Trunk muscular strength in pre-pubertal children with and without back pain

OBJECTIVE: While in adulthood there is no proven relationship between back pain and trunk muscle strength, in pre-pubertal subjects this topic has been poorly studied. The aim of the study was to evaluate isometric and isokinetic trunk muscle strength in children with or without previous back pain. METHODS: The recent occurrence of back pain (last 6 months) among 144 children (77 males, 67 females, age 11.9 +/- 0.3 years) was assessed using a questionnaire. Extensor and flexor trunk muscle strength was measured through isometric and isokinetic (60, 90, 120 degrees/s) tests. Peak torque (PT), PT angle, PT flexor/PT extensor ratio and intra-session coefficient of variation (COV) were determined. RESULTS: Flexor and extensor muscle PT, but not PT angle, were significantly higher in males than in females, irrespective of back pain occurrence. PT flexor/PT extensor ratio at 90 degrees angular velocities increased significantly only in males with back pain, compared with males without back pain. The COV trend was similar for flexor and extensor muscles. CONCLUSIONS: Isometric and isokinetic trunk muscle strength probably play a minor role in back pain occurrence in children. The isokinetic testing velocity may be important in determining trunk strength differences between children with and without back pain.     

Synthesis and biological evaluation of analogues of 7-chloro-4,5-dihydro-4- oxo-8-(1,2,4-triazol-4-yl)-1,2,4-triazolo[1,5-a]quinoxaline-2-carboxylic acid (TQX-173) as novel selective AMPA receptor antagonists

In recent papers (Catarzi, D.; et al. J. Med. Chem. 2000, 43, 3824-3826; 2001, 44, 3157-3165) we reported chemical and biological studies on 4,5-dihydro-4-oxo-1,2,4-triazolo[1,5-a]quinoxaline-2-carboxylates (TQXs) bearing different nitrogen-containing heterocycles at position-8. In particular, from these studies it emerged that both the 7-chloro-4,5-dihydro-4-oxo-8-(1,2,4-triazol-4-yl)-1,2,4-triazolo[1,5-a] quinoxaline-2-carboxylic acid TQX-173 (compound B) and its corresponding ethyl ester (compound A) were the most active and selective compounds of this series. In pursuing our investigation on the structure-activity relationships of these TQX derivatives, different electron-withdrawing groups (CF(3), NO(2)) were introduced at position 7 on the TQX ring system, replacing the 7-chloro substituent of B and of other selected 8-heteroaryltriazoloquinoxaline-2-carboxylates previously described. All the newly synthesized compounds were biologically evaluated for their binding at the Gly/NMDA, AMPA, and KA high-affinity receptors. Gly/NMDA binding assays were performed to assess the selectivity of the reported compounds toward the AMPA receptor. Compounds endowed with micromolar binding affinity for the KA high-affinity binding site were also evaluated for their binding at the KA low-affinity receptor. Some selected compounds were also tested for their functional antagonist activity at the AMPA and NMDA receptor-ion channel complex. The results obtained in this study have pointed out that 4,5-dihydro-7-nitro-4-oxo-8-(3-carboxypyrrol-1-yl)-1,2,4-triazolo[1,5-a]quinoxaline-2-carboxylic acid (9b) and its corresponding ethyl ester (9a) are the most potent and selective AMPA receptor antagonists reported to date among the TQX series.     

1,2,4-triazolo[4,3-a]quinoxalin-1-one moiety as an attractive scaffold to develop new potent and selective human A3 adenosine receptor antagonists: synthesis, pharmacological, and ligand-receptor modeling studies

In the past few years much effort in our laboratory has been directed toward the study of adenosine receptor antagonists, and recently we focused our attention on 2-aryl-1,2,4-triazolo[4,3-a]quinoxaline-1,4-diones and 2-aryl-1,2,4-triazolo[4,3-a]quinoxalin-4-amino-1-ones, some of which were potent and/or selective A(3) receptor antagonists. In the present paper, a new series of triazoloquinoxaline derivatives is described. Most of the new compounds, biologically evaluated in radioligand binding assays at bovine (b) A(1) and A(2A) and at human (h) A(1) and A(3) adenosine receptors, showed high hA(3) adenosine receptor affinity and selectivity. In particular, 2-(4-nitrophenyl)-1,2,4,5-tetrahydro-1,2,4-triazolo[4,3-a]quinoxaline-1,4-dione (1), also tested at the hA(2A) ARs, shows the best binding profile with a high hA(3) affinity (K(i) = 0.60 nM) and strong selectivity vs hA(1) and vs hA(2A) receptors (both selectivity ratios greater than 16 600). To interpret our experimental results, we decided to theoretically depict the putative transmembrane binding motif of our triazoloquinoxaline analogues on hA(3) receptor. Structure-activity relationships have been explained analyzing the three-dimensional structure of the antagonist-receptor models obtained by molecular docking simulation.     

Comparison of long-term effect of coronary artery bypass grafting in patients with ischemic cardiomyopathy with viable versus nonviable left ventricular myocardium

In this study, 63% of patients with a substantial amount of viable myocardium showed an increased left ventricular ejection fraction (LVEF) 12 +/- 3 months after coronary artery bypass grafting. In 93% of these patients, increased LVEF persisted at 4.5 +/- 1 years of follow-up. Conversely, in nonviable patients, LVEF did not increase at 12 +/- 3 months or at follow-up of 4.5 +/- 1 years.     

Time-course variations of oxyradical metabolism, DNA integrity and lysosomal stability in mussels, Mytilus galloprovincialis, during a field translocation experiment

Harbours can be considered as model environments for developing and validating field monitoring procedures and to investigate mechanistic relationships between different biological responses. In this study, several biomarkers were investigated in marine mussels caged for 4 weeks into an industrialised harbour of north-west Italy. Organisms were collected at different time intervals to better characterise the sensitivity, temporal variations and interactions of analysed responses. Besides single antioxidants (catalase, glutathione S-transferases, glutathione reductase, total glutathione), the total oxyradical scavenging capacity (TOSC) assay was used to analyse the capability of the whole antioxidant system to neutralise specific forms of radicals: these data were further integrated by measurement of DNA integrity, oxidised bases and the impairment of lysosomal membrane stability in haemocytes. Results showed a biphasic trend for single antioxidants and TOSC, with no variation or increase during the first 2 weeks of exposure to the polluted site followed by a progressive decrease up to a severe depletion in the final part of the experiment. These findings suggest an initial counteractive response of mussels toward the enhanced prooxidant challenge, while antioxidants appeared overwhelmed at longer exposure periods. The hypothesis of reactive oxygen species (ROS) mediated toxicity is supported by the appearance of cell damages (DNA integrity and lysosome membrane stability), which exhibited a progressive enhancement during the course of the experiment with a maximum impairment after 30 days of exposure.     

Nitric oxide produced by the enterocyte is involved in the cellular regulation of ion transport

The role of nitric oxide (NO) in the intestinal basal ion transport and under conditions of enterotoxin-induced ion secretion is controversial. Namely it is not clear whether NO enhances or counteracts intestinal ion secretion and whether the effects on transport result from a direct interaction with the enterocyte. The cell origin of NO is also unclear. We have tested the hypothesis that NO produced by the enterocyte directly regulates ion transport processes either in basal condition or in response to cholera toxin-induced secretion. Electrical variables reflecting transepithelial ion transport were measured in Caco-2 cell monolayers mounted in Ussing chambers exposed to the NO synthase inhibitor Nomega-nitro-l-arginine methyl ester, in the presence or absence of cholera toxin. cAMP concentrations were also measured. NO release was determined by nitrite-nitrate concentration. NO synthase activities were assayed by Western blot analysis. Nomega-nitro-l-arginine methyl ester had a secretory effect, as judged by increased basal short-circuit current and cAMP concentration. It also increased cholera toxin-induced electrical response and cAMP production. Either cholera toxin or the cAMP analog 8-bromo-cAMP induced a rapidly progressive and Ca2+-dependent increase in NO concentration, suggesting a homeostatic up-regulation of the constitutive form of NO synthase. Western blot analysis showed an increase in constitutive NO synthase enzyme isoform. These results indicate that the enterocyte regulates its own ion transport processes, either in basal condition or in the presence of active secretion, through the activation of a constitutive NO synthase-NO pathway, functioning as a braking force of cAMP-induced ion secretion.     

EPIC-Italy cohorts and multipurpose national surveys. A comparison of some socio-demographic and life-style characteristics

BACKGROUND: EPIC-Italy cohort study recruited subjects who voluntarily accepted to participate in the project. From the self-selected bases of the population sample, some bias could derive in the data interpretation when risk estimation for cancer disease related to life-style factors is the principal concern. Knowledge of the bias related to self-selected sampling is important for better directing the interpretation of the EPIC-Italy study results. METHODS: We investigated the characteristics of volunteer subjects recruited in the EPIC-Italy cohorts and compared them with those of the randomly selected subjects recruited in the Multipurpose ISTAT Surveys realized in the same period (1993-1998) in which the EPIC-cohorts were recruited. RESULTS: We found some differences, and in particular a different attitude towards cigarettes smoking and wine consumption, between the EPIC cohort and the Multipurpose ISTAT Surveys, as well as among geographical areas within the EPIC cohort. CONCLUSIONS: The uneven distribution of some characteristics suggests that the self-selected subjects were characterized by an overall lower consumption of wine and cigarette smoking even when the educational level was considered. This could suggest a generally more healthy life-style among subjects recruited on a volountary bases.     

In situ detection of telomeres by fluorescence in situ hybridization and telomerase activity in glioblastoma multiforme: correlation with p53 status, EGFR, c-myc, MIB1, and Topoisomerase IIalpha protein expression

Aberrations of genes/proteins regulating cell cycle and growth, increased proliferation and telomerase activity (TA) are documentable in glioblastoma multiforme. TA is more frequently detectable in secondary glioblastoma, which is also characterized by p53 mutation/overexpression. Discordant telomere (Te) length values have been reported in glioblastomas with and without TA. In 31 glioblastomas, in which pre-existing astrocytoma was not documented, we compared cases with and without TA for the expression of p53, EGFR, c-Myc, MIB-1 and Topoisomerase IIalpha; p53 mutations were also investigated by SSCP-PCR. Correlations were made with Te parameters [TePs: number (TeNo), length and area] as evaluated by image analysis in interphase nuclei of fluorescence in situ hybridization (FISH)-processed sections. We found no differences in the expression of the proteins evaluated and in TePs, except Te/nuclear area %, which was significantly lower in TA+ cases (p=0.02). TePs were, instead, inversely correlated with TA (p=0.0001). TA was positively correlated with MIB1 staining index in the TA+ cases (p=0.033), which also showed a positive correlation between TeNo and EGFR expression (p=0.042), and a trend towards a negative correlation between TeNo and p53 expression (p=0.05). Tumors overexpressing EGFR had a significantly shorter lifetime (p=0.0001). TeNo seems to be inversely correlated to tumor proliferation and lifetime in glioblastoma multiforme.