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1.
Free Radic Res ; : 1-10, 2020 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-32183595

RESUMO

The widely used antimalarial drug amodiaquine (AQ) contains a 7-Cl-quinoline unit, a substituted 4-aminophenol part connected through the amino group and a tertiary amine part. The 4-aminophenol unit can be easily oxidized through radical intermediates to iminoquinone. This reaction also takes place in vitro and in vivo enzymatic reactions. The reaction is expected to have an important role in degradation of AQ in surface waters and also during degradation in advanced oxidation processes. In this paper by means of radiation chemical techniques the one-electron oxidation and reduction of AQ were studied using transient kinetics, kinetics of AQ degradation, formation and decay of end-products of radical reactions. The hydroxyl radicals were shown to add both to the quinoline (∼ 38%) and aminophenol (∼ 50%) parts via formation of hydroxycyclohexadienyl radicals and by H-abstraction or by an electron removal from the tertiary amine part of the molecule (∼ 12%). The dihydroxycyclohexadienyl radical formed on the aminophenol part is suggested to transform to aminophenoxy radical. The hydrated electrons can also effectively contribute to AQ degradation. Chemical oxygen demand and total organic carbon content investigations were also made in order to characterize the ionizing radiation-induced oxidation and mineralization. In aerated 0.1 mmol dm-3 solution, at 2.5 kGy absorbed dose AQ and its higher molecular mass degradation products demolished completely. Ionizing irradiation is a capable technique for degradation of AQ under both oxidative and reductive circumstances.

2.
Orv Hetil ; 161(11): 425-433, 2020 Mar.
Artigo em Húngaro | MEDLINE | ID: mdl-32148096

RESUMO

Introduction: Endometrial cancer is the most common invasive gynecologic malignancy in developed countries. The best survival rates are expected after surgical removal, thus the aim of a complex treatment is to achieve resecability in locally and locoregionally advanced disease. Aim: The primary purpose of this study was to evaluate if the neoadjuvant systemic treatment leads to better overall survival compared to irradiation solely. Method: From January 2015 to December 2018, we enrolled 28 patients diagnosed with irresecable, locally and locoregionally advanced high-risk endometrial carcinoma. Patients were treated by neoadjuvant paclitaxel-carboplatin, then radical hysterectomy, bilateral oophorectomy and lymphadenectomy were performed. Results: After administration of 6 cycles of carboplatin-paclitaxel, the control MR test showed tumor shrinkage in all patients. Complete resection was achieved in the case of every patient. Tumor residuum in lymph nodes was verified in 4 cases by pathological evaluation. The 2-year survival and the 2-year progression-free survival rates were 65,1% and 66,1%, respectively. The median overall survival was 16,5 months. Conclusion: Neoadjuvant treatment can be an effective approach in providing the conditions for complete tumor resection, which may result in survival advantage. Despite multimodal treatment, prognosis is poor. Orv Hetil. 2020; 161(11): 425-433.


Assuntos
Carboplatina/uso terapêutico , Neoplasias do Endométrio/tratamento farmacológico , Neoplasias do Endométrio/cirurgia , Terapia Neoadjuvante , Paclitaxel/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica , Cisplatino/uso terapêutico , Neoplasias do Endométrio/mortalidade , Feminino , Humanos , Excisão de Linfonodo , Estadiamento de Neoplasias , Ovariectomia , Taxa de Sobrevida , Resultado do Tratamento
3.
Med Hypotheses ; 137: 109564, 2020 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-31954994

RESUMO

Parkinson's disease (PD) is a neurodegenerative amyloid disorder with debilitating motor symptoms due to the loss of dopamine-synthesizing, basal ganglia-projecting neurons in the substantia nigra. An interesting feature of the disease is that most of PD patients have gastrointestinal problems and bacterial dysbiosis, years before the full expression of motor symptoms. We hypothesized that antibiotic consumption might be a contributing factor of gut microbiome dysbiosis in PD, favoring curli-producing Enterobacteria. Curli is a bacterial α-synuclein (αSyn) which is deposited first in the enteric nervous system and amyloid deposits are propagated in a prion like manner to the central nervous system. In addition, antibiotics result in a low-grade systemic inflammation, which also contributes to damage of neurons in enteric- and central nervous system. To support our hypothesis, by comparing PD prevalence change with antibiotic consumption data in EU countries, we found significant positive correlation between use narrow spectrum penicillin + penicillinase resistant penicillin and increased prevalence of the disease.

4.
Brain Behav Immun ; 84: 218-228, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31821847

RESUMO

Chronic stress is often accompanied by gastrointestinal symptoms, which might be due to stress-induced shift of gut microbiome to pathogenic bacteria. It has been hypothesized that stress alters gut permeability and results in mild endotoxemia which exaggerates HPA activity and contributes to anxiety and depression. To reveal the relationship between microbiome composition, stress-induced gastrointestinal functions and behavior, we treated chronically stressed mice with non-absorbable antibiotic, rifaximin. The "two hits" stress paradigm was used, where newborn mice were separated from their mothers for 3 h daily as early life adversity (maternal separation, MS) and exposed to 4 weeks chronic variable stress (CVS) as adults. 16S rRNA based analysis of gut microbiome revealed increases of Bacteroidetes and Proteobacteria and more specifically, Clostridium species in chronically stressed animals. In mice exposed to MS + CVS, we found extenuation of colonic mucosa, increased bacterial translocation to mesenteric lymph node, elevation of plasma LPS levels and infiltration of F4/80 positive macrophages into the colon lamina propria. Chronically stressed mice displayed behavioral signs of anxiety-like behavior and neophobia. Rifaximin treatment decreased Clostridium concentration, gut permeability and LPS plasma concentration and increased colonic expression of tight junction proteins (TJP1, TJP2) and occludin. However, these beneficial effects of rifaximin in chronically stressed mice was not accompanied by positive changes in behavior. Our results suggest that non-absorbable antibiotic treatment alleviates stress-induced local pathologies, however, does not affect stress-induced behavior.

5.
Spectrochim Acta A Mol Biomol Spectrosc ; 229: 117970, 2020 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-31887674

RESUMO

Microbial cells are well known to be capable of remaining viable when desiccated, and a variety of beneficial microorganisms can thus be preserved for storage. For the ubiquitous widely studied soil bacterium Azospirillum brasilense (wild-type strain Sp7), which has a significant agrobiotechnological potential owing to its plant-growth-promoting capabilities perspective for its use in biofertilisers, Fourier transform infrared (FTIR) spectroscopy (in the diffuse reflectance mode, DRIFT) was used to control the state of biomass, together with 57Fe transmission Mössbauer spectroscopy to monitor intracellular iron speciation in live rapidly frozen cell suspension and in the lyophilised biomass (both measured at T = 80 K). It has been shown for the first time that a relatively large part of ferrous iron in live cells (22% of the whole cellular iron pool, represented by two high-spin Fe(II) forms, in the 18-h culture grown on 57Fe(III) complex with nitrilotriacetic acid as the sole source of iron) gets largely oxidised upon lyophilisation. The remaining part of iron(II) in the resulting dry biomass was found to be ca. 3% only. The major part of ferric iron in the dry biomass was shown to be comprised of ferritin-like ferric species (giving a typical magnetically split sextet at T = 5 K), while the iron(III) formed from cellular iron(II) by oxidation in air in the course of drying remained in a paramagnetic state even at T = 5 K. The possibility of intracellular iron(II) oxidation to iron(III) upon desiccation may be a specific natural strategy to avoid cell damage caused by Fenton-type reactions in dormant (frozen, dried) cells. The results obtained may have important implications related to iron speciation and redox transformations in dried bacterial preparations intended for long-term storage.

6.
Artigo em Inglês | MEDLINE | ID: mdl-31683468

RESUMO

INTRODUCTION: With the aging of the population, the screening of frail patients, especially before high-risk surgery, come to the fore. The background of the frail state is not totally clear, most likely inflammatory processes are involved in the development. METHODS: Our survey of patients over age of 65 who were on cardiac surgery were performed with Edmonton Frail Scale (EFS). Patients' demographic, perioperative data, incidence of complications and correlations of inflammatory laboratory parameters were studied with the severity of the frail state. RESULTS: On the basis of EFS, 313 patients were divided into non-frail (NF,163,52%), pre-frail (PF,89,28.5%) and frail (F,61,19.5%) groups. Number of complications in the three groups were different (NF:0.67/patient, PF:0.76/patient, F:1.08/patient). We showed significant difference between NF and F in both intensive care and hospital stay, but there was no statistical difference between the groups in hospital deaths (NF:5/163, PF:3/89, F:5/61). We also found a significant difference between NF and F patients in preoperative fibrinogen-, CRP- and white blood cell count levels. CONCLUSIONS: We first present the incidence of frailty in patients with heart surgery in a Central-European population. According to our results, inflammatory processes are likely to play a role in the development of the frail state.

7.
Biotechnol Biofuels ; 12: 215, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31528203

RESUMO

Background: Animal bedding remains an underutilized source of raw material for bioethanol production, despite the economic and environmental benefits of its use. Further research concerning the optimization of the production process is needed, as previously tested pretreatment methods have not increased the conversion efficiency to the levels necessary for commercialization of the process. Results: We propose steam pretreatment of animal bedding, consisting of a mixture of straw and cow manure, to deliver higher ethanol yields. The temperature, residence time and pH were optimized through response-surface modeling, where pretreatment was evaluated based on the ethanol yield obtained through simultaneous saccharification and fermentation of the whole pretreated slurry. The results show that the best conditions for steam pretreatment are 200 °C, for 5 min at pH 2, at which an ethanol yield of about 70% was obtained. Moreover, the model also showed that the pH had the greatest influence on the ethanol yield, followed by the temperature and then the residence time. Conclusions: Based on these results, it appears that steam pretreatment could unlock the potential of animal bedding, as the same conversion efficiencies were achieved as for higher-quality feedstocks such as wheat straw.

8.
Cells ; 8(8)2019 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-31387265

RESUMO

Obesity and adipocyte malfunction are related to and arise as consequences of disturbances in signaling pathways. Tyrosine kinase substrate with four Src homology 3 domains (Tks4) is a scaffold protein that establishes a platform for signaling cascade molecules during podosome formation and epidermal growth factor receptor (EGFR) signaling. Several lines of evidence have also suggested that Tks4 has a role in adipocyte biology; however, its roles in the various types of adipocytes at the cellular level and in transcriptional regulation have not been studied. Therefore, we hypothesized that Tks4 functions as an organizing molecule in signaling networks that regulate adipocyte homeostasis. Our aims were to study the white and brown adipose depots of Tks4 knockout (KO) mice using immunohistology and western blotting and to analyze gene expression changes regulated by the white, brown, and beige adipocyte-related transcription factors via a PCR array. Based on morphological differences in the Tks4-KO adipocytes and increased uncoupling protein 1 (UCP1) expression in the white adipose tissue (WAT) of Tks4-KO mice, we concluded that the beigeing process was more robust in the WAT of Tks4-KO mice compared to the wild-type animals. Furthermore, in the Tks4-KO WAT, the expression profile of peroxisome proliferator-activated receptor gamma (PPARγ)-regulated adipogenesis-related genes was shifted in favor of the appearance of beige-like cells. These results suggest that Tks4 and its downstream signaling partners are novel regulators of adipocyte functions and PPARγ-directed white to beige adipose tissue conversion.

9.
Eur Rev Aging Phys Act ; 16: 13, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31417661

RESUMO

Background: Data in the literature concerning the effects of physical activity on lipid and IGF-1levels are controversial in postmenopausal women. The aim of the present study was to determine the combined effects of a 12 weeks home-based walking program aiming to achieve 10,000 steps daily and a center- based aerobic exercise training on functional capacity, some important cardio-metabolic parameters, IGF-1 level and psychological items among elderly female patients. Sixty female patients (67.4 ± 5 years) with moderate to high cardiovascular risk were randomly assigned either to an exercise training program for 12 weeks or to the control group. Results: Our organized training program resulted in a significantly improved daily physical activity (4232 [IQR: 3162-7219] to 8455 [IQR: 6757-11,488]; p < 0.001 ft-steps), functional capacity (MET) (8.17 ± 1.57 to 8.87 ± 1.76) (p = 0.002), metabolic status including total cholesterol (5.17 ± 1.13 to 4.77 ± 1.12 mmol/l), LDL cholesterol (3.37 ± 1.05 to 2.81 ± 0.98 mmol/l), triglyceride (1.68 ± 0.71 to 1.28 ± 0.71 mmol/l) and HgbA1c (6.24 ± 0.67 to 6.06 ± 0.58 mmol/l), as well as IGF-1 (59.68 ± 27.37 to 66.79 ± 22.74 ng/ml) levels (p < 0.05) in the training group. From psychological tests only physical functionality improved significantly (p = 0.03) in the training group. The training group significantly differed from the control group in four parameters including MET (p = 0.003), LDL-cholesterol (p = 0.046), triglyceride (p = 0.001) and IGF-1 levels (p < 0.001) after the intervention. Conclusion: The applied home-, and- center based training program effectively increased the daily physical activity of the elderly female patients and improved several cardio-metabolic parameters. Further investigations are needed on larger patient population to establish our findings and examine how these positive changes may decrease CV events and mortality.

10.
Chem Biol Interact ; 306: 78-88, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-30954465

RESUMO

SALEN- and SALAN-based complexes with catalytically active metal centers are very promising small molecules to be utilized as part of antioxidant therapies. Here we discuss a modified SALAN-type molecule armed with two phosphonate groups that significantly increase its water solubility and aid to furnish mono- or dinuclear complexes with Cu2+ ions. The regulation of the SOD-mimicking (i.e., catalytic) disproportionation reaction of the superoxide radical anion (O2•-) at pH ~7.5 could be achieved by adjusting the metal-to-ligand stoichiometry as confirmed by McCord-Fridovich and pulse radiolysis tests. The higher antioxidant activity of the dicopper complex can be explained by the better access of O2•- to the copper centers and their more positive Cu(II)/Cu(I) redox potential. Simultaneously the analysis of in vitro effect on cells morphology indicates that cytotoxicity is also affected by the metal-to-ligand ratio, however, the active complex molecules do not show notable cytotoxicity that, together with the observed SOD-like activities, makes them potential candidates for antioxidant therapies.


Assuntos
Antioxidantes/metabolismo , Cobre/farmacologia , Compostos Organometálicos/metabolismo , Superóxido Dismutase/metabolismo , Células 3T3-L1 , Animais , Antioxidantes/química , Antioxidantes/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Cobre/química , Ligantes , Camundongos , Conformação Molecular , Compostos Organometálicos/química , Compostos Organometálicos/farmacologia , Oxirredução
11.
Ideggyogy Sz ; 72(3-4): 135-139, 2019 Mar 30.
Artigo em Húngaro | MEDLINE | ID: mdl-30957469

RESUMO

We report the case of a 60-year-old man who exhibited trigeminal autonomic symptoms on his right side (numbness of the face, reddening of the eye, nasal congestion) occurring several times a day, for a maximum of 60 se-conds, without any pain. The complaints were similar to trigeminal autonomic cephalalgia, just without any headache. Our 60-year-old male patient underwent a craniocervical MRI as part of his neurological workup, which revealed lesions indicative of demyelination. Further testing was guided (ophthalmological examination, VEP, CSF test) by the presumptive diagnosis of multiple sclerosis. It is likely that in his case the cause of these trigeminal and autonomic paroxysms is MS. Here we present an overview of the few cases we found in the literature, although we did not find any similar case reports. Perhaps the most interesting among these is one in which the author describes a family: a 54-year-old female exhibiting the autonomic characteristics of an episodic cluster headache, only without actual headache, her son, who had typical episodic cluster headaches with autonomic symptoms, and the woman's father, whose short-term periorbital headaches were present without autonomic symptoms. We had not previously encountered a case of trigeminal autonomic cephalalgia without headache in our practice, nor have we had an MS patient exhibiting similar neurologic symptoms. The significance of our case lies in its uniqueness.


Assuntos
Encéfalo/diagnóstico por imagem , Esclerose Múltipla/diagnóstico , Cefalalgias Autonômicas do Trigêmeo/diagnóstico , Sistema Nervoso Autônomo/fisiopatologia , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Dor
12.
Sci Rep ; 9(1): 6224, 2019 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-30996341

RESUMO

Glucose is a major fuel for the central nervous system and hypoglycemia is a significant homeostatic stressor, which elicits counterregulatory reactions. Hypothalamic metabolic- and stress-related neurons initiate these actions, however recruitment of glia in control such adaptive circuit remain unknown. Groups of fed- and fasted-, vehicle-injected, and fasted + insulin-injected male mice were compared in this study. Bolus insulin administration to fasted mice resulted in hypoglycemia, which increased hypothalamo-pituitary-adrenal (HPA) axis- and sympathetic activity, increased transcription of neuropeptide Y (Npy) and agouti-related peptide (Agrp) in the hypothalamic arcuate nucleus and activated IBA1+ microglia in the hypothalamus. Activated microglia were found in close apposition to hypoglycemia-responsive NPY neurons. Inhibition of microglia by minocycline increased counterregulatory sympathetic response to hypoglycemia. Fractalkine-CX3CR1 signaling plays a role in control of microglia during hypoglycemia, because density and solidity of IBA1-ir profiles was attenuated in fasted, insulin-treated, CX3CR1 KO mice, which was parallel with exaggerated neuropeptide responses and higher blood glucose levels following insulin administration. Hypoglycemia increased Il-1b expression in the arcuate nucleus, while IL-1a/b knockout mice display improved glycemic control to insulin administration. In conclusion, activated microglia in the arcuate nucleus interferes with central counterregulatory responses to hypoglycemia. These results underscore involvement of microglia in hypothalamic regulation of glucose homeostasis.

13.
Invest Ophthalmol Vis Sci ; 60(5): 1478-1490, 2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-30973576

RESUMO

Purpose: In the eye, chronic hypoxia/reoxygenation (H/R) contributes to the development of a number of ocular disorders. H/R induces the production of reactive oxygen species (ROS), leading to poly(ADP-ribose) polymerase-1 (PARP1) activation that promotes inflammation, cell death, and disease progression. Here, we analyzed the protective effects of the PARP1 inhibitor olaparib in H/R-induced retina injury and investigated the signaling mechanisms involved. Methods: A rat retinal H/R model was used to detect histologic and biochemical changes in the retina. Results: H/R induced reductions in the thickness of most retinal layers, which were prevented by olaparib. Furthermore, H/R caused increased levels of Akt and glycogen synthase kinase-3ß phosphorylation, which were further increased by olaparib, contributing to retina protection. By contrast, H/R-induced c-Jun N-terminal kinase and p38 mitogen-activated protein kinases (MAPK) phosphorylation and activation were reduced by olaparib, via mitogen-activated protein kinase phosphatase 1 (MKP-1) expression. In addition, H/R-induced hypoxia-inducible factor 1α (HIF1α) levels were decreased by olaparib, which possibly contributed to reduced VEGF expression. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) expression was slightly increased by H/R and was further activated by olaparib. Nuclear factor-κB (NFκB) was also activated by H/R through phosphorylation (Ser536) and acetylation (Lys310) of the p65 subunit, although this was significantly reduced by olaparib. Conclusions: Olaparib reduced H/R-induced degenerative changes in retinal morphology. The protective mechanisms of olaparib most probably involved Nrf2 activation and ROS reduction, as well as normalization of HIF1α and related VEGF expression. In addition, olaparib reduced inflammation by NFκB dephosphorylation/inactivation, possibly via the PARP1 inhibition-MKP-1 activation-p38 MAPK inhibition pathway. PARP inhibitors represent potential therapeutics in H/R-induced retinal disease.


Assuntos
Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , Ftalazinas/uso terapêutico , Piperazinas/uso terapêutico , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , Traumatismo por Reperfusão/prevenção & controle , Doenças Retinianas/prevenção & controle , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Animais , Doença Crônica , Citocinas/metabolismo , Modelos Animais de Doenças , Técnica Indireta de Fluorescência para Anticorpo , Hipóxia/complicações , Immunoblotting , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Masculino , Estresse Oxidativo , Oxigênio/toxicidade , Fosforilação , Poli(ADP-Ribose) Polimerase-1/antagonistas & inibidores , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo , Traumatismo por Reperfusão/metabolismo , Doenças Retinianas/metabolismo
14.
Virchows Arch ; 475(1): 95-104, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30903272

RESUMO

The aim of this study was to evaluate the nuclear expression of histone methyltransferase enhancer of zeste homolog 2 (EZH2) in endocervical neoplastic lesions such as invasive endocervical adenocarcinoma (ECA) and cervical in situ adenocarcinoma (AIS) in comparison with normal endocervix and non-neoplastic counterparts. A total of 54 consecutive neoplastic cases (37 ECA, 17 AIS) and 32 non-neoplastic endocervical lesions (15 reactive atypia, 9 microglandular hyperplasia, 3 tuboendometrioid metaplasia, 3 tunnel cluster, 2 endometriosis) were included in the study with adjacent normal endocervix if present. EZH2 immunoreactivity was evaluated semiquantitatively by three independent experts in lesions and adjacent normal glandular epithelium as well. EZH2 expression was defined robust if at least two of the three experts rated partial or diffuse positivity. Robust EZH2 expression was statistically compared among the neoplastic, non-neoplastic, and normal glandular epithelium samples. Diagnostic test capability of robust EZH2 expression was calculated. Fifty-three out of the 54 neoplastic cases (98%) showed robust EZH2 expression. Robust EZH2 expression was significantly less often (4 out of 32 cases, 12.5%) found in the non-neoplastic endocervical lesions (p < 0.0001) and never (0 out of 66 samples) in the adjacent normal glandular epithelium. Robust EZH2 overexpression had a sensitivity and specificity of over 95% in detecting neoplastic lesions versus non-neoplastic lesions or normal glandular epithelium. EZH2 may play a role in the pathogenesis of endocervical neoplasia, and the detection of robust expression of EZH2 might be a useful differential diagnostic tool in problematic endocervical lesions in histology and cytology as well.


Assuntos
Adenocarcinoma in Situ/enzimologia , Adenocarcinoma/enzimologia , Biomarcadores Tumorais/análise , Neoplasia Intraepitelial Cervical/enzimologia , Proteína Potenciadora do Homólogo 2 de Zeste/análise , Neoplasias do Colo do Útero/enzimologia , Adenocarcinoma/patologia , Adenocarcinoma in Situ/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Núcleo Celular/enzimologia , Núcleo Celular/patologia , Neoplasia Intraepitelial Cervical/patologia , Feminino , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Neoplasias do Colo do Útero/patologia
15.
J Mol Neurosci ; 68(3): 408-419, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30443839

RESUMO

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide that exerts general cytoprotective effects, including protection in different kidney disorders. The aim of our study was to investigate the ischemia/reperfusion-induced kidney injury of male and female rats to confirm the protective effects of PACAP in the kidney and to reveal possible gender differences.Male and female Wistar rats underwent unilateral renal artery clamping followed by 24-h, 48-h, or 14-day reperfusion. PACAP was administered intravenously before arterial clamping in half of the rats. Tubular damage, cytokine expression pattern, oxidative stress marker, antioxidative status and signaling pathways were evaluated using histology, immunohistology, cytokine array, PCR, and Western blot. Tubular damage was significantly less severe in the PACAP-treated male and female rats compared to controls. Results of female animals were significantly better in both treated and untreated groups. Cytokine expression, oxidative stress marker and antioxidative status confirmed the histological results. We also revealed that PACAP counteracted the decreased PKA phosphorylation, influenced the expression of BMP2 and BMP4, and increased the expression of the protein Smad1.We conclude that PACAP is protective in ischemia/reperfusion-induced kidney injury in both sexes, but females had markedly less pronounced injury after ischemia/reperfusion, possibly also involving further protective factors, the investigation of which could have future therapeutic value in treating ischemic kidney injuries.


Assuntos
Lesão Renal Aguda/tratamento farmacológico , Anti-Inflamatórios/uso terapêutico , Antioxidantes/uso terapêutico , Rim/efeitos dos fármacos , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/uso terapêutico , Traumatismo por Reperfusão/tratamento farmacológico , Lesão Renal Aguda/etiologia , Animais , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Proteínas Morfogenéticas Ósseas/genética , Proteínas Morfogenéticas Ósseas/metabolismo , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Citocinas/sangue , Feminino , Rim/irrigação sanguínea , Rim/metabolismo , Masculino , Estresse Oxidativo , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/farmacologia , Ratos , Ratos Wistar , Traumatismo por Reperfusão/complicações , Fatores Sexuais , Proteína Smad1/genética , Proteína Smad1/metabolismo
16.
Behav Brain Res ; 360: 244-254, 2019 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-30550948

RESUMO

Negative affective aspects of opiate abstinence contribute to the persistence of substance abuse. Importantly, interconnected brain areas involved in aversive motivational processes, such as the ventral tegmental area (VTA) and medial prefrontal cortex (mPFC), become activated when animals are confined to withdrawal-paired environments. In the present study, place aversion was elicited in sham and adrenalectomized (ADX) animals by conditioned naloxone-precipitated drug withdrawal following exposure to chronic morphine. qPCR was employed to detect the expression of brain derived neurotrophic factor (Bdnf) and the immediate early genes (IEG) early growth response 1 (Egr-1) and activity-regulated cytoskeletal-associated protein (Arc) mRNAs in the VTA and mPFC at different time points of the conditioned place aversion (CPA) paradigm: after the conditioning phase and after the test phase. Sham + morphine rats exhibited robust CPA, which was impaired in ADX + morphine animals. Egr-1 and Arc were induced in the VTA and mPFC after morphine-withdrawal conditioning phase. Furthermore, Bdnf expression was enhanced in the VTA during the test phase. Bdnf induction seemed to be glucocorticoid-dependent, given that was correlated with HPA axis function and was not observed in morphine-dependent ADX animals. In addition, BDNF regulation and function was opposite in the VTA and mPFC during aversive-withdrawal memory retrieval. Our results suggest that IEGs and BDNF in these brain regions may play key roles in mediating the negative motivational component of opiate withdrawal.


Assuntos
Complexo Relacionado com a AIDS/metabolismo , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Encéfalo/metabolismo , Proteína 1 de Resposta de Crescimento Precoce/metabolismo , Glucocorticoides/metabolismo , Síndrome de Abstinência a Substâncias/patologia , Complexo Relacionado com a AIDS/genética , Adrenalectomia , Animais , Aprendizagem da Esquiva/efeitos dos fármacos , Fator Neurotrófico Derivado do Encéfalo/genética , Modelos Animais de Doenças , Proteína 1 de Resposta de Crescimento Precoce/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Glucocorticoides/farmacologia , Masculino , Morfina/efeitos adversos , Dependência de Morfina/complicações , Naloxona/uso terapêutico , Antagonistas de Entorpecentes/uso terapêutico , Entorpecentes/efeitos adversos , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Síndrome de Abstinência a Substâncias/tratamento farmacológico , Síndrome de Abstinência a Substâncias/etiologia , Síndrome de Abstinência a Substâncias/metabolismo
17.
Planta ; 249(3): 751-763, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30382344

RESUMO

MAIN CONCLUSION: Fe uptake machinery of chloroplasts prefers to utilise Fe(III)-citrate over Fe-nicotianamine complexes. Iron uptake in chloroplasts is a process of prime importance. Although a few members of their iron transport machinery were identified, the substrate preference of the system is still unknown. Intact chloroplasts of oilseed rape (Brassica napus) were purified and subjected to iron uptake studies using natural and artificial iron complexes. Fe-nicotianamine (NA) complexes were characterised by 5 K, 5 T Mössbauer spectrometry. Expression of components of the chloroplast Fe uptake machinery was also studied. Fe(III)-NA contained a minor paramagnetic Fe(II) component (ca. 9%), a paramagnetic Fe(III) component exhibiting dimeric or oligomeric structure (ca. 20%), and a Fe(III) complex, likely being a monomeric structure, which undergoes slow electronic relaxation at 5 K (ca. 61%). Fe(II)-NA contained more than one similar chemical Fe(II) environment with no sign of Fe(III) components. Chloroplasts preferred Fe(III)-citrate compared to Fe(III)-NA and Fe(II)-NA, but also to Fe(III)-EDTA and Fe(III)-o,o'EDDHA, and the Km value was lower for Fe(III)-citrate than for the Fe-NA complexes. Only the uptake of Fe(III)-citrate was light-dependent. Regarding the components of the chloroplast Fe uptake system, only genes of the reduction-based Fe uptake system showed high expression. Chloroplasts more effectively utilize Fe(III)-citrate, but hardly Fe-NA complexes in Fe uptake.


Assuntos
Ácido Azetidinocarboxílico/análogos & derivados , Brassica napus/metabolismo , Cloroplastos/metabolismo , Compostos Férricos/metabolismo , Ferro/metabolismo , Ácido Azetidinocarboxílico/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Espectroscopia de Mossbauer , Transcriptoma
18.
Biotechnol Biofuels ; 11: 281, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30337960

RESUMO

Background: Current EU directives demand increased use of renewable fuels in the transportation sector but restrict governmental support for production of biofuels produced from crops. The use of intercropped lucerne and wheat may comply with the directives. In the current study, the combination of ensiled lucerne (Medicago sativa L.) and wheat straw as substrate for hydrogen and methane production was investigated. Steam-pretreated and enzymatically hydrolysed wheat straw [WSH, 76% of total chemical oxygen demand (COD)] and ensiled lucerne (LH, 24% of total COD) were used for sequential hydrogen production through dark fermentation and methane production through anaerobic digestion and directly for anaerobic digestion. Synthetic co-cultures of extreme thermophilic Caldicellulosiruptor species adapted to elevated osmolalities were used for dark fermentation. Results: Based on 6 tested steam pretreatment conditions, 5 min at 200 °C was chosen for the ensiled lucerne. The same conditions as applied for wheat straw (10 min at 200 °C with 1% acetic acid) would give similar sugar yields. Volumetric hydrogen productivities of 6.7 and 4.3 mmol/L/h and hydrogen yields of 1.9 and 1.8 mol/mol hexose were observed using WSH and the combination of WSH and LH, respectively, which were relatively low compared to those of the wild-type strains. The combinations of WSH plus LH and the effluent from dark fermentation of WSH plus LH were efficiently converted to methane in anaerobic digestion with COD removal of 85-89% at organic loading rates of COD 5.4 and 8.5 g/L/day, respectively, in UASB reactors. The nutrients in the combined hydrolysates could support this conversion. Conclusions: This study demonstrates the possibility of reducing the water addition to WSH by 26% and the phosphorus addition by 80% in dark fermentation with Caldicellulosiruptor species, compared to previous reports. WSH and combined WSH and LH were well tolerated by osmotolerant co-cultures. The yield was not significantly different when using defined media or hydrolysates with the same concentrations of sugars. However, the sugar concentration was negatively correlated with the hydrogen yield when comparing the results to previous reports. Hydrolysates and effluents from dark fermentation can be efficiently converted to methane. Lucerne can serve as macronutrient provider in anaerobic digestion. Intercropping with wheat is promising.

19.
Curr Pharm Des ; 24(30): 3534-3542, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30246634

RESUMO

PURPOSE: Pituitary adenylate Cyclase-Activating Polypeptide (PACAP) is a neuroprotective peptide that has been shown to exert protective effects in different models of neurodegenerative diseases, including retinal degenerations. Data obtained from PACAP-deficient (PACAP KO) mice provide evidence that endogenous PACAP has a neuroprotective role in different pathologies. PACAP KO mice show enhanced sensitivity to different insults, such as oxidative stress, hypoxia and inflammation. The aim of the present study was to investigate the protective effects of endogenous PACAP in retinal inflammation. METHODS: Endotoxin-induced eye inflammation was induced by intraperitoneal injection of lipopolysaccharide (LPS) in PACAP KO and wild-type (Wt) mice. After LPS treatment, retinas were processed for histological examination. To detect the alterations of different proteins and cytokines, immunohistochemical, western blot and cytokine array were used. We also performed dark-adapted electroretinography (ERG) to detect the functional differences. RESULTS: The thickness of nearly all layers was significantly less in LPS-injected PACAP KO mice compared to Wt animals. Increased expression of Glial Fibrillary Acidic Protein (GFAP) was induced in Müller glial cells after LPS treatment, which was more intense in PACAP KO mice. The levels of pAkt and pGSK were decreased in PACAP KO group during inflammation. LPS treatment significantly increased cytokines (sICAM-1, JE, TIMP-1) in both treated groups, but it was more expressed in PACAP KO animals. Furthermore, ERG responses were disturbed after LPS injection in PACAP KO mice. CONCLUSION: Our results showed that endogenous PACAP has a protective role in LPS-caused retinal inflammation.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Inflamação/tratamento farmacológico , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/farmacologia , Animais , Inflamação/induzido quimicamente , Inflamação/metabolismo , Injeções Intraperitoneais , Lipopolissacarídeos/administração & dosagem , Masculino , Camundongos , Camundongos Knockout
20.
Int J Clin Exp Hypn ; 66(4): 404-427, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30152735

RESUMO

It is increasingly clear that oxytocin and cortisol play an intricate role in the regulation of behavior and emotions impacting health, relationships, and well-being. Their long-term, cross-generational effect makes them an important focus of the present study. This exploratory research examined changes in oxytocin and cortisol levels and their correlations with different phenomenological measures in both hypnotist and subject during active-alert hypnosis. The level of oxytocin increased whereas the level of cortisol decreased in the hypnotist. When comparing the oxytocin changes of subjects with their hypnotizability, those with low hypnotizability scores experienced an increase in oxytocin, and those with medium and high hypnotizability scores showed no change or decrease. This could explain why clients' hypnotizability is not considered an important factor during hypnotherapy.


Assuntos
Hidrocortisona/análise , Hipnose , Ocitocina/análise , Feminino , Humanos , Hidrocortisona/fisiologia , Ocitocina/fisiologia , Testes Psicológicos , Saliva/química , Inquéritos e Questionários , Adulto Jovem
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