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Selected AbstractsA new approach for modelling simultaneous storage and growth processes for activated sludge systems under aerobic conditionsBIOTECHNOLOGY & BIOENGINEERING, Issue 5 2005Gürkan Sin Abstract By critically evaluating previous models, a new mechanistic model is developed to describe simultaneous storage and growth processes occurring in activated sludge systems under aerobic conditions. Identifiability was considered an important criterion during the model development since it among others helps to increase the realiability and applicability of models to full-scale WWTPs. A second order model was proposed for description of the degradation of the storage products under famine conditions. The model is successfully calibrated by only using OUR data obtained from batch experiments. Calibrations were performed with biomass from full-scale WWTPs in Belgium and Spain. Predictions of the calibrated model were successfully confirmed using off-line PHB measurements, supporting the validity of the model. An iterative experimental design procedure was successfully applied and found to remarkably improve the parameter estimation accuracy for the growth on storage parameters K1 and K2, which used to have large confidence intervals when using standard experiments. The estimated biomass growth yield on substrate (0.58 mgCOD/mgCOD) is quite close to the theoretically expected range for heterotrophic growth. This became possible by properly accounting for the storage process. Moreover, the maximum growth rate was predicted in the range 0.7,1.3 per day. This range, albeit quite lower than the values reported for the growth-based ASM models, is believed to be more realistic. Finally, the new model is expected to better and more mechanistically describe simultaneous storage and growth activities of activated sludge systems and as such could contribute to improved design, operation and control of those systems. © 2005 Wiley Periodicals, inc. [source] Viability of Preadipocytes In Vitro: The Influence of Local Anesthetics and pHDERMATOLOGIC SURGERY, Issue 8 2009MAIKE KECK MD BACKGROUND Autogenous fat transfer with lipoinjection for soft tissue augmentation is a commonly used surgical technique. Abundant donor tissue availability and relative ease of harvesting have made autologous fat an attractive soft tissue filler. The overall reliability of this technique is often disputed, and different authors describe different results after autologous fat transplantation despite using similar techniques. In this study, we examined the influence of different local anesthetics commonly used in fat harvest and the pH of the anesthetic solution on the viability of harvested preadipocytes. METHODS AND MATERIALS Preadipocytes were incubated with 1% lidocaine, 1% articaine plus epinephrine 1:200,000, 0.75% ropivacaine, and 1% prilocaine or our standardized tumescent solution (1 L of 0.9% sodium chloride solution plus 25 mL of 1% articaine plus epinephrine 1:200,000 plus 25 mL of bicarbonate) for 30 minutes. Additionally, we incubated cells with the local anesthetics as described above but diluted 1:2 with phosphate buffered saline (pH 7.4). Viability was measured using trypan blue dying as well as propidium iodine staining and fluorescence-activated cell sorting analysis. RESULTS There are significant differences in the viability of preadipocytes under the influence of various local anesthetics. DISCUSSION Our data could partially explain the varying results after autogenous fat transfer. [source] Pain Sensation during Intradermal Injections of Three Different Botulinum Toxin Preparations in Different Doses and DilutionsDERMATOLOGIC SURGERY, Issue 7 2006GOTTFRIED KRANZ MD BACKGROUND Pain sensation associated with injections of botulinum neurotoxin (BoNT) is commonly reported. To date differences in pain sensation between the commercially available products containing BoNT have not been quantified. OBJECTIVES The pain sensations during injection of Dysport, Botox, Neurobloc, and pure saline (control) were compared. In addition, the nociceptive effect of different volumes used for the dilution of the same BoNT dose was investigated. METHODS In a prospective, double-blind, controlled trial, 10 healthy subjects were injected intradermally with Dysport (12 U), Botox (3 and 4 U), Neurobloc (150 and 300 U) reconstituted in 0.9% saline, and pure saline. Pain sensation was quantified during injections. RESULTS Neurobloc injections caused significantly more injection pain than Botox, Dysport, and saline. No significant differences between Dysport, Botox, and saline were found, although there was a trend toward less pain with pure saline injections. Higher pain levels with higher volumes could not be demonstrated significantly. CONCLUSION Our data demonstrate that BoNT type B injections are associated with substantial pain. There is a considerable difference between the commercially available BoNT type B compared to the two BoNT type A preparations. Therefore, considering mitigation of injection pain seems necessary when using BoNT type B. [source] T-cell interleukin-6 receptor binding in interferon-,-1b-treated multiple sclerosis patientsEUROPEAN JOURNAL OF NEUROLOGY, Issue 6 2000P. Bongioanni Multiple sclerosis (MS) is a T-cell-mediated autoimmune demyelinating disease of the central nervous system, associated with an altered cytokine network. We previously assayed peripheral blood T-lymphocyte binding for two prototypic cytokines, tumour necrosis factor-, (TNF-,) and interleukin-6 (IL-6), and found that T cells from MS patients had significantly more TNF-, and IL-6 receptors than those from healthy controls. In the present work, paralleling a previous one on T-cell TNF-, binding, we studied the effect of interferon (IFN)-,-1b treatment on T-lymphocyte IL-6 binding in patients with relapsing,remitting MS. T cells from MS patients had significantly (P < 0.001) higher amounts of IL-6 receptors than those from controls [292 ± 6 vs. 228 ± 8 (mean ± SEM) receptors per cell, respectively], whereas the ligand-receptor affinity values were similar in the two groups [26.2 ± 0.7 and 25.7 ± 0.4 (mean ± SEM) pmoles/l, respectively]. After a 3-month IFN-,-1b treatment, they showed a significant decrease in IL-6 binding [266 ± 7 (mean ± SEM) receptors per cell]. After 6 and 9 months, T-cell IL-6 Bmax values were even lower [258 ± 8 and 251 ± 8 (mean ± SEM) receptors per cell]. Since an increased IL-6 binding might be linked to a lymphocyte activation, our data give further support for an enhanced immune response in patients with MS. Our data seem to demonstrate that the major effects of IFN-,-1b treatment result in a decrease of T-cell activation. [source] Haplotype Analysis Confirms the Association Between the HCRTR2 Gene and Cluster HeadacheHEADACHE, Issue 7 2008Innocenzo Rainero MD Background., Several studies suggested that genetic factors play a role in cluster headache (CH) susceptibility. We found a significant association between the 1246 G>A polymorphism of the hypocretin receptor-2 (HCRTR2) gene and the disease. This association was confirmed in a large study from Germany but was not replicated in a dataset of CH patients from Northern Europe. Objective., The purpose of this study was to further evaluate the association between CH and the HCRTR2 gene using new polymorphisms, estimating the frequency of different gene haplotypes, searching for gene mutations, and evaluating the effects of the examined polymorphisms on hypocretin binding sites. Methods., We genotyped 109 CH patients and 211 healthy controls for 5 new polymorphisms of the HCRTR2 gene and we inferred different gene haplotypes. Complete HCRTR2 sequencing was undertaken for 11 independent CH patients, 5 of whom had a positive family history. The effects of the 1246 G>A polymorphism on the hypocretin binding sites were evaluated using different computer-assisted analyses. Results., Three new polymorphisms of the HCRTR2 gene resulted significantly associated with CH. The GTAAGG haplotype resulted more frequent in cases than in controls (OR: 3.68; 95% CI: 1.85-7.67). No point mutation of the HCRTR2 gene was found. Binding analyses showed that the 1246 G>A polymorphism (substitution of valine at position 308 by isoleucine) has no effect on the hypocretin binding sites but could influence the dimerization process of the receptor. Conclusion., Our data confirm previous studies suggesting that the HCRTR2 gene or a linked locus significantly modulates the risk for CH. In addition, we suggest that the V308I substitution of the HCRTR2 may interfere with the dimerization process of the receptor, thereby influencing its functional activity. [source] Subclinical Left Ventricular Dysfunction in Migraine AttacksHEADACHE, Issue 1 2006Manuel Vidalón MD Objective.,The aim of the present study was to evaluate cardiac performance of patients with migraine attacks during the overload produced by phenylephrine infusion. Background.,It is known that circulatory changes occur during migraine. However, the relationship between this finding and transient cardiac dysfunction is still unknown. Methods.,By means of two-dimensional direct M-mode echocardiography, we measured fractional shortening, ejection fraction, and mean velocity of circumferential fibers shortening in 18 patients with migraine and in 10 normal subjects as a control group. These measures were performed in two different periods: during attack-free intervals and during attacks. Pain intensity of typical migraine attack was evaluated on a 0 to 10 scale. Results.,Cardiac size and function were normal at rest in both groups. However, during migraine attacks, phenylephrine infusion provoked significant decrease in fractional shortening, EF, and mean velocity of circumferential fibers shortening, followed by concomitant increase of headache severity. On the other hand, during the attack-free interval and in the control group phenylephrine infusion did not show significant changes in cardiac function parameters. Conclusions.,Our data suggest that left ventricular dysfunction during the phenylephrine test could participate in the complex pathophysiological mechanism of migraine attacks. [source] Methyl palmitate inhibits lipopolysaccharide-stimulated phagocytic activity of rat peritoneal macrophagesJOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY, Issue 6 2006Swapna Sarkar Abstract Macrophages, in general, are critical effectors of body's immune system. Chemical inhibition of phagocytic activity of such macrophages as Kupffer cells has been extensively studied. We have earlier shown that methyl palmitate (MP) inhibits the activation of Kupffer cells. To evaluate the potential of MP to inhibit the activation of other macrophages, we treated rat peritoneal macrophages with varying concentrations of MP. Its treatment led to a dose-dependent inhibition of phagocytic activity, which was found to be 34%, 47%, and 66% at 0.25, 0.50, and 1.0 mM MP, respectively, as measured by latex bead uptake. When MP-treated peritoneal macrophages were stimulated with lipopolysaccharide (LPS), the nitric oxide (.NO) release was inhibited at 6 h, while cyclooxygenase-2 expression decreased after 24 h. The treatment with MP increased the release of interleukin (IL)-10 in the LPS-treated cells at 6 h, while IL-6 and tumor necrosis factor-, were significantly increased both at 6 and 24 h. Our data suggest that MP inhibits phagocytic activity and . NO production similar to that observed in isolated Kupffer cells. Therefore, inhibition of phagocytosis by MP may be a general phenomenon, and it could be used as an inhibitor of macrophage function. © 2006 Wiley Periodicals, Inc. J Biochem Mol Toxicol 20:302,308, 2006; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20150 [source] Abnormalities of whole body protein turnover, muscle metabolism and levels of metabolic hormones in patients with chronic heart failureJOURNAL OF INTERNAL MEDICINE, Issue 1 2006H. NØRRELUND Abstract. Objective., It is well known that chronic heart failure (CHF) is associated with insulin resistance and cachexia, but little is known about the underlying substrate metabolism. The present study was undertaken to identify disturbances of basal glucose, lipid and protein metabolism. Design., We studied eight nondiabetic patients with CHF (ejection fraction 30 ± 4%) and eight healthy controls. Protein metabolism (whole body and regional muscle fluxes) and total glucose turnover were isotopically assayed. Substrate oxidation were obtained by indirect calorimetry. The metabolic response to exercise was studied by bicycle ergometry exercise. Results., Our data confirm that CHF patients have a decreased lean body mass. CHF patients are characterised by (i) decreased glucose oxidation [glucose oxidation (mg kg,1 min,1): 1.25 ± 0.09 (patients) vs. 1.55 ± 0.09 (controls), P < 0.01] and muscle glucose uptake [a , v diffglucose (,mol L,1): ,10 ± 25 (patients) vs. 70 ± 22 (controls), P < 0.01], (ii) elevated levels of free fatty acids (FFA) [FFA (mmol L,1): 0.72 ± 0.05 (patients) vs. 0.48 ± 0.03 (controls), P < 0.01] and 3-hydroxybutyrate and signs of elevated fat oxidation and muscle fat utilization [a , v diffFFA (mmol L,1): 0.12 ± 0.02 (patients) vs. 0.05 ± 0.01 (controls), P < 0.05] and (iii) elevated protein turnover and protein breakdown [phenylalanine flux (,mol kg,1 h,1): 36.4 ± 1.5 (patients) vs. 29.6 ± 1.3 (controls), P < 0.01]. Patients had high circulating levels of noradrenaline, glucagon, and adiponectin, and low levels of ghrelin. We failed to observe any differences in metabolic responses between controls and patients during short-term exercise. Conclusions., In the basal fasting state patients with CHF are characterized by several metabolic abnormalities which may contribute to CHF pathophysiology and may provide a basis for targeted intervention. [source] Circulating adiponectin reflects severity of liver disease but not insulin sensitivity in liver cirrhosisJOURNAL OF INTERNAL MEDICINE, Issue 3 2005S. KASER Abstract. Background., The adipocytokine adiponectin has been proposed to play important roles in the regulation of energy homeostasis, insulin sensitivity and shows anti-inflammatory properties. Aim., In this study we investigated the role of circulating adiponectin in different chronic liver diseases, its regulation by systemic anti-tumour necrosis factor (TNF)- , treatment and its hepatic metabolism. Patients and methods., Plasma adiponectin levels were determined in 87 patients with liver cirrhosis of different aetiologies, seven patients with alcoholic steatohepatitis undergoing systemic anti-TNF- , treatment, in 11 patients with liver cirrhosis receiving transjugular intrahepatic portosystemic shunt implantation and in 21 healthy controls. Results., Adiponectin levels were significantly higher in all subjects with liver cirrhosis of different aetiologies when compared with healthy controls and increased dependent on Child-Pugh classification. In subjects with alcoholic steatohepatitis, systemic anti-TNF- , treatment caused a significant decrease in circulating adiponectin. Adiponectin concentrations were similar in portal, hepatic and peripheral veins. No correlation between adiponectin levels and insulin resistance was found in any patient group. Conclusions., Our data suggest that circulating adiponectin is increased in liver cirrhosis independent of the aetiology of liver disease. We suggest that high adiponectin levels in chronic liver disease might reflect one of the body's anti-inflammatory mechanisms in chronic liver diseases. [source] The Impairment of Sexual Function Is Less Distressing for Menopausal than for Premenopausal WomenTHE JOURNAL OF SEXUAL MEDICINE, Issue 3 2010Marta Berra MD ABSTRACT Introduction., Menopause requires psychological and physical adjustments because of the occurring significant hormonal changes. Sexuality is one of the aspects that undergoes the most profound modifications. Preliminary data suggest that sometimes women do not regard sexual changes as problematic and often readjust their life and relationship according to their new physical status. Aim., The aim of our study was to evaluate sexual function and the way women feel by comparing healthy postmenopausal and premenopausal women. Methods., One hundred menopausal (M) and 100 premenopausal (pM) healthy women were asked to complete anonymous questionnaires to assess sexual function and stress related to sexual activity. Main Outcome Measures., Female Sexual Function Index (FSFI), Female Sexual Distress Scale (FSDS) were completed by M and pM women. Results., Medium FSFI score was 20.5 ± 9.6 and 26.4 ± 7.7 (P < 0.0005) and medium FSDS score was 12.1 ± 11.7 (95% CI 9.7,14.4) and 11.3 ± 10.2 (P = 0.917) for M and pM women, respectively. Twenty-five of the 69 M women and 20 of the 31 pM women with a pathological score in the FSFI questionnaire scored higher than 15 in the FSDS (P < 0.0005). The overall prevalence of sexual dysfunction was 20% and 25% (P = 0.5) in the M and pM women. Conclusions., Our data confirm that menopause is associated with changes in sexual function that may be compatible with sexual dysfunction. However, personal distress caused by these changes in sexual life appears to be lower among menopausal women (36.2%) as compared with premenopausal women (64.5%). These data suggest that medical treatment for sexual health in menopause must be highly personalized and carefully prescribed. Berra M, De Musso F, Matteucci C, Martelli V, Perrone AM, Pelusi C, Pelusi G, and Meriggiola MC. The impairment of sexual function is less distressing for menopausal than for premenopausal women. J Sex Med 2010;7:1209,1215. [source] Does Circumcision Make a Difference to the Sexual Experience of Gay Men?THE JOURNAL OF SEXUAL MEDICINE, Issue 11 2008Findings from the Health in Men (HIM) Cohort ABSTRACT Introduction., The relevance of circumcision in preventing male-to-male sexual transmission of HIV is poorly understood, in particular because any potential beneficial effect could be diminished by the impact of circumcision on sexual behavior. Aim., We examined the impact of circumcision on sexual experience. Methods., Univariate and multivariate logistic regressions were performed on data from 1,426 HIV-negative homosexually active men. Main Outcome Measures., We compared the sexual behaviors and preferences of circumcised with uncircumcised men, and men who were circumcised at infancy with those who were circumcised after infancy. Results., Overall, 66% of men (N = 939) in the cohort were circumcised. After adjusting for age and ethnicity, we found no differences between circumcised and uncircumcised men in any insertive or receptive anal intercourse, difficulty using condoms, or sexual difficulties (e.g., loss of libido). Among the circumcised men, we compared those circumcised at infancy (N = 854) with those circumcised after infancy (N = 81). The majority cited phimosis (i.e., an inability to fully retract the foreskin) and parents' decision as the main reasons for circumcision after infancy. After adjusting for age and ethnicity, the men circumcised after infancy were more likely to practice any receptive anal sex (88% vs. 75%, P < 0.05) and to experience erection difficulties (52% vs. 47%, P < 0.05), but less likely to practice any insertive anal sex (79% vs. 87%, P < 0.05) and to experience premature ejaculation (15% vs. 23%, P < 0.05) than those circumcised at infancy. Conclusions., Our data suggest that overall circumcision status does not affect the HIV-negative gay men's anal sexual behaviors, experience of condom use, or likelihood of sexual difficulties. However, there is some suggestion of differences in sexual practices and preferences among circumcised gay men depending on the age at circumcision. In particular, gay men circumcised later are more likely to engage in and prefer receptive anal intercourse. Mao L, Templeton DJ, Crawford J, Imrie J, Prestage GP, Grulich AE, Donovan B, Kaldor JM, and Kippax SC. Does circumcision make a difference to the sexual experience of gay men? Findings from the health in men (HIM) cohort. J Sex Med 2008;5:2557,2561. [source] Female Sexual Dysfunction in Urogenital Prolapse Surgery: Colposacropexy vs.THE JOURNAL OF SEXUAL MEDICINE, Issue 1 2008Hysterocolposacropexy ABSTRACT Introduction., Colposacropexy (CSP), with or without hysterectomy, is a valid technique for the repair of severe urogenital prolapse. For many years, uterine prolapse has represented an indication for hysterectomy, apart from the presence or absence of uterine disease and the patient's desires. Nevertheless, sparing the uterus is essential to women not only to have normal sexual functioning but to maintain physical and anatomical integrity as well. Aim., To assess sexual function in a group of patients who underwent CSP or hysterocolposacropexy (HSP). Materials and Methods., We enrolled 37 patients who underwent surgery for urogenital prolapse (15 HSP, mean age 53 years; 22 CSP, mean age 56 years). Based on a preliminary sexual history and sexual questionnaire, all patients were sexually active before surgery. At a mean follow-up of 39 months, we reassessed the patients using the Female Sexual Function Index (FSFI). Main Outcome Measure., We considered sexual activity with a score of 30 = good, 23,29 = intermediate, and <23 = poor. Results., In patients who underwent CSP and HSP, sexual activity was good in 13% and 26%, intermediate in 33% and 21%, and poor in 54% and 53%, respectively; considering also five patients who no longer had sexual activity postoperatively. Nevertheless, the statistical analysis, performed based on the data obtained from the FSFI questionnaire, showed that there were no significant differences between the two groups of points in terms of total score,CSP 21.1 (1.2,33.5) vs. HSP 22.8 (3.6,34.5),and single domains (desire, arousal, lubrication, orgasm, satisfaction, and pain) (P = not significant). Conclusions., Our data demonstrated no substantial differences regarding sexual activity in patients in which the uterus has been spared as opposed to those in whom it has been removed. Furthermore, in a small percentage of cases, surgery actually reduced regular sexual activity. Zucchi A, Costantini E, Mearini L, Fioretti F, Bini V, and Porena M. Female sexual dysfunction in urogenital prolapse surgery: Colposacropexy vs. hysterocolposacropexy. J Sex Med 2008;5:139,145. [source] Effect of Hyperprolactinemia in Male Patients Consulting for Sexual DysfunctionTHE JOURNAL OF SEXUAL MEDICINE, Issue 5 2007Giovanni Corona MD ABSTRACT Introduction., The physiological role of prolactin (PRL) in male sexual function has not been completely clarified. Aim., The aim of this study is the assessment of clinical features and of conditions associated with hyperprolactinemia in male patients consulting for sexual dysfunction. Methods., A consecutive series of 2,146 (mean age 52.2 ± 12.8 years) male patients with sexual dysfunction was studied. Main Outcome Measures., Several hormonal and biochemical parameters were studied along with validated structured interviews (ANDROTEST and the Structured Interview on Erectile Dysfunction [SIEDY]). Mild hyperprolactinemia (MHPRL; PRL levels of 420,735 mU/L or 20,35 ng/mL) and severe hyperprolactinemia (SHPRL, PRL levels >735 mU/L, 35 ng/mL) were considered. Results., MHPRL and SHPRL were found in 69 (3.3%) and in 32 (1.5%) patients, respectively. Mean age and the prevalence of gynecomastia were similar in the two groups and in subjects with normal prolactin values. MHPRL was not confirmed in almost one-half of the patients after repetitive venous sampling. Hyperprolactinemia was associated with the current use of antidepressants, antipsychotic drugs, and benzamides. SHPRL was also associated with hypoactive sexual desire (HSD), elevated thyrotropin (TSH), and hypogonadism. The association between HSD and SHPRL was confirmed after adjustment for testosterone and TSH levels, and use of psychotropic drugs (hazard ratio [HR] = 8.60[3.85,19.23]; P < 0.0001). In a 6-month follow-up of patients with SHPRL, testosterone levels and sexual desire were significantly improved by the treatment. Conclusions., Our data indicate that SHPRL, but not MHPRL, is a relevant determinant of HSD. Gynecomastia does not help in recognizing hyperprolactinemic subjects, while the use of psychotropic medications and HSD are possible markers of disease. In the case of MHPRL, repetitive venous sampling is strongly encouraged. Corona G, Mannucci E, Fisher AD, Lotti F, Ricca V, Balercia G, Petrone L, Forti G, and Maggi M. Effect of hyperprolactinemia in male patients consulting for sexual dysfunction. J Sex Med 2007;4:1485,1493. [source] Reduced signal transduction by 5-HT4 receptors after long-term venlafaxine treatment in ratsBRITISH JOURNAL OF PHARMACOLOGY, Issue 3 2010R Vidal BACKGROUND AND PURPOSE The 5-HT4 receptor may be a target for antidepressant drugs. Here we have examined the effects of the dual antidepressant, venlafaxine, on 5-HT4 receptor-mediated signalling events. EXPERIMENTAL APPROACH The effects of 21 days treatment (p.o.) with high (40 mg·kg,1) and low (10 mg·kg,1) doses of venlafaxine, were evaluated at different levels of 5-HT4 receptor-mediated neurotransmission by using in situ hybridization, receptor autoradiography, adenylate cyclase assays and electrophysiological recordings in rat brain. The selective noradrenaline reuptake inhibitor, reboxetine (10 mg·kg,1, 21 days) was also evaluated on 5-HT4 receptor density. KEY RESULTS Treatment with a high dose (40 mg·kg,1) of venlafaxine did not alter 5-HT4 mRNA expression, but decreased the density of 5-HT4 receptors in caudate-putamen (% reduction = 26 ± 6), hippocampus (% reduction = 39 ± 7 and 39 ± 8 for CA1 and CA3 respectively) and substantia nigra (% reduction = 49 ± 5). Zacopride-stimulated adenylate cyclase activation was unaltered following low-dose treatment (10 mg·kg,1) while it was attenuated in rats treated with 40 mg·kg,1 of venlafaxine (% reduction = 51 ± 2). Furthermore, the amplitude of population spike in pyramidal cells of CA1 of hippocampus induced by zacopride was significantly attenuated in rats receiving either dose of venlafaxine. Chronic reboxetine did not modify 5-HT4 receptor density. CONCLUSIONS AND IMPLICATIONS Our data indicate a functional desensitization of 5-HT4 receptors after chronic venlafaxine, similar to that observed after treatment with the classical selective inhibitors of 5-HT reuptake. [source] Radiation-induced cutaneous carcinoma of the head and neck: is there an early role for p53 mutations?CLINICAL & EXPERIMENTAL DERMATOLOGY, Issue 6 2006A. Franchi Summary Background., Little is known about the molecular mechanisms underlying ionizing radiation-induced carcinogenesis of the skin. Aims., To investigate the possible role of p53 in radiodermatitis and in the development of radiation-induced cutaneous carcinomas. Methods., The study group comprised six patients affected by cutaneous carcinomas arising in radiodermatitis (one squamous cell carcinoma and five basal cell carcinomas), and seven patients presenting only chronic radiodermatitis. Skin specimens were evaluated for p53 immunohistochemical expression. Using laser-assisted microdissection, areas with different p53 immunoreactivity were separately submitted to DNA isolation and p53 gene analysis. Results., In the majority of cases (9/12, 75%), p53 immunoreactivity was detected in radiation-damaged epidermis. In carcinomas p53 oncoprotein was expressed by several neoplastic cells in one case (16.7%%), or by nearly all neoplastic cells in four (66.7%). SSCP band shifts were detected in 9/25 samples (36%) microdissected from irradiated epidermis and in 3/6 (50%) carcinomas. DNA sequencing demonstrated two repeatedly found mutations: a G deletion at codon 244 and an A,G transition at codon 205, as well as hallmarks of ultraviolet mutagenic action, including a C,T transition occurring at a dipyrimidine site and a CC,TT tandem double-base transition. Conclusion., Our data indicate that irradiation induces significant p53 alterations that may be relevant in the modification of epithelial maturation processes and may be responsible for the high risk for development of carcinomas in radiodermatitis. [source] | |||||||||||||||||||