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AIMS: The effect of polyphenolic fraction of Lonicera caerulea (PFLC) and alkaloid fraction of Macleaya cordata (AFMC) mix on the production of inflammatory mediators in human gingival fibroblasts pretreated with lipopolysaccharide (LPS) was investigated. In addition, protective effects of mucoadhesive paste containing combination of PFLC and AFMC (0.05% and 0.01%, respectively; n=15, Group A) and placebo (n=15, Group B) were evaluated in patients after surgical extraction of lower third molars. METHODS: Gingival fibroblasts were pre-treated with LPS (10 µg/mL; 24 h) and PFLC/AFMC (25/0.25; 50/0.25; 100/0.25; 25/0.5; 50/0.5; 100/0.5 µg/mL) in serum-free medium was applied for 4 h. Then the interleukin-6 (IL-6), reactive oxygen species (ROS) generation, level of intracellular glutathione (GSH) and expression of cyclooxygenase-2 (COX-2) were evaluated. The study was a 6-day, single-center, randomized, double-blind and placebo-controlled trial consisting of two parallel treatment arms. A modified Oral health impact profile questionnaire including both general oral condition and extraction related questions, was used to evaluate the oral condition and other changes before (day 0) and on the days 1, 3 and 6 after surgical extraction. RESULTS AND CONCLUSION: The combination of PFLC with AFMC caused a reduction of ROS generation, reduced IL-6 production and suppressed the expression of COX-2. In group A the paste treatment contributed to improvement of oral health-related quality of life. Topical application of PFLC and AFMC into the extraction wound improved post-extraction site wound healing probably by antioxidant and anti-inflammatory mechanisms.
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Alcaloides , Tercer Molar , Humanos , Especies Reactivas de Oxígeno/metabolismo , Especies Reactivas de Oxígeno/farmacología , Tercer Molar/cirugía , Tercer Molar/metabolismo , Interleucina-6 , Lipopolisacáridos/farmacología , Calidad de Vida , Ciclooxigenasa 2/farmacología , Fenoles/farmacología , Cicatrización de Heridas , Alcaloides/farmacología , Fibroblastos/metabolismoRESUMEN
The alarming rise of bacterial antibiotic resistance requires the development of new compounds. Such compounds, lipophosphonoxins (LPPOs), were previously reported to be active against numerous bacterial species, but serum albumins abolished their activity. Here we describe the synthesis and evaluation of novel antibacterial compounds termed LEGO-LPPOs, loosely based on LPPOs, consisting of a central linker module with two attached connector modules on either side. The connector modules are then decorated with polar and hydrophobic modules. We performed an extensive structure-activity relationship study by varying the length of the linker and hydrophobic modules. The best compounds were active against both Gram-negative and Gram-positive species including multiresistant strains and persisters. LEGO-LPPOs act by first depleting the membrane potential and then creating pores in the cytoplasmic membrane. Importantly, their efficacy is not affected by the presence of serum albumins. Low cytotoxicity and low propensity for resistance development demonstrate their potential for therapeutic use.
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Antibacterianos , Bacterias Grampositivas , Albúminas , Antibacterianos/química , Membrana Celular , Bacterias Gramnegativas , Pruebas de Sensibilidad Microbiana , Relación Estructura-ActividadRESUMEN
Successful surgeries involving orthopedic implants depend on the avoidance of biofilm development on the implant surface during the early postoperative period. Here, we investigate the potential of novel antibacterial compounds-second-generation lipophosphonoxins (LPPOs II)-as additives to surgical bone cements. We demonstrate (i) excellent thermostability of LPPOs II, which is essential to withstand elevated temperatures during exothermic cement polymerization; (ii) unchanged tensile strength and elongation at the break properties of the composite cements containing LPPOs II compared to cements without additives; (iii) convenient elution kinetics on the order of days; and (iv) the strong antibiofilm activity of the LPPO II-loaded cements even against bacteria resistant to the medicinally utilized antibiotic, gentamicin. Thus, LPPOs II display promising potential as antimicrobial additives to surgical bone cements.
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Human skin explant (HSE) seems to be a useful model for dermatological/cosmetic testing. HSE prepared from donor superfluous skin from plastic surgery operations is cheap and easily obtainable compared to reconstructed models. The HSE use, however, may be limited by the degeneration processes during cultivation. The aim was to monitor changes in metabolic activity and selected apoptotic, inflammatory and antioxidant parameters during 7 day cultivation. The significant changes were found in the superoxide dismutase-2 level from day 5, glutathione S-reductase level from day 6, metabolic activity and fibulin-5 level from day 4, cyclooxygenase-2, interleukin-6 and interleukin-10 from day 1 to 2. Other selected markers (lipid peroxidation products and glutathione level, glutathione S-transferase, catalase, superoxide dismutase and glutathione S-reductase activity, glutathione peroxidase and glutathione S-reductase levels) were not modified significantly due to high inter-individual variability of skin donors. The HSE microstructure as well as cytokeratin-10 and proliferation marker Ki67 expression was also only minimally affected during cultivation. Collectively, the results demonstrate that HSE represents a good model for short-term studies focused on the physical and chemical agent toxicity, protective potential of compounds or metabolic biotransformation. However, reduced metabolic activity, increased inflammation and the high inter-individual variability and sensitivity of donors have to be taken into consideration.
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Antioxidantes/metabolismo , Biomarcadores/metabolismo , Piel , Técnicas de Cultivo de Tejidos/métodos , Ciclooxigenasa 2/metabolismo , Glutatión Peroxidasa/metabolismo , Glutatión Reductasa/metabolismo , Humanos , Interleucina-6/metabolismo , Modelos Biológicos , Piel/inmunología , Piel/metabolismo , Piel/patología , Superóxido Dismutasa/metabolismo , Factores de TiempoRESUMEN
Nrf2 and NF-κB transcription factors act in wound healing via their anti-inflammatory and anti-oxidant effects or through the immune response. Studying this process is a matter of some importance given the high cost of wound treatment. A major contribution in this regard is being made by models that enable investigation of the involvement of multiple factors in wound healing and testing new curative substances. This literature review was carried out via searches in the PubMed and Web of Science databases up to 2016. It covers skin wound healing, available models for its study (part I), the role of Nrf2 and NF-κB, substances that influence them and whether they can be used as markers (part II). Was found that in vitro assays are used for their availability but a holistic view must be established in vivo. In silico approaches are facilitating assessment of a vast amount of research data. Nfr2 and NF-κB play a crucial and reciprocal role in wound healing. Nrf2 controls repair-associated inflammation and protects against excessive accumulation of ROS while Nf-κB activates the innate immune reaction, proliferation and migration of cells, modulates expression of matrix metalloproteinases, secretion and stability of cytokines and growth factors for wound healing.
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Factor 2 Relacionado con NF-E2/fisiología , FN-kappa B/fisiología , Piel , Cicatrización de Heridas/fisiología , Animales , Bioensayo/métodos , Movimiento Celular/inmunología , Movimiento Celular/fisiología , Proliferación Celular/fisiología , Humanos , Inmunidad Innata/fisiología , Modelos Biológicos , Factor 2 Relacionado con NF-E2/antagonistas & inhibidores , FN-kappa B/antagonistas & inhibidores , Estrés Oxidativo/fisiología , Especies Reactivas de Oxígeno/metabolismo , Cicatrización de Heridas/inmunologíaRESUMEN
Wear testing of total joint replacement (TJR) is mandatory in preclinical testing before implantation of TJR into the human body. Testing is governed by current international standards that recommend bovine serum (BS) as a lubricating fluid to replace synovial fluid (SF). Recently, the use of BS has been criticized because of differences in content, fluid characteristics, and nonhuman origin. As a result, a more realistic lubricant mimicking SF is needed. To define SF composition, we analyzed SF obtained during revisions of total hip and knee arthroplasties and compared it with SF obtained during primary arthroplasties and from patients without TJR. Samples were acquired from 152 patients. We found that the median total protein concentration for all SF was 36.8 mg/mL, which is significantly higher than concentrations currently recommended by the ISO standards. The γ-globulin concentration was significantly higher and the phospholipid concentration significantly lower in patients with revision of TJR compared with patients without TJR. No significant difference was found in hyaluronic acid concentration and viscosity among the groups. Our results support the need to improve the definition of a more clinically relevant wear testing lubricant in the ISO standards. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1422-1431, 2017.
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Materiales Biomiméticos/química , Lubricantes/química , Fosfolípidos/análisis , Líquido Sinovial/química , gamma-Globinas/análisis , Adulto , Anciano , Artroplastia de Reemplazo de Cadera , Artroplastia de Reemplazo de Rodilla , Femenino , Humanos , Masculino , Persona de Mediana Edad , Fosfolípidos/metabolismo , Líquido Sinovial/metabolismo , gamma-Globinas/metabolismoRESUMEN
Asporin has been reported as a tumor suppressor in breast cancer, while asporin-activated invasion has been described in gastric cancer. According to our in silico search, high asporin expresion associates with significantly better relapse free survival (RFS) in patients with low-grade tumors but RFS is significantly worse in patients with grade 3 tumors. In line with other studies, we have confirmed asporin expression by RNA scope in situ hybridization in cancer associated fibroblasts. We have also found asporin expression in the Hs578T breast cancer cell line which we confirmed by quantitative RT-PCR and western blotting. From multiple testing, we found that asporin can be downregulated by bone morphogenetic protein 4 while upregulation may be facilited by serum-free cultivation or by three dimensional growth in stiff Alvetex scaffold. Downregulation by shRNA inhibited invasion of Hs578T as well as of CAFs and T47D cells. Invasion of asporin-negative MDA-MB-231 and BT549 breast cancer cells through collagen type I was enhanced by recombinant asporin. Besides other investigations, large scale analysis of aspartic acid repeat polymorphism will be needed for clarification of the asporin dual role in progression of breast cancer.
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Neoplasias de la Mama/patología , Proteínas de la Matriz Extracelular/metabolismo , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/mortalidad , Supervivencia sin Enfermedad , Femenino , Fibroblastos/metabolismo , Fibroblastos/patología , Humanos , Estimación de Kaplan-Meier , Pronóstico , Microambiente Tumoral/fisiologíaRESUMEN
Four novel bile acid ethyl amides were synthetized using a well-known method. All the four compounds were characterized by IR, SEM, and X-ray crystal analyses. In addition, the cytotoxicity of the compounds was tested. Two of the prepared compounds formed organogels. Lithocholic acid derivative 1 formed hydrogels as 1% and 2% (w/v) in four different aqueous solutions. This is very intriguing regarding possible uses in biomedicine.
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Amidas/química , Materiales Biocompatibles/química , Hidrogeles/química , Ácido Litocólico/química , Células 3T3 , Animales , Materiales Biocompatibles/síntesis química , Materiales Biocompatibles/toxicidad , Ácido Litocólico/síntesis química , Ácido Litocólico/toxicidad , Ratones , Modelos Moleculares , Conformación Molecular , Agua/químicaRESUMEN
Most research on American cranberry in the prevention of urinary tract infection (UTI) has used juices. The spectrum of components in juice is limited. This study tested whether whole cranberry fruit powder (proanthocyanidin content 0.56%) could prevent recurrent UTI in 182 women with two or more UTI episodes in the last year. Participants were randomized to a cranberry (n = 89) or a placebo group (n = 93) and received daily 500 mg of cranberry for 6 months. The number of UTI diagnoses was counted. The intent-to-treat analyses showed that in the cranberry group, the UTIs were significantly fewer [10.8% vs. 25.8%, p = 0.04, with an age-standardized 12-month UTI history (p = 0.01)]. The Kaplan-Meier survival curves showed that the cranberry group experienced a longer time to first UTI than the placebo group (p = 0.04). Biochemical parameters were normal, and there was no significant difference in urinary phenolics between the groups at baseline or on day180. The results show that cranberry fruit powder (peel, seeds, pulp) may reduce the risk of symptomatic UTI in women with a history of recurrent UTIs.
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Extractos Vegetales/uso terapéutico , Infecciones Urinarias , Vaccinium macrocarpon , Adulto , Femenino , Frutas , Humanos , Persona de Mediana Edad , Proantocianidinas , Semillas , Infecciones Urinarias/tratamiento farmacológico , Infecciones Urinarias/prevención & control , Vaccinium macrocarpon/química , Adulto JovenRESUMEN
Recently, due to their unique properties, gold nanoparticles (AuNPs) have been used in many biological applications. However, little is known about their toxicity when they come into contact with a biological system. Based on the proposal that AuNPs can have a positive effect on wound healing, the present study investigated the influence of negatively-charged-surface AuNPs (average diameter 25-50 nm) on the viability of normal human dermal fibroblasts (NHDF) and normal human epidermal keratinocytes (NHEK). Moreover, we evaluated the effect of AuNPs on the secretion of proteins involved in wound healing, such as interleukin-8 and - 12 (IL-8, IL-12), tumour necrosis factor-alpha (TNF-α), vascular endothelial growth factor (VEGF), basic fibroblast grow factor (bFGF), and granulocyte-macrophage colony-stimulating factor (GM-CSF). The results showed that AuNPs were not toxic to NHDF and NHEK. They showed a decrease in AuNPs' production of pro-inflammatory cytokines IL-6, IL-12 and TNF-α, as well as proteins involved in angiogenesis such as VEGF and bFGF. Thus, we suggest that AuNPs could have anti-inflammatory and anti-angiogenic activity.
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The aim of this study is to consider the relevance of in situ measurements of bovine serum film thickness in the optical test device that could be related to the function of the artificial hip joint. It is mainly focussed on the effect of the hydrophobicity or hydrophilicity of the transparent surface and the effect of its geometry. Film thickness measurements were performed using ball-on-disc and lens-on-disc configurations of optical test device as a function of time. Chromatic interferograms were recorded with a high-speed complementary metal-oxide semiconductor digital camera and evaluated with thin film colorimetric interferometry. It was clarified that a chromium layer covering the glass disc has a hydrophobic behaviour which supports the adsorption of proteins contained in the bovine serum solution, thereby a thicker lubricating film is formed. On the contrary, the protein film formation was not observed when the disc was covered with a silica layer having a hydrophilic behaviour. In this case, a very thin lubricating film was formed only due to the hydrodynamic effect. Metal and ceramic balls have no substantial effect on lubricant film formation although their contact surfaces have relatively different wettability. It was confirmed that conformity of contacting surfaces and kinematic conditions has fundamental effect on bovine serum film formation. In the ball-on-disc configuration, the lubricant film is formed predominantly due to protein aggregations, which pass through the contact zone and increase the film thickness. In the more conformal ball-on-lens configuration, the lubricant film is formed predominantly due to hydrodynamic effect, thereby the film thickness is kept constant during measurement.
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Prótesis de Cadera , Interferometría/métodos , Lubricantes/química , Ensayo de Materiales/métodos , Suero/química , Adsorción , Animales , Fenómenos Biomecánicos , Bovinos , Interacciones Hidrofóbicas e Hidrofílicas , HumectabilidadRESUMEN
The quaternary benzo[c]phenanthridine alkaloids (QBAs) are an important subgroup of plant secondary metabolites. Their main representatives, sanguinarine (SG) and chelerythrine (CHE), have pleiotropic biological effects and a wide spectrum of medicinal applications. The biotransformation of SG and CHE has only been partially studied while subsequent oxidative transformation of their dihydro derivates, the main metabolites, is practically unknown. The aim of this study was to characterize the biotransformation of CHE and dihydrochelerythrine (DHCHE) in detail, with respect to their more extensive biotransformation than SG. Phase I as well as phase II biotransformation of both compounds was examined in human hepatocyte suspensions. Liquid chromatography with electrospray-quadrupole time-of-flight mass spectrometry (LC-ESI-QqTOF MS) was used for analysis of the metabolites. Using the LC-ESI-QqTOF MS method, we analyzed and then suggested the putative structures of 11 phase I and 5 phase II metabolites of CHE, and 11 phase I and 6 phase II metabolites of DHCHE. For the most abundant metabolites of CHE, DHCHE and O-demethylated DHCHE, their cytotoxicity on primary cultures of human hepatocytes was analyzed. Both metabolites were nontoxic up to 50µM concentration and this indicates decreasing toxic effects for CHE biotransformation products, i.e. DHCHE and O-demethylated DHCHE.
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Benzofenantridinas/farmacocinética , Hepatocitos/metabolismo , Espectrometría de Masa por Ionización de Electrospray/métodos , Biotransformación , Células Cultivadas , Cromatografía Líquida de Alta Presión , HumanosRESUMEN
UVA photons are less energetic than UVB photons but they are more abundant in solar radiation. Modern tools have shown that UVA light has serious adverse effects on the skin. We investigated the effect of consuming Lonicera caerulea berries on UVA-induced damage in SKH-1 mice. The mice were fed a diet containing L. caerulea berries (10%, w/w) for 14 days before a single UVA (30 J/cm(2)) treatment. Effects on haematological and antioxidant parameters were evaluated 4 and 24h after irradiation. The bioavailability of L. caerulea phenolics was also assessed. Consuming the L. caerulea berry-enriched diet caused reduced malondialdehyde production and increased catalase activity and glutathione levels were found in skin and erythrocytes. UVA-induced NADPH:quinone oxidoreductase-1 and gamma-L-glutamate-L-cysteine ligase protein in skin were reduced in mice fed L. caerulea berries. Enhanced heme oxygenase-1 level in skin, interleukin-17 in plasma and reduced interleukin-12 levels in plasma were found in the mice on the experimental diet. Histological (pyknotic) changes in the nuclei of basal cells induced by UVA exposure were reduced in L. caerulea berry consuming animals. HLPC-MS analysis showed high concentrations of hippuric acid, one of the main metabolites of aromatic amino acids and phenolic compounds, in skin, liver, urine and faeces of mice consuming the berries. Taken together, consumption of L. caerulea berries affords protection from the adverse effects of a single UVA exposure mainly via modulation of antioxidant parameters.
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Dieta , Lonicera/química , Piel/efectos de la radiación , Rayos Ultravioleta , Animales , Antioxidantes/metabolismo , Enzimas/metabolismo , Eritrocitos/metabolismo , Eritrocitos/efectos de la radiación , Femenino , Frutas/química , Frutas/metabolismo , Glutatión/metabolismo , Hipuratos/análisis , Hipuratos/orina , Interleucina-12/sangre , Interleucina-17/sangre , Hígado/química , Lonicera/metabolismo , Malondialdehído/metabolismo , Ratones , Ratones Pelados , Piel/metabolismo , Piel/patologíaRESUMEN
Solar ultraviolet radiation is a major environmental factor that has serious adverse effects on the structure and function of the skin. Although the UVB waveband (295-315 nm) represents only 5-10% of incoming UV light, it is very damaging to the skin. The aim of this study was to investigate the effect of Lonicera caerulea berries on UVB-induced damage to SKH-1 hairless mice. Mice were fed a L. caerulea berry-enriched diet (10%, w/w) for 14 days before a single UVB (1000 mJ cm(-2)) treatment. Effects on health status, antioxidant enzyme activity and expression, and DNA damage were evaluated. The bioavailability of L. caerulea phenolic components was also assessed. We found that feeding with L. caerulea berries prevented a decrease in catalase activity and stimulated NADPH quinone oxidoreductase-1, heme oxygenase-1, and gamma-glutamylcysteine synthetase catalytic and modulatory subunit expression in UVB exposed mice. Administration of the L. caerulea berry-enriched diet led to an increase in UVB-reduced interleukin-17 levels and a decrease in keratinocyte-derived chemokine protein expression that was enhanced after UVB treatment. Further, L. caerulea berries reduced UVB-induced DNA damage evaluated as number of single strand breaks, cyclobutane-pyrimidine dimer formation and H2AX phosphorylation, a marker of double strand breaks. Taken together, we provide evidence that oral administration of L. caerulea berries to mice affords at least partial protection from the adverse effects of a single UVB exposure via modulation of antioxidant enzyme activity/expression and reduction of DNA damage.
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Dieta , Frutas/química , Lonicera/química , Rayos Ultravioleta , Animales , Catalasa/metabolismo , Daño del ADN/efectos de la radiación , Eritrocitos/metabolismo , Eritrocitos/efectos de la radiación , Femenino , Frutas/metabolismo , Glutamato-Cisteína Ligasa/metabolismo , Hemo-Oxigenasa 1/metabolismo , Histonas/metabolismo , Interleucina-17/metabolismo , Hígado/enzimología , Hígado/efectos de la radiación , Lonicera/metabolismo , Ratones , Ratones Pelados , NAD(P)H Deshidrogenasa (Quinona)/metabolismo , Fenoles/análisis , Fenoles/orina , Proyectos Piloto , Piel/enzimología , Piel/patología , Piel/efectos de la radiaciónRESUMEN
BACKGROUND: Solar light generates inflammatory responses in exposed skin. These effects are generally attributed to UVB light. However, skin is expose d to a huge quantum of UVA photons as UVA is a predominant part of sunlight and the radiation used in tanning beds. We examined the effects of a single exposure to UVA and UVB wavebands on cytokine levels in skin and plasma, myeloperoxidase (MPO) activity, expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2) in skin. METHODS: Hairless mice were irradiated with either UVA (10 or 20 J/cm²) or UVB (200 or 800 mJ/cm²). The effects were assessed after 4/24 h. Plasma cytokine levels were evaluated using a Bio-Plex cytokine assay. Cytokine, iNOS and COX-2 levels in skin were determined by Western blot. Skin MPO activity was monitored spectrophotometrically. RESULTS: UVB induced up-regulation of interleukin-1ß (IL-1ß) and interleukin-6 (IL-6) and decrease in interleukin-10 (IL-10) mainly after 4 h. In contrast, UVA caused increase in levels of tumor necrosis factor-alpha (TNF-α) and IL-6 after 4 h and up-regulated IL-10 and interleukin-12 (IL-12) after 24 h. The increase in MPO activity from infiltrated leucocytes was observed only in UVB irradiated animals. iNOS was up-regulated 4 h after UVA and UVB treatment. No significant effect on COX-2 expression was detected. CONCLUSIONS: UVA and UVB light affected several inflammatory markers. For individual waveband, changes in plasma parameters did not correlate with those in skin. Thus evaluation of plasma samples cannot simply be replaced by determination in skin specimens and vice versa.
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Citocinas , Piel , Rayos Ultravioleta/efectos adversos , Animales , Western Blotting , Ciclooxigenasa 2/metabolismo , Ciclooxigenasa 2/efectos de la radiación , Citocinas/sangre , Citocinas/efectos de la radiación , Femenino , Ratones , Ratones Pelados , Óxido Nítrico Sintasa de Tipo II/metabolismo , Óxido Nítrico Sintasa de Tipo II/efectos de la radiación , Peroxidasa/metabolismo , Peroxidasa/efectos de la radiación , Piel/metabolismo , Piel/efectos de la radiación , Espectrofotometría , Factores de TiempoRESUMEN
Kidney transplantation (KT) is one of the best treatments for patients with chronic renal disease. It leads to improved kidney function, but the oxidative stress (OS) is only partially eliminated after KT. This study evaluated the effect of KT on outcomes, such as (a) specific kidney functions, (b) metabolic parameters, as well as (c) OS-related markers in 70 patients (46 males, 24 females; mean age = 54 ± 11) before and 1 year after KT. Post KT, the patients were divided into two groups: those receiving only cyclosporine A (N = 36) and those receiving only tacrolimus (N = 34). Improved kidney function (creatinine, urea, and glomerular filtration rate) and biochemical and hematological parameters were found 1 year after KT. OS-related markers (total antioxidant capacity, advanced oxidation protein, and lipid peroxidation products) decreased, but glutathione level increased after KT. Alterations in superoxide dismutase and catalase activities were also found. Glutathione peroxidase levels were unchanged. The level of oxidized low-density lipoprotein was surprisingly, not significantly increased. There was no significant difference between calcineurin inhibitors in any of the measured parameters. Improved renal function after KT is linked to reduction in OS but independent of immunosuppressive therapy.
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Calcineurina/farmacología , Inmunosupresores/farmacología , Trasplante de Riñón/fisiología , Riñón/metabolismo , Estrés Oxidativo/efectos de los fármacos , Adulto , Biomarcadores/metabolismo , Femenino , Tasa de Filtración Glomerular , Humanos , Pruebas de Función Renal , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Insuficiencia Renal Crónica/fisiopatología , Insuficiencia Renal Crónica/cirugía , Resultado del TratamientoRESUMEN
AIMS: Restoration of renal function after kidney transplantation (KT) is expected to improve oxidative stress (OS). However, little is known about the influence of calcineurin inhibitors on oxidized low-density lipoproteins (ox-LDL) after KT. The aim of this study was to evaluate ox-LDLs and related markers of OS, advanced oxidation protein products (AOPP) and total antioxidant status (TAS) in patients after KT on either cyclosporin A (CyA) or tacrolimus (Tac) treatment. METHODS: This was a prospective, randomized, single-center 12 month study evaluating time-dependent changes in biomarkers of OS before and after KT. Twenty nine patients (mean age 54.4 ± 11.1; 55% male and 45% female) were treated with CyA (Group A) and twenty four patients (mean age 52.9 ± 9.9; 75% male and 25% female) were treated with Tac (Group B). The ox-LDL, AOPP, TAS, lipid metabolism parameters, creatinine and glomerular filtration were assessed on day 1 before KT and on days 1 and 7, and in months 1, 3, 6 and 12 after KT. RESULTS: Over the 12 months, the ox-LDL for group A changed from 69.2±32.9 to 65.1±17.1 U/L (P=0.665), while AOPP significantly decreased from 233.0±159.6 to 156.5±90.1 µmol/L (P=0.025) and TAS from 1.87±0.31 to 1.68±0.20 mmol/L (P=0.030). For group B the ox-LDL changed from 62.9±29.7 to ± 61.4±14.6 U/L (P=0.168) and TAS from 1.87±0.51 to 1.68±0.20 mmol/L (P=0.168), while AOPP significantly decreased from 180.5±90.0 to 123.9±37.7 µmol/L (P=0.019). CONCLUSION: AOPP is more sensitive than ox-LDL for assessing OS after KT. TAS values appear to be insufficiently sensitive for monitoring OS in patients after KT.
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Antioxidantes/metabolismo , Proteínas Sanguíneas/metabolismo , Ciclosporina/uso terapéutico , Inmunosupresores/uso terapéutico , Trasplante de Riñón , Lipoproteínas LDL/sangre , Estrés Oxidativo , Tacrolimus/uso terapéutico , Inhibidores de la Calcineurina , Femenino , Humanos , Masculino , Persona de Mediana Edad , Oxidación-ReducciónRESUMEN
Solar ultraviolet (UV) radiation is an important risk factor in skin carcinogenesis. This has been attributed mainly to the UVB waveband because the high-energetic photons are capable of interacting with DNA and inducing DNA damage. Recently, UVA light has also gained increasing interest in relation to DNA alteration. Although UVA photons are less energetic than UVB, they comprise a major fraction of sunlight UV radiation and penetrate deep into the skin. The study was carried out to compare the acute effects of UVA and UVB light on SKH-1 mice in relation to DNA damage and associated parameters. Mice were exposed to UVA (10 and 20 J/cm(2)) or UVB (200 and 800 mJ/cm(2)) radiation. The number of DNA single-strand breaks (SSB) in lymphocytes, amount of phosphorylated histone H2AX (gamma-H2AX) and apoptosis or DNA fragmentation (TUNEL-positive cells) in skin sections and level of gamma-H2AX, activated caspase-3 and phosphorylated p53 in skin were evaluated after 4 and 24 h. SSB analyzed by alkaline comet assay were found to be 4 and 24 h following UVB and UVA treatment, respectively. TUNEL and gamma-H2AX-positive cell were observed only in UVB exposed animals at both time intervals. The level of activated caspase-3 and phospho-p53 was increased 24 h after UVA and UVB radiation and was more apparent in UVB treated mice. The results indicate that the mechanism of DNA damage caused by acute UVA exposure includes formation of SSB (oxidative damage), but not double-strand breaks.
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Daño del ADN , ADN/efectos de la radiación , Piel/efectos de la radiación , Rayos Ultravioleta/efectos adversos , Animales , Apoptosis/efectos de la radiación , Caspasa 3/efectos de la radiación , Roturas del ADN de Cadena Simple , Fragmentación del ADN , Femenino , Histonas/efectos de la radiación , Ratones , Ratones Pelados , Distribución Aleatoria , Luz Solar/efectos adversos , Proteína p53 Supresora de Tumor/efectos de la radiaciónRESUMEN
Patients with chronic renal disease have a high prevalence of oxidative stress (OS), which is associated with the cardiovascular complications occurring in this population. The restoration of kidney function after kidney transplantation (KT) can lead to reduction in the metabolic abnormalities and elimination of the OS. Time-dependent changes in OS-related markers and specific kidney function and metabolic parameters were evaluated in patients (N = 39; 23 males; 16 females; mean age = 57 ± 10 years) before (day 0) and after KT (day 1, 7, 30, 90, and 180) to monitor the graft. In particular, total antioxidant capacity (TAC), levels of advanced oxidation protein products (AOPP), lipid peroxidation as thiobarbituric acid-reactive substances (TBARS) and reduced glutathione (GSH); activities of glutathione peroxidase, catalase, and superoxide dismutase; and kidney function markers were measured. AOPP, TAC, and TBARS were significantly decreased, whereas GSH was significantly increased after KT. Antioxidant enzyme activities were not significantly changed during the monitored period after KT. Apropos specific kidney function markers and glomerular filtration significantly increased and creatinine level significantly decreased after transplantation. Changes in high-density lipoprotein cholesterol were also found. Our results show that successful KT results in normalization of the antioxidant status and lipid metabolism that is connected with both improved renal function and reduced cardiovascular complications.
Asunto(s)
Biomarcadores/sangre , Glutatión/sangre , Fallo Renal Crónico/cirugía , Trasplante de Riñón/fisiología , Estrés Oxidativo , Superóxido Dismutasa/sangre , Sustancias Reactivas al Ácido Tiobarbitúrico/metabolismo , Femenino , Estudios de Seguimiento , Humanos , Fallo Renal Crónico/sangre , Pruebas de Función Renal , Peroxidación de Lípido , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Factores de TiempoRESUMEN
Design, synthesis, and characterization of six novel bile acid-cysteamine conjugates together with investigation of their structural studies, gelation properties, and preliminary toxicity evaluation, are reported. Solid state properties of selected compounds were studied by means of X-ray diffraction and (13)C CPMAS NMR spectroscopy. N-(2-thioethyl)-3α,7α,12α-trihydroxy-5ß-cholan-24-amide was shown to exhibit (pseudo)polymorphism, and a single crystal structure of its non-stoichiometric hydrate is reported herein. Cholyl and dehydrocholyl derivatives bearing three functionalities in their steroidal backbone were shown to undergo self-assembly leading to gelation in certain organic solvents. Preliminary morphology studies of the formed gels by scanning electron microscopy (SEM) were performed. The standard model mouse fibroblast cell line together with the MTT and NR tests were utilized for evaluating the toxicity of the prepared compounds. Lithocholyl, ursodeoxycholyl, and dehydrocholyl derivatives turned out to be relatively non-toxic in the conditions studied.