VC (vascular calcification) is highly prevalent in patients with CKD (chronic kidney disease), but its mechanism is multifactorial and incompletely understood. In addition to increased traditional risk factors, CKD patients also have a number of non-traditional cardiovascular risk factors, which may play a prominent role in the pathogenesis of arterial calcification, such as duration of dialysis and disorders of mineral metabolism. The transformation of vascular smooth muscle cells into chondrocytes or osteoblast-like cells seems to be a key element in VC pathogenesis, in the context of passive calcium and phosphate deposition due to abnormal bone metabolism and impaired renal excretion. The process may be favoured by the low levels of circulating and locally produced VC inhibitors. VC determines increased arterial stiffness, left ventricular hypertrophy, a decrease in coronary artery perfusion, myocardial ischaemia and increased cardiovascular morbidity and mortality. Although current therapeutic strategies focus on the correction of phosphate, calcium, parathyroid hormone or vitamin D, a better understanding of the mechanisms of abnormal tissue calcification may lead to development of new therapeutic agents, which could reduce VC and improve cardiovascular outcome in CKD patients. The present review summarizes the following aspects: (i) the pathophysiological mechanism responsible for VC and its promoters and inhibitors, (ii) the methods for detection of VC in patients with CKD, including evaluation of arterial stiffness, and (iii) the management of VC in CKD patients.

The process of melanin synthesis and distribution is called melanogenesis, a process that is based on melanocytes present among the basal cells of the epidermis. Pigments formed in melanocyte melanosomes are then stored in the basal layer of epidermal cells, as well as in dermal macrophages, which become melanophores. From the embryological point of view, melanocytes derive from the melanoblasts of the neural crest, from where they migrate during the first months of life into the skin, eye, cochlea, bone, peripheral nervous system, heart and adipose tissue. The melanic pigments, eumelanin and pheomelanin, are the final product of complex biochemical reactions starting from the amino acid L-tyrosine. Melanin has a major role in skin homeostasis through the photoprotection it offers from the harmful effect of ultraviolet radiation. Melanin absorbs and/or reflects ultraviolet radiation but is also involved in the neutralizing process of free radicals and reactive oxygen species. Pigmentogenesis is a dependent oxygen process and is controlled by intrinsic factors (genetic and hormonal) as well as extrinsic factors (ultraviolet radiation). Melanogenesis is stimulated by stimulant melanocytic hormone, adrenocorticotropin hormone, estrogens and progesterone. The present review aimed to provide a summary of recent data about melanogenesis physiology.

The concept of tissue renin-angiotensin systems (RAS) is now well established and it is now usual to think in terms of renal and tissue systems. At the same time it has emerged that angiotensin II (Ang II) is not the only biologically active peptide generated by the RAS. At least three others have been identified: the heptapeptide Ang III, the hexapeptide Ang IV and Ang 1-7. Specific receptors exits for the last two peptides. In addition, the range of possible physiological and pathophysiological properties for Ang II has been expanding. The current perception of the RAS is therefore that of a much more complex system than previously believed, with autocrine, paracrine and endocrine properties extending beyond the cardiovascular system. This mini-review focuses on the synthetic pathways of the Ang peptides and describes some of their pleiotropic actions. IntroductionOver the last three decades it has become increasingly clear that bioactive angiotensin peptides can be generated not only in the systemic circulation but also as local hormones in several tissues and organs. Classically, the renin-angiotensin system (RAS) has been considered a hormonal circulating system whose final and bioactive product angiotensin II (Ang II) is produced with participation of two critical enzymes, e.g. renin and the angiotensinconverting enzyme (ACE).

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In hemodialysis, volume overload is an important contributor to increased arterial stiffness and modifies cardiovascular status especially by LV hypertrophy. Achieving normohydration may significantly ameliorate cardiac abnormalities and arterial stiffness and may impact major clinical events and CV mortality.

Endothelium-dependent changes in vasomotor tone, whether evoked by vasoactive agents or physical forces, are recognized as essential for the local hemodynamic control in various normal and pathological circumstances. They are based on a complex signaling network within the vascular wall. In recent years, substantial efforts have been made to analyze how such signals are generated and used in the endothelium-dependent control of vascular smooth muscle. The underlying mechanisms vary with species, age, sex, hormonal status, vascular bed studied, caliber of the blood vessels, triggering stimuli, pre-existing vascular tone, oxidative stress, and pathology. Such aspects and many others will be addressed specifically by the authors contributing to this volume.

The skin is an organ with multiple functions, where important inflammatory and immunological processes take place. The integrity of the skin barrier is necessary for it to fulfill its roles. An intact skin barrier requires a physiological keratinization process, but also a normal cutaneous microbial flora. Any change in the proliferation and differentiation of keratinocytes entails the disruption of the skin barrier and the triggering of inflammatory and immunological processes at this level, in response to the aggression of external pathogens. Also, there are several specialised immune cells in the skin (Langerhans cells, T regulator cells, T helper cells), that maintain a balance between pro-inflammatory and anti-inflammatory processes at this level. Disturbing the immune homeostasis causes inflammation and allergic skin reaction. Psoriasis and atopic dermatitis are two inflammatory diseases of the skin, characterized by perturbation of the mechanisms of skin barrier formation. The immune system of the skin is also involved in the pathophysiology of vitiligo and pemphigus. The aim of this review is to offer a brief presentation of the inflammatory and immunological processes that occur in the skin.

Allopurinol is a prodrug converted to oxypurinol by xanthine oxidase, a process followed by an efficient enzyme inhibition. Using a lucigenin-enhanced chemiluminescence method, we found that, under alkaline conditions, superoxide radicals are produced in large amounts in the first step of the interaction between the enzyme and the inhibitor. A comparison between lucigenin and cytochrome c as final detectors revealed that only the chemiluminescence technique is able to detect the superoxide anions from allopurinol oxidation. The allopurinol-xanthine oxidase-lucigenin system can be used for the quantification of various free-radical scavengers, in particular superoxide dismutase mimics. Three manganese compounds from different structural classes [manganese(II) chloride, manganese N,N'-bis(salicylidiene)ethylenediamine chloride, and manganese(III) meso-tetrakis(N-ethylpyridinium-2-yl)porphyrin] were compared at five concentrations (0.01, 0.1, 1, 10, and 100 μM). The method is fast, 16 times more sensitive than the cytochrome c assay at pH 10.1 and could be used for in vivo investigations avoiding the lucigenin redox cycle. If the concentrations of the reagents are increased and Tween 20 is added, the method is also operative at pH 7.4.