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Biomedical subjects

C Di Campli

Publications and source records attributed to C Di Campli.

At least 19 recordsLinked to original sources
PubMed2006

Rescue therapy by portal infusion of autologous stem cells in a case of drug-induced hepatitis.

Recent efforts have been directed toward new therapeutic options to approach drug-induced hepatitis. We report a case of acute liver failure associated with Nimesulide in a 67-year-old man, with a medical history of chronic alcohol abuse. The biopsy was compatible with chronic alcoholic liver disease and acute drug-induced injury. The patient was enrolled to receive G-CSF followed by apheresis and selection of peripheral-blood stem cells. After ultrasound-guided injection of CD34+cells in the portal vein, we observed a rapid improvement of synthetic liver function, with particular reference to coagulation parameters. Liver biopsy performed 20 days after, showed wide areas of regeneration. In the next 30 days the laboratory signs of acute decompensation progressively improved. Unfortunately he died of multiple-organ failure related to bacterial infection. Intrahepatic injection of peripheral-blood stem cells seemed safe and produced good periprocedural results with improvement of synthetic profile, suggesting a possible role of stem cells in the regeneration process.

Aged↗
PubMed2005

Increased carotid intima-media thickness in patients with inflammatory bowel disease.

BACKGROUND: Patients with inflammatory bowel disease have an increased risk of thrombotic complications; moreover, mesenteric microvascular thrombosis has been hypothesized as a contributing factor in the pathogenesis of inflammatory bowel disease. AIM: To assess the extent of subclinical atherosclerosis in inflammatory bowel disease by measuring the intima-media thickness of the common carotid artery. METHODS: Fifty-two patients were enrolled in the study. Patients aged >45 years, with a history of cardiovascular disease and known risk factors for atherosclerosis were excluded from the study. Twenty healthy subjects were studied as controls. Carotid ultrasonography was performed in all patients and controls. intima-media thickness was measured proximal to the carotid bifurcation over both right and left common carotid arteries. The clinical characteristics and the laboratory parameters relevant to disease activity were recorded for all inflammatory bowel disease patients. In particular, plasma homocysteine, a well-known risk factor for thrombosis, was assessed. RESULTS: Common carotid artery intima-media thickness was significantly higher in inflammatory bowel disease patients (0.63 +/- 0.15 mm) compared with controls (0.53 +/- 0.08 mm). Multiple regression analysis revealed a significant association of carotid intima-media thickness with homocysteine levels and age. CONCLUSIONS: Inflammatory bowel disease patients have an increased risk of early atherosclerosis than healthy controls as showed by greater values of carotid intima-media thickness. Homocysteine levels and age resulted independently associated with the increased arterial wall thickness.

Adult↗
PubMed2005

How does human stem cell therapy influence gene expression after liver injury? Microarray evaluation on a rat model.

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.

Animals↗
PubMed2004

A human umbilical cord stem cell rescue therapy in a murine model of toxic liver injury.

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.

Animals↗
PubMed2004

Enhanced oxidative stress in workers with a standing occupation.

BACKGROUND: Several epidemiological studies have shown a statistically significant association between standing work and chronic venous insufficiency of lower limbs. This condition has been associated with an enhanced oxidative stress that, according to the literature, could represent a risk factor for cardiovascular and other systemic diseases. AIMS AND METHODS: To evaluate venous pressure of the lower limbs and reactive oxygen species (ROS) before and after work in 62 workers with a standing occupation (surgery room nurses) and 65 outpatient department nurses who can walk during their working time. RESULTS: After work, a statistically significant increase of venous pressure of the lower limbs levels was observed in both the study group and controls. Standing workers showed significantly higher mean levels of ROS after work.

Adult↗
PubMed2003

Review article: a medicine based on cell transplantation -- is there a future for treating liver diseases?

Cell-based therapies, comprising isolated hepatocyte transplantation, ex vivo gene therapy and bioartificial liver devices, may actually design a new scenario in the treatment of patients with liver failure. Recent advances in the liver repopulation field and the considerable excitement surrounding the use of haematopoietic stem cells for a 'regenerative medicine', allow us to see under a new light the alternative cell sources actually under investigation. In particular, the major drawbacks and the most important advantages of xenogenic primary cells, tumour-derived cell lines, immortalised hepatocytes and stem cells in the wide range of experimental and clinical applications are presented. Even if up to now none of them represent a 'gold standard' in the clinical practice, the intersecting advances in the development of mechanical components of artificial devices and in the liver biology and bioengineering will open tantalising possibilities to treat patients with liver failure, by tailoring the therapeutic choice on the basis of the aetiology and the stage of liver disease.

Artificial Organs↗
PubMed2003

Real time endoscopic imaging of oxyradical generation in pig stomach during ischemia-reperfusion.

BACKGROUND: Oxygen-free radicals generation is considered to be a major cause of gastric injury during reperfusion. Chemiluminescence has been used to assess real-time free radical release on the surface of isolated organs. AIMS: To evaluate the combined use of chemiluminescence and gastroendoscopy techniques and to assess the real-time production of free radicals during ischemic damage of the gastric wall in an animal model. PATIENTS AND METHODS: For the experiment, an optical junction was set up between a fibroendoscope and a luminograph apparatus. Three pigs were submitted to gastrofibroendoscopy before, during and after 30 min of clamping of the coeliac artery. Under basal conditions, at the end of the ischemic phase and at the beginning of reperfusion, 1 mM of lucigenin, a specific superoxide enhancer, was injected in the left gastric artery of the animal. The endoscopic live images and chemiluminescence emission were recorded and successively superimposed to measure rate and spatial distribution of photon emission (photons/s). RESULTS: Free radical production was not observed under basal conditions or during the ischemic phase, but significantly increased during reperfusion reaching a maximum peak after 15 min (0.6+/-0.2 photons x 10(5)/s) and decreased progressively thereafter. The superimposition of live and chemiluminescence images allowed the determination of the regional production rate and distribution of photons. CONCLUSIONS: Preliminary observations, in an animal model, on an innovative imaging system which allows the visualization of rate and spatial distribution of reactive oxygen species formation are presented. This new endoscopic technique could be useful for the assessment of oxidative gastric mucosal injury in several gastric diseases; however, further studies remain necessary to determine the applicability of this technique in humans.

Animals↗
PubMed2003

Stem cells: new tools in gastroenterology and hepatology.

Stem cells play a key role in tissue homeostasis and renewal after damage, so learning more about them may become a sort of 'Pandora's box', which when opened will make it possible to clarify the nature and the pathophysiology of several human diseases and to find new treatments for pathologies, such as cancers, degenerative, autoimmune and genetic disorders, that are currently untreatable. The characteristics of the gastrointestinal tract and of the liver, in terms of genesis and regeneration and their special relationship with the haemolymphopoietic system, allow stem cell research to outline interesting therapeutic perspectives in these fields. We aim to summarize the knowledge acquired on gastrointestinal and hepatic stem cell biology, focusing attention on the issues that remain to be addressed, and to present the main perspectives of treatment offered by these 'new tools' in gastroenterology and hepatology.

Bone Marrow Cells↗
PubMed2003

Oral desensitizing treatment in food allergy: clinical and immunological results.

BACKGROUND: The possibility of inducing oral desensitization in patients with food allergy is still controversial and no standardized programmes are yet available. AIM: To evaluate the safety and efficacy of oral desensitization in patients with allergy induced by the most common food allergens. METHODS: Fifty-nine patients with food allergy underwent an oral desensitizing treatment according to standardized protocols. The control group consisted of age- and sex-matched subjects, who followed a strict elimination diet. Specific immunoglobulin E and immunoglobulin G4 were assessed at baseline and after 6, 12 and 18 months. RESULTS: The majority of patients (83.3%) successfully completed the treatment. During treatment, 51.1% of subjects experienced some mild side-effects, easily controlled by the oral administration of antihistamines or sodium cromolyn. Specific immunoglobulin E showed a significant decrease, whilst specific immunoglobulin G4 showed a significant increase in all patients. CONCLUSIONS: The immunological findings induced by oral desensitization in food allergy allow us to hypothesize that oral tolerance may be mediated by the same mechanisms as those involved in traditional desensitizing treatments for respiratory allergies. Moreover, the proposed standardized oral desensitization protocols may represent an effective alternative approach in the management of food-allergic patients.

Administration, Oral↗
PubMed2003

Advances in extracorporeal detoxification by MARS dialysis in patients with liver failure.

Although liver transplantation has become standard procedure for patients with liver failure, a number of issues in the management of these patients remains to be addressed. Alternative approaches have been tested, such as hepatocytes containing liver-support systems and filtration devices. However, the replacement of detoxification has been difficult, as the majority of toxins accumulating in liver failure is albumin-bound. Albumin dialysis (MARS system) is characterized by the specific removal of albumin-bound toxins through an innovative membrane transport. In particular, the albumin acts as a specific molecular adsorbent that is regenerated on line in a recycling system. Nowadays MARS represents the most frequently used liver support system. This treatment has been shown to remove albumin-bound molecules, such as bilirubin, bile acids, aromatic amino acids and copper. The removal of these toxins is clinically accompanied with an improvement of liver, cardiovascular and renal functions and hepatic encephalopathy. In several trials MARS was found to improve the clinical situation in patients with acute exacerbation of chronic liver failure and acute hepatic failure, but also in hepatorenal syndrome and primary graft non function or chronic rejection after liver transplantation. In summary, a critical analysis of the literature confirms that MARS device can be a safe therapeutic choice to achieve a better clinical outcome, and, sometimes, a survival advantage in patients with liver failure, even if a multi-center randomized trial is the only reliable way to enforce today's results. Further advances in the MARS components will definitively state whether albumin dialysis may represent the future in the field of artificial liver devices.

Adsorption↗
PubMed2002

Relationship between gastric localization of hepatitis C virus and mucosa-associated lymphoid tissue in Helicobacter pylori infection.

BACKGROUND: Hepatitis C virus (HCV) has been localized in several extra-hepatic sites. Recent evidence suggests that the stomach can harbour HCV. We therefore evaluated the prevalence of gastric localization of HCV and its possible relationship with the chronic inflammatory response to Helicobacter pylori infection. METHODS: Sixty patients with HCV infection (group A) and 60 subjects without HCV infection (control group), who underwent upper endoscopy for dyspeptic symptoms, were consecutively enrolled. Biopsy specimens of gastric mucosa obtained from each patient were assessed for H. pylori and chronic inflammatory infiltrates (classified as mild, moderate or marked). Furthermore, polymerase chain reaction (PCR) analyses were performed on the gastric biopsies to detect HCV and immunoglobulin heavy-chain (IgH) gene rearrangements of mucosal B cells. RESULTS: In group A, 24 of 36 patients with H. pylori infection and 6 of 24 without H. pylori hosted HCV in their stomach (P = 0.0017). In these subjects, the presence of both HCV in the gastric mucosa and H. pylori was significantly associated with marked or moderate inflammatory infiltrates. Oligoclonal IgH gene rearrangements were detected in three group A patients who harboured both H. pylori and HCV in their stomach. In the control group, PCR analyses failed to find HCV in the gastric mucosa, and polyclonal patterns were detected in all individuals. CONCLUSIONS: HCV is frequently localized in the stomach and is associated with the chronic lymphocytic inflammatory response to H. pylori. H. pylori and HCV, when both present, may favour the selection of clonal B cells.

Adult↗
PubMed2001

Nonneutralizing human antibody fragments against hepatitis C virus E2 glycoprotein modulate neutralization of binding activity of human recombinant Fabs.

Evidence from clinical and experimental studies indicates that hepatitis C virus E2 (HCV/E2) glycoprotein is the major target of a putatively protective immune response. However, even in the presence of a vigorous production of anti-HCV/E2 antibodies, reinfection can occur. Dissection of the human immune response against HCV/E2 indicated that blocking of binding of HCV/E2 to target cells [neutralization of binding (NOB) activity] varies widely among antibody clones. Moreover, in vivo, simultaneous binding of antibodies to distinct epitopes can induce conformational changes and synergies that may be relevant to understanding the anti-HCV immune response. In this study, human recombinant Fabs were generated by affinity-selecting a phage display repertoire library with antibody-coated HCV/E2. These Fabs, which share the same complementarity-determining region DNA sequences, had higher affinity than other anti-HCV/E2 Fabs but showed no NOB activity even at the highest concentrations. Binding of Fabs to HCV/E2 caused conformational changes modifying Fab-binding patterns and reducing, with a negative synergistic effect, Fab-mediated NOB activity. These data suggest that some antibody clones have the potential to modify HCV/E2 conformation and that, in this state, binding of this glycoprotein to its cellular target is less prone to inhibition by some antibody clones. This can explain why high anti-HCV/E2 antibody titers do not directly correlate with protection from infection. Information on the interactions among different antibody clones can contribute to understanding virus-host interplay and developing more effective vaccines.

Amino Acid Sequence↗
PubMed2001

Gender affects reperfusion injury in rat liver.

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 malondialdehyde lactic dehydrogenase values were also determined. Chemiluminescence increased during reperfusion in both groups, but was significantly greater in livers from female rats. Malondyaldehyde 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.

Animals↗
PubMed2001

Oxygen free radical production in rat liver: dose-related effect of ethanol on reperfusion injury.

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.

Adenosine Triphosphate↗
PubMed2001

Mapping B-cell epitopes of hepatitis C virus E2 glycoprotein using human monoclonal antibodies from phage display libraries.

Clinical and experimental evidence indicates that the hepatitis C virus (HCV) E2 glycoprotein (HCV/E2) is the most promising candidate for the development of an effective anti-HCV vaccine. Identification of the human epitopes that are conserved among isolates and are able to elicit protective antibodies would constitute a significant step forward. This work describes the mapping of the B-cell epitopes present on the surface of HCV/E2, as recognized by the immune system during infection, by the analysis of the reciprocal interactions of a panel of human recombinant Fabs derived from an HCV-infected patient. Three unrelated epitopes recognized by antibodies with no neutralization-of-binding (NOB) activity were identified; a fourth, major epitope was defined as a clustering of minor epitopes recognized by Fabs endowed with strong NOB activity.

Antibodies, Monoclonal↗
PubMed2000

Association between Helicobacter pylori cytotoxic type I CagA-positive strains and migraine with aura.

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.

Adult↗
PubMed2000

No evidence of Helicobacter pylori sequences in pancreatic juices of patients affected by chronic pancreatitis.

BACKGROUND: The course of chronic pancreatitis is often unpredictable and many factors are likely to be involved in the progression of the disease. In physiological condition, pancreatic juice exerts significant antibacterial activity, which is impaired in patients with chronic pancreatitis. AIM: Hypothesizing that Helicobacter pylori could, in these conditions, lead to an ascending infection, we aimed to assess the presence of H. pylori sequences in pancreatic juices of patients with chronic pancreatitis. METHODS: 40 patients (mean age 52+/-3 yr) with alcoholic chronic pancreatitis and H. pylori infection were examined. Pancreatic juices were collected during endoscopic retrograde cholangiopancreatography. Using polymerase chain reaction (PCR) with two primers homologous to a portion of urease-C gene, H. pylori DNA was detected. Gastric biopsies, microscopically positive to H. pylori were used as positive controls. RESULTS: All gastric biopsies produced H. pylori-specific DNA products. Conversely, no H. pylori urease-C gene sequences have been detected in any of the pancreatic juices. CONCLUSION: Our data suggest that the impaired antibacterial activity of pancreatic juices in patients affected by chronic pancreatitis does not have a permissive role for a superimposing H. pylori infection in the pancreas. The possibility that Helicobacter species other than pylori may be involved in a superimposing infection requires further investigation.

Chronic Disease↗