In Vitro And Clinical Efficacy Of The Use Of Phytoestrogensbased Topical Cosmetic Use In Photoaged Skin [eficácia In Vitro E Clínica Do Uso Cosmético Tópico De Fitoestrógenos Em Pele Fotoenvelhecida]

Introdução: Introduction: Skin aging is a challenge to treat. Objectives: To evaluate the in vitro and in vivo efficacy and clinical safety of a phytoestrogens-based cosmetic in the management of photoaging. Methods: The in vitro investigation was performed using the analysis of the genic expression of fibronectin and procollagen, evaluation of the immunomodulatory activity (proinflammatory and anti-inflammatory cytokines synthesis) and histochemistry and immunofluorescence analyses of the skin and the dermoepidermal junction. The in vivo investigation - performed in 76 women randomized into Group A (phytoestrogens complex cream and SPF 20 twice daily) or Group B (the same product plus a commercially available anti-aging cream applied overnight). The study lasted for 120 days, with physician- and patient-led evaluations, in addition to monthly ultrasound (20 MHz) and photographic analysis. Skin biopsies of the face were performed before and after treatment. Results: The study showed In vitro: increase in the expression of fibronectin, in procollagen, immunomodulator potential, represented by an increase in IL-1α and a decrease in IL-10; improvement in the integrity of the dermoepidermal junction; increase in the viability and thickness of the epidermis; increase in collagen synthesis.In vivo: subjective global improvement of the skin's appearance; reduction in the count and intensity of spots, erythema, skin pores, and cutaneous porphyrin. The ultrasound and biopsy revealed increased dermal density (52.7%) and dermal fibers (22.3%), respectively. Conclusions: The topical use of phytoestrogens-based cosmetics improves the overall condition of the skin.41137149Makrantonaki, E., Zouboulis, C.C., Molecular mechanisms of skin aging: state of the art (2007) Ann N Y Acad Sci, 1119, pp. 40-50Slominski, A., Wortsman, J., Neuroendocrinology of the Skin (2000) Endocrine Rev, 21, pp. 457-487Trautinger, F., Mechanisms of photodamage of the skin and its functional consequences for skin ageing (2001) Clin Exp Dermatol, 26, pp. 573-577Ma, W., Wlaschek, M., Tantcheva-Poor, I., Schneider, L.A., Naderi, L., Razi-Wolf, Z., Chronological ageing and photoageing of the fibroblasts and the dermal connective tissue (2001) Clin Exp Dermatol, 26, pp. 592-599Zouboulis, C.H.C., Intrinsic skin aging. A critical appraisal of the role of hormones (2003) Hautarzt, 54 (9), pp. 825-832Robert, L., Fodil-Bourahla, I., Bizbiz, L., Robert, A.M., Effect of L-fucose and fucose-rich polysaccharides on elastin biosynthesis, in vivo and in vitro (2004) Biomed Pharmacother, 58, pp. 123-128Robert, L., Fodil-Bourahla, I., Bizbiz, L., Robert, A.M., Effects of L-fucose and fucose-rich oligo and polysaccharides (FROP-s) on collagen biosynthesis by human skin fibroblasts. Modulation of the effect of retinol, ascorbate and alfa-tocopherol (2004) Biomed Pharmacother, 58, pp. 65-70Tzaphlidou, M., The role of collagen and elastin in aged skin: an image processing approach (2004) Micron, 35, pp. 173-177Wierzbicka-Patynowski, I., Schwarzbauer, J.E., The ins and outs of fibronectin matrix assembly (2003) J Cell Sci, 116 (16), pp. 3269-3276Ruoslahti, E., Proteoglycans in cell regulation (1989) J Biol Chem, 264 (23), pp. 13369-13372Rocquet, C., Bonte, F., Molecular aspects of skin ageing - recent data (2002) Acta APA, 11 (3), pp. 71-94Pieraggi, M.T., Julian, M., Bouissou, H., Stocker, S., Grimaud, J.A., Dermal aging, Immunofluorescence study of collagens I and III and fibronectin (1984) Ann Pathol, 4 (3), pp. 185-194Agius, E., Lacy, K.E., Vukmanovic-Stejic, M., Jagger, A.L., Papageorgiou, A.P., Hall, S., Decreased TNF-alpha synthesis by macrophages restricts cutaneous immunosurveillance by memory CD 4+ T cells during aging (2009) J Exp Med, 206 (9), pp. 1929-1940Assaf, H., Adly, M.A., Hussein, M.R., Aging and Intrinsic Aging: Pathogenesis and Manifestations (2010) Textbook of Skin Aging, pp. 130-132. , Farage MA, Miller KW, Maibach HI. Berlin: Springer-VerlagFisher, G.J., Talwar, H.S., Lin, J., Voorhees, J.J., Molecular mechanisms of photoaging in human skin in vivo and their prevention by all-trans retinoic acid (1999) Photochem Photobiol, 69 (2), pp. 154-157Schieke, S.M., Photoaging and infrared radiation. Novel aspects of molecular mechanisms (2003) Hautarzt, 54 (9), pp. 822-824Scharffetter-Kochanek, K., Brenneisen, P., Wenk, J., Herrmann, G., Ma, W., Kuhr, L., Meewes, C., Wlaschek, M., Photoaging of the skin from phenotype to mechanisms (2000) Exp Gerontol, 35 (3), pp. 307-316Miller, E.J., Gay, S., The collagens: Na overview and update (1987) Methods Enzymol, 144, pp. 3-41Montagner, S., Costa, A., Bases biomoleculares do fotoenvelhecimento (2009) An Bras Dermatol, 84 (3), pp. 263-26

Cytomegalovirus (CMV) genotype in allogeneic hematopoietic stem cell transplantation

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Background: Based on sequence variation in the UL55 gene that encodes glycoprotein B (gB), human cytomegalovirus (CMV) can be classified into four gB genotypes. Previous studies have suggested an association between CMV gB genotype and clinical outcome in patients who underwent an allogeneic hematopoietic stem cell transplant (HSCT). The goals of this study were identify patients with active infection caused by CMV in recipients of HSCT; determine the prevalence of CMV genotypes in the study group; correlate genotype with CMV disease, acute GVHD and overall survival. Methods: The diagnosis of active CMV infection after allogeneic HSCT was detected by antigenemia (AGM) and/or nested-PCR (N-PCR). Positive samples from patients with active CMV infection were submitted to genotyping using N-PCR to amplify a region of UL55, followed by restriction analysis based on HinfI and RsaI digestion. Real-time PCR (qPCR) was used to determine the viral load during active CMV infection and antiviral treatment. Results: Sixty-three allogeneic HSCT recipients were prospectively evaluated; 49/63 (78%) patients were infected with CMV genotypes - gB1 19/49 (39%), gB2 17/49 (35%), gB3 3/49 (6%), gB4 7/49 (14%) - and 3 (6%) had mixed CMV genotypes (gB1 + gB3, gB1 + gB4 and gB2 + gB4). Characterized by gastrointestinal disease, CMV disease occurred in 3/49 (6.1%) patients, who had CMV gB3 genotype. These gB3 genotype patients presented an increasing AGM number, mean 125 (+/- 250) (P = 0.70), and qPCR copies/ml, mean 37938 (SD +/- 50542) (P = 0.03), during antiviral treatment, when compared with other CMV genotypes. According to CMV genotypes, stratified overall survival was 55% for gB1, 43% for gB2; 0% for gB3 and 57% for gB4 (P = 0.03). Conclusions: One of the restrictions of the presented study was the low number of CMV gB sub-cohorts). However, we demonstrated that the frequency of active CMV infection in this HSCT population was high, and the most prevalent genotype in these patients with active CMV infection was gB1 and gB2 genotype (74%). In Brazil, HSCT recipients seem to carry mainly gB1 and gB2 CMV genotype.13Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)FAPESP [07/52388-1

Preliminary safety assessment of C-8 xylitol monoester and xylitol phosphate esters

Synopsis Objectives Most of the cosmetic compounds with preservative properties available in the market pose some risks concerning safety, such as the possibility of causing sensitization. Due to the fact that there are few options, the proper development of new molecules with this purpose is needed. Xylitol is a natural sugar, and the antimicrobial properties of xylitol-derived compounds have already been described in the literature. C-8 xylitol monoester and xylitol phosphate esters may be useful for the development of skincare products. As an initial screen for safety of chemicals, the combination of in silico methods and in vitro testing can aid in prioritizing resources in toxicological investigations while reducing the ethical and monetary costs that are related to animal and human testing. This study was designed to evaluate the safety of C-8 xylitol monoester and xylitol phosphate esters regarding carcinogenicity, mutagenicity, skin and eye irritation/corrosion and sensitization through alternative methods. Methods For the initial safety assessment, quantitative structure-activity relationship methodology was used. The prediction of the parameters carcinogenicity/mutagenicity, skin and eye irritation/corrosion and sensitization was generated from the chemical structure. The analysis also comprised physical-chemical properties, Cramer rules, threshold of toxicological concern and Michael reaction. In silico results of candidate molecules were compared to 19 compounds with preservative properties that are available in the market. Additionally, in vitro tests (Ames test for mutagenicity, cytotoxicity and phototoxicity tests and hen's egg test - chorioallantoic membrane for irritation) were performed to complement the evaluation. Results In silico evaluation of both molecules presented no structural alerts related to eye and skin irritation, corrosion and sensitization, but some alerts for micronucleus and carcinogenicity were detected. However, by comparison, C-8 xylitol monoester, xylitol phosphate esters showed similar or better results than the compounds available in the market. Concerning experimental data, phototoxicity and mutagenicity results were negative. As expected for compounds with preservative activity, xylitol-derived substances presented positive result in cytotoxicity test. In hen's egg test, both molecules were irritants. Conclusion Our results suggested that xylitol-derived compounds appear to be suitable candidates for preservative systems in cosmetics.Most of the cosmetic compounds with preservative properties available in the market pose some risks concerning safety, such as the possibility of causing sensitization. Due to the fact that there are few options, the proper development of new molecules with this purpose is needed. Xylitol is a natural sugar, and the antimicrobial properties of xylitol-derived compounds have already been described in the literature. C-8 xylitol monoester and xylitol phosphate esters may be useful for the development of skincare products. As an initial screen for safety of chemicals, the combination of in silico methods and in vitro testing can aid in prioritizing resources in toxicological investigations while reducing the ethical and monetary costs that are related to animal and human testing. This study was designed to evaluate the safety of C-8 xylitol monoester and xylitol phosphate esters regarding carcinogenicity, mutagenicity, skin and eye irritation/corrosion and sensitization through alternative methods. Methods For the initial safety assessment, quantitative structure-activity relationship methodology was used. The prediction of the parameters carcinogenicity/mutagenicity, skin and eye irritation/corrosion and sensitization was generated from the chemical structure. The analysis also comprised physical-chemical properties, Cramer rules, threshold of toxicological concern and Michael reaction. In silico results of candidate molecules were compared to 19 compounds with preservative properties that are available in the market. Additionally, in vitro tests (Ames test for mutagenicity, cytotoxicity and phototoxicity tests and hen's egg test - chorioallantoic membrane for irritation) were performed to complement the evaluation. Results In silico evaluation of both molecules presented no structural alerts related to eye and skin irritation, corrosion and sensitization, but some alerts for micronucleus and carcinogenicity were detected. However, by comparison, C-8 xylitol monoester, xylitol phosphate esters showed similar or better results than the compounds available in the market. Concerning experimental data, phototoxicity and mutagenicity results were negative. As expected for compounds with preservative activity, xylitol-derived substances presented positive result in cytotoxicity test. In hen's egg test, both molecules were irritants. Conclusion Our results suggested that xylitol-derived compounds appear to be suitable candidates for preservative systems in cosmetics381415

Tracking research trends and hotspots in sperm DNA fragmentation testing for the evaluation of male infertility: a scientometric analysis

BACKGROUND: This article describes the research trends in sperm DNA fragmentation (SDF) over the past 20 years (1999-2018) using a scientometric approach. METHODS: A stepwise approach was adopted to retrieve scientometric data (articles per year, authors, affiliations, journals, countries) from Scopus and analyze the publication pattern of SDF with reference to key areas of research in the field of Andrology. RESULTS: A total of 2121 articles were retrieved related to SDF. Our data revealed an increasing research trend in SDF (n = 33 to n = 173) over the past 20 years (R2 = 0.894). Most productive country in publications was the USA (n = 450), while Agarwal A. (n = 129) being the most productive author. Most of the articles in SDF were primarily focused on lifestyle (n = 157), asthenozoospermia (n = 135) and varicocele (130). Mechanistic studies on SDF were published twice as much as prognostic/diagnostic studies, with significant emphasis on oxidative stress. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) was the most widely used technique to evaluate SDF. Publications on SDF related to assisted reproductive techniques also showed a linear increasing trend (R2 = 0.933). CONCLUSIONS: Our analysis revealed an increasing trend in SDF publications predominantly investigating lifestyle, asthenozoospermia and varicocele conditions with TUNEL being the most widely used technique. A substantial increase in research is warranted to establish SDF as prognostic/diagnostic parameter to evaluate clinical scenarios and ART outcomes