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Gabriela Radu,1,2,* Constantin Luca,3,* Lucian Petrescu,3,* Diana Aurora Bordejevic,2,3,* Mirela Cleopatra Tomescu,1,2 Minodora Andor,1,2 Ioana Cîtu,1,2 Adelina Mavrea,1,2 Valentina Buda,4 Cătălin Tomescu,1,2 Florin Borcan,4 Liana Dehelean5 1Department of Internal Medicine I, Cardiology Clinic, “Victor Babeş” University of Medicine and Pharmacy, Timişoara, Romania; 2City Emergency Hospital Timisoara, Timişoara, Romania; 3Department of Cardiology, “Victor Babeş” University of Medicine and Pharmacy, Timişoara, Romania; 4Department of Pharmacology and Clinical Pharmacy, “Victor Babeş” University of Medicine and Pharmacy, Timişoara, Romania; 5Department of Neurosciences and Psychiatry, “Victor Babeş” University of Medicine and Pharmacy, Timişoara, Romania*These authors contributed equally to this workCorrespondence: Valentina Buda 2 nd E. Murgu Square, Timişoara 300041, RomaniaTel +40755100408Email buda.valentina.oana@gmail.comPurpose: This study aimed to assess the serum levels of intracellular adhesion molecule (sICAM-1), and vascular cell adhesion molecule (sVCAM-1), in the first psychotic episode schizophrenia (SZ) patients, before and after six months of antipsychotic treatment.Patients and Methods: The study included 50 patients with a first hospitalization for SZ and 50 healthy control subjects that were patient-matched regarding age, gender, body mass index and smoking status. The evaluation included the presence of cardiovascular risk factors, measurements of systolic and diastolic blood pressure, body mass index, smoking status, ankle-brachial index, carotid intima-media thickness, and echocardiography. The Brief Psychiatric Rating Scale (BPRS) score was calculated for the patients. The plasma levels of fasting glucose, total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, sICAM-1 and sVCAM-1 were determined at baseline in all subjects and after six months of antipsychotic treatment. Thirty patients (60%) were treated with olanzapine and 20 (40%) with risperidone.Results: The average age of patients experiencing their first episode of SZ was 29.7± 6.6 years, and 23 (46%) were men. The initial sICAM-1 levels of the patients were lower than those of the control group (P< 0.0001), and increased after treatment (P=0.02), but remained lower than in the healthy controls (P=0.026). The initial levels of sVCAM-1 levels were higher in the patients (P< 0.0001) and decreased after treatment (P< 0.0001) to values that were similar to those of the control group (P=0.39). The only independent predictor of a baseline BPRS over 120 was the baseline sVCAM-1 level (P< 0.0001). Antipsychotic treatment induced significant decreases in BPRS score (P< 0.0001), in systolic (P=0.005) and diastolic (P< 0.0001) blood pressure, in HDL-c (P=0.02), as well as significant increases in blood glucose (P< 0.01) and LDL-c (P< 0.001), with no differences between olanzapine and risperidone.Conclusion: In the patients experiencing an FEP of SZ, the levels of sICAM-1 were lower, while the levels of sVCAM-1 were higher than in the healthy control subjects. The antipsychotics used in the treatment of schizophrenia increased sICAM-1 and decreased sVCAM. The baseline level of sVCAM-1 was an independent predictor of a BPRS score > 120 at baseline.Keywords: sICAM-1, sVCAM-1, schizophrenia, inflammation, atherosclerosis, cardiac dysfunction

Florin Borcan,1 Adela Chirita-Emandi,2,3 Nicoleta Ioana Andreescu,2,3 Livia-Cristina Borcan,4 Ramona Carmen Albulescu,5 Maria Puiu,2,3 Mirela Cleopatra Tomescu41The 1st Department (Analytical Chemistry), Faculty of Pharmacy, “Victor Babes” University of Medicine and Pharmacy, Timisoara, Romania; 2The 2nd Department (Genetics), Faculty of Medicine, “Victor Babes” University of Medicine and Pharmacy, Timisoara, Romania; 3Center of Genomic Medicine, “Victor Babes” University of Medicine and Pharmacy, Timisoara, Romania; 4The 5th Department (Internal Medicine I), Faculty of Medicine, “Victor Babes” University of Medicine and Pharmacy, Timisoara, Romania; 5The 11th Department (Pediatrics), Faculty of Medicine, “Victor Babes” University of Medicine and Pharmacy, Timisoara, RomaniaBackground and aim: The extract of ginger, obtained from the rhizome of Zingiber officinale, contains 6-gingerol, 6-shogaol, 8-gingerol, and 10-gingerol. It has many therapeutic effects such as being chemopreventive against stroke and heart diseases, malabsorption, bacterial infections, indigestion, and nausea, which have been observed since ancient times. The main aim of this study is to evaluate the polyurethane (PU) as a proper material for the hollow nanoparticles’ preparation.Methods: The PU nanoparticles were obtained by a spontaneous emulsification, in the presence of a nonionic surfactant, combined with an interfacial polyaddition process between an aliphatic diisocyanate and different mixtures of etheric and esteric polyols. The synthesis was done without any PU additives, such as catalysts, blowing agents, chains promoters, cross-linking agents, and stabilizers.Results: The particles present almost neutral pH values and low water solubility. They are heat resistant up to 280°C. Decreased irritation level was found in the assay of PU nanoparticles loaded with pure ginger extract (GE) on the murine skin tests than the irritation level recorded for pure GE.Conclusion: This research shows the reduced noxiousness of these PU nanoparticles and consequently the possibility of their use as a possible cardiovascular protector.Keywords: CD1 Nu/Nu mice, drug carrier, hollow nanoparticles, noxiousness, Zeta potential

Livia-Cristina Borcan,1,* Zoltan Dudas,2,3,* Adel Len,2,4 Janos Fuzi,2,4 Florin Borcan,5 Mirela Cleopatra Tomescu1 1The 5th Department (Internal Medicine I), Faculty of Medicine, “Victor Babes” University of Medicine and Pharmacy, Timisoara, Romania; 2Neutron Spectroscopy Department, Institute for Solid State Physics and Optics, Wigner Research Centre for Physics, Hungarian Academy of Sciences, Budapest, Hungary; 3Inorganic Department, Institute of Chemistry, Romanian Academy, Timisoara, Romania; 4Faculty of Engineering and Information Technology, University of Pécs, Pécs, Hungary; 5The 1st Department (Analytical Chemistry), Faculty of Pharmacy, “Victor Babes” University of Medicine and Pharmacy, Timisoara, Romania *These authors contributed equally to this work Purpose: Red chili peppers have been highly valued in gastronomy and traditional medicine since ancient times; it seems that it is not just an ingredient for food but also a good remedy for various medical conditions such as increased blood pressure and high levels of serum triglycerides and cholesterol, myocardial infarction, arthritis, and migraines. The objective of this study is the characterization of a new carrier used for encapsulated extract. Methods: Chili pepper extract was obtained and was physically entrapped inside polyurethane microparticles in order to diminish the irritative potential of this extract. The particles were evaluated by Zetasizer measurements, small-angle neutron scattering and thermal analysis, scanning electron microscopy (SEM), and Fourier transform infrared spectroscopy; the encapsulation efficacy and the drug release profile were assessed by UV-Vis spectroscopy. Bioevaluations on mice skin were performed to predict the irritative potential of the samples. Results: Two different types of samples were compared: hollow polyurethane microparticles vs polyurethane particles containing the natural extract. The sizes of the particles were very similar, but the sample containing the extract presents three particle populations (the polydispersity index increases from 0.3 to 0.6 from one sample to another). The zeta-potential measurements and SEM images indicate a medium tendency to form clusters, while the UV-Vis study revealed an almost 70% encapsulation efficacy. Conclusion: The results suggest that encapsulation of a chili pepper extract inside polyurethane microparticles leads to a non-irritative product with a prolonged release: ~30% of encapsulated extract is released within the first 8 days and a maximum 45% is reached in 2 weeks. Keywords: corneometry, drug delivery system, erythema, FTIR, SANS, UV-Vis, zeta-potential

Transdermal drug carrier systems are used to ensure a constant level of drug during the administration. Polyurethane derivatives were recently considered as possible material in the field. The study intends to obtain a possible drug carrier at nano level. Polyether-urethane (PEU) nanostructures were synthesized by using the technique of interfacial polycondensation combined to spontaneous emulsification. For synthesis, it were used an organic phase which contain lysine diisocyante ester (LDI) and a lipophilic surfactant (Span®85) in water-miscible solvent (acetone) and an homogeneous aqueous phase formed by water, diol or polyether and a hydrophilic surfactant (Tween®20 or Tween®60). The obtained nanostructures were finally characterized. [ABSTRACT FROM AUTHOR]

The paper presents a few aspects of a lab study and its industrial implementation in the case of some original polyurethane systems used to obtain the frontally injected shoe soles. First, the optimal reception of microcellular polyurethane elastomer, the synthesis method of the hydroxyl and of the isocyanate component that are going to be used in the case of the industrial experiment and the technical conditions of the foaming insulation are presented. Than, the working variants for the microcellular polyurethane elastomer are summarized. In the end, the physical and mechanical characteristics of the obtained soles (density, Shore hardness, traction resistance, 100 % modulus, and break elongation and abrasion resistance) were established and the best variants of the microcellular polyurethane elastomer were chosen in order to be used for the series industrial production. [ABSTRACT FROM AUTHOR]

This paper, with a special practical and interface aspect, combine elements of chemistry (the structure and stabilization of the polyurethane foams), physical methods for the material characterization (thermal and mechanical, dynamical and mechanical analyses) with a mathematical algorithm put into effect like a software used for the analysis of the data given by the characterization devices (DMA and TMA). The first part of the study that was made is a chemical research over the polyurethane foam degradation, but the whole study has a major didactical aspect. This is due to the fact that the graduated students learnt only how to assay and how to read the results offered by the analysis devices. It is so wrong that the students not learn the device working procedure and the steps of the device software. [ABSTRACT FROM AUTHOR]

This paper presents the results of an experimental study made to obtain a bicomponent polyurethane system used to replace the classic rubber in the manufacture of automotive belts. There are presented a few characteristics of the raw materials used to obtain polyurethane variants: the hydroxyl component (polyester polyols, chain extender and catalyst) and diisocyanate or isocyanate semiprepolymer (which form the isocyanate component) and the compact structure of nine synthesized polyurethane variants too. The rubber variants with linen insertion and the nine polyurethane variants are physically and mechanically characterized. The explanation of the obtained results makes us to draw conclusions and to mark on recommended variants for the production of the automotive belts. [ABSTRACT FROM AUTHOR]

This paper presents the results of an experimental lab study regarding the thermal stability of the compounds which were obtained from the reactions between 2,4-toluylen-diisocyanate and mono- and bi-functional stabilizers, phenol sterical hindered, benzophenone and pyperidynol type. The thermal stability of the obtained compounds offers important information about the thermal behaviour of thermal and photo-oxidative additive and reactive stabilized polyurethanes. [ABSTRACT FROM AUTHOR]

The experimental research that was done aimed at proving that the cycocel had an action on some morphological, physiological and qualitative characteristics, but also on productive capacities of some wheat varieties, cultivated around Lugoj city (Timiş county). This kind of action depends on: the climatic variables (precipitations, temperature), the soil characteristics (type, pH and contents), the applied dose, the number of treatments, the application stage and the quantity of active substance used. The influence of the cycocel had been observed through the morphological modifications that had been noticed in the case of some comparative crops with five wheat varieties. This was done by measurement the length of the straw, the number of knots, but also by watching the development of the root system and of the foliage apparatus in connection to the dose of the active substance used, to the application stage of the treatment and the number of treatments. [ABSTRACT FROM AUTHOR]

Abstract Background Polymers have been considered as important materials in fabrication of microstructures for various medical purposes including drug delivery. This study evaluates polyurethane as material for hollow microstructures preparation. Results Polyurethane microstructures were obtained by interfacial polyaddition combined with spontaneous emulsification and present slightly acid pH values. Scanning electron microscopy revealed the existence of irregular shapes and agglomerated microstructures. The material is heat resistant up to 280°C. Good results were recorded on murine skin tests in case of polyurethane microstructures based on isophorone diisocyanate. Mesenchymal stem cells viability presents good results for the same sample after 48 hours based on the Alamar Blue test. Conclusions The research revealed the reduced noxiousness of this type of microstructures and consequently the possibility of their use for therapeutic purposes.

Abstract Background Aiming to obtain the highest triterpene content in the extraction products, nine bark samples from the forest abundant flora of Apuseni Mountains, Romania were Raman spectroscopically evaluated. Three different natural extracts from Betula pendula Roth birch bark have been obtained and characterized using Fourier transform vibrational spectra. Results This study shows that principal components of the birch tree extract can be rapidly recognized and differentiated based on their vibrational fingerprint band shape and intensity. The vibrational spectroscopy results are supported by the GC-MS data. Based on IR and Raman analysis, one can conclude that all the extracts, independent on the solvent(s) used, revealed dominant betulin species, followed by lupeol. Conclusions Since Raman measurements could also be performed on fresh plant material, we demonstrated the possibility to apply the present results for the prediction of the highest triterpene content in bark species, for the selection of harvesting time or individual genotypes directly in the field, with appropriate portable Raman equipment.

Determining the safety of a newly developed experimental product is a crucial condition for its medical use, especially for clinical trials. In this regard, four hydrogel-type formulations were manufactured, all of which were based on carbomer (Blank-CP940) and encapsulated with caffeine (CAF-CP940), phosphorus derivatives (phenyl phosphinic (CAF-S1-CP940) and 2-carboxyethyl phenyl phosphinic acids (CAF-S2-CP940)). The main aim of this research was to provide a comprehensive outline of the biosafety profile of the above-mentioned hydrogels. The complex in vitro screening (cell viability, cytotoxicity, morphological changes in response to exposure, and changes in nuclei morphology) on two types of healthy skin cell lines (HaCaT-human keratinocytes and JB6 Cl 41-5a-murine epidermal cells) exhibited a good biosafety profile when both cell lines were treated for 24 h with 150 μg/mL of each hydrogel. A comprehensive analysis of the hydrogel's impact on the genetic profile of HaCaT cells sustains the in vitro experiments. The biosafety profile was completed with the in vivo and in ovo assays. The outcome revealed that the developed hydrogels exerted good biocompatibility after topical application on BALB/c nude mice's skin. It also revealed a lack of toxicity after exposure to the hen's chicken embryo. Further investigations are needed, regarding the in vitro and in vivo therapeutic efficacy and safety for long-term use and potential clinical translatability.

Introduction: Lactate is a useful prognostic marker, as its level increases in hypoxic tissue and/or during accelerated aerobic glycolysis due to excessive beta-adrenergic stimulation and decreased lactate clearance. The Surviving Sepsis Campaign Bundle 2018 Update suggests premeasurement of lactate within 2-4 h so that physicians perform, assist, administer, and introduce lactate-guided resuscitation to reduce mortality due to sepsis., Methods: A total of 108 patients with septic shock who underwent continuous renal replacement therapy (CRRT) for acute kidney injury were enrolled in this observational study. Demographic, clinical, and laboratory data were collected, and patients were divided into two groups: survivors and non-survivors., Results: Multivariate analysis demonstrated that lactate levels at 24 h after initiation of CRRT treatment, but not lactate levels at intensive care unit (ICU) admission, were associated with mortality. Lactate clearance was associated with lower mortality among the survivors (OR = 0.140) at 6 h after ICU admission and late mortality (OR = 0.260) after 24 h. The area under the ROC curves for mortality was 0.682 for initial lactate; 0.797 for lactate at 24 h; and 0.816 for lactate clearance at 24 h., Conclusions: Our result reinforces that the determination of lactate dynamics represents a good predictor for mortality, and serial lactate measurements may be more useful prognostic markers than initial lactate in patients with septic shock.

Background and Objectives : Nucleotide delivery has emerged as a noteworthy research trend in recent years because of its potential utility in addressing a range of genetic defects resulting in the presence of incorrect nucleotides. The primary goals of this research were to create and to characterize polyurethane microstructures, with the aim of utilizing them for nucleotide transport. Materials and Methods : Two samples were prepared using an aliphatic diisocyanate in reaction with a mixture of polyethylene glycol and polycaprolactone diol, where 2'-deoxycytidinic acid was used as the active agent and glycerol 1,2-diacetate was used as an enhancer of the aqueous solubility. The solubility, pH, size distribution, and surface charge of the samples were measured, and encapsulation efficacy and release, cell proliferation, and irritation tests on mouse skin were conducted. Results : The results showed almost neutral acidic-basic structures with a high heterogeneity, and a medium tendency to form clusters with non-cytotoxic and non-irritative potentials. Conclusions : Future research could explore the efficacy of this carrier in delivering other nucleotides, as well as investigating the long-term effects and safety of these microstructures in vivo.

The delivery of nucleosides represents an interesting research trend in recent years due to their application in various viral infections. The main aims of this study were to develop and to characterize polyurethane particles that are intended to be used for the transport of nucleosides. Three samples have been prepared using aliphatic diisocyanates, a mixture of polyethylene glycol, polycaprolactone, and diols, respectively. The samples were characterized through refractivity measurements, drug loading efficacy, release and penetration rate investigations, FTIR and Raman spectroscopy, thermal analyses, Zetasizer, SEM, HDFa cells viability, and irritation tests on mice skin. The results indicate the obtaining of particles with sizes between 132 and 190 nm, positive Zeta potential values (28.3-31.5 mV), and a refractivity index around 1.60. A good thermal stability was found, and SEM images show a medium tendency to agglomerate. The samples' color, pH, and electrical conductivity have changed only to a small extent over time, and the evaluations indicate an almost 70% encapsulation efficacy, a prolonged release, and that around 70% of particles have penetrated an artificial membrane in the first 24 h. The synthesized products should be tested in further clinical trials, and the current tests on cell cultures and mice skin revealed no side effects.

This study presents phytochemical characterization and biological evaluation of Origanum vulgare L. essential oil (OEO) formulated as polymeric micelles drug delivery systems as a possible non-invasive approach for the management of skin tags. GC-MS analysis of Romanian OEO revealed the identification and quantification of 43 volatile compounds (thymol and carvacrol being the main ones). The antioxidant activity was shown by four consecrated methods: CUPRAC, ABTS, ORAC and DPPH. OEO was incorporated by micellar solubilization into a binary hydrogel based on a Pluronic F 127/L 31 block-copolymers mixture. The pH, consistency, spreadability, particle size, polydispersity index and zeta potential of the OEO-loaded poloxamer-based binary hydrogel (OEO-PbH) were investigated. OEO-PbH was skin compatible in terms of pH and exhibited adequate spreadability and consistency. The minimal inhibitory concentrations of the tested OEO were similar to those obtained for the formulation, lower (2.5 µg/mL) for yeast and higher (40-80 µg/mL) for Gram-negative bacilli. As keratinocytes are among main components of skin tags, an in vitro evaluation was conducted in order to see the effect of the formulation against HaCaT human keratinocytes. OEO-PbH decreased HaCaT cells migration and proliferation and elicited a cytotoxic and pro-apoptotic effect in a dose- and time-dependent manner. No harmful effect on the viability of dendritic cells (DCs) was detected following the incubation with different concentrations (0-200 µg/mL) of the 5% formulation. Treatment in inflammatory DCs (+LPS) indicated a decrease in cytokine production of IL-6, TNF-α and IL-23 but no significant effect on IL-10 in any of the tested concentrations.

This study aimed to investigate the antifungal and antimycotoxicogenic effect of binary and tertiary mixtures of Thymus vulgaris , Origanum sativum , and Coriandrum sativum essential oils (EOs), as well as emulsions based on EO mixtures, on fungi developed on wheat grains destined for the bakery industry. The chemical composition of the EO mixtures, the physical characteristics of the emulsions, and the influence of treatments on the proximate composition of wheat seeds were also studied. The methods used included the microbiological analysis of fungi developed on wheat seeds, the ELISA technique for determining the deoxynivalenol content (DON), gas chromatography coupled with mass spectrometry (GC-MS) to detect the chemical composition of the EOs, Zetasizer to analyse the particle sizes and their electric charge at the surface, and NIR analysis of the proximate composition of wheat. The chemical composition analysis revealed that thymol and o-cymene were the major components in the binary mixture of the EOs with thyme, linalool in the binary mixtures of the EOs with coriander and carvacrol, and o-cymene in the binary mixtures of the EOs with oregano. The results showed that, based on the zeta potential, the tertiary mixture ensured maximum emulsion stability, while the emulsion based on thyme and oregano was the less stable system. Regarding the antifungal and antimycotoxicogenic effect, the results showed that the highest inhibition potential on fungi was observed with the binary mixtures of the EOs based on thyme and oregano, and on deoxynivalenol (DON) when the binary emulsion based on the same EOs was applied to wheat seeds. The proximate composition of wheat seeds contaminated with DON showed an increase in protein content and mineral substances, and there were changes in the colour of the wheat seeds after treatment with the EOs. In conclusion, the results obtained in this study showed the possibility of using binary/tertiary mixtures of EOs and emulsions as healthy and environmentally friendly alternatives in the bakery industry.

The KIDSCREEN-27 represents a standardized, worldwide instrument, employed to assess the health-related quality of life in children. The purpose of the present study is to validate the KIDSCREEN-27 questionnaire for 6-year-old preparatory school children and verify its reliability, as well as to perform a comparison regarding the quality of children's lives living in two cities in Romania: Arad, a provincial city, versus the second most developed city in the country, Cluj-Napoca. A total of 256 children of 6 years of age, who come from families with both parents, with a medium to high socioeconomic status and a good health status, were included in the analysis, using the KIDSCREEN-27 questionnaire at three assessment time points with a re-test period of two weeks. Results indicated that the KIDSCREEN-27 turned out to be suitable for use in 6-year-old Romanian children. Analysis regarding the psychometric properties showed that the Cronbach's alpha ranged from 0.554 to 0.661 at the end of the study. The Pearson correlation coefficients showed statistically significant differences between the items of each area investigated. In conclusion, there is a growing need to periodically monitor the health status of children to avoid possible problems which may occur.

Medicinal plants and essential oils (EOs), in particular, were intensively studied in recent years as viable alternatives for antiproliferative chemical synthetic agents. In the same lines, the present study focuses on investigating the effects of natural preparations (emulsions) based on EOs obtained from Citrus bergamia Risso (bergamot-BEO), Citrus sinensis Osbeck (orange-OEO), and Syzygium aromaticum Merill et L. M. Perry (clove-CEO) on different healthy (human immortalized keratinocytes-HaCaT and primary human gingival fibroblasts-HGF) and human tumor cell lines (human melanoma-A375 and oral squamous carcinoma-SCC-4) in terms of the cells' viability and cellular morphology. The obtained results indicate that the CEO emulsion (ECEO) induced a dose-dependent cytotoxic in both healthy (HaCaT and HGF) and tumor (A375 and SCC-4) cells. OEO emulsion (EOEO) increased cell viability percentage both for HaCaT and A375 cells and had an antiproliferative effect at the highest concentration in HGF and SCC-4 cells. BEO emulsion (EBEO) decreased the viability percentage of SCC-4 tumor cells. By associating OEO with CEO as a binary mixture in an emulsified formulation, the inhibition of tumor cell viability increases. The E(BEO/OEO) binary emulsion induced an antiproliferative effect on oral health and tumor cells, with a minimal effect on skin cells. The non-invasive tests performed to verify the safety of the test compound's emulsions at skin level indicated that these compounds do not significantly modify the physiological skin parameters and can be considered safe for human skin.

Background and Objectives : The present study demonstrates that apart from the well-known toxicity of liposoluble vitamins, some hydrosoluble vitamins may also exert toxicity; thus, routine supplementation with vitamins or ingestion of fortified foods should not be considered harmless. The study addresses the possible correlations between the physico-chemical properties and the side effects of vitamins when taken in high doses or for a too long a period. Materials and Methods : The FAFDrugs4.0 computational tool was used for computational assessment of the ADMET profile of several hydro- and liposoluble vitamins. Results : ADMET analysis revealed the following major data: vitamin B3 and B13 showed reduced structural complexity; thus, a relative toxicological potential may be exerted. Vitamins B1 and B7 were found to have good oral absorption and thus good bioavailability, while Vitamin B3 was found to have decreased oral absorption. In addition, all of the liposoluble vitamins reflected higher complexity, much greater than most of the potentially therapeutically-proven compounds. Conclusions : The present study emphasizes the importance between the physico-chemical properties of vitamins and their possible toxicological impact.

The skin integrity is essential due to its pivotal role as a biological barrier against external noxious factors. Pentacyclic triterpenes stand as valuable plant-derived natural compounds in the treatment of skin injuries due to their anti-inflammatory, antioxidant, antimicrobial, and healing properties. Consequently, the primary aim of the current investigation was the development as well as the physicochemical and pharmaco-toxicological characterization of betulin- and lupeol-based oleogels (Bet OG and Lup OG) for topical application in skin injuries. The results revealed suitable pH as well as organoleptic, rheological, and textural properties. The penetration and permeation of Bet and Lup oleogels through porcine ear skin as well as the retention of both oleogels in the skin were demonstrated through ex vivo studies. In vitro, Bet OG and Lup OG showed good biocompatibility on HaCaT human immortalized cells. Moreover, Bet OG exerted a potent wound-healing property by stimulating the migration of the HaCaT cells. The in ovo results demonstrated the non-irritative potential of the developed formulations. Additionally, the undertaken in vivo investigation indicated a positive effect of oleogels treatment on skin parameters by increasing skin hydration and decreasing erythema. In conclusion, oleogel formulations are ideal for the local delivery of betulin and lupeol in skin disorders.

Melissa officinalis (MO) is a medicinal plant well-known for its multiple pharmacological effects, including anti-inflammatory, anticancer and beneficial effects on skin recovery. In this context, the present study was aimed to investigate the in vitro and in vivo safety profile of an MO aqueous extract by assessing cell viability on normal (HaCaT-human keratinocytes) and tumor (A375-human melanoma) cells and its impact on physiological skin parameters by a non-invasive method. In addition, the antioxidant activity and the antiangiogenic potential of the extract were verified. A selective cytotoxic effect was noted in A375 cells, while no toxicity was noticed in healthy cells. The MO aqueous extract safety profile after topical application was investigated on SKH-1 mice, and an enhanced skin hydration and decreased erythema and transepidermal water loss levels were observed. The in ovo CAM assay, performed to investigate the potential modulating effect on the angiogenesis process and the blood vessels impact, indicated that at concentrations of 100 and 500 µg/mL, MO aqueous extract induced a reduction of thin capillaries. No signs of vascular toxicity were recorded at concentrations as high as 1000 μg/mL. The aqueous extract of MO leaves can be considered a promising candidate for skin disorders with impaired physiological skin parameters.

Chronic autoimmune thyroiditis (CAT) is the most common thyroid disorder in the pediatric population. Ultrasound evaluation may suggest the diagnosis. Additionally, shear-wave elastography (SWE) proved to be a valuable additional diagnosis tool in adults with CAT by assessing thyroid stiffness (TS). This study aims to assess its use also in detecting children with CAT. The study group consisted of 50 children with confirmed diagnosis of CAT, who were compared to the control group, consisting of 50 children with no thyroid pathology and with an adult group of 50 subjects with CAT. The evaluation included, besides bioimmunochemical evaluation, also thyroid ultrasound evaluation and elastography measurements in the same session (Aixplorer Mach 30, Supersonic imagine, France). The mean TS values were significantly lower for children in the CAT group compared to adults with CAT (15.51 ± 4.76 kPa vs. 20.96 ± 6.31 kPa; p < 0.0001) and higher compared to the healthy aged matched controls (15.51 ± 4.76 kPa vs. 10.41 ± 2.01 kPa; p < 0.0001). SWE elastography definitely seems a promising technique in the evaluation of children with autoimmune thyroid pathology.

THE Herpes simplex viruses (HSV-1, HSV-2) are responsible for a wide variety of conditions, from cutaneous-mucosal to central nervous system (CNS) infections and occasional infections of the visceral organs, some of them with a lethal end. Acyclovir is often used intravenously, orally, or locally to treat herpetic infections but it must be administered with caution to patients with kidney disease and to children of early age. The main objectives of this study were to synthesize and evaluate new polyurethane nanoparticles that might be used as proper transmembrane carriers for acyclovir. Polyurethane particles were obtained by a polyaddition process: a mixture of two aliphatic diisocyanates used as organic phase was added to a mixture of butanediol and polyethylene glycol used as aqueous phase. Two different samples (with and without acyclovir, respectively) were synthesized and characterized by UV-Vis spectra in order to assess the encapsulation efficacy and the release profile, FT-IR, DSC, SEM, and SANS for structural characterization, as well as skin irritation tests. Nearly homogeneous samples with particle sizes between 78 and 91 nm have been prepared and characterized revealing a medium tendency to form clusters and a high resistance to heat up to 300 °C. The release profile of these nanoparticles is characteristic to a drug delivery system with a late discharge of the loaded active agents. Very slight increases in the level of transepidermal water loss and erythema were found in a 15-day evaluation on human skin. The results suggest the synthesis of a non-irritative carrier with a high encapsulation efficacy that can be successfully used for the transmembrane transfer of acyclovir.

Since ancient times complementary therapies have been based on the use of medicinal plants, natural preparations and essential oils in the treatment of various diseases. Their use in medical practice is recommended in view of their low toxicity, pharmacological properties and economic impact. This paper aims to test the antimicrobial effect of natural preparation based on clove, orange and bergamot essential oils on a wide range of microorganisms that cause infections in humans including: Streptococcus pyogenes , Staphylococcus aureus , Shigella flexneri , Candida parapsilosis , Candida albicans , Pseudomonas aeruginosa , Escherichia coli, Salmonella typhimurium and Haemophilus influenza . Three natural preparations such as one-component emulsions: clove (ECEO), bergamote (EBEO), and orange (EOEO), three binary: E(BEO/CEO), E(BEO/OEO), E(CEO/OEO) and a tertiary emulsion E(OEO/BEO/CEO) were obtained, characterized and tested for antimicrobial effects. Also, the synergistic/antagonistic effects, generated by the presence of the main chemical compounds, were studied in order to recommend a preparation with optimal antimicrobial activity. The obtained results underline the fact that the monocomponent emulsion ECEO shows antimicrobial activity, while EOEO and EBEO do not inhibit the development of the analyzed strains. In binary or tertiary emulsions E(BEO/CEO), E(CEO/OEO) and E(OEO/ BEO/CEO) the antimicrobial effect of clove oil is potentiated due to the synergism exerted by the chemical compounds of essential oils.

The current study was aimed to evaluate the phenolic composition parameters of two hydro-alcoholic extracts of Ocimum basilicum L. (OB) obtained from the aerial part (without leaves) and leaves, in order to determine their contribution to the antioxidant activity (AOA). Both hydro-alcoholic extracts have proven to be rich in polyphenolic compounds, flavonoids, flavonols and tannins. Therefore, the leaves' extracts reveal an inhibition percentage of 89%, almost comparable with the standard reference (95%). To complete the toxicological profile, the study also assessed the potential cytotoxicity of basil hydro-alcoholic extracts on immortalized human keratinocytes (HaCaT), skin human fibroblasts (1BR3), mice epidermis (JB6Cl41-5a) and primary human melanocytes (HEMa) cells, correlated to A375 antitumor in vitro activity. The extracts did not induce significant cytotoxic effect on any of the selected normal cell lines but showed relevant activity on A375 cells. Considering the low values obtained regarding the irritative effects in the chorionallantoic membrane of the egg on blood vessels, we can emphasize that both extracts can be considered as biocompatible ingredients. Regarding the potential activity of hydro-alcoholic extracts on human skin, the decrease of erythema values after the application of extracts was a relevant observation which indicates the anti-inflammatory potential of Ocimum basilicum L.

Albendazole is a benzimidazole derivative with documented antitumor activity and low toxicity to healthy cells. The major disadvantage in terms of clinical use is its low aqueous solubility which limits its bioavailability. Albendazole was incorporated into stable and homogeneous polyurethane structures with the aim of obtaining an improved drug delivery system model. Spectral and thermal analysis was used to investigate the encapsulation process and confirmed the presence of albendazole inside the nanoparticles. The in vitro anticancer properties of albendazole encapsulated in polyurethane structures versus the un-encapsulated compound were tested on two breast cancer cell lines, MCF-7 and MDA-MB-231, in terms of cellular viability and apoptosis induction. The study showed that the encapsulation process enhanced the antitumor activity of albendazole on the MCF-7 and MDA-MB-23 breast cancer lines. The cytotoxic activity manifested in a concentration-dependent manner and was accompanied by changes in cell morphology and nuclear fragmentation.

Chronic autoimmune thyroiditis (CAT) defines a diffuse intrathyroidal lymphocytic infiltration associating a destructive process of the thyroid follicles, most commonly in evolution developing hypothyroidism. Typical ultrasound changes may suggest the presence of the disease. This study aims to evaluate the performance of strain elastography in detecting autoimmune thyroiditis as an additional tool to the conventional ultrasound examination. A total of 250 patients were enrolled in the study; 180 had biochemical confirmation of CAT, the other 70 healthy subjects represented the control group. All patients were examined clinically and by means of conventional thyroid ultrasound (US) and real-time elastography using a Hitachi Preirus machine (5-15 MHz linear probe). Five valid measurements for the parenchyma/muscle strain ratios (SR) were taken for each subject, considering the mean value for analysis. A mean SR value above 1.64 was found to predict the presence of CAT with sensitivity (Sen) 69%, specificity p92%, positive predictive value (PPV) 95.4%, negative predictive value (NPV) 54% and area under receiver operating characteristic (AUROC) 0.87. Moreover, when comparing the mean values for SR, significantly higher values were found in CAT patients compared with the controls (2.81 ± 2.11 vs. 1.03 ± 0.51; p < 0.0001). Of the 180 CAT subjects, 92 were on thyroid hormone replacement therapy; significantly higher values were detected for patients under therapy compared with asymptomatic cases (3.45 ± 2.53 vs. 2.15 ± 1.27, p < 0.0001). A cut-off value of 2.94 was established for identifying CAT patients who needed hormonal treatment (Sen 52.3%, Sp 83.7%, PPV 75.4%, NPV 64.7% and AUROC 0.66). No correlation was found between stiffness and antibody titers nor for functional status. Elastography does add valuable information to the US evaluation of cases with autoimmune thyroiditis.

Due to their effect of vasodilatation, isosorbide nitrates represent one of the most important and most used solutions for angina pectoris. Unfortunately, these compounds have multiple dose-related adverse drug reactions such as headache, weakness, mild dizziness, and occasionally heart rate changes, nausea, vomiting, and sweating. The main aims of this research were to obtain and to evaluate new polyurethane (PU) structures that can be used as a proper transmembrane carrier with an improved release kinetic. Chitosan-based PU structures were obtained by a polyaddition process between hexamethylene diisocyanate and a mixture of chitosan, butanediol, and polyethylene glycol in the presence of caffeine as a synthesis catalyst. The obtained samples (with and without isosorbide nitrates) were characterized regarding the encapsulation and release rate (UV-Vis spectra), chemical composition (FTIR), thermal stability (thermal analysis), morphology changes (SEM and SANS), and in vivo irritation tests. These methods revealed no significant differences between the two sample structures. Multipopulational structures with sizes between 73 and 310 nm, with an increased tendency to form clusters and a high resistance to heat (up to 280°C), were obtained. This study presents an alternative administration of isosorbide derivatives based on a PU carrier with a high biocompatibility and a prolonged release., (Copyright © 2020 Borcan, Len, Bordejevic, Dudás, Tomescu and Valeanu.)

Objectives: Chronic kidney disease is a rising cause of morbidity and mortality in developed countries, including end-stage renal disease (ESRD). The prevalence of thyroid comorbidities in persons with chronic kidney disease is documented higher than in normal population. The study aims to investigate the prevalence of morphological and functional thyroid disorders in patients with chronic kidney disease, with renal replacement therapy (hemodialysis)., Methods: A cross-sectional study was performed on 123 consecutive patients with chronic kidney disease stage 5, on hemodialysis during a period of one month (May 2019-June 2020). All patients were enrolled for maintenance hemodialysis in B Braun Hemodialysis Center Timisoara and were examined on conventional 2B ultrasound. Thyroid blood tests were done, including serum free thyroxin (FT4), free triiodothyronine (FT3) and thyroid-stimulating hormone (TSH) at the time of starting hemodialysis., Results: We evaluated 123 patients (male to female ratio 70/53) mean age 62.2 ± 11.01, mostly above 65 years old, enrolled in the end-stage renal disease program, on renal replacement therapy. From the cohort, 76/123 presented thyroid disease, including autoimmune hypothyroidism, nodular goiter or thyroid cancer. Among them, 63 patients presented nodular goiter, including 3 thyroid cancers, confirmed by surgery and histopathological result, 22 patients had thyroid autoimmune disease. The serum thyroid-stimulating hormone levels found in the cohort was 3.36 ± 2.313 mUI/mL, which was in the normal laboratory reference range. The thyroid volume was 13 ± 7.18 mL. A single patient in the cohort presented Graves Basedow disease, under treatment and three patients present subclinical hyperthyroidism. We have found that thyroid disease risk is increased by 3.4-fold for the female gender and also the increase of body mass index (BMI) with one unit raises the risk of developing thyroid disease with 1.083 times ( p = 0.018)., Conclusion: To conclude, this study aimed to quantify the prevalence of thyroid disease in end-stage kidney disease population, especially nodular goiter, important for differential diagnosis in cases with secondary hyperparathyroidism. Thyroid autoimmune disease can be prevalent among these patients, as symptoms can overlap those of chronic disease and decrease the quality of life. We have found that thyroid disease has a high prevalence among patients with end-stage renal disease on hemodialysis. Thyroid goiter and nodules in ESRD patients were more prevalent than in the general population. Clinical surveillance and routine screening for thyroid disorders can improve the quality of life in these patients.

Polyurethane nano- and micro-structures have been studied intensively in the last decade as drug delivery systems for various herbal extracts as well as pure active biological substances. Their biocompatibility, haemocompatibility, safe degradation, and low-cost production are just a few advantages of these materials that were already used in numerous medical applications (catheters, surgical drapes, wound dressing). The primary purposes of this study include obtaining empty polyurethane microstructures and the assessment of their modifications in media with different pH values. A mixture of two aliphatic diisocyanates and an aqueous phase based on a polyether were used during the synthesis process. The size, homogeneity, and surface charge were studied using a Cordouan Technol. Zetasizer, while the pH measurements were conducted with a portable pH Meter Checker®, Hanna Instruments. The results showed the obtaining of an almost homogeneous sample containing microstructures with sizes ranging between 139 and 151 nm, with a pH value of approximately 6.78 and a Zeta potential of 24.6. Expected decreases in microparticles' sizes were observed in all types of media during a 15-days experiment, but the process was accelerated by a low pH when an increase of the Zeta potential value was noticed as well. Our data provide new information about the degradation process of the polyurethane microstructures on the one hand and the drug release rate of these materials when used as drug carriers, on the other hand., (©Carol Davila University Press.)

Given the increased prevalence of thyroid nodules in the general population (~50%), the real challenge resides in correctly recognizing the suspicious ones. This study proposes to compare four important Thyroid Imaging and Reporting Data Systems (TI-RADS) and evaluate the contribution of elastography and 4D Color Doppler assessment of vascularity in estimating the risk of malignancy. In the study, 133 nodules with histopathological examination were included. Of these, 35 (26.31%) proved to be malignant. All nodules were classified using the four selected systems and our proposed improved score. The American College of Radiology (ACR) and EU TI-RADS had good sensitivity (94.28%, 97.14%) and NPV (93.33%, 95.83%), but fairly poor specificity (31.81%, 23.46%) and PPV (35.48%, 31.19%), with an accuracy of 42.8% and 45.8%, respectively. Horvath TI-RADS had better accuracy of 66.9% and somewhat improved specificity (62.24%), but poorer sensitivity (80%). Russ' French TI-RADS includes elastography in the risk assessment strategy. This classification proved superior in all aspects (Se: 91.42%, Sp:82.65%, NPV:96.42%, PPV:65.30%, and Acc of 84.96%). The mean strain ratio (SR) value for malignant lesions was 5.56, while the mean SR value for benign ones was significantly lower, 2.54 ( p < 0.05). It also correlated well with the response variable: histopathological result ( p < 0.001). Although, adding 4D vascularity to the French score generated a similar calculated accuracy and from a statistical point of view, the parameter itself proved beneficial for predicting the malignancy risk ( p < 0.001) and may add important knowledge in uncertain situations. Advanced ultrasound techniques definitely improved the risk estimation and should be used more extensively.

Background: Alzheimer's disease (AD) is considered a severe, irreversible and progressive neurodegenerative disorder. Currently, the pharmacological management of AD is based on a few clinically approved acethylcholinesterase (AChE) and N-methyl-D-aspartate (NMDA) receptor ligands, with unclear molecular mechanisms and severe side effects., Methods: Here, we reviewed the most recent bioinformatics, cheminformatics (SAR, drug design, molecular docking, friendly databases, ADME-Tox) and experimental data on relevant structurebiological activity relationships and molecular mechanisms of some natural and synthetic compounds with possible anti-AD effects (inhibitors of AChE, NMDA receptors, beta-secretase, amyloid beta (Aβ), redox metals) or acting on multiple AD targets at once. We considered: (i) in silico supported by experimental studies regarding the pharmacological potential of natural compounds as resveratrol, natural alkaloids, flavonoids isolated from various plants and donepezil, galantamine, rivastagmine and memantine derivatives, (ii) the most important pharmacokinetic descriptors of natural compounds in comparison with donepezil, memantine and galantamine., Results: In silico and experimental methods applied to synthetic compounds led to the identification of new AChE inhibitors, NMDA antagonists, multipotent hybrids targeting different AD processes and metal-organic compounds acting as Aβ inhibitors. Natural compounds appear as multipotent agents, acting on several AD pathways: cholinesterases, NMDA receptors, secretases or Aβ, but their efficiency in vivo and their correct dosage should be determined., Conclusion: Bioinformatics, cheminformatics and ADME-Tox methods can be very helpful in the quest for an effective anti-AD treatment, allowing the identification of novel drugs, enhancing the druggability of molecular targets and providing a deeper understanding of AD pathological mechanisms., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

This study evaluates the diagnostic value of two-dimensional shear wave elastography (2 D-SWE) technique in the evaluation of hyperplastic parathyroid glands in cases with secondary and tertiary hyperparathyroidism. A total of 59 patients (end-stage renal disease, under supplemental dialysis program) with visible parathyroid hyperplastic glands on ultrasound, confirmed by biochemical assay and scintigraphy, were enrolled; they were examined on grayscale ultrasound and 2 D shear wave elastography. We determined the elasticity index (EI) in the parathyroid gland, thyroid parenchyma and surrounding muscles, and the elasticity ratio of hyperplastic parathyroid glands compared to muscle, specifically sternocleidomastoid muscle. Patients presented fibrocystic bone disease with secondary hyperparathyroidism induced by end-stage chronic kidney disease; being on prolonged chronic dialysis therapy, they had positive sestamibi scintigraphy and high values of serum parathormone (1141.04 pg/mL). Nodules placed posterior to the thyroid capsule that were cystic, had a hypoechoic aspect, and were homogenous with an independent afferent artery were found. Mean EI in the parathyroid gland was 7.83 kPa, the median value in thyroid parenchyma was 13.76 kPa, and mean muscle EI value was 15.78 kPa. The observed mean parathyroid/muscle SWE ratio was 0.5356 and the value for parathyroid/normal thyroid parenchyma was 0.5995. Using receiver operating characteristic (ROC) analysis, we found that EI below 9.74 kPa correctly identifies parathyroid tissue, with a sensitivity of 94.8%, specificity of 90.7%, and accuracy of 92.26% when compared to normal thyroid tissue. Compared with the muscle tissue, we identified that EI below 9.98 kPa has a sensitivity, specificity, and accuracy of 93.8%, 90.7%, and 91.75%, respectively. Ultrasound elastography is a helpful tool in identifying parathyroid hyperplasia in patients with chronic kidney disease. A cutoff value of 9.98 kPa can be used in 2 D-SWE for accurate diagnosis of parathyroid disease.

Fine needle aspiration (FNA) is considered the gold standard in the diagnostic of thyroid nodules. Using the recommended BETHESDA reporting system, up to 20% of results are classified as intermediate cytology. As there is no consensus whether ultrasound evaluation, lobectomy or surgery is the best treatment option, intermediate cytology results are considered a grey zone of the FNA. The main aim of our study was to evaluate the performance of combined advanced ultrasound techniques in the process of diagnosis and evaluation of the intermediate cytology cases after FNA. We evaluated 54 consecutive cases with intermediate cytology on FNA, using conventional B-mode ultrasound (2B), and strain elastography, using a linear multifrequency 6-13 MHz linear probe (Hitachi Prerius Machine, Hitachi Inc, Japan). All nodules were classified with our Thyroid Imaging Report and Data System (TI-RADS) proposed model, considering: vertical appearance, with antero-posterior diameter bigger than the transvers diameter, the so called taller than wide shape, irregular borders, intranodular inhomogeneity, marked hypoecogenicity, micro calcifications, the presence of suspect lymph nodes, and increased stiffness as suspicious for malignancy. The classification outcomes were compared with the pathology results, considered the gold standard diagnosis. The prevalence of cancer was 28.8%, with 13/45 cases having a clear diagnostic of cancer. Six cases were diagnosed with borderline follicular neoplasia, a category with unclear evolution, also considered as malignant in the analysis of the imaging results. In total, 16/19 cancer cases had increased stiffness on elastography. The cancer prevalence increased with TI-RADS category, being 25% in TI-RADS 4b category and 92.8% in TI-RADS 5 category. The AUROC (Area Under Receiver Operating Curve) of elastography alone, in differentiation of malignant thyroid nodules was 74.9%; the combination of elastographic and conventional ultrasound characteristics generated an even better AUROC, of 84.5%. The combined conventional ultrasound and elastography identified thyroid cancer in cases with intermediate cytology with a sensitivity of 89.5% with a specificity of 50%. High risk thyroid nodules, identified by combined high risk conventional ultrasound characteristics and increased stiffness, on strain elastography, are highly predictive for malignancy, in the intermediate cytology cases.

Background: Melanoma is known as the most dangerous form of skin cancer; whereas the malignant choroidal melanoma is an orphan disease known as the most common primary intraocular malignancy in adults. Literature suggests that the consumption of garlic and mistletoe leads to a reduced risk of developing cancer., Objective: The aim of this study was the obtaining and the characterization of polymer structures containing mistletoe or garlic extract., Methods: The structures were obtained in a polyaddition process combined with a spontaneous emulsification; they were characterized by pH, size, Zeta potential and DSC measurements, evaluation of encapsulation efficacy, penetrability through membranes and in vitro cytotoxicity tests., Results: The microstructures present sizes between 1.05 and 2.60 µm and Zeta potentials between -7 and +36 mV. A good encapsulation was observed on different evaluations (88-92%). It was determined that approx. 30% of polymer microstructures containing vegetal extracts pass through an artificial membrane in 4 days. An in vitro cytotoxicity test revealed that these products are safe for administration. The analysis of antitumor efficacy indicates that garlic extracts have important effects after 48 and 72 hours on A375 cells; however, polymer microstructures with herbal extracts did not reveal antiproliferative activities on A375 cells because these polymer structures present a slow degradation., Conclusion: Sterile eye drops solutions based on polymer microstructures containing garlic or mistletoe extracts were obtained; the sample based on garlic extracts may be used in the pharmaceutical field as drug carrier with an antiproliferative effect which occurs after a prolong period., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Context: Oleanolic and ursolic acids are antitumor and antibacterial agents which are extensively studied. Their major disadvantage is the poor water solubility which limits their applications., Objectives: Oleanolic and ursolic acid were encapsulated into polyurethane nanostructures that act as drug carriers. In order to evaluate the effectiveness of the particles, anti-microbial and anti-proliferative activity compared to un-encapsulated active compounds was tested., Materials and Methods: Using an interfacial polycondensation technique, combined with spontaneous emulsification, structures with nanoscale dimensions were obtained. Scanning electron microscopy, differential scanning calorimetry and X-ray assays confirmed the encapsulation process. Concentrations of 10 and 30 μM particles and un-encapsulated compounds were tested by MTT viability assay for several breast cancer lines, with an exposure time of 72 h. For the antibacterial studies, the dilution method with MIC determination was used., Results: Ursolic acid had an excellent inhibitory effect with IC 50 value of 2.47, 1.20, 1.26 and 1.34 μM on MCF7, T47D, MDA-MB-231 and MDA-MB-361, respectively. Oleanolic acid did not show anti-proliferative activity. The pure compounds showed their antibacterial activity only against Bacillus species and Candida albicans, but MIC values were too high to be considered efficient antimicrobial agents (2280 and 4570 μg mL  -   1 , respectively). Polyurethane nanoparticles which incorporated the agents did not show any biological activity., Discussion and Conclusion: Although the active compounds did not fully exert their anti-proliferative activity following encapsulation inside polymeric nanoparticles, in vivo evaluation is needed in order to obtain an exhaustive conclusion, as the active compounds could be released as a result of metabolic activity.

The increased susceptibility of men as compared to women to develop different types of cancer, including skin cancer, is well known; however, the mechanisms involved in this process are still a matter of debate. This study aimed to obtain animal models of photo-chemically-induced skin carcinogenesis by exposure to ultraviolet radiation B (UVB) coupled with topical applications of a tumor initiator (7,12-dimethylbenz(a)anthracene, DMBA) and a tumor promoter (12-O-tetradecanoylphorbol-13-acetate, TPA) in order to characterize the gender disparities regarding the skin lesions developed by the female and male SKH-1 hairless mice included in this study. Histopathological analysis confirmed the presence of malignant lesions in both cases, in female and male mice, following chronic exposure (24 weeks) to the noxious effects of the carcinogens applied, whereas the tumors in male mice had a more severe histological grade. In addition, tumor incidence, size and multiplicity were higher in male mice than in female mice., (Copyright © 2016 Elsevier Ltd. All rights reserved.)