemia–reperfusion injury seems to be a dose-related response, with an additional toxic effect only at high doses of ethanol.

Sex mismatch is a well-known risk factor for chronic rejection of liver allografts, but the mechanisms involved remain unclear. Since experimental observations suggest that female liver is more sensitive to reperfusion injury than male liver, we assessed the influence of gender on oxidative stress. Livers from male and female rats were exposed to warm ischemia and reperfused by an oxygenated buffer. Chemiluminescence was continuously recorded. Reduced and oxidized glutathione and malondialdheyde lactic dehydrogenase values were also determined. Chemiluminescence increased during reperfusion in both groups, but was significantly greater in livers from female rats. Malondyaldheide and lactic dehydrogenase progressively increased in all animals, reaching significantly greater values in female rats. Livers from female rats showed an increase in all the parameters of oxidative stress compared to male animals. A greater susceptibility to reperfusion injury may be evoked as an alternative mechanism to explain the poor outcome of female organ after liver transplantation.

Background: Acid suppression plus two antibiotics is considered the reference anti-Helicobacter pylori treatment. Reported eradication rates are around 65–80%. Human Lactobacillus acidophilus shows an in vitro inhibitory effect on the attachment of H. pylori to gastric epithelial cell lines. Culture supernatant of this bacillus seems to decrease the in vitro viability of H. pylori. Aim: To evaluate whether the supplementation with an inactivated preparation of L. acidophilus could improve the efficacy of a standard anti-H. pylori therapy. Methods: One-hundred and twenty H. pylori-positive patients were randomly assigned to a 7-day triple therapy based on rabeprazole (20 mg b.d.), clarithromycin (250 mg t.d.s.) and amoxicillin (500 mg t.d.s.) (RCA group: 60 subjects), or to the same regimen supplemented with a lyophilized and inactivated culture of Lactobacillus acidophilus (t.d.s.) (RCAL group: 60 subjects). Results: In the RCA group, eradication was successful in 72% (42 out of 58 patients) from a per protocol (PP) analysis, or 70% (42 out of 60 patients) using an intention-to treat (ITT) analysis. In the RCAL group a significant increase in the eradication rate was observed: 88% (52 out of 59 patients) from PP analysis (P=0.03), 87% (52 out of 60 patients) from ITT analysis (P=0.02). Conclusions: These results seem to confirm the in vitro anti-H. pylori effect of L. acidophilus, suggesting that the inactivated L. acidophilus could be effective in increasing eradication rates of a standard anti-H. pylori therapy.

Recent studies have suggested an association between Helicobacter pylori infection and migraine. However, various strains of the bacterium are present, some endowed with greater pathogenicity. In particular, H. pylori type I CagA-positive strains induce a higher release of proinflammatory substances by the gastric mucosa that could trigger systemic vasospasms. The aim of the present study was to assess the prevalence of H. pylori CagA-positive strains in subjects with migraine. One hundred and seventy-five patients affected by migraine (49 with aura, 126 without aura) were consecutively enrolled and matched for sex, age, social background and geographical origin with 152 controls. Helicobacter pylori infection was assessed through 13C-urea breath test. Specific serological IgG against CagA were detected through ELISA. The prevalence of H. pylori infection was similar in migraine patients and in controls (40% vs. 39%, respectively). Among migraine patients, prevalence of infection was not related to presence or absence of aura (45% vs. 37%, respectively). However, among infected subjects, a significantly higher prevalence of CagA-positive strains was observed in patients affected by migraine with aura when compared with those affected by migraine without aura (41% vs. 19%, P < 0.01) and with controls (41% vs. 17%, P < 0.01). CagA-positive H. pylori strains were found to be strongly associated with migraine with aura. A higher inflammatory response of the gastric mucosa to more virulent strains could release substances that may act as triggers of vasospasm in peculiar cerebral arterial districts, probably implicated in the ‘aura’ phenomenon.

Migraine is the most frequent subtype of primary headache. It affects about 18% of females and 6% of males in the general population. Despite this high frequency the disease is substantially underdiagnosed and undertreated. Several hypotheses have been put forward to explain the pathogenesis of migraine; at present, a derangement of vascular tone is believed to be an essential component for the development of clinical attacks of the disease.

Background Patients with insulin-dependent diabetes mellitus (IDDM) are often affected by chronic infections; however, antibiotic absorption may be influenced by the disease. Helicobacter pylori, the most common gastric infection worldwide, is the main acquired factor in the pathogenesis of gastritis and peptic ulcer. The aim of the study was to compare the H. pylori eradication rate obtained with a standard 7-day antibiotic regimen in a group of IDDM H. pylori infected patients and in a control group of infected dyspeptic patients. Methods Thirty-one patients (18 male, 13 female, 39 ± 12 years) affected by IDDM and H. pylori infection, and 50 dyspeptic infected patients (23 male, 17 female, 37 ± 10 years) were evaluated. H. pylori infection was assessed through 13 C-urea breath test A triple therapy with amoxycillin (1 g b.i.d.), clarithromycin (250 mg ti.d.) and pantoprazole (40 mg b.i.d.) was given to both groups at the time of diagnosis for 7 days. Cure was defined as the absence of H. pylori infection, assessed by 13 C-urea breath test, 6 weeks after completing anti-microbial therapy. Effects of H. pylori eradication on gastrointestinal symptoms (pyrosis, epigastric pain, belching, bloating, halitosis and nausea) were also evaluated. Results All enrolled patients completed the study. When compared to dyspeptic patients, the eradication rate was significantly lower in IDDM patients: 92% (46/50) versus 65% (20/31), respectively (P < 0.002). IDDM patients infected by H. pylori showed a different prevalence of some of the gastrointestinal symptoms assessed when compared to the infected dyspeptic patients; in particular, pyrosis, epigastric pain and belching were significantly more prevalent in the infected dyspeptic group. After H. pylori eradication, both groups showed a significant reduction of the intensity of all the gastrointestinal symptoms evaluated, except for nausea. Conclusions IDDM patients showed a significantly lower H. pylori eradication rate when compared to that observed in dyspeptic subjects. The dosage and/or the duration of a standard eradication regimen does not appear to be sufficient to eradicate the infection in IDDM patients. The impairment of the gastrointestinal mucosa microvasculature with a reduction of antibiotic absorption, or the frequent use of antibiotics for other infections with development of resistant strains, may be the mechanisms underlying the observation.

Background . The hemodynamic significance of patent mammary graft side branches is still controversial. This study was designed to evaluate the potential for flow steal of patent mammary side branches in different hemodynamic conditions. Methods . Echo-Doppler measurement of mammary graft flow was performed at rest and after dipyridamole-induced coronary vasodilatation in 10 patients with angiographic demonstration of evident mammary graft side branches (study group) and in 10 matched control patients (control group). Concomitant thallium-201 myocardial scintigraphy was performed to assess the adequacy of mammary flow to the myocardial oxygen demand. Patients of the study group were also submitted to flow evaluation in condition of selective muscular or combined systemic and coronary relaxation. Results . No difference in mammary flow and adequacy to myocardial oxygen demand was detected between patients of the study and control groups both at rest and after dipyridamole infusion. In patients with patent side branches the systolic-to-diastolic flow ratio was maintained in case of combined coronary and peripheral vasodilatation, whereas selective muscular relaxation led to an increase in the systolic and a reduction in the diastolic flow. Conclusions . Flow steal from patent mammary graft side branches is possible only in case of selective muscular vasodilatation. As this situation is unlikely to occur in the clinical setting, the potential for flow steal of mammary side branches in cardiac surgery patients seems to be minimal.

Reports in the literature have shown plasma fibrinogen and factor XIII (FXIII) levels to be higher in patients with arteriopathy than in healthy subjects. Fibrinogen constitutes the basic matrix for the blood-clotting process. Excessive levels of fibrinogen in the blood result in increased clotting activity and increased aggregation of erythrocytes, leukocytes, and platelets, which can be important factors in thrombotic and atherosclerotic events. FXIII stabilizes fibrin monomers, facilitating the incorporation of alpha 2 -antiplasmin into the stabilized fibrin. In addition, this mechanism promotes the deposit of fibrin on arterial walls and within the arterial lumina; it also can delay activation of the fibrinolytic system and render it incapable of removing fibrin. Therefore, hyperfibrinogenemia and increased FXIII activity can lead to atherosclerosis. The aim of this study was to evaluate the possibility of a pharmacologic reduction of fibrinogen levels and FXIII activity in patients with peripheral arterial occlusive disease. Results of the study demonstrated that acute intravenous administration of high-dose defibrotide reduced both factors in these patients.

Insulin-dependent diabetes mellitus (IDDM) is the result of an autoimmune destruction of pancreatic Langerhans beta cells. Helicobacter pylori infection, the most common cause of gastritis and peptic ulcer, has been associated with some autoimmune diseases. The aim of this study was to evaluate the prevalence of H. pylori infection and gastrointestinal (GI) symptoms in patients with IDDM.116 patients (50 males and 66 females, mean age: 35 +/- 11 years) affected by IDDM were evaluated; 50 healthy subjects matched for age and sex were utilized as a control group. H. pylori infection was determined by a [13C]urea breath test. IDDM duration, daily dosage of insulin and prevalence of GI symptoms (bloating, pyrosis, epigastric pain, belching, halitosis, nausea) were assessed.The prevalence of H. pylori infection was similar in IDDM patients and in controls (37 vs 34%, respectively). In both groups, the mean age was higher in infected subjects. The mean IDDM duration was significantly greater in infected patients (19 +/- 12 vs 13 +/- 10 years, P0.006). Prevalence of infection was directly related to the duration of IDDM (1 year, 23%; 1-3 years, 32%;3 years, 40%). The daily dosage of insulin did not differ between infected and non-infected subjects. H. pylori contaminated patients showed a significantly higher prevalence of bloating, pyrosis and epigastric pain when compared with non-infected subjects; conversely, prevalence of belching, halitosis and nausea did not differ between groups.The prevalence of H. pylori infection is high in patients affected by IDDM; however, it does not differ from the infection rate observed in a control group. The rate of infection increases with IDDM duration. Bloating, pyrosis and epigastric pain appear to define infection status better.

Objective: To evaluate the flow reserve and adequacy to meet myocardial requests in stress conditions of mammary artery-left anterior descending (IMA-LAD) grafts using a non-invasive method. Methods: Patients (20) with angiographic evidence of normofunctioning left IMA-LAD grafts were submitted to dypiridamole Tl 201 myocardial scintigraphy and concomitant transthoracic echo-doppler evaluation of the IMA flow at a mean interval of 32.5 months after surgery. Results: Under basal conditions, the mean peak and end flow velocities in systole were 0.39 and 0.06 m/s, respectively. In diastole, the mean peak and end flow velocities were 0.27 and 0.02 m/s and mean tele-diastolic flow velocity was 0.14 m/s, with a mean systolic/diastolic ratio of 1.51. After dypiridamole infusion, mean systolic velocities were 0.47 (peak) and 0.23 (end) m/s, respectively + 20 and + 283%, whereas mean diastolic velocities were 0.56 (peak) and 0.06 (end) m/s, + 107 and + 200%, respectively. Mean tele-diastolic flow velocity increased to 0.32 m/s (+ 128%) and the systolic-diastolic index changed to 0.85. In all cases no significant scintigraphic evidence of induced ischemia was demonstrated in the LAD region. Conclusions: Transthoracic echo-doppler evaluation combined with Tl 201 myocardial scintigraphy is a useful tool for the assessment of IMA flow reserve and adequacy to stress conditions. In the late postoperative period, the IMA shows the possibility of increasing the flow velocity, almost 2-fold: the increase in flow is prevalently diastolic and leads to a complete reversal of the physiological systolic/diastolic flow ratio. The flow reserve of IMA is always able to meet the augmented myocardial oxygen demand after dypiridamole infusion.

Helicobacter pylori, the most important cause ofgastritis and peptic ulcer, recently has been associatedwith several extradigestive diseases. The aim of thisstudy was to assess the prevalence of Helicobacter pylori infection and the effects of bacteriumeradication in 42 consecutive patients affected byidiopathic chronic urticaria. Helicobacter pylori wasassessed by [13C]urea breath test.Amoxicillin, clarithromycin, and lansoprazole were given to infectedpatients for seven days. Urticaria and gastrointestinalsymptoms were assessed on enrollment and aftereradication. Fifty-five percent of patients proved to beinfected by Helicobacter pylori. Prevalence ofgastrointestinal symptoms did not differ betweeninfected and uninfected patients. Eighty-eight percentof infected patients in whom the bacterium waseradicated after therapy showed a total or partial remission ofurticaria symptoms. Conversely, symptoms remainedunchanged in all uninfected patients. In conclusion,Helicobacter pylori affects a high percentage ofpatients with idiopathic chronic urticaria; however,typical gastrointestinal symptoms do not identifyinfection status. Bacterium eradication is associatedwith a remission of urticaria symptoms, suggesting apossible role of Helicobacter pylori in the pathogenesisof this skin disorder.

The reoxygenation phase after a period of anoxia leads to oxyradical formation, responsible for damage to cell membranes. Ageing is associated with functional and structural changes in liver cells, which modify their sensitivity to reoxygenation injury. The aim of this study was to determine the effects of ageing on the sensitivity of hepatocytes to anoxia/reoxygenation.Oxyradical formation and cell injury were evaluated in hepatocytes isolated from rats of different ages exposed to 2 h of anoxia and 1 h of reoxygenation. Anion superoxide was measured by lucigenin-enhanced chemiluminescence, hydrogen peroxide by luminol-enhanced chemiluminescence, and cell damage by lactate dehydrogenase (LDH) release.During anoxia, oxyradical production dropped to background levels in both groups. LDH release was significantly greater in ageing hepatocytes. During reoxygenation, a massive generation of anion superoxide and hydrogen peroxide, followed by a sharp increase in LDH release, was observed in both groups. However, both oxyradicals and cell injury were significantly greater in liver cells obtained from ageing rats.The data confirm that hepatocytes produce high levels of free radicals during post-ischemic reoxygenation and suggest that ageing cells are more sensitive to reperfusion injury.

Raynaud's phenomenon is defined by anintermittent vasospasm of the arterioles of the distallimbs. Helicobacter pylori infection has been recentlyassociated with Raynaud's phenomenon. The aim of this study was to assess the effects of H. pylorieradication on Raynaud's attacks. Forty-six patientsaffected by primary Raynaud's phenomenon were evaluated.H. pylori infection was assessed by [13C]urea breath test. Eradication therapy was given toinfected patients for seven days. Discomfort and theduration and frequency of attacks of Raynaud'sphenomenon per week were assessed. Thirty-six subjectswere infected with H. pylori; the bacterium waseradicated in 83% of these after therapy. Attacks ofRaynaud's phenomenon completely disappeared in 17% ofthe patients with H. pylori eradication. Discomfort and the duration and frequency of attacks ofRaynaud's phenomenon were significantly reduced in 72%of the remaining patients. Conversely, attacks ofRaynaud's disease did not change significantly during the 12-week follow-up period either in the H.pylori-negative patients or in the infected subjects inwhom the bacterium was not eradicated by therapy. Thestudy shows that H. pylori eradication causes a significant decrease in clinical attacks ofRaynaud's disease. The reduction of vasoactivesubstances determined by the eradication of thebacterium may be the pathogenetic mechanism underlyingthe phenomenon.

Objective: To investigate the chronic consequences of radial artery removal for coronary artery bypass surgery on the forearm circulation. Methods: Thirty-ninepatients submitted to radial artery removal for coronaryartery bypass were submitted to serial Echo-Doppler evaluationof the flow and morphology of the forearm arteries until 10 years follow-up. Results: The peak systolic velocity of the ulnar artery of the operated side was significantly higher than the control site. The intima-media thickness of the ulnar artery was always significantly higher on the operated side, and this difference reached statistical significance at 10 years follow-up. There was a significantly higher prevalence of atherosclerotic plaques in the ulnar artery (UA) of the operated versus control arm (11/39 vs 0/39; p = 0.005). Conclusions: Radial artery removal for coronary artery bypass surgery leads to a chronic increase in ulnar flow accompanied by increased intima-media thickness and accelerated atherosclerotic disease. These findings may have potentially important implications for surgical indications and patients management. # 2005 Elsevier B.V. All rights reserved.

The sensitivity of liver cells to anoxia is a major problem afflicting liver preservation and transplantation. Intermittent ischemia has been proposed to reduce reperfusion injury. The aim of the study was to assess oxygen free radical formation and cell injury during continuous or intermittent anoxia/reoxygenation in rat hepatocytes. Anion superoxide was measured by lucigenin-enhanced chemiluminescence and cell damage by LDH release and trypan blue uptake. During anoxia, superoxide generation dropped to background level in both groups; trypan blue uptake and LDH release, which increased progressively, were significantly greater in hepatocytes exposed to continuous compared to intermittent anoxia. During reoxygenation, a massive generation of superoxide anion formation, followed by a sharp increase in LDH release, was observed in both groups. However, both oxyradical generation and cell injury were significantly greater in cells exposed to continuous compared to intermittent anoxia. The data, showing that intermittent oxygen deprivation reduce liver cell injury and oxygen free radical formation determined by anoxia/reoxygenation, suggest a novel possible approach to the reduction of reperfusion injury.

The measurement of partial oxygen pressure in arterial blood by use of transcutaneous pulse oximetry (tcPo2) is a technique relatively new to clinical practice. However, there are notable differences of values both in healthy and arteriopathic subjects, depending on which part of the limb the measurement is carried out. The authors define a cutaneous reference map for oximetric measurements in both healthy and arteriopathic subjects. In a group of 200 healthy subjects and a group of 82 subjects affected by obliterative arteriopathy of the lower limbs at the second Fontaine stage, oximetric measurements were carried out under rest conditions. By comparing the oximetric ranges at all examined levels, it can be seen that there is a wide band of overlap between the minimum values of healthy subjects and those of the arteriopathic subjects. In a group of 30 healthy subjects and in a group of 30 subjects affected by obliterative arteriopathy of the lower limbs at the second Fontaine stage, oximetric measurements were taken at I, II, III back levels of the leg during maximal treadmill test. In this case, by comparing the oximetric ranges between the two groups, it can be seen that all arteriopathic subjects present significantly lower values as compared with those of the healthy subjects at each examined level. This permits a confident diagnosis of pathology. The authors conclude that in order to make a correct diagnosis of arteriopathy by using transcutaneous oximetry, it is necessary to consider both the measurements carried out under rest conditions and those carried out during maximal treadmill test.

Inflammatory processes are considered important in the pathogenesis of Alzheimer's disease (AD). Intercellular adhesion molecule-1 (ICAM-1) is an important mediator of inflammatory response and immune cell activation, is expressed on cerebrovascular endothelium and neuritic plaques in brain of AD patients, and seems to be implicated in the process of neuro-degeneration. A common polymorphism of the ICAM-1 gene (K469E) has been recently reported. In this case-control study, we evaluated the distribution of E/K alleles and genotypes of the ICAM-1 gene in 98 patients affected by sporadic AD and 115 age- and sex-matched controls. The frequency of the EE genotype was significantly higher in AD patients (P

Interleukin-6 (IL-6) is a multifunctional cytokine playing a crucial role in inflammation and tissue injury. A role for this molecule in neurodegeneration and Alzheimer's disease (AD) has been proposed. The aim of this study was to evaluate the association between a common polymorphism of the IL-6 gene promoter and AD in the Italian population. We found that the frequency of the GG genotype was significantly higher in AD patients than controls on both univariate ( rho< 0.0001) and multivariate analysis ( rho< 0.0001). In contrast, the CC genotype seems to be associated with a reduced risk of disease ( rho< 0.0001). Our data indicate that the IL-6 gene polymorphism is associated with AD in Italians and confirm that IL-6 is crucial in the pathophysiology of neurodegenerative disorders.

The therapeutic effects of defibrotide, a polydesoxyribonucleotide derivative with antithrombotic, fibrinolytic, and anti-ischemic activity, were explored in 15 patients with occlusion of the central vein (5 cases) or peripheral branches of the retinal venous system (10 cases). Defibrotide was administered by slow intravenous infusion in doses of 2 gm daily for 21 days: at the start and end of the study, all patients underwent ophthalmologic examination with measurements of visual acuity and funduscopy by direct and indirect ophthalmoscopy. Visual acuity improved in 11 patients, while it remained unchanged in four cases; the difference between means was statistically significant ( P P P

A Haake viscosimeter was used to determine the viscosity of amniotic fluid and this value correlated with fetal lung maturity. The results were evaluated along the weeks of pregnancy and compared to those obtained using Gluck's method (lecithin/sphingomyelin ratio (L/S). Using 91 separate amniotic fluid samples, free of meconium and blood contamination, we found that the new method was quick and easy to perform. Thirty-one neonates were delivered within 48 h of the amniotic fluid sampling and the percentage of correct prediction of respiratory distress syndrome (RDS) was 71% with a mature L/S ratio and 83% with viscosity less than 1.17 cP. In cases with an immature L/S ratio (value below 2) the correct prediction of RDS was 64%; with the fluorescence polarization (FP) technique it was 91%. We conclude that the amniotic fluid FP value is a reliable index of fetal lung maturity and risk for developing RDS and has also specific technical and diagnostic advantages over the L/S ratio.

Case-control study.As inflammation plays a key role in the etiology of intervertebral disc degeneration, we suggest a possible contribution of pro-inflammatory gene polymorphisms in the pathogenesis of adolescent idiopathic scoliosis (AIS).The nucleus pulposus of scoliotic discs responds to exogenous stimuli by secreting interleukin-6 (IL-6) and other inflammatory cytokines. The association between matrix metalloproteinases (MMPs) and disc degeneration has been reported by several investigators. A human MMP-3 promoter 5A/6A gene polymorphism regulates MMP-3 genes expression, while the G/C polymorphism of the promoter region of IL-6 gene influences levels and functional activity of the IL-6 protein.We conducted a case-control study to investigate whether the 5A/6A polymorphism of the MMP-3 gene and the G/C polymorphism of the promoter region of IL-6 gene were associated with susceptibility to AIS.The frequency of the 5A/5A genotype of MMP-3 gene polymorphism in patients with scoliosis was almost 3 times higher than in controls (30.2% vs. 11.2%, p 0.001), and the frequency of the G/G genotype of IL-6 gene polymorphism in patients with scoliosis was almost 2 times higher than in controls (52.8% vs. 26.2%, P0.001). 5A/5A genotype of MMP-3 gene polymorphism and G/G genotype of IL-6 gene polymorphism are independently associated with a higher risk of scoliosis (odds ratio, respectively, 3.34 and 10.54).This is the first study that has evaluated the possibility that gene variants of IL-6 and MMPs might be associated with scoliosis and suggests that MMP-3 and IL-6 promoter polymorphisms constitute important factors for the genetic predisposition to scoliosis.

Background: Cerebellar hypoxia is responsible for important aspects of cognitive deterioration and motor disturbances in neurological disorders, such as stroke, vascular dementia, and neurodegeneration. In the cerebellum, VEGF is significantly upregulated after hypoxia and is able to induce angiogenesis, reduce neuronal apoptosis, and regulate neuronal differentiation, proliferation, and migration. But, VEGF is not sufficient to provide neuroprotection. A crucial role is played by growth associated protein-43 (GAP43), for which important activities have been described. The purpose of this study was to investigate the role of the developmental Sonic hedgehog (Shh) signaling pathway in postnatal hypoxic cerebellum and its relationship with VEGF and GAP43 expression. Methods: We used adult C57BL/6J mice, ptc1-lacZ mice, and GAP43−/− mice for these experiments. Ptc1-lacZ mice carry a non-disruptive insertion of the lacZ gene under the control of the ptc1 promoter. Ptc1 is a downstream-transcriptional target of Shh and its upregulation indicates activation of the Shh pathway. Mice were exposed to systemic normobaric hypoxia (6%O 2 ) for 6 hours and the expression of Shh, Ptc1, VEGF, and GAP43 were investigated. Results: After exposure to hypoxia, Shh-positive staining was detected in Purkinje cells (PCs). The same cells were also lacZ(ptc1)-positive, indicating that PCs are both Shh-producing and -responding elements. Also the cells of the internal granular layer (IGL) were lacZ(ptc1)-positive, indicating that these cells are Shh-responsive. LacZ(ptc1)-positive IGL cells were also immunopositive for VEGF and GAP-43. We also found that ptc1 expression is lost in PCs of GAP43−/− mice, indicating that Shh requires GAP43 to activate its downstream target genes in PCs. Finally, when cultures enriched in granular cells were stimulated with Shh recombinant protein, GAP43 phosphorylation was increased. This effect was inhibited by Shh-inhibitor cyclopamine. Conclusions: This is the first time that hypoxia is reported to activate the Shh pathway in the adult. Our data suggest that the Shh pathway might be important for the cerebellar response to hypoxia, through interactions with VEGF and GAP43.

Objectives. Single nucleotide polymorphisms in genes encoding inflammatory molecules may determine genetic profiles associated with increased risk of development and progression of cardiovascular diseases. In this study, we evaluated distribution and reciprocal interaction of a set of functionally important polymorphisms of genes encoding prototypical inflammatory molecules in subjects with peripheral arterial occlusive disease (PAOD) and critical limb ischemia (CLI). We also investigated whether synergistic interactions between these pro-inflammatory gene polymorphisms influence the risk of PAOD and CLI. Design, subjects and methods. In a genetic association study that included 157 PAOD patients and 206 controls, the following gene polymorphisms were analysed: C-reactive protein (CRP) 1059 G/C, interleukin-6 (IL-6)-174 G/C, macrophage migration inhibitory factor (MIF)-173 G/C, monocyte chemoattractant protein (MCP-1) – 2518 A/G, E-selectin (E-Sel) Ser128Arg, intercellular adhesion molecule-1 (ICAM-1) 469 E/K, matrix metalloproteinase (MMP)−1 -1607 1G/2G, MMP-3-1171 5A/6A and MMP-9-1563 C/T. Results: We found that IL-6, E-sel, ICAM-1, MCP-1, MMP-1 and MMP-3 gene polymorphisms were significantly and independently associated with PAOD. We also found that these pro-inflammatory polymorphisms determine genetic profiles that are associated with different levels of risk for PAOD and CLI, depending on the number of high-risk genotypes concomitantly carried by a given individual. Conclusions: Pro-inflammatory genetic profiles are significantly more common in subjects with PAOD. Synergistic effects between pro-inflammatory genotypes might be potential markers for the presence and severity of atherosclerotic disorders.

Background Healthy workers who stand for prolonged periods show enhanced production of reactive oxygen species (ROS) in their systemic circulation. Oxidative stress is thought to be a risk factor for chronic venous insufficiency and other systemic diseases. Aim To evaluate the effectiveness of compression stockings in the prevention of oxidative stress at work. Methods ROS and venous pressure of the lower limbs were measured in 55 theatre nurses who stood in the operating theatre for >6 h, 23 industrial ironers who stood for up to 5 h during their shift and 65 outpatient department nurses and 35 laundry workers who acted as controls. Subjects and controls were examined on two consecutive days before and after work and with and without compression stockings. Results Without compression stockings, lower limb venous pressure increased significantly after work in all subjects and controls (P < 0.001), while only operating theatre nurses showed significantly higher mean levels of ROS (P < 0.001). There was no significant difference in venous pressures and ROS levels after work in subjects or controls when wearing compression stockings. Conclusions Our data suggest a preventive role of compression stockings against oxidative stress in healthy workers with a standing occupation.

Blood coagulation factor XIII (FXIII) plays a role in inflammatory processes and a pathogenetic role of inflammation in neurodegenerative disorders has been proposed. FXIIIa subunit was immunohistochemically detected in a subpopulation of reactive microglia in Alzheimer's disease (AD). Aim of the present study is to evaluate whether a common polymorphism of the FXIII gene is associated with sporadic AD. We examined 90 patients affected by sporadic AD and 139 age- and sex-matched controls to assess the distribution of V/L alleles and genotypes of the FXIIIa-subunit gene. The LL genotype showed a significantly higher frequency in AD patients (p

Helicobacter pylori infection is the major agent of gastric damage. Coeliac disease may affect the morphology and function of the entire gastrointestinal tract from the stomach to the colon. The aim of this study was to assess the gastric histological pattern in patients with H. pylori and untreated coeliac disease.We retrospectively enrolled 183 H. pylori-positive patients with (85, group A) and without (98, group B) untreated coeliac disease. The groups were similar for age, gender and smoking habit, and all the patients came from the same geographical area. Histological evaluation of gastric pattern was performed on 4 biopsies (2 in the antrum, 2 in the corpus). Gastric damage was classified according to the modified Sydney System. Diagnosis of H. pylori infection was based on positivity to histology. The chi-square test was used to assess differences between groups. A p-value0.05 was considered significant.Group A showed a significantly higher prevalence of follicular gastritis than group B (23.5% versus 12.2%, p=0.045). A significantly lower prevalence of atrophic gastritis was observed in group A compared with that in group B (6% versus 22.5%, p=0.002). The prevalence of chronic superficial gastritis, activity degree and intestinal metaplasia was similar between the two groups.In patients with H. pylori infection, untreated coeliac disease could represent a risk factor for follicular gastritis and is associated with a lower prevalence of atrophic gastritis. The complex interaction between H. pylori and untreated coeliac disease on Th-1/Th-2 balance in the gastric mucosa could explain these results.

Blood loss after total knee arthroplasty (TKA) is often associated with cardiovascular complications and a high transfusion rate of allogenic blood. In our study we focused our attention on developing a new intra-surgical procedure that appears safe, easy to perform and effective in the reduction of bleeding in TKA. We evaluated 84 patients who underwent TKA and met our inclusion criteria; they were assigned to two groups: 55 controls in which a saline solution was used to wash the surgical field before tourniquet release, and a second group of 29 patients, in which a saline solution containing a low dose of norepinephrine was locally applied before tourniquet release. The local administration of a low dose of norepinephrine has induced a significant reduction of perioperative blood loss and blood transfusion requirements; in addition, this method was characterised by the absence of complications or adverse effects. In conclusion, our data suggest that intraoperative local administration of a low dose of norepinephrine could represent an effective and safe method of reducing blood loss and preventing blood transfusions in patients with TKA.