Polyamines are aliphatic cations that play critical roles in cell proliferation and differentiation and in cancer development. Abnormally high polyamine levels have been demonstrated in various types ...of cancer, but few studies have investigated the prognostic significance of tissue polyamine levels. In this study we evaluated the disease-free survival of patients with colorectal adenocarcinoma according to the polyamine levels in neoplastic tissue and uninvolved surrounding mucosa.
A total of 111 patients with colorectal carcinoma were included in this study. Tissue polyamine levels were evaluated by high performance liquid chromatography (HPLC).
Significantly higher single and total polyamine levels were found in colorectal carcinoma compared to those from normal surrounding mucosa. Further, tumor spermine levels were a significant prognostic factor for disease recurrence.
Differences in tumor spermine levels may affect the biological properties of the tumor and such differences could have a significant role in determining the outcome of colorectal cancer patients.
CKD is utilized as a paradigm, a chronic disease which allows decades of life conquered with great effort through a machine, a life with many losses and many dependencies. We must understand the ...patient's needs, which are not related to availability of drugs and machines and hospitals. We cannot provide good medical care with the limited amount of national product devoted to health care. Society is much older than ever before. We need a new cadre of economists working on health care with vision and ability, keeping in mind that there are no resources and there are no expenses which can be cut in medical care nowadays. We have to switch from curative medicine towards prevention, by implementing clinical research, bearing in mind that in the Western world, democracy was granted through the correct allocation of resources. The search for happiness and good quality of life are old concepts born in the Mediterranean area over the centuries, starting with Hesiod and Homer, and sleep and dreams were being investigated centuries before Freud was born.
Under-enrolment of women to randomized clinical trials, including chronic hepatitis C, has long been recognized. The aim of this study was to identify factors predictive of sustained virological ...response (SVR) to PEG IFN/Ribavirin antiviral therapy in relation to gender and reproductive status of female patients involved. Seven hundred and forty-six treatment-naive patients (431 men, 315 women) treated with Peg-IFN alpha -2a (180 mu g/week) or Peg-IFN alpha -2b (1.5 mu g/kg/week) plus ribavirin (800-1400 mg/day) for 24 or 48weeks were studied between 2006 and 2010. Differences in SVR rate, overall and by gender were assessed after adjustment and propensity score matching. SVR was obtained in 44.2% of Peg-IFN alpha -2a-treated patients and in 51.2% of Peg-IFN alpha -2b-treated patients (intention-to-treat; P=0.139). Age, fibrosis stage and genotype 2 and 3 were independently associated with SVR by multivariate analysis. Analysing by gender, the difference in SVR between PEG-IFN alpha types was not significant in men but highly significant in women (Peg-IFN alpha -2a:39.1%vs Peg-IFN alpha -2b:54.4%, P=0.007). This was attributable to a higher SVR rate with Peg-IFN alpha -2b in the difficult postmenopausal population (26.9% Peg-IFN alpha -2a vs 46.0% Peg-IFN alpha -2b, P=0.040). In women, absence of menopause, genotype 2 hepatitis C virus infection and use of Peg-IFN alpha -2b were independently associated with SVR. In conclusion, predictive factors for SVR are different in men and women. Factors differing between genders are menopause, severe steatosis and peg-interferon used. The higher SVR rate with Peg-IFN alpha -2b in menopausal women is likely attributable to more favourable pharmacokinetics that allows Peg-IFN alpha -2b to reach visceral fat and oppose the increased cytokine production and enhanced inflammatory status in menopause.
Alterations of the p53 gene and/or its abnormal protein accumulation have been observed in gastric cancer and preneoplastic lesions. Our aim was to assess possible associations between different H. ...pylori strains and p53 abnormalities in patients with dyspepsia and with gastric cancer.
Seventy-five dyspeptic patients and 40 patients with gastric adenocarcinoma entered the study. H. pylori status was determined by the rapid urease test, histology, and polymerase chain reaction (PCR) analysis. Overexpression of the p53 protein was evaluated by immunohistochemistry. Detection of p53 mutations was done by direct DNA sequencing.
Fifty-four of the 75 (72.0%) dyspeptic patients and 27 of the 40 (67.5%) gastric cancer patients showed H. pylori infection. Cytotoxin-associated gene ( cagA)-positive strains were found in 31 of the 54 (58%) dyspeptic patients and in 25 of the 27 (92.6%) neoplastic patients. As regards vacA, s2 strains showed the highest prevalence among dyspeptic patients (24 of 54 patients; 44.4%), whereas s1 strains were more expressed among cancer patients (23 of 27; 85.2%). Among the dyspeptic patients, 1 patient with duodenal ulcer showed p53 overexpression. Three mutations were identified by DNA sequencing: one in a patient with normal endoscopic findings and two in patients suffering from gastritis. Among the neoplastic patients, 16 subjects (40%) showed p53 overexpression (9 had diffuse-type and 7 intestinal-type cancer). Four mutations (10%) occurred in patients with intestinal-type gastric cancer. No association between p53 abnormalities (overexpression/mutation) and H. pylori infection was found in either group of patients.
These results lead us to hypothesize that H. pylori infection does not affect the p53 pattern in gastric mucosa. Moreover, mutations of the p53 gene do not seem to be a predominant event in gastric carcinogenesis, at least in our populations.
Farnesyl diphosphate synthase (FPPs) produces FPP which is considered a branch-point intermediate in the synthesis of sterols and isoprenylated cellular metabolites. In this study we investigated ...whether detectable FPPs activity was present in human colorectal cancer (CRC), also evaluating in vitro the role of this enzyme in the growth and apoptosis of CRC cells by using Pamidronate (PAM), a FPPs activity inhibitor.
The activity level of FPPs was determined in CRC and the normal surrounding mucosa of 50 patients by radiochemical assay. The FPPs mRNA expression was investigated in 15 of 50 patients by quantitative reverse transcriptase polymerase chain reaction (RT-PCR). K-ras mutation was evaluated using PCR and restriction enzyme analysis. Cell growth and apoptosis, after PAM treatment, in human CRC cell line DLD-1 were measured by MTT test and DNA fragmentation, respectively.
FPPs activity was detectable in human CRC. FPPs activity and its mRNA were significantly more abundant in cancer samples than in normal mucosa. In vitro PAM resulted in a significant reduction of cell growth and also gave rise to a marked proapoptotic effect.
This study provides the first evidence of the presence of FPPs activity in human CRC. Moreover, FPPs enzyme was found to play a significant role in colon cancer proliferation.
The electroretinogram (ERG) elicited by alternating gratings at constant mean luminance (pattern ERG) is a focal response reflecting the activity of the directly stimulated retinal area. In addition, ...pattern ERG is related, unlike the flash ERG, to ganglion cell activity. Therefore, this technique may be used to evaluate the integrity of inner retinal layers in the macular region. In this study, the steady-state pattern ERG, in response to alternating gratings (1.7 cycles/deg spatial frequency; 9 degrees field size) temporally modulated at 8 Hz, was recorded in 42 type I (insulin-dependent) diabetic patients with zero to four microaneurysms on fluorescein angiography and a duration of disease less than 11 yr. No patient had concomitant ocular or systemic complications. Mean pattern-ERG amplitude was significantly reduced in patients compared with age-matched control subjects (analysis of variance, F = 25.6, P less than 0.0001). Significant differences were observed between control and diabetic subjects without retinopathy (Scheffé F test, P less than 0.0001), between control and retinopathic subjects (Scheffé F test, P less than 0.0001), and between diabetic patients without retinopathy and those with early retinopathy (Scheffé F test, P less than 0.02). Pattern-ERG amplitude was inversely correlated with duration of diabetes (r = 0.22, P less than 0.05). Our results suggest a macular dysfunction in early diabetes resulting from metabolic and/or vascular injuries in the neurosensory retina.
This paper deals with nondestructive testing of high strength concrete. An experimental program was carried out, involving both destructive and nondestructive methods applied to different concrete ...mixtures, with cube strength varying from 30 up to 150 MPa. Relationships were derived for pulse velocity, rebound hammer, pull-out, probe penetration, microcoring, and combined methods. The results show good behavior for some methods, like pulse velocity, rebound hammer, and combined SonReb methods. By keeping the analytical form of the relationship usually adopted for normal-strength concrete unchanged, only the constants have been changed for these methods. Some problems arose with the pull-out and probe penetration tests, for which the available commercial testing systems are not adequate at very high strength levels. The relationships for the various methods were compared in terms of dimensionless sensitivity, for different strength levels. The results showed decreasing sensitivity, with increasing strength.
The production of 6-kcto prosta-landin F
lα
(6-keto-PGF
1α
), stable metabolyte of prostacyclin, by cultured human endothelial cells in contact with carbon- and collagen-coated polyethylene ...terephthalate (PC), was assessed by enzyme immunoassay. As control
material, tissue culture-treated polystyrene was used. The cultures were put in contact with the materials for 48 h and then were stimulated with 0.1 mM arachidonic acid for 3 h. The stimulation induced a highly signilicant increase of 6-keto-PGF
1α
in the cultures in contact
with the control material. PC induced only insignificant variations in stimulated cultures compared to unstimulated ones. In conclusion, PC determined a decrease in the endothelial cell response to stimulation with arachidonic acid.
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