In vitro effects of beetroot juice and chips on oxidative metabolism and apoptosis in neutrophils from obese individuals

Oxidative stress and inflammation are involved in the development of obesity. Beetroot (Beta vulgaris var. rubra) is a food ingredient containing betalain pigments that show antioxidant activity. The in vitro effect of beetroot juice and chips on oxidative metabolism and apoptosis in neutrophils from obese individuals has been investigated. Fifteen obese women (aged 45 +/- 9 years, BMI >30 kg/m2) and nine healthy controls (women, aged 29 +/- 11 years, BMI = 22.2 +/- 1.6 kg/m2) were examined. The investigated products were used as concentrates and after transport and digestion in an artificial gastrointestinal tract. Neutrophil oxidant production, in response to phorbol 12-myristate 13-acetate, was characterized by luminol-dependent chemiluminescence and a flow cytometric dichlorofluorescin oxidation assay. Caspase-3 activity, a marker of apoptosis, was measured by cleavage of the fluorogenic substrate Ac-DEVD-AMC. Neutrophils from obese individuals had a significantly higher ROS production compared with the controls (p < 0.05). Beetroot products inhibited neutrophil oxidative metabolism in a concentration-dependent manner. Also observed were the pro-apoptotic effects of beetroot at a concentration range of 0.1-10% in 24 h culture of stimulated neutrophils. These natural products (in both the liquid and solid state) have antioxidant and antiinflammatory capacity, and could be an important adjunct in the treatment of obesity.     

Dietary Natural Compounds and Vitamins as Potential Cofactors in Uterine Fibroids Growth and Development

An analysis of the literature generated within the past 20 year-span concerning risks of uterine fibroids (UFs) occurrence and dietary factors was carried out. A link between Vitamin D deficiency and UFs formation is strongly indicated, making it a potent compound in leiomyoma therapy. Analogs of the 25-hydroxyvitamin D3, not susceptible to degradation by tissue 24-hydroxylase, appear to be especially promising and tend to show better therapeutic results. Although research on the role of Vitamin A in the formation of fibroids is contradictory, Vitamin A-enriched diet, as well as synthetic retinoid analogues, may be preventative or limit the growth of fibroids. Unambiguous conclusions cannot be drawn regarding Vitamin E and C supplementation, except for alpha-tocopherol. Alpha-tocopherol as a phytoestrogen taking part in the modulation of estrogen receptors (ERs) involved in UF etiology, should be particularly avoided in therapy. A diet enriched in fruits and vegetables, as sources of carotenoids, polyphenols, quercetin, and indole-3-carbinol, constitutes an easily modifiable lifestyle element with beneficial results in patients with UFs. Other natural substances, such as curcumin, can reduce the oxidative stress and protect against inflammation in leiomyoma. Although the exact effect of probiotics on uterine fibroids has not yet been thoroughly evaluated at this point, the protective role of dairy products, i.e., yogurt consumption, has been indicated. Trace elements such as selenium can also contribute to antioxidative and anti-inflammatory properties of a recommended diet. In contrast, heavy metals, endocrine disrupting chemicals, cigarette smoking, and a diet low in antioxidants and fiber were, alongside genetic predispositions, associated with UFs formation.     

Inverse Regulation of Serum Osteoprotegerin and B-Type Natriuretic Peptide Concentrations by Free Fatty Acids Elevation in Young Healthy Humans

Osteoprotegerin (OPG) and B-type natriuretic peptide (BNP) are cardiovascular risk factors, interrelated with each other, with possible associations with insulin sensitivity and glucose homeostasis. The aim of this study was to assess association between OPG and BNP concentrations in a young healthy population, their relation to insulin sensitivity and obesity and their regulation by hyperinsulinemia and serum free fatty acids (FFA) elevation. The study group consisted of 59 male volunteers, 30 of whom were of a normal weight (BMI < 25 kg/m²), and 29 were overweight/obese (BMI > 25 kg/m²). Insulin sensitivity was assessed with the 2-h hyperinsulinemic-euglycemic clamp (HEC). In the subgroup of 20 subjects, the clamp was prolonged to 6 h. After one week, another 6-h clamp, with concurrent Intralipid/heparin infusion, was performed. Serum OPG was positively associated with insulin sensitivity (p = 0.002) and negatively with BMI (p = 0.019) and serum BNP (p = 0.025). In response to 6-h hyperinsulinemia, circulating BNP decreased (p < 0.001). In response to HEC with Intralipid/heparin infusion, OPG decreased (p < 0.001) and BNP increased (p < 0.001). Our data show that OPG and BNP are differentially regulated by FFA, which suggests their association with lipid-induced insulin resistance. The assessment of these cardiovascular risk factors should take into account both long-term and short-term effects associated with insulin resistance.     

Fragment-Resistant Property Optimization within Ballistic Inserts Obtained on the Basis of Para-Aramid Materials

A high protection level without an excessive weight is a basic assumption in the design of modern armors and protection systems. Optimizing armors is a task of development of the utmost importance, and is the subject of the work contained within this article. Optimization of ballistic inserts was carried out using multicriterial analysis (MCA), which enables the selection of the optimal composition, taking into account properties such as ballistic resistance, physicomechanical, and/or functional properties. For this purpose, various types of composite systems were produced and tested in terms of their fragment-resistant properties according to STANAG 2920 and the composite areal density of different ballistic inserts: Soft inserts made of Twaron^® para-aramid sheets, hard ballistic inserts made of multilayer hot-pressed preimpregnated sheets, and hybrid hard ballistic inserts prepared on the basis of multilayer hot-pressed preimpregnated sheets and ceramics. The application of MCA and performance of experimental fragment resistance tests for a wide spectrum of para-aramid inserts are part of the novelty of this work. The obtained test results showed that depending on the composition of the composite system, we could obtain a wide range of fragmentation resistance in the range of 300 to >1800 m/s, which depended on the areal density and type of composite system used. The results also confirmed that MCA is a good computational tool to select the optimal design of para-aramid ballistic inserts.     

Synthesis and 5-HT1A/5-HT2A receptor activity of N-(4-arylpiperazin-1-yl)alkyl derivatives of 2-azaspiro([4.4]nonane and [4.5]decane-1,3-dione

Two series of N-[(4-arylpiperazin-1-yl)-alkyl]-2-azaspiro[4.4]nonane (5-10) and [4.5]decane-1,3-dione (11-16) derivatives were synthesized and their serotonin 5-HT1A and 5-HT2A receptor affinities were determined. Compounds with the methylene spacer (5-7 and 11-13) exhibited low 5-HT1A/5-HT2A receptor affinity, in contrast to their ethylene analogues regarded as potent 5-HT1A ligands, especially those containing a cyclohexane moiety (14-16; Ki = 5.1, 2.7 and 4.3 nM, respectively) in the 3-position of the pyrrolidine-2,5-dione ring. Moreover, derivatives with 3-chloro substituent (10 and 14) showed distinct affinity for 5-HT2A receptors. The functional activity of compounds 10, 14, 15 and 16 was tested in vivo in the commonly used animal models. In those experiments, the tested compounds showed features of agonists of pre- and postsynaptic (14), agonists of presynaptic and antagonists of postsynaptic (10, 15), or agonists of postsynaptic (16) 5-HT1A receptors. Additionally, 10 and 16 exhibited properties of potential 5-HT2A receptor antagonists. The above results suggested a crucial role of the spacer between the amide fragment and 4-arylpiperazine moiety, as well as of the size of the cycloalkyl ring at the 3-position of pyrrolidine-2,5-dione ring in functional 5-HT1A/5-HT2A properties.     

Characterization of pigmented dermo‐epidermal skin substitutes in a long‐term in vivo assay

In our laboratory, we have been using human pigmented dermo‐epidermal skin substitutes for short‐term experiments since several years. Little is known, however, about the long‐term biology of such constructs after transplantation. We constructed human, melanocyte‐containing dermo‐epidermal skin substitutes of different (light and dark) pigmentation types and studied them in a long‐term animal experiment. Developmental and maturational stages of the epidermal and dermal compartment as well as signs of homoeostasis were analysed 15 weeks after transplantation. Keratinocytes, melanocytes and fibroblasts from human skin biopsies were isolated and assembled into dermo‐epidermal skin substitutes. These were transplanted onto immuno‐incompetent rats and investigated 15 weeks after transplantation. Chromameter evaluation showed a consistent skin colour between 3 and 4 months after transplantation. Melanocytes resided in the epidermal basal layer in physiological numbers and melanin accumulated in keratinocytes in a supranuclear position. Skin substitutes showed a mature epidermis in a homoeostatic state and the presence of dermal components such as Fibrillin and Tropoelastin suggested advanced maturation. Overall, pigmented dermo‐epidermal skin substitutes show a promising development towards achieving near‐normal skin characteristics and epidermal and dermal tissue homoeostasis. In particular, melanocytes function correctly over several months whilst remaining in a physiological, epidermal position and yield a pigmentation resembling original donor skin colour.