Serotonin and experimental pain in healthy young volunteers

OBJECTIVE: The role of serotonin in the modulation of nociceptive input has been widely studied, and a link between serum serotonin (S-5HT) and pain thresholds elicited in patients with chronic painful pathologies has been shown. In the light of contradictory concepts on pain message modulation by S-5HT, this study tries to define whether S-5HT displays a nociceptive or antinociceptive role in experimental pain evaluation in healthy volunteers. DESIGN: In 20 healthy young volunteers, 10 men and 10 women (21 +/- 2 years old), blood serotonin measurements were made, pressure pain thresholds was determined, and statistical analysis was performed. RESULTS: This study showed a significant negative correlation of total blood serotonin with experimental pain detection threshold (P < 0.05, r = 0.444), but not with pain tolerance, while sex-related correlations of serotonin and thresholds were not significant. Lower serotonin concentration (P = 0.02), higher pain threshold (P < 0.01), and higher pain tolerance (P = 0.02) in men than in women were observed. CONCLUSION: Low pain detection thresholds may be explained by a peripheral nociceptive effect of serotonin. Pain tolerance does not, however, encompass a similar pattern of serotoninergic involvement in pain control and may include other components that remain to be elucidated. These results call for further studies on a larger population.     

Study of a chitin-based gel as injectable material in periodontal surgery.

The optimal conditions of injection of a chitin gel for applications in periodontal surgery have been studied as a function of various parameters. They correspond to a time of 2 min 15s (+/- 15"). They are achieved for acetylation parameters corresponding to: a molar ratio acetic anhydride/glucosamine residue, R = 1.5, a temperature of the master solution of 12 degrees C, a mixture of hydroalcoholic solution/acetylating reactive stirred for 45s at room temperature and a chitin concentration of 3.6%. This concentration allows us to limit the syneresis. to improve the mechanical properties of the gel and to obtain a viscosity suitable for the injection. Doping of the gel by means of chitosan powder insoluble under these conditions allows us to consider an improvement of the biological activity of the gel.     

Expression analysis of recombinant lysyl oxidase (LOX) in myofibroblastlike cells

Lysyl oxidase (LOX), originally known as the enzyme required for initiation of covalent cross-linking in collagens and elastin, is now known to be a member of a family of genetically related proteins. LOX, or a related protein, has also been localized intracellularly, both in association with the cytoskeleton and in the cell nucleus. To determine the structural requirements for secretion, maturation, and nuclear location of LOX in a cellular context, we have devised an homologous cell model for expression of the recombinant protein. Murine recombinant LOX was expressed in 3T6-5 myofibroblast-like cells as a 51-kD precursor, which was observed in the cytoplasm but not in the nucleus. To investigate whether potential alternative translation initiation sites were involved in specifying a nuclear form of LOX, constructs mutated or deleted for ATG(+1) were used, but alternative initiation at CTG(-315) or ATG(+418) did not lead to the expression of intranuclear forms. Residues 23 to 157 of the proregion were essential for export of the precursor, while mutation of the putative site for maturation by procollagen C-proteinase abolished processing to the mature form of the enzyme. Cross-linking of collagen, as measured by pyridinoline analysis, increased twofold with the recombinant cells, compared to non-transfected controls. This shows the specific contribution of LOX, as opposed to other genetic forms of the enzyme, to cross-linking in a cellular context.     

Model-based interpretation of cardiac beats by evolutionary algorithms: signal and model interaction

This paper presents a new approach for cardiac beat interpretation, based on a direct integration between a model and observed ECG signals. Physiological knowledge is represented by means of a semi-quantitative model of the cardiac electrical activity. The interpretation of cardiac beats is formalized as an optimization problem, by minimizing an error function defined between the model's output and the observations. Evolutionary algorithms (EAs) are used as the search technique in order to obtain the set of model parameters reproducing at best the observed phenomena. Examples of model adaptation to three different kinds of cardiac beats are presented. Preliminary results show the potentiality of this approach to reproduce and explain complex pathological disorders and to better localize their origin.     

Initiation of the breakage-fusion-bridge mechanism through common fragile site activation in human breast cancer cells: the model of PIP gene duplication from a break at FRA7I

Gene amplification plays a critical role in tumor progression. Hence, understanding the factors triggering this process in human cancers is an important concern. Unfortunately, the structures formed at early stages are usually unavailable for study, hampering the identification of the initiating events in tumors. Here, we show that the region containing the PIP gene, which is overexpressed in 80% of primary and metastatic breast cancers, is duplicated in the breast carcinoma cell line T47D. The two copies are organized as a large palindrome, lying 'in loco' on one chromosome 7. Such features constitute the landmark of the breakage-fusion-bridge (BFB) cycle mechanism. In hamster cells selected in vitro to resist cytotoxic drugs, common fragile site (CFS) activation has been shown to trigger this mechanism. Here, we characterize FRA7I at the molecular level and demonstrate that it lies 2 Mb telomeric to the PIP gene and sets the distal end of the repeated sequence. Moreover, our results suggest that the BFB process was frozen within the first cycle by healing of the broken chromosome. T47D cells thus offer a unique opportunity to observe the earliest products of the BFB cycle mechanism. Our findings constitute the first evidence that this amplification mechanism can be initiated in vivo by fragile site activation.     

Long-term clinical and biologic effects of the lipidosterolic extract of Serenoa repens in patients with symptomatic benign prostatic hyperplasia

Permixon, the lipidosterolic extract of Serenoa repens, is widely used for the treatment of symptoms associated with benign prostatic hyperplasia (BPH). This open study assessed the efficacy and tolerability of Permixon 160 mg twice daily administered for 2 years. One hundred fifty-five men with clinically diagnosed BPH and complaints of prostatic symptoms were enrolled in the study. At 6, 12, 18, and 24 months, the International Prostate Symptom Score (I-PSS), quality of life, and sexual function score were recorded, and urodynamics and biologic values were measured. Adverse events were recorded every 3 months. I-PSS and quality of life improved significantly from baseline at each evaluation time point. At the end of the study and at each evaluation, maximum urinary flow also improved significantly. Prostate size decreased. Sexual function remained stable during the first year of treatment and significantly improved (P = .001) during the second year. Prostate-specific antigen was not affected, and no changes in plasma hormone levels were observed. Nine patients reported 10 adverse events, none related to treatment. Improvements in efficacy parameters began at 6 months and were maintained up to 24 months. These data demonstrate the long-term efficacy and tolerability of Permixon and support its use as a first-line medical therapy for uncomplicated symptomatic BPH.     

CT quantification of pulmonary emphysema: assessment of lung structure and function

Accurate diagnosis and quantification of pulmonary emphysema in vivo is important to understand the natural history of the disease, to assess the extent of the disease, and to evaluate and follow-up therapeutic interventions. Because pulmonary emphysema is defined by pathology, new diagnostic methods for quantification should be validated by reference to pathological and histological standards. Recent studies have addressed the capability of computed tomography (CT) to accurately quantify pulmonary emphysema. These studies that have been overviewed in this article have been based on CT scans obtained after deep inspiration or expiration, on subjective visual grading, and on objective measurements of attenuation values by using dedicated software providing numerical data on two-dimensional and on three-dimensional approaches, and compared CT data with pulmonary function tests. More recently, fractal and textural analyses were applied to CT scans to assess the presence, extent, and types of emphysema. Quantitative CT has already been used in patient selection for surgical treatment of pulmonary emphysema and in pharmacotherapeutical trials. However, despite numerous and extensive studies already available, this technique has not yet been standardized, and important questions about how to best use CT for the quantification of pulmonary emphysema remain to be addressed.