The aim of this study was to compare the effects of dexmedetomidine and dexamethasone as adjuvants to preoperative epidural administration of local anesthetic (ropivacaine) in thoracic surgery on the ...postoperative level of pain, use of analgesics, inflammation, and oxidative stress. The study enrolled 42 patients who underwent elective thoracic surgery in a one-year period at the University Hospital Dubrava (Zagreb, Croatia). Based on a computer-generated randomization list the patients were assigned to the dexmedetomidine (
= 18) or dexamethasone (
= 24) group. Postoperatively, patients of dexmedetomidine group reported lower pain (VAS value 1 h post surgery, 3.4 ± 2.7
5.4 ± 1.8, dexmedetomidine
dexamethasone,
< 0.01) and had lower anal-gesic requirements in comparison with dexamethasone group. Thus, dexmedetomidine in comparison with dexamethasone was more efficient in lowering pain and analgesia requirements 24 h after the surgery. On the contrary, dexamethasone had better anti-inflammatory properties (CRP level 24 h post surgery, 131.9 ± 90.7
26.0 ± 55.2 mg L
, dexmedetomidine
dexamethasone,
< 0.01). Both dexmedetomidine and dexamethasone exhibited antioxidant effects, however, their antioxidant properties should be further explored. The results of this study improve current knowledge of pain control in thoracic surgery.
Psoriasis is a common chronic inflammatory skin disease which affects 0.5–1 % of children and 2–3 % of the adult population. In Croatia, 1.6 % of the population suffer from psoriasis. Distribution of ...the disease is bimodal, with the first peak at the age of 20–30, and the second at the age of 50–60. The etiopathogenesis of the disease is multifactorial, the key factors being genetic predisposition combined with immunological disorders, environmental factors and skin barrier damage. There are several clinical variants of the disease. The main signalling pathways in psoriasis include TNF-α, IL-23 and IL-17. Topical agents are used for the treatment of the mild form, and the systemic conventional therapy is used for the treatment of moderate to severe forms of the disease. In cases where’s no response, or intolerance or contraindications are present, new targeted medications are to be administered. Development in the field of immunogenetics of psoriasis leads to personalized medicine.
The development of efficient drug formulations for Parkinson’s disease (PD) treatment is challenged by achieving pharmacokinetic profiles, reduced side effects, and better permeability through the ...blood–brain barrier (BBB). As nanoparticles may facilitate the delivery of drugs in the brain due to their high-loading capacity and ability to cross biological barriers, we designed two different types of selenium nanoparticles (SeNPs) that may increase the transport of drugs across the BBB and may act as antioxidants at the site of action. The SeNPs were functionalized with polyvinylpyrrolidone (PVP) and polysorbate 20 (Tween) and characterized in terms of their size, size distribution, shape, surface charge, and colloidal stability in relevant biological media. Their drug-loading capacity was tested using dopamine and l-DOPA as therapeutically active agents for PD. Thermodynamic analysis revealed that binding processes occurred spontaneously through hydrogen bond/van der Waals interactions or electrostatic interactions. The strongest interaction was observed between PVP-SeNPs and l-DOPA or dopamine, which was characterized by a binding constant several orders of magnitude higher than for Tween-SeNPs. However, the addition of human transferrin as a model plasma protein significantly reduced this difference, which indicates the crucial role of protein corona formation in the design of drug nanodelivery systems. In vitro evaluation by cell-free and cellular transwell models showed efficient internalization of SeNP-loaded l-DOPA/dopamine by human endothelial brain cells, while facilitated BBB permeability for l-DOPA, and dopamine was achieved using PVP-SeNPs. Overall, the high potential of SeNPs as drug-delivery vehicles in PD treatment was demonstrated.
Increasing use of nano-enabled products provides many benefits in various industrial processes and medical applications, but it also raises concern about release of nanoparticles (NPs) into the ...environment and subsequent human exposure. While potential toxicity of individual NPs types has been well described in scientific literature, exposure and health-related effects of nanomixtures has been poorly described. This study aimed to evaluate the combined effect of silver (AgNP) and polystyrene NPs (PSNP) on the human macrophages. AgNP are one of the most commercialized NPs due to efficient antimicrobial activity, while PSNP are ubiquitous in terrestrial and aquatic environments due to plastic pollution and degradation of polystyrene-based products. Differentiated monocytic cell line THP-1 were used as an in vitro model of human macrophages. Multiple aspects of cellular response to AgNP-PSNP nanomixture were analyzed including cell death, induction of apoptosis, oxidative stress response, expression of pro- and anti-inflammatory cytokines, and nanomechanical properties of cells. NPs uptake was visualized by confocal microscopy and quantified using flow cytometry. Results show that nanomixture increased apoptosis and cell death, expression of IL-6, IL-8 and TNFa, oxidative stress and mitochondrial dysfunction in cells compared to AgNP and PSNP applied as single treatments, indicating mixture additive action. Anti-inflammatory cytokines IL1b, IL-4 and IL-10 were not affected by combined exposure compared to single NPs. Visualization of NPs uptake and internalization showed that AgNP and PSNP were localized mostly in cytoplasm, with small fraction of AgNP translocated into cell nuclei, which explain increased number of double-stranded DNA breaks following exposure of cells to AgNPs alone or in the mixture. Study outcomes represent clear warnings on the human co-exposure to AgNP and PSNP that needs to be implemented in risk assessment approaches towards toxic-free environment.
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•Response of human macrophages to nanomixture was evaluated.•Nanomixture consisted of silver (AgNP) and polystyrene nanoparticles (PSNP).•Nanomixture showed increased toxicity compared to AgNP and PSNP.•Nanomixture increased oxidative stress, apoptosis and inflammatory response in macrophages.
Ferritin is the main intracellular storage of iron. Animal studies show that female liver and kidney express more ferritin and accumulate more iron than male. However, no study so far has ...investigated sex and age differences in light (FtL) and heavy (FtH) ferritin chain expression. To address this, we relied on specific antibodies and immunochemical methods to analyse the expression of both ferritin chains in the liver and kidney of 3-month and 2-year-old male and female Wistar rats. To see how sex hormones may affect expression we also studied adult animals gonadectomised at the age of 10 weeks. FtL and FtH were more expressed in both organs of female rats, while gonadectomy increased the expression in males and decreased it in females, which suggests that it is stimulated by female and inhibited by male steroid hormones. Normal kidney ferritin distribution and change with aging warrant more attention in studies of (patho) physiological and toxicological processes.
Many personal care products on the market contain endocrine disrupting chemicals, including parabens. Parabens are well known chemical additives used as preservatives. They have been found in mammary ...glands and breast cancer tissues. At the same time, the general public is increasingly exposed to plastic micro- and nanoparticles generated during plastic production and waste disposal. Exposure to chemical cocktails is a realistic scenario of high public health interest, in which many types of compounds such as these two may exhibit synergistic or additive adverse effects. This study evaluated the effects of plastic nanoparticles, parabens, and their mixture on the viability and proliferation of two human breast cancer cell lines: MDA-MB 231, which lacks oestrogen receptors, and MCF-7, which expresses these receptors. Parabens increased proliferation of oestrogen-sensitive breast cancer cells, and this effect became synergistic in the presence of plastic nanoparticles. The mechanism behind synergy may be related to the translocation and adsorption properties of nanoplastics, which served as a Trojan horse to expose cells to parabens more efficiently. These preliminary findings support growing evidence warning about the urgent problem of human exposure to combinations of plastic waste and contingent chemicals.
olive pomace extract (OPE) is a rich source of health promoting polyphenols (hydroxytyrosol (HTS) and tyrosol (TS)) and can be used as a nutraceutical ingredient of dietary supplements and functional ...foods. Its adequate bioavailability is a prerequisite for excreting biological activity and can be significantly and specifically affected by different food matrices.
in order to investigate food effects on polyphenol bioaccessibility, OPE was co-digested with different foods according to internationally harmonized in vitro digestibility method. Impact of particular nutrients on HTS and TS permeability was assessed on Caco-2 cell monolayer.
HTS and TS bioaccessibility and transepithelial permeability can be significantly affected by foods (nutrients), especially by casein and certain types of dietary fiber. Those effects are polyphenol-and nutrient-specific and are achieved either through complexation in gastrointestinal lumen and/or through direct effects of nutrients on intestinal monolayer.
obtained results emphasize the significance and complexity of polyphenol interactions within the food matrix and the necessity of individual investigational approaches with respect to particular food/nutrient and interacting phenolic compounds.
The purpose of this paper was to outline the development of short peptide targeting of the human prostate specific antigen (hPSA), and to evaluate its effectiveness in staining PSA in human prostate ...cancer tissue. The targeting of the hPSA antigen by means of antisense peptide AVRDKVG was designed according to a three-step method involving: 1. The selection of the molecular target (hPSA epitope), 2. the modeling of an antisense peptide (paratope) based on the epitope sequence, and 3. the spectroscopic evaluation of sense-antisense peptide binding. We then modified standard hPSA immunohistochemical staining practice by using a biotinylated antisense peptide instead of the standard monoclonal antibody and compared the results of both procedures. Immunochemical testing on human tissue showed the applicability of the antisense peptide technology to human molecular targets. This methodology represents a new approach to deriving peptide ligands and potential lead compounds for the development of novel diagnostic substances, biopharmaceuticals and vaccines.
Nanotechnology has the potential to provide formulations of antitumor agents with increased selectivity towards cancer tissue thereby decreasing systemic toxicity. This
study evaluated the potential ...of novel nanoformulation based on poly(lactic-
-glycolic acid) (PLGA) to reduce the cardiotoxic potential of doxorubicin (DOX).
toxicity of PLGADOX was compared with clinically approved non-PEGylated, liposomal nanoformulation of DOX (LipoDOX) and conventional DOX form (ConvDOX). The study was performed using Wistar Han rats of both sexes that were treated intravenously for 28 days with 5 doses of tested substances at intervals of 5 days. Histopathological analyses of heart tissues showed the presence of myofiber necrosis, degeneration processes, myocytolysis, and hemorrhage after treatment with ConvDOX, whereas only myofiber degeneration and hemorrhage were present after the treatment with nanoformulations. All DOX formulations caused an increase in the troponin T with the greatest increase caused by convDOX. qPCR analyses revealed an increase in the expression of inflammatory markers IL-6 and IL-8 after ConvDOX and an increase in IL-8 expression after lipoDOX treatments. The mass spectra imaging (MSI) of heart tissue indicates numerous metabolic and lipidomic changes caused by ConvDOX, while less severe cardiac damages were found after treatment with nanoformulations. In the case of LipoDOX, autophagy and apoptosis were still detectable, whereas PLGADOX induced only detectable mitochondrial toxicity. Cardiotoxic effects were frequently sex-related with the greater risk of cardiotoxicity observed mostly in male rats.
Metallothioneins are peculiar cysteine rich, heat resistant, small cellular plasma proteins expressed through almost all life forms. The currently established biological functions of metallothioneins ...are the homeostasis of essential metals and protection against toxic transitional metals (TM) alongside defence from oxidative stress by direct scavenging of reactive oxygen and nitrogen species (ROS and RNS). In mammals, among the four main evolutionary conserved forms, only the ubiquitously expressed metallothionein 1 and 2 (here abbreviated as MT) are inducible by TM, oxidative stress, glucocorticoids and starvation among various other stimuli. However, more than sixty years after being discovered, metallothioneins still bear unresolved issues about their possible physiological function and regulation. The biological function of MTs has still not been associated with the
-demonstrated capacity of MT interaction with cellular molecules glutathione (GSH) or adenosine triphosphate (ATP), or with the possibility of direct iron-MT binding in the reducing intracellular environment of some organelles, e.g. lysosomes. Iron as the most abundant cellular TM is also one of the main physiological sources of ROS. Moreover, iron exhibits strain, sex and age differences that reflected ROS generation and MT induction in (patho)physiology and toxicology studies. A recent study showed that iron sex differences follows expression of both ferritin and MT leading to wide implications from essential TM interconnectivity to aging. This review places emphasis on biochemically proven but physiologically ignored interactions of MT with iron to stimulate advanced research for establishing a wide frame of the biological roles of MTs important for health and longevity.
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