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Biomedical subjects

A Papa

Publications and source records attributed to A Papa.

At least 19 recordsLinked to original sources

Activated platelets are the source of elevated levels of soluble CD40 ligand in the circulation of inflammatory bowel disease patients.

BACKGROUND: The CD40/CD40L system, a key regulator and amplifier of immune reactivity, is activated in inflammatory bowel disease (IBD) mucosa. AIMS: To determine whether plasma levels of sCD40L are elevated in Crohn's disease (CD) and ulcerative colitis (UC) patients compared with normal controls, to investigate the cellular source of sCD40L, and to explore CD40L induction mechanisms. PATIENTS: CD, UC, and normal control subjects were studied. METHODS: The concentration of sCD40L in plasma and supernatants of freshly isolated platelets and autologous peripheral blood T cells (PBT) was measured by ELISA. Surface CD40L expression level was measured by flow cytometry in resting and thrombin activated platelets, and unstimulated and CD3/CD28 stimulated PBT before and after coculture with human intestinal microvascular endothelial cells (HIMEC). RESULTS: Compared with normal controls, plasma sCD40L levels were significantly higher in both CD and UC patients and proportional to the extent of mucosal inflammation. Platelets from IBD patients displayed a significantly higher surface CD40L expression than those from control subjects, and released greater amounts of sCD40L than autologous PBT. Contact with IL-1beta activated HIMEC induced significant upregulation of CD40L surface expression and release by platelets. CONCLUSIONS: Elevated levels of sCD40L in the circulation of IBD patients reflect enhanced surface expression and release of CD40L by platelets. This phenomenon translates to an increased platelet activation state apparently induced by passage through an inflamed mucosal microvascular bed, a conclusion supported by the positive correlation of plasma sCD40L levels with the extent of anatomical involvement by IBD. These results suggest that platelet-endothelial interactions critically contribute to activation of the CD40 pathway in IBD.

Adult↗

Crimean-Congo hemorrhagic fever in Albania, 2001.

During the spring and summer of 2001, an outbreak of eight cases of Crimean-Congo hemorrhagic fever (CCHF) occurred in Albania. The epidemiological investigation, the clinical presentation of the cases, and the course of the disease are described. Seven of the cases were laboratory confirmed. A nosocomial infection and a cluster of cases within a family were observed. Genetic analysis of the CCHF virus strain that caused the outbreak showed that it was clustered together with other European CCHF virus strains except the Greek one (strain AP92). The Greek strain, which forms an independent clade, differed from the causative strain by 25.3% at the nucleotide level.

Adult↗

Interdisciplinary treatment of a female outpatient population. Organizational model and preliminary results.

OBJECTIVE: To compare the efficacy of diet alone vs interdisciplinary therapy. METHOD: 256 women were divided into an interdisciplinary therapy group composed of 102 subjects and a control group composed of 154 subjects treated by means of diet alone. RESULTS: 21.56% of the interdisciplinary group did not come for the 2 check-ups compared with 49.35% of the diet group (p < 0.001). A weight loss of 5.88 kg and 4.18 kg for the interdisciplinary and the diet group was recorded 8 weeks after the start of the programme (second check-up). DISCUSSION: Interdisciplinary therapy is necessary to personalize treatment and satisfy the patient's desire and need for appropriate and effective management.

Adolescent↗

Role of Helicobacter pylori CagA+ infection in determining oxidative DNA damage in gastric mucosa.

BACKGROUND: Although Helicobacter pylori is a risk factor for gastric cancer, the role of the bacterium in the development of this malignancy is not defined precisely. Reactive oxygen species (ROS) could play an important role in carcinogenesis by inducing DNA damage. The aims of the present study were: 1) to assess the production of ROS and 8-hydroxy-2'-deoxyguanosine (8-OHdG), a sensitive marker of oxidative DNA injury, in gastric mucosa, according to H. pylori status and cytotoxic associated gene product A (CagA); 2) to determine the relationship between ROS generation and amount of 8-OHdG. METHODS: Gastric biopsy specimens were obtained from 60 consecutive patients. ROS generation was measured by luminol enhanced chemiluminescence. 8-OHdG detection was performed by an immunoperoxidase method, using a specific anti 8-OHdG monoclonal antibody. RESULTS: 40/60 patients (67%) were H. pylori-positive. ROS generation was significantly higher in patients positive for H. pylori infection as compared to negative. 8-OHdG detection was performed in 30 patients in which CagA presence was also investigated. High expression of 8-OHdG was detected in 14/20 (70%) H. pylori-positive patients (13 CagA+ and 1 CagA-) and in 2/10 (20%) H. pylori-negative patients. A significant correlation was found between ROS production and 8-OHdG content. CONCLUSION: H. pylori infection by a CagA+ strain is associated with the highest production of ROS to which a severe oxidative DNA damage corresponds. This sequence of events could support the hypothesis that the oxygen-free radicals-mediated damage due to H. pylori cytotoxic strains could be a driving force that leads from chronic gastritis to gastric carcinoma.

8-Hydroxy-2'-Deoxyguanosine↗

Hantavirus infections in Greece--an update.

Hantaviruses are emerging viruses spread worldwide and cause hemorrhagic fever with renal syndrome (HFRS) or hantavirus pulmonary syndrome (HPS). Two pathogenic hantaviruses are present in Greece: Dobrava/Belgrade virus (DOBV) and Puumala virus (PUUV). The predominant one is DOBV, carried in Greece by the rodent Apodemus flavicollis. Most human infections are sporadic, but epidemic outbreaks were also described. The severity of the disease ranges from a mild or moderate form to severe and fatal cases. Several endemic foci for HFRS have been identified. Phylogenetic analysis of hantavirus sequences revealed a stable geographical distribution.

Animals↗

Relative lymphocyte count: a prognostic indicator of mortality in elderly patients with congestive heart failure.

BACKGROUND: A reduction in the relative lymphocyte count is a marker of the stress response; however, its prognostic value remains undetermined. The objective of this study was to investigate the predictive value of the relative lymphocyte count for survival in elderly patients with congestive heart failure (CHF). METHODS AND RESULTS: One thousand two hundred seventy-four consecutive patients above the age of 65 years hospitalized with heart disease were enrolled in the CHF Italian Study and followed up for 3 years. Of these, 413 patients were excluded because of factors that could affect the lymphocyte count. Of the remaining 861 patients, 423 (49%) met the criteria for the diagnosis of CHF (mean age 76 +/- 7 years, 51% men), of whom 162 patients (38%) had a relative lymphocyte count < or = 20%. The 3-year all-cause mortality in patients with CHF and a relative lymphocyte count < or = 20% was 64% compared with 40% in patients with a relative lymphocyte count > 20% (P < .0001). The age- and sex-adjusted hazard ratio for death in patients with CHF and low relative lymphocyte count was 1.76 (95% confidence interval 1.34-2.32, P = .0001). After adjustment for baseline differences and variables associated with or known to affect lymphocyte count, the hazard ratio remained significantly different from 1.0 (hazard ratio 1.73, 95% confidence interval 1.21-2.48, P = .0026). CONCLUSION: A low relative lymphocyte count is an independent marker of poor prognosis in elderly patients with CHF. The relative lymphocyte count is a simple, accurate, widely available, and inexpensive marker that can help to identify elderly patients with CHF who are at increased risk for mortality. The pathophysiologic mechanism of this observation remains to be determined.

Aged↗

Helicobacter pylori CagA-positive strains affect oxygen free radicals generation by gastric mucosa.

BACKGROUND: Helicobacter pylori plays a key role in production of reactive oxygen metabolites (ROMs). However, the importance of virulent CagA-positive H. pylori strains remains to be determined. The aim of this study was to assess ROMs production in gastric biopsies of patients infected by H. pylori. Results were correlated to CagA status and acute inflammatory infiltration. METHODS: Patients undergoing gastroscopy were enrolled. H. pylori infection was assessed by histology and 13C urea breath test. CagA status was assessed through serology. ROMs were assayed in gastric biopsies by luminol-enhanced chemiluminescence (CLS). Gastric mucosal inflammation was histologically graded and neutrophils were individually counted. Macroscopical damage was scored according to a modified Lanza score. RESULTS: 40 out of 60 patients evaluated were H. pylori (HP) positive. Of the 40 infected patients, 24 were CagA-positive. CLS emission was significantly higher in HP-CagA-positive patients than in HP-CagA-negatives and uninfected. ROMs production showed a significant correlation to neutrophil infiltrate in all groups. CONCLUSIONS: Gastric mucosa of patients infected by HP-CagA-positive strains is characterized by a higher generation of ROMs and by greater neutrophil counts than that observed in HP-CagA-negative subjects. Since ROMs production is associated with DNA oxidative damage, a long-term stimulation by these strains might be relevant in the pathogenesis of gastric malignancies. Assessment of CagA status might be useful to discriminate patients in which H. pylori eradication is advisable.

Antigens, Bacterial↗

Hyperhomocysteinemia and prevalence of polymorphisms of homocysteine metabolism-related enzymes in patients with inflammatory bowel disease.

OBJECTIVES: Patients with inflammatory bowel disease (IBD) have an increased risk of thrombotic complications. Moreover, a hypercoagulable state has been hypothesized as a contributing factor in the pathogenesis of IBD. Recently, a growing amount of interest has focused on mild-to-moderate hyperhomocysteinemia as a risk factor for thromboembolic disease. We aimed to evaluate the prevalence of hyperhomocysteinemia in patients with IBD and to investigate the contribution of genetic defects in the enzymes involved in homocysteine (Hcy) metabolism and vitamin status in determining increased levels of plasma total Hcy (tHcy). METHODS: The concentrations of tHcy, folate, and vitamin B12 as well as the prevalence of methylenetetrahydrofolate reductase (MTHFR) 677C to T mutation and the 68-bp insertion at exon 8 of cystathionine beta-synthase (CBS) were measured in patients with IBD and healthy controls. RESULTS: In all, 17 out of 64 IBD patients (26.5%) and four out of 121 (3.3%) controls had hyperhomocysteinemia with a statistically significant difference (p < 0.0001). No significant difference was found between IBD patients and controls with regard to the prevalence of homozygotes for the C677T variant (TT) of MTHFR or the prevalence of heterozygotes for the CBS-gene mutation (IN). Among the IBD patients the only independent factor significantly associated with hyperhomocysteinemia was folate deficiency (p = 0.0002), regardless of the MTHFR or the CBS genotype. CONCLUSIONS: IBD patients have a higher prevalence of hyperhomocysteinemia than do healthy controls. Folate deficiency is the only independent risk factor in developing hyperhomocysteinemia.

Adult↗

Isolation of Dobrava virus from Apodemus flavicollis in Greece.

Dobrava virus (DOBV) carried by Apodemus flavicollis is the causative agent of severe hemorrhagic fever with renal syndrome (HFRS). DOBV was isolated from an A. flavicollis mouse trapped in northeastern Greece. This is the third DOBV cell culture isolate in the world, clustering together with other Greek DOBV sequences from HFRS patients and rodents.

Animals↗

[Sequencing and comparative analysis of the complete glycoprotein gene of three Crimean-Congo hemorrhagic fever virus Chinese isolates].

OBJECTIVE: To determine the complete sequences of glycoprotein (M) gene of Crimean-Congo hemorrhagic fever virus (CCHFV) Chinese isolates (Xinjiang hemorrhagic fever virus, XHFV) BA66019, BA8402 BA88166 and to compare and analyze the relationships among the viruses. METHODS: Based on the conserved reverse complementarity of the CCHFV genomic termini, a primer PCM-Tag was designed and used together with random hexmers to initiate reverse transcription of viral RNA to synthesize cDNA. The latter was amplified with single primer PCM-Tag using the proof-reading DNA polymerase to produce the complete M gene. The PCR products were gel-purified and the whole M segment was sequenced and the comparison and analysis were performed aided by computer for the phylogenesis and coding strategy. RESULTS: Comparison of the whole M gene sequences of XHFV reference strain BA66019 with international prototype CCHFV IbAr10200 showed an excess of 5 base pairs in length, resulting in 5,365 bp; while BA8402 and BA8816 are 5,365 bp long, 4 more base pairs than IbAr10200. The first start codons of long ORFs were located at the 78th base pair in M gene of BA66019, BA8402 and BA88166, which were 15 base pairs prior to that of IbAr10200. The precursors encoded by these M genes were totaled 1,689 amino acids (AA), 6 AAs more than that of IbAr10200. The similaries between CCHFV M genes in nucleotide level were: 80.9% (IbAr10200-BA66019), 80.2% (IbAr10200-BA8402), 80.2% (IbAr10200-BA88166), 83.7% (BA8402-BA66019), 83.6% (BA88166-BA66019), and 99.0% (BA8402-BA88166), respectively. The corresponding similarities in amino acid level were 85.1%, 86.3%, 86.6%, 87.8%, 88.0%, and 98.8%, respectively. The similarities of M genes of CCHFVs and Dugbe virus in both nucleotide and amino acid levels were around 55% and 37%, which were much lower than those among CCHFVs. CONCLUSION: The M genes of XHFVs and IbAr10200 formed respective independent phylogenetic branches genetically and the human-origin isolate BA88166 might be a variant of tick-borne BA8402, suggesting that there was only one kind virus prevailing in Xinjiang epidemic areas in 1980s.

Amino Acid Sequence↗

Genetic heterogeneity of HIV-1 in Greece.

The aim of this study was to detect and determine the genetic variation of HIV-1 in Greece and to analyze the phylogenetic relationships and transmission dynamics of identified variants. Eighty-six blood samples from HIV-1 seroconverted patients of different risk groups were collected from the AIDS clinic, AHEPA Hospital, Thessaloniki, Greece. Retroviral DNA was extracted from uncultured peripheral blood mononuclear cells. HIV-1 DNA sequences encoding a 500-bp fragment of the gp120 C2-C3 region were amplified from each study subject, and they were genetically subtyped by heteroduplex mobility assay and DNA sequencing. Genetic distances and phylogenetic relationships of DNA sequences were estimated using PHYLIP software. Our results revealed that 82 out of 86 (95.3%) subjects carried subtype B sequences, while four (4.7%) carried subtype A sequences. Subtype A in Greek individuals not having traveled abroad was documented. An average of intrasubtype B genetic divergence of 15% was noted. Our findings demonstrate the presence of at least two genetic subtypes of HIV-1 in northern Greece--subtype B and subtype A. The predominant subtype is subtype B, which was transmitted into Greece by multiple sources. Our observations lend support to the argument that the distribution of HIV-1 subtypes is determined by founder effects or other processes rather than any tropism for particular cell types or mode of transmission.

Adult↗

Review article: potential therapeutic applications and mechanisms of action of heparin in inflammatory bowel disease.

Unfractioned heparin was recently reported to be beneficial in the treatment of inflammatory bowel disease. The available uncontrolled data show that it may be effective in steroid-resistant ulcerative colitis with a percentage of complete clinical remission of over 70% after an average of 4-6 weeks of therapy. The administration of unfractioned heparin is not currently justified by the very limited available data. The worsening of rectal bleeding is infrequent in treated ulcerative colitis patients and only rarely does it require blood transfusion or a colectomy. Low molecular weight heparin was used in a single trial in patients with steroid-refractory ulcerative colitis, with results similar to those observed with unfractioned heparin. Since a prothrombotic state has been described in inflammatory bowel disease, and microvascular intestinal occlusion seems to play a role in the pathogenesis of inflammatory bowel disease, it is reasonable that part of the beneficial effects of unfractioned heparin in inflammatory bowel disease may result from its anticoagulant properties. However, beyond its well-known anticoagulant activity, unfractioned heparin also exhibits a broad spectrum of immunomodulating and anti-inflammatory properties, by inhibiting the recruitment of neutrophils and reducing pro-inflammatory cytokines. Moreover, it can restore the high-affinity receptor binding of basic fibroblast growth factor and this would aid healing of the ulcerated mucosa. In conclusion, unfractioned heparin may represent a safe therapeutic option for severe, steroid-resistant ulcerative colitis, although randomized, controlled trials are needed to confirm these data.

Anticoagulants↗