Patogeneza i leczenie otyłości u osób w podeszłym wieku

W ciągu ostatnich kilkunastu lat wykazano, że komórki tłuszczowe wydzielają wiele związków o charakterze hormonalnym, z których najlepiej poznano właściwości leptyny, adiponektyny, rezystyny i adipsyny. Obok znanych stymulatorów funkcji adipocytów, takich jak noradrenalina, insulina i glukagon, na komórki te oddziaływają też hormony tarczycy i steroidowe, hormon wzrostu, prostaglandyny, czynniki wzrostowe (IGF-1, EGF) i cytokiny (TNF, IL-6). Nowe dane pozwalają na lepsze zrozumienie patomechanizmów powstawania otyłości. U osób w wieku podeszłym otyłość można zdiagnozować za pomocą prostych metod klinicznych. Intensywne działania oświatowe umożliwiają osiągnięcie umiarkowanej redukcji masy ciała. Jak dotąd brakuje wystarczających danych, aby ocenić wartość interwencji farmakologicznej lub chirurgicznej. Na redukcji masy ciała najbardziej skorzystają osoby o znacznym ryzyku sercowo-naczyniowym. Możliwe jest też uzyskanie pewnej poprawy funkcji ruchowych. Leczenie otyłości w tej grupie wiekowej powinno obejmować zapobieganie utracie masy kości

Zagrożenia zdrowotne wśród dzieci i młodzieży. T. 3

Praca recenzowana / Peer-reviewed pape

Effect of Corrosion Protection Method on Properties of RSW and RFSSW Lap Joints Applied in Production of Thin-Walled Aerostructures

Aluminum structures, and in particular an element of aerostructures, are strongly exposed to the effects of weather conditions. In the case of using new techniques of joining these structural elements, the selection of proper corrosion protection without losing the required properties of the joint may determine its potential application. This paper presents the results of experimental research concerning the influence of corrosion protection on the microstructure and mechanical strength of resistance spot welded (RSW) and refill friction stir spot welded (RFSSW) joints. The tests were carried out on 2024 T3 aluminum alloy, both sides alcladed. For comparison purposes, the following joints were welded: without any protection, with the primer layer, with anodic oxide coating, and with anodic oxide coating plus sealant between the overlapping surface of the welded metal sheet. The samples were visually inspected, and metallographic and mechanical strength examination was conducted. The test results indicate that the application of the protective layers and its type have an impact on the strength of RSW and RFSSW joints. The use of an adhesive or sealant in welded joints provides an increase in the load capacity of the joint

High-Dose Fenofibrate Stimulates Multiple Cellular Stress Pathways in the Kidney of Old Rats

We investigated the age-related effects of the lipid-lowering drug fenofibrate on renal stress-associated effectors. Young and old rats were fed standard chow with 0.1% or 0.5% fenofibrate. The kidney cortex tissue structure showed typical aging-related changes. In old rats, 0.1% fenofibrate reduced the thickening of basement membranes, but 0.5% fenofibrate exacerbated interstitial fibrosis. The PCR array for stress and toxicity-related targets showed that 0.1% fenofibrate mildly downregulated, whereas 0.5% upregulated multiple genes. In young rats, 0.1% fenofibrate increased some antioxidant genes’ expression and decreased the immunoreactivity of oxidative stress marker 4-HNE. However, the activation of cellular antioxidant defenses was impaired in old rats. Fenofibrate modulated the expression of factors involved in hypoxia and osmotic stress signaling similarly in both age groups. Inflammatory response genes were variably modulated in the young rats, whereas old animals presented elevated expression of proinflammatory genes and TNFα immunoreactivity after 0.5% fenofibrate. In old rats, 0.1% fenofibrate more prominently than in young animals induced phospho-AMPK and PGC1α levels, and upregulated fatty acid oxidation genes. Our results show divergent effects of fenofibrate in young and old rat kidneys. The activation of multiple stress-associated effectors by high-dose fenofibrate in the aged kidney warrants caution when applying fenofibrate therapy to the elderly

Piceatannol, a Structural Analog of Resveratrol, Is an Apoptosis Inducer and a Multidrug Resistance Modulator in HL-60 Human Acute Myeloid Leukemia Cells

Acute myeloid leukemia is characterized by uncontrolled clonal proliferation of abnormal myeloid progenitor cells. Despite recent advances in the treatment of this disease, the prognosis and overall long-term survival for patients remain poor, which drives the search for new chemotherapeutics and treatment strategies. Piceatannol, a polyphenolic compound present in grapes and wine, appears to be a promising chemotherapeutic agent in the treatment of leukemia. The aim of the present study was to examine whether piceatannol induces autophagy and/or apoptosis in HL-60 human acute myeloid leukemia cells and whether HL-60 cells are able to acquire resistance to piceatannol toxicity. We found that piceatannol at the IC90 concentration of 14 µM did not induce autophagy in HL-60 cells. However, it induced caspase-dependent apoptosis characterized by phosphatidylserine externalization, disruption of the mitochondrial membrane potential, caspase-3 activation, internucleosomal DNA fragmentation, PARP1 cleavage, chromatin condensation, and fragmentation of cell nuclei. Our findings also imply that HL-60 cells are able to acquire resistance to piceatannol toxicity via mechanisms related to MRP1 activity. Our results suggest that the use of piceatannol as a potential chemotherapeutic agent may be associated with the risk of multidrug resistance, warranting its use in combination with other chemotherapeutic agents

The Changes in Mitochondrial Morphology and Physiology Accompanying Apoptosis in <i>Galleria mellonella</i> (Lepidoptera) Immunocompetent Cells during <i>Conidiobolus coronatus</i> (Entomophthorales) Infection

Mitochondria have been shown to play an important role in apoptosis using mammalian cell lines. However, their role in insects is not fully understood; thus, more indepth studies of insect cell apoptosis are necessary. The present study investigates mitochondrial involvement during Conidiobolus coronatus-induced apoptosis in Galleria mellonella hemocytes. Previous research has shown that fungal infection could induce apoptosis in insect hemocytes. Our findings indicate that mitochondria undergo several morphological and physiological changes during fungal infection, e.g., loss of mitochondrial membrane potential, megachannel formation, disturbances in intracellular respiration, increased nonrespiratory oxygen consumption in mitochondria, decreased ATP-coupled oxygen consumption and increased non-ATP–coupled oxygen consumption, decreased extracellular and intracellular oxygen consumption, and increased extracellular pH. Our findings confirm that G. mellonella immunocompetent cells demonstrate Ca2+ overload in mitochondria, translocation of cytochrome c-like protein from mitochondrial to cytosol fraction, and higher activation of caspase-9-like protein after C. coronatus infection. Most importantly, several of the changes observed in insect mitochondria are similar to those accompanying apoptosis in mammalian cells, suggesting that the process is evolutionarily conserved

Effect of Tool Eccentricity on Microstructure and Properties of FSW Joints Made of Al 7075 T6 Alloy

The aim of this paper was to present preliminary results of researches conducted in PZL Mielec within the FAST_FSW project (INNOLOT program) on influence of tool eccentricity on microstructure and mechanical properties of 1.6 mm and 0.8 mm thick Al 7075 T6 sheets joints. Samples were performed using CNC milling machine. Range of tool eccentricity was 0-0.3 mm, rotational speed and feed rate were variable. The influence of applied welding parameters on microstructure and mechanical properties of joints was assessed on the basis of metallographic inspections and tensile tests. Microstructural observations have shown that the change of FSW tool eccentricity affects the weld geometry: the mixing zone depth, the weld width, or the shape of the contact line

Octanoic Acid—An Insecticidal Metabolite of <i>Conidiobolus coronatus</i> (Entomopthorales) That Affects Two Majors Antifungal Protection Systems in <i>Galleria mellonella</i> (Lepidoptera): Cuticular Lipids and Hemocytes

The food flavour additive octanoic acid (C8:0) is also a metabolite of the entomopathogenic fungus Conidiobolus coronatus, which efficiently infects and rapidly kills Galleria mellonella. GC-MS analysis confirmed the presence of C8:0 in insecticidal fraction FR3 extracted from C. coronatus filtrate. Topical administration of C8:0 had a dose-dependent effect on survival rates of larvae but not on pupation or adult eclosion times of the survivors. Topically applied C8:0 was more toxic to adults than larvae (LD100 for adults 18.33 ± 2.49 vs. 33.56 ± 2.57 µg/mg of body mass for larvae). The administration of C8:0 on the cuticle of larvae and adults, in amounts corresponding to their LD50 and LD100 doses, had a considerable impact on the two main defense systems engaged in protecting against pathogens, causing serious changes in the developmental-stage-specific profiles of free fatty acids (FFAs) covering the cuticle of larvae and adults and damaging larval hemocytes. In vitro cultures of G. mellonella hemocytes, either directly treated with C8:0 or taken from C8:0 treated larvae, revealed deformation of hemocytes, disordered networking, late apoptosis, and necrosis, as well as caspase 1–9 activation and elevation of 8-OHdG level. C8:0 was also confirmed to have a cytotoxic effect on the SF-9 insect cell line, as determined by WST-1 and LDH tests

Diet influences the bacterial and free fatty acid profiles of the cuticle of Galleria mellonella larvae.

The evolutionary success of insects is arguably due to their ability to build up a complex, highly-adaptable and very effective defense system against numerous pathogens, including entomopathogenic fungi. This system relies on the humoral immune system and cellular defense reactions. The first line of defense against biological pathogens is a cuticle formed of several layers. The cuticular lipids may contain hydrocarbons, free fatty acids (FFA), alcohols, waxes, glycerides, aldehydes and sterols. Cuticular fatty acids may also play a role in defending against fungal invasion. Our present findings show that the diet of insects can have a significant effect on their sensitivity and defense response to pathogens; for example, while G. mellonella larvae fed on beeswax had a similar appearance to those reared on a semi-artificial diet, they possessed a different cuticular free fatty acid (FFA) profile to those fed on a semi-artificial diet, and were less sensitive to Conidiobolus coronatus infection. It is possible that the presence of heneicosenoic acid (C21:1) and other long-chain free fatty acids (C22:0, C24:0, C26:0), as well as Brevibacillus laterosporus bacteria, on the cuticle of larvae fed on beeswax, plays a protective role against fungal invasion. Insect pests represent a global problem. An understanding of the basic mechanisms underlying the fungal infection of insects might provide a clearer insight into their defenses, thus allowing the design of more effective, and environmentally-friendly, means of controlling them. The greater wax moth is an excellent model for the study of immunology resistance. Knowledge of the influence of diet on pathogen resistance in insects can be also useful for creating a model of human diseases caused by pathogens, such as Candia albicans