Aetiology and Pathogenesis of Cutaneous Melanoma: Current Concepts and Advances

Melanoma develops from malignant transformations of the pigment-producing melanocytes. If located in the basal layer of the skin epidermis, melanoma is referred to as cutaneous, which is more frequent. However, as melanocytes are be found in the eyes, ears, gastrointestinal tract, genitalia, urinary system, and meninges, cases of mucosal melanoma or other types (e.g., ocular) may occur. The incidence and morbidity of cutaneous melanoma (cM) are constantly increasing worldwide. Australia and New Zealand are world leaders in this regard with a morbidity rate of 54/100,000 and a mortality rate of 5.6/100,000 for 2015. The aim of this review is to consolidate and present the data related to the aetiology and pathogenesis of cutaneous melanoma, thus rendering them easier to understand. In this article we will discuss these problems and the possible impacts on treatment for this disease.     

Serum Concentrations of Endothelin-1 and Matrix Metalloproteinases-2, -9 in Pre-Hypertensive and Hypertensive Patients with Type 2 Diabetes

Endothelin-1 (ET-1) is one of the most potent vasoconstrictors known to date. While its plasma or serum concentrations are elevated in some forms of experimental and human hypertension, this is not a consistent finding in all forms of hypertension. Matrix metalloproteinases -2 and -9 (MMP-2 and MMP-9), which degrade collagen type IV of the vascular basement membrane, are responsible for vascular remodeling, inflammation, and atherosclerotic complications, including in type 2 diabetes (T2D). In our study, we compared concentrations of ET-1, MMP-2, and MMP-9 in pre-hypertensive (PHTN) and hypertensive (HTN) T2D patients with those of healthy normotensive controls (N). ET-1, MMP-2, and MMP-9 were measured by ELISA. Concentrations of ET-1 in PHTN and N were very similar, while those in HTN were significantly higher. Concentrations of MMP-2 and MMP-9 in PHTN and HTN were also significantly higher compared to N. An interesting result in our study is that concentrations of MMP-2 and MMP-9 in HTN were lower compared to PHTN. In conclusion, we showed that increased production of ET-1 in patients with T2D can lead to long-lasting increases in blood pressure (BP) and clinical manifestation of hypertension. We also demonstrated that increased levels of MMP-2 and MMP-9 in pre-hypertensive and hypertensive patients with T2D mainly reflect the early vascular changes in extracellular matrix (ECM) turnover.     

Anticonvulsant Effects of Topiramate and Lacosamide on Pilocarpine-Induced Status Epilepticus in Rats: A Role of Reactive Oxygen Species and Inflammation

Background: Status epilepticus (SE) is a neurological disorder characterized by a prolonged epileptic activity followed by subsequent epileptogenic processes. The aim of the present study was to evaluate the early effects of topiramate (TPM) and lacosamide (LCM) treatment on oxidative stress and inflammatory damage in a model of pilocarpine-induced SE. Methods: Male Wistar rats were randomly divided into six groups and the two antiepileptic drugs (AEDs), TPM (40 and 80 mg/kg, i.p.) and LCM (10 and 30 mg/kg, i.p.), were injected three times repeatedly after pilocarpine administration. Rats were sacrificed 24 h post-SE and several parameters of oxidative stress and inflammatory response have been explored in the hippocampus. Results: The two drugs TPM and LCM, in both doses used, succeeded in attenuating the number of motor seizures compared to the SE-veh group 30 min after administration. Pilocarpine-induced SE decreased the superoxide dismutase (SOD) activity and reduced glutathione (GSH) levels while increasing the catalase (CAT) activity, malondialdehyde (MDA), and IL-1β levels compared to the control group. Groups with SE did not affect the TNF-α levels. The treatment with a higher dose of 30 mg/kg LCM restored to control level the SOD activity in the SE group. The two AEDs, in both doses applied, also normalized the CAT activity and MDA levels to control values. In conclusion, we suggest that the antioxidant effect of TPM and LCM might contribute to their anticonvulsant effect against pilocarpine-induced SE, whereas their weak anti-inflammatory effect in the hippocampus is a consequence of reduced SE severity.     

Genetic Analysis of Quantitative Signs of White Lupin (Lupinus albus L.) Genotypes

Genetic variability in the base population plays an important role in crop-breeding program. A comprehensive assessment on the quantitative signs of white lupin genotypes was performed to be included in the selection process. Two limits of the environment were applied, i.e., dense and sparse sowing. Positive true heterosis was established in PI533704×Zuter and PI533704×Lucky801 crosses by using the traits of the weight of nodules and fresh root mass weight at both limits of the environment. In more favorable growing conditions, the number and weight of nodules, as well as fresh aboveground mass weight had greater influence on the inheritance of epistatic gene interactions. In the case of dense sowing, the dominant gene actions for the weight of seeds were found more significant. With a high coefficient of inheritance in both environments, the hybrids of PI533704×Zuter and Lucky801×PI533704 were characterized by number and weight of nodules, Zuter×PI533704 by fresh root and aboveground mass weight, and almost all hybrids by seed weight per plant. The assessment of the initial material makes it highly likely to speed up the process of creating new varieties of white lupin.     

Polycrystalline materials in MoO<Subscript>3</Subscript>–ZrO<Subscript>2</Subscript>–V<Subscript>2</Subscript>O<Subscript>5</Subscript> system

Melt quenching technique was applied to study tendency for phase formation and amorphization in the MoO₃–ZrO₂–V₂O₅ system. By X-ray diffraction were detected the main crystalline phases separated during the quenching: Zr(MoO₄)₂, V₂MoO₈, (Mo_0.3V_0.7)₂O₅, V_0.95Mo_0.97O₅ but in a wide concentration range the dominant crystalline phase was monoclinic ZrO₂. The average particle sizes of the obtained crystal phases were in the range 30–50 nm. A narrow glass formation area was situated, near MoO₃–V₂O₅ side. The glass-crystalline samples were obtained in the MoO₃- and V₂O₅-rich compositions. The phase formation was proven by IR analysis also. IR data showed that the main structural units built up the glass network are corner shared VO₅ and MoO₆ groups while in the corresponding crystal V₂MoO₈ phase MeO₆ (Me = V, Mo) octahedra are corner and edge shared (band at 580 cm⁻¹).