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Biomedical subjects

P Pola

Publications and source records attributed to P Pola.

At least 19 recordsLinked to original sources

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↗

Local infusion of norepinephrine reduces blood losses and need of transfusion in total knee arthroplasty.

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.

Aged↗

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↗

Rifaximin dose-finding study for the treatment of small intestinal bacterial overgrowth.

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.

Adult↗

Abnormal breath tests to lactose, fructose and sorbitol in irritable bowel syndrome may be explained by small intestinal bacterial overgrowth.

BACKGROUND: 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. AIM: To assess the extent to which small intestinal bacterial overgrowth may influence the results of hydrogen sugar breath tests in irritable bowel syndrome patients. METHODS: 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. RESULTS: 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 (P < 0.05), fructose breath test (P < 0.01) and sorbitol breath test (P < 0.01) 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: P < 0.0001). CONCLUSIONS: 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.

Adult↗

Helicobacter pylori infection and ischaemic heart disease: an overview of the general literature.

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.

Animals↗

Hydrogen glucose breath test to detect small intestinal bacterial overgrowth: a prevalence case-control study in irritable bowel syndrome.

BACKGROUND: Studies assessing the prevalence of small intestinal bacterial overgrowth in irritable bowel syndrome gave contrasting results. Differences in criteria to define irritable bowel syndrome patients and methods to assess small intestinal bacterial overgrowth may explain different results. Moreover, no data exist on small intestinal bacterial overgrowth prevalence in a significant population of healthy non-irritable bowel syndrome subjects. AIM: To assess the prevalence of small intestinal bacterial overgrowth by glucose breath test in patients with irritable bowel syndrome symptoms with respect to a consistent control group. METHODS: Consecutive patients with irritable bowel syndrome according to Rome II criteria were enrolled. The control population consisted of 102 sex- and age-matched healthy subjects without irritable bowel syndrome symptoms. All subjects underwent glucose breath test. A peak of H2 values >10 p.p.m above the basal value after 50 g of glucose ingestion was considered suggestive of small intestinal bacterial overgrowth. RESULTS: A total of 65 irritable bowel syndrome patients and 102 healthy controls were enrolled. Positivity to glucose breath test was found in 31% of irritable bowel syndrome patients with respect to 4% in the control group, the difference between groups resulting statistically significant (OR: 2.65; 95% CI: 3.5-33.7, P < 0.00001). CONCLUSIONS: The present case-control study showed an epidemiological association between irritable bowel syndrome and small intestinal bacterial overgrowth. Placebo-controlled small intestinal bacterial overgrowth-eradication studies are necessary to clarify the real impact of small intestinal bacterial overgrowth on irritable bowel syndrome symptoms.

Adult↗

Atrophic gastritis as a cause of hyperhomocysteinaemia.

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; chi2=5.2; P=0.01) and low vitamin B12 (odds ratio, 3.7; 95% confidence interval, 1.03-22.08; chi2=3.6; P<0.05) were both predictors of hyperhomocysteinaemia. None of the other variables considered in the analysis, including H. pylori status, showed a significant association with hyperhomocysteinaemia. CONCLUSIONS: The present study suggests that atrophic gastritis, rather than H. pylori infection per se, may be a contributing factor to hyperhomocysteinaemia, possibly via vitamin B12 malabsorption.

Female↗

Sacroileitis and peripheral arthropathy associated with ulcerative colitis: effect of infliximab on both articular and intestinal symptoms.

Infliximab has been proven to be an effective therapy in a miscellany of rheumatic diseases and has been approved for the treatment of moderate-to-severe Crohn's disease with an inadequate response to conventional therapy and for the management of enterocutaneous fistulas. Data about the role of infliximab in ulcerative colitis are still controversial. Here, we report a case of a patient with sacroileitis and peripheral arthropathy associated with left-sided ulcerative colitis who achieved a sustained clinical remission after infliximab therapy.

Adult↗

Prevalence of the K469E polymorphism of intercellular adhesion molecule 1 gene in Italian patients with inflammatory bowel disease.

BACKGROUND: Intercellular adhesion molecule 1 plays an important role in the recruitment of leucocytes at sites of inflammation and is up-regulated in intestinal mucosa of inflammatory bowel disease. Intercellular adhesion molecule 1 gene lies on chromosome 19p13, implicated in determining susceptibility to inflammatory bowel disease. Recently, the polymorphism K469E of intercellular adhesion molecule 1 gene has been identified. AIM: To assess the potential association of this polymorphism with inflammatory bowel disease. PATIENTS: A total of 165 inflammatory bowel disease patients, 75 with Crohn's disease and 90 with ulcerative colitis, and 187 controls were studied. METHODS: The K469E polymorphism was detected by polymerase chain reaction and restriction enzyme analysis. Statistical analysis was performed by chi2-test. RESULTS: In inflammatory bowel disease, the distribution of intercellular adhesion molecule 1 genotypes was 24.9% E/E, 44.2% E/K and 30.9% K/K. In controls, 11.8% showed E/E genotype, 55.6% E/K and 32.6% K/K. The frequency of the E/E genotype was significantly higher in inflammatory bowel disease (Crohn's disease and ulcerative colitis) patients than in controls. Subgroup analysis showed that the frequency of the E469 allele was significantly increased only in Crohn's disease patients with ileocolonic location of disease and penetrating behaviour compared with controls. CONCLUSIONS: We found an association of inflammatory bowel disease with the E/E genotype of intercellular adhesion molecule 1 gene, while allele E469 was associated with a subgroup of Crohn's disease patients with more extensive location of disease and penetrating behaviour. However, further studies are needed to confirm our findings.

Adolescent↗

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↗

Comparative analysis of the in vivo angiogenic properties of stable prostacyclin analogs: a possible role for peroxisome proliferator-activated receptors.

OBJECTIVE: Until recently, prostacyclin (PGI2) biological activities were thought to be exclusively mediated by cell surface receptors named IP. Recent studies have instead identified a novel pathway of PGI2 signaling, occurring through activation of peroxisome proliferator-activated receptors (PPARs) located in the nucleus. The availability of stable PGI2 analogs with different affinity for IP receptors and PPARs provides the possibility to test the importance and function of this dual pathway in vitro and in vivo. In this study, the in vivo angiogenic properties of different PGI2 analogs and the potential relationship between PPAR-mediated pathways, vascular endothelial growth factor (VEGF), and angiogenesis were investigated. METHODS AND RESULTS: By using the murine corneal model of angiogenesis, we found that PGI2 analogs able to act on nuclear PPARs, such as iloprost and carbaprostacyclin (cPGI), induce angiogenesis in vivo. In contrast, cicaprost, a PGI2 analog that only acts on IP receptors, has no in vivo angiogenic activity. Interestingly, angiogenesis induced by iloprost and cPGI does not differ in extent and morphology from that induced by VEGF and is associated with local increment of VEGF mRNA expression and protein levels. Finally, iloprost-induced angiogenesis is significantly decreased by systemic inhibition of VEGF activity, obtained by gene transfer of a soluble form of the VEGF receptor Flt-1. CONCLUSIONS: These data demonstrate that stable PGI2 analogs may have angiogenic properties in vivo, depending on their ability to act on PPARs. The resulting angiogenic process appears to be mediated by VEGF. These findings indicate that important physiological activities in the cardiovascular system, such as angiogenesis and VEGF induction, may be modulated by PGI2 through specific activation of the PPAR signaling pathway in vivo, with potentially important fundamental and clinical implications.

Animals↗

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↗

The -174 G/C polymorphism of the interleukin-6 gene promoter and essential hypertension in an elderly Italian population.

Several studies have proposed a relationship between blood pressure and inflammation. Interleukin-6 (IL-6) is a multifunctional cytokine involved in inflammation and tissue injury and potentially influencing blood pressure. Recently, a common polymorphism of the IL-6 gene, associated with differences in the transcription rate of the protein, has been described. The aim of this study was to investigate a possible association between genetic variations of the -174GC polymorphism of the IL-6 gene promoter and hypertension in humans. IL-6 gene promoter polymorphism was evaluated by polymerase chain reaction followed by restriction enzyme analysis in 210 elderly Italian patients affected by essential hypertension (EH) and 177 age- and sex-matched controls. The distribution of IL-6 genotypes was 85 GG, 88 GC, 37 CC in the hypertensive patients and 65 GG, 73 GC, 39 CC in the control subjects. In this elderly cohort, no statistically significant association was found between the two groups (P = 0.45 for GG homozygous, P = 0.89 for GC heterozygous and P = 0.27 for CC homozygous). In conclusion the -174 GC polymorphism of the IL-6 gene promoter is not a marker for EH in this sample of elderly Italians.

Aged↗