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Aloisi A.M.,University of Siena | Ceccarelli I.,University of Siena | Carlucci M.,University of Siena | Suman A.,University of Siena | And 6 more authors.
Reproductive Biology and Endocrinology | Year: 2011

Background: In male patients suffering from chronic pain, opioid administration induces severe hypogonadism, leading to impaired physical and psychological conditions such as fatigue, anaemia and depression. Hormone replacement therapy is rarely considered for these hypogonadic patients, notwithstanding the various pharmacological solutions available.Methods: To treat hypogonadism and to evaluate the consequent endocrine, physical and psychological changes in male chronic pain patients treated with morphine (epidural route), we tested the administration of testosterone via a gel formulation for one year. Hormonal (total testosterone, estradiol, free testosterone, DHT, cortisol), pain (VAS and other pain questionnaires), andrological (Ageing Males' Symptoms Scale - AMS) and psychological (POMS, CES-D and SF-36) parameters were evaluated at baseline (T0) and after 3, 6 and 12 months (T3, T6, T12 respectively).Results: The daily administration of testosterone increased total and free testosterone and DHT at T3, and the levels remained high until T12. Pain rating indexes (QUID) progressively improved from T3 to T12 while the other pain parameters (VAS, Area%) remained unchanged. The AMS sexual dimension and SF-36 Mental Index displayed a significant improvement over time.Conclusions: In conclusion, our results suggest that a constant, long-term supply of testosterone can induce a general improvement of the male chronic pain patient's quality of life, an important clinical aspect of pain management. © 2011 Aloisi et al; licensee BioMed Central Ltd.


Shklover J.,Technion - Israel Institute of Technology | Weisman-Shomer P.,Technion - Israel Institute of Technology | Yafe A.,Technion - Israel Institute of Technology | Yafe A.,Pain Medicine Unit | Michael F.,Technion - Israel Institute of Technology
Nucleic Acids Research | Year: 2010

Gene promoters are enriched in guanine clusters that potentially fold into quadruplex structures. Such quadruplexes were implicated in the regulation of gene expression, plausibly by interacting with transcription factors. We showed previously that homodimers of the myogenic transcription factor MyoD bound in vitro most tightly bimolecular quadruplexes of promoter sequences of muscle-specific genes. By contrast, MyoD-E47 heterodimers formed tighter complexes with d(CANNTG) E-box motifs that govern muscle gene expression. Here, we show that DNA quadruplexes enhance in vivo MyoD and E-box-driven expression of a firefly luciferase (FL) reporter gene. HEK293 cells were transfected with FL expressing p4RTK-FL vector alone or together with MyoD expressing pEMSV-MyoD plasmid, with quadruplexes of α7 integrin or sarcomeric mitochondrial creatine kinase (sMtCK) muscle gene promoters or with a combination thereof. Whereas MyoD elevated by ̃10-fold the levels of FL mRNA and protein, the DNA quadruplexes by themselves did not affect FL expression. However, together with MyoD, quad-ruplex DNA increased by ̃35-fold the amounts of FL mRNA and protein. Without affecting its expression, DNA quadruplexes bound MyoD in the cells. Based on these results, we propose models for the regulation of muscle gene transcription by direct interaction of MyoD with promoter quadruplex structures. © The Author(s) 2010. Published by Oxford University Press.

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