Oxidative Stress in Female Athletes Using Combined Oral Contraceptives

Background Oxidative stress in female athletes is understudied. We investigated oxidative stress in sportswomen of different disciplines according to combined oral contraceptive (OC) use and lifestyle/alimentary habits. Methods Italian sportswomen (n\u2009=\u2009144; mean age 23.4\u2009\ub1\u20094.2 years; body mass index 21.2\u2009\ub1\u20092.2 kg m 122; sport activity 9.2\u2009\ub1\u20094.1 h week 121) were analyzed; 48 % were volleyball players, 12.5 % soccer players, 10.4 % track-and-field sports, and followed by other disciplines\u2019 athletes. Oxidative stress was evaluated by free oxygen radical test (FORT) assessing blood hydroperoxides and free oxygen radical defense (FORD) assay evaluating antioxidant capacity in OC users (n\u2009=\u200942) compared to non-OC users. Results Elevated oxidative stress levels ( 65310 FORT units) were found in 92.9 % of OC users and in 23.5 % of non-OC users (crude OR\u2009=\u200942, 95 % CI 12\u2013149, p\u2009<\u20090.001; adjusted OR\u2009=\u200960, 95 % CI 11\u2013322, p\u2009<\u20090.001). Continuous values of hydroperoxides were twofold higher in OC users versus non-OC users (median 484 versus 270 FORT units, p\u2009<\u20090.001) and were inversely related to FORD units in OC users (p\u2009=\u20090.01). Hydroperoxides were not associated with weekly hours of exercise. In OC users, lifestyle/alimentary habits were not correlated to hydroperoxides. In non-OC users only, hydroperoxide values were positively correlated with weight and BMI and inversely correlated with chocolate and fish consumption. Conclusions The markedly elevated oxidative stress we revealed in OC-user athletes could be detrimental to physical activity and elevate cardiovascular risk (as thromboembolism). Further research is needed to extend our results, to clarify the biochemical pathways leading to increased hydroperoxides (mainly lipid peroxides) and reduced antioxidant defense, and to elucidate the potential effects on athletic performance. OC use should be considered when developing gender-focused strategies against oxidative stress

Interleukin 1 receptor antagonist gene variable number of tandem repeats polymorphism and cutaneous melanoma

Immunity and cytokines serve crucial roles in cutaneous melanoma. The present study investigated whether a variable number tandem repeat (VNTR) polymorphism of interleukin-1 receptor antagonist (IL-1RA) gene (IL-1RN) located in intron 2 (rs2234663) is associated with cutaneous melanoma. A total of 515 subjects were studied, 133 of which were cutaneous melanoma cases (72 stage I+II non-metastatic melanoma cases and 61 stage III+IV metastatic melanoma cases), and 382 subjects were matching healthy controls from the Friuli-Venezia-Giulia Region located in Northeast Italy, an area with a high melanoma incidence. The IL-1RN-VNTR polymorphism was determined by DNA fragment length analysis following PCR amplification. According to the number of 86-bp repeats, five different IL-1RN alleles were identified: Allele 1 (4-repeats), allele 2 (2-repeats, short allele), allele 3 (5-repeats), allele 4 (3-repeats) and allele 5 (6-repeats). Alleles with three or more 86-bp repeats, i.e. allele 1, 3, 4 and 5 were collectively denoted as long (L) repeats. The present study revealed that IL-1RN-VNTR 1/2 and 2/L genotypes were more frequent among patients with cutaneous melanoma (43.6 and 45.1%, respectively) compared with healthy controls [29.6 and 30.6%, respectively; odds ratio (OR), 1.84; CI, 1.22-2.77; P=0.003; and OR, 1.66; CI, 1.24-2.79; P=0.002, respectively]. Conversely, the IL-1RN-VNTR 1/1 genotype was less frequent among melanoma cases (45.9%) compared with healthy controls (57.9%; OR, 0.62; CI, 0.41-0.92; P=0.017). Comparison of metastatic vs. non-metastatic melanoma cases identified no significant differences. The present study first demonstrated that carriage of the 1/1 IL-1RN-VNTR genotype was protective, whereas 1/2 and 2/L was a risk factor for patients with cutaneous melanoma vs. healthy controls. The short allele 2 was associated with higher expression levels of IL-1RA, a potent competitive inhibitor of the proinflammatory cytokines IL-1\u3b1 and IL-1\u3b2. VNTR-IL-1RN polymorphism may affect susceptibility to melanoma and, thus, it is a potential novel diagnostic biomarker for melanoma. The present study increased the understanding of genetic melanoma susceptibility/carcinogenesis, and may indicate novel strategies in the personalized prevention of cutaneous melanoma

BsmI (rs1544410) and FokI (rs2228570) vitamin D receptor polymorphisms, smoking, and body mass index as risk factors of cutaneous malignant melanoma in northeast Italy

Objective: To investigate whether vitamin D receptor gene (VDR) BsmI-rs1544410 and FokI-rs2228570 polymorphisms, smoking duration, and body mass index (BMI) are risk factors for cutaneous melanoma, especially metastatic melanoma. Methods: We studied 120 cutaneous melanoma cases [68 stage I and II non-metastatic melanoma (NMetM) patients, plus 52 Stage III and IV metastatic melanoma (MetM) patients], and 120 matching healthy controls from northeast Italy. VDR polymorphisms were measured by restriction fragment length polymorphism analysis. Absence or presence of BsmI and FokI restriction sites was denoted by \u201cB\u201d and \u201cF\u201d or by \u201cb\u201d and \u201cf,\u201d respectively. Results: VDR-BsmI bb genotype was more frequent among MetM (32.7%) than among NMetM cases (13.2%), with odds ratio (OR)=3.18. Comparison of all melanoma patients vs healthy controls showed that the following biomarkers were at risk: 6520 years of smoking (OR=2.43); 6520 years of smoking combined with bb (OR=4.78), Bb+bb (OR=2.30), Ff (OR=3.04), and Ff+ff (OR=3.08); obesity (BMI>30 kg/m2 ) alone (OR=3.54); and obesity combined with Bb+bb (OR=3.52), Ff (OR=4.78), and Ff+ff (OR=6.56). Comparison of MetM vs NMetM patients revealed that the following biomarkers were at risk: 6520 years of smoking (OR=2.39), 6520 years of smoking combined with bb (OR=5.13), Bb+bb (OR=3.07), and Ff+ff (OR=2.66); and obesity combined with Bb+bb (OR=5.27), Ff (OR=6.28), and Ff+ff (OR=9.18). Triple combination of 6520 years of smoking, obesity, and Bb+bb yielded OR=9.65 for melanoma patients vs healthy controls and OR=12.2 for MetM vs. NMetM patients. Conclusions: Risk factors for cutaneous MetM include two VDR polymorphisms combined with smoking duration and obesity. Results suggest gene-environment implications in melanoma susceptibility and severity. Future studies in larger cohorts and in subjects with different genetic background are warranted to extend our findings

Clinical and Capillaroscopic Modifications of the Psoriatic Plaque during Therapy: Observations with Oral Acitretin

Psoriasis is considered to be an inflammatory autoimmune disease, where angiogenesis plays an undefined pathogenetic role. The well-known changes of the superficial microvasculature in the psoriatic plaque can be easily assessed in vivo by videocapillaroscopy. In the last years, several studies reported the clinical and capillaroscopic response of the psoriatic plaque during different topical and systemic treatments. In the present work we evaluated the effects of acitretin (0.8 mg/kg/day) on videocapillaroscopic alterations and the clinical response in 11 patients affected by plaque psoriasis at the baseline (T0) and after 4 (T1), 8 (T2), and 12 (T3) weeks. A clinical improvement during the treatment with a complete clinical healing of the plaque in 7 of the 11 patients was observed. The typical “basket-weave” capillaries of the psoriatic lesions showed a reduction of 65.4% in diameter at the end of the study; only 3 patients returned to a normal capillaroscopic pattern. As observed during previous our studies, we found a discrepancy between clinical and capillaroscopic results, with a far greater improvement in the first than in the second. This finding could be in agreement with a secondary role of blood vessels in the pathogenesis and persistence of psoriatic lesions

Immunohistochemical evaluation of vitamin D receptor (VDR) expression in cutaneous melanoma tissues and four VDR gene polymorphisms

ObjectiveVitamin D receptor (VDR) mediates vitamin D activity. We examined whether VDR expression in excised melanoma tissues is associated with VDR gene (VDR) polymorphisms. MethodsWe evaluated VDR protein expression (by monoclonal antibody immunostaining), melanoma characteristics, and carriage of VDR-FokI-rs2228570 (C>T), VDR-BsmI-rs1544410 (G>A), VDR-ApaI-rs7975232 (T>G), and VDR-TaqI-rs731236 (T>C) polymorphisms (by restriction fragment length polymorphism). Absence or presence of restriction site was denoted by a capital or lower letter, respectively: \u201cF\u201d and \u201cf\u201d for FokI, \u201cB\u201d and \u201cb\u201d for BsmI, \u201cA\u201d and \u201ca\u201d for ApaI, and \u201cT\u201d and \u201ct\u201d for TaqI endonuclease. Seventy-four Italian cutaneous primary melanomas (52.1\ub112.7 years old) were studied; 51.4% were Stage I, 21.6% Stage II, 13.5% Stage III, and 13.5% Stage IV melanomas. VDR expression was categorized as follows: 100% positive vs. <100%; over the median 20% (high VDR expression) vs. 6420% (low VDR expression); absence versus presence of VDR-expressing cells. ResultsStage I melanomas, Breslow thickness of <1.00 mm, level II Clark invasion, Aa heterozygous genotype, and AaTT combined genotype were more frequent in melanomas with high versus low VDR expression. Combined genotypes BbAA, bbAa, AATt, BbAATt, and bbAaTT were more frequent in 100% versus <100% VDR-expressing cells. Combined genotype AATT was more frequent in melanomas lacking VDR expression (odds ratio=14.5; P=0.025). VDR expression was not associated with metastasis, ulceration, mitosis >1, regression, tumor-infiltrating lymphocytes, tumoral infiltration of vascular tissues, additional skin and non-skin cancers, and melanoma familiarity. ConclusionsWe highlighted that VDR polymorphisms can affect VDR expression in excised melanoma cells. Low VDR expression in AATT carriers is a new finding that merits further study. VDR expression possibly poses implications for vitamin D supplementation against melanoma. VDR expression and VDR genotype may become precise medicinal tools for melanoma in the future

BsmI, ApaI and TaqI Polymorphisms in the Vitamin D Receptor Gene (VDR) and Association with Lumbar Spine Pathologies: An Italian Case-Control Study.

Three adjacent single nucleotide polymorphisms of the vitamin D receptor gene (VDR) BsmI (rs1544410), ApaI (rs7975232), and TaqI (rs731236) are commonly studied in several pathologies. We aimed to evaluate the distribution of VDR BsmI, ApaI, and TaqI allele, genotype, and haplotype frequencies in an Italian cohort of 266 patients with lumbar spine disorders assessed by Magnetic Resonance Imaging and 252 asymptomatic controls. The exposure to putative risk factors was evaluated by a questionnaire. Polymorphisms were detected by PCR-RFLP and TaqMan\uae SNP Genotyping Assay. The results were statistically adjusted for the identified conventional risk factors. The three SNPs were in linkage disequilibrium. For all cases BbAaTT was a 3-fold risk factor OR = 3.38), whereas bbAATT (OR = 0.22), and bbaaTT (OR = 0.47) genotypes were found to be protective. Specifically, for patients affected by disc herniation only (n = 88) and all lumbar pathologies excluding stenosis and/or spondylolistesis (n = 215) B allele, Bb, Aa, and BbAaTT genotypes were risky, whereas b allele, bb, aa, and bbaaTT genotypes were protective. In patients affected by osteochondrosis with or without disc hernation (n = 50), T allele, Aa, and bbAaTT genotypes were risky, whereas t allele, AA, tt genotypes were protective. In patients affected by stenosis and/or spondylolistesis (n = 51) no significant associations were found. This is the first study showing an association of the three genetic VDR variants BsmI, ApaI, and TaqI and lumbar spine pathologies. Our study contributes to delineate genetic risk factors for specific subgroups of patients with lumbar spine pathologies highlighting the importance of haplotype analysis, and of detailed clinical evaluation of the patients for identification of genetic biomarkers

Blastic plasmacytoid dendritic cell neoplasm: case series and a brief review of literature

Blastic plasmacytoid dendritic cell neoplasm is a very aggressive disease wich has been classified by the World Health Organization among \u201cacute myeloid leukemia and related precursor neoplasms\u201d in 2008. In aerly stages the skin is almost always the first affected site. Histological exam and immunophenotype are mandatory and necessary for the right diagnosis; its management is still a challenge. It is a rare (only 0.7% of cutaneous leukemia in western countries). Recently five patients affected by blastic plasmacytoid dendritic cell neoplasm came to our attention. They had different clinical manifestations at firts visit and diferent behaviour at the beginning, but they had the same immunohistochemical pattern and the same poor prognosis

Oxidative Stress Is Increased in Combined Oral Contraceptives Users and Is Positively Associated with High-Sensitivity C-Reactive Protein

Information concerning the mechanisms underlying oxidative stress and low-grade inflammation in young healthy women predisposing eventually to future diseases is scarce. We investigated the relationship of oxidative stress and high-sensitivity C-reactive protein (hsCRP) in fertile-age women by oral combined contraceptive (OC) use. Caucasian Italian healthy non-obese women (n = 290; 100 OC-users; 190 non-OC-users; mean age 23.2 ± 4.7 years) were analyzed. Blood hydroperoxides, as oxidative stress biomarkers, were assessed by Free Oxygen Radical Test (FORT). Serum hsCRP was determined by an ultra-sensitive method (hsCRP). Markedly elevated oxidative stress (≥400 FORT Units) was found in 77.0% of OC-users and 1.6% of non-OC-users, odds ratio (OR) = 209, 95% CI = 60.9–715.4, p p s = 0.622, p s = 0.442, p s = 0.426, p < 0.001). Women with hydroperoxides ≥ 400 FORT Units were eight times as likely to have hsCRP ≥ 2 mg/L. In non-OC-users only, hydroperoxides values were positively correlated with weight and body mass index, but negatively correlated with red meat, fish and chocolate consumption. Our research is the first finding a strong positive correlation of serum hydroperoxides with hsCRP, a marker of low-grade chronic inflammation, in young healthy women. Further research is needed to elucidate the potential role of these two biomarkers in OC-use associated side-effects, like thromboembolism and other CVDs