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Transforming growth factor beta 1 (TGF-beta1) is a pro-fibrotic cytokine with a key role in wound repair and regeneration, including induction of fibroblast-to-myofibroblast transition. Genistein is a naturally occurring selective estrogen receptor modulator with promising anti-fibrotic properties. In the present study we aimed to investigate whether genistein modulates TGF-beta1 (canonical and non-canonical) signaling in normal dermal fibroblasts at the protein level (Western blot and immunofluorescence). We demonstrated that TGF-beta1 induces the myofibroblast-like phenotype in the studied fibroblast signaling via canonical (SMAD) and non-canonical (AKT, ERK1/2, ROCK) pathways. Genistein induced only ERK1/2 expression, whereas the combination of TGF-beta1 and genistein attenuated the ERK1/2 and ROCK signaling. Of note, the other studied pathways remained almost unaffected. From this point of view, genistein does not impair conversion of normal fibroblasts to myofibroblast-like cells.
Assuntos
Fibroblastos/efeitos dos fármacos , Genisteína/farmacologia , Fitoestrógenos/farmacologia , Fator de Crescimento Transformador beta1/metabolismo , Avaliação Pré-Clínica de Medicamentos , Fibroblastos/metabolismo , Humanos , Cultura Primária de Células , Transdução de Sinais/efeitos dos fármacos , Fator de Crescimento Transformador beta1/antagonistas & inibidoresRESUMO
AIM: Asymptomatic atrial fibrillation (AF) detection and pulmonary veins isolation (PVI) outcome prediction remain challenging. Our aim was to study the association between apelin and paroxysmal AF in patients undergoing radiofrequency catheter PVI. METHODS: Sixty-three consecutive patients (55 ± 8years, 12 females) with paroxysmal AF without a structural heart disease and implanted ECG loop recorders undergoing PVI and healthy control group of 34 persons (41 ± 9.5years, 21 females) were included. Apelin plasmatic concentrations were measured before and three months after PVI. AF burden was continually assessed for three years. RESULTS: Apelin was significantly decreased in AF patients compared to the healthy controls (0.79 ± 0.09 vs 0.98 ± 0.06 ng/ml; p < 0.00001). Apelin plasmatic concentration of 0.89 ng/ml had 94 % specificity and 89â % sensitivity for AF prediction with the area under the curve (AUC) of 0.96. After propensity matching to sex, age and comorbidities, apelin concentration was significantly lower in AF group (0.78 ± 0.1 vs 0.99 ±0.06 ng/ml; p < 0.0001; AUC: 0.97). There was a significant inverse correlation between apelin concentration and AF burden both before and after PVI (Rho = â0.22; p = 0.05) and (Rho = â0.51; p = 0.006), respectively. There was no significant association between pre-PVI apelin and PVI long-term outcome. CONCLUSION: In patients without a structural heart disease apelin showed a significant specificity and sensitivity for AF prediction and inversely correlated with AF burden (Tab. 3, Fig. 3, Ref. 34).
Assuntos
Fibrilação Atrial , Ablação por Cateter , Veias Pulmonares , Apelina , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/cirurgia , Feminino , Humanos , Recidiva , Resultado do TratamentoRESUMO
An empirically scaled version of the explicitly correlated F12 correction to second-order Møller-Plesset perturbation theory (MP2-F12) is introduced. The scaling eliminates the need for many of the most costly terms of the F12 correction while reproducing the unscaled explicitly correlated F12 interaction energy correction to a high degree of accuracy. The method requires a single, basis set dependent scaling factor that is determined by fitting to a set of test molecules. We present factors for the cc-pVXZ-F12 (X = D, T, Q) basis set family obtained by minimizing interaction energies of the S66 set of small- to medium-sized molecular complexes and show that our new method can be applied to accurately describe a wide range of systems. Remarkably good explicitly correlated corrections to the interaction energy are obtained for the S22 and L7 test sets, with mean percentage errors for the double-zeta basis of 0.60% for the F12 correction to the interaction energy, 0.05% for the total electron correlation interaction energy, and 0.03% for the total interaction energy, respectively. Additionally, mean interaction energy errors introduced by our new approach are below 0.01 kcal mol-1 for each test set and are thus negligible for second-order perturbation theory based methods. The efficiency of the new method compared to the unscaled F12 correction is shown for all considered systems, with distinct speedups for medium- to large-sized structures.
RESUMO
Ultraviolet-C (UV-C) radiation is efficient in reducing the development of diseases in many species, including strawberry (Fragaria × ananassa). Several studies suggest that UV-C radiation is effective not only because of its disinfecting effect but also because it may stimulate plant defenses. In this study, the effect of preharvest UV-C radiation applied during strawberry cultivation on plant growth, fruit quality, and susceptibility to major fungal diseases such as gray mold, powdery mildew, and soft rot was evaluated. UV-C treatments had an impact on flowering initiation and fruit development. Flowering occurred earlier for UV-C-treated plants than for nontreated plants. At harvest, a larger amount of fruit was produced by treated plants despite their slight decrease in leaf area. UV-C treatment did not improve strawberry shelf life but did not alter the physical integrity of strawberry fruit. Natural infection of leaves to powdery mildew and of fruit to Rhizopus spp. strongly decreased in response to UV-C treatment.
Assuntos
Doença , Fragaria , Frutas , Humanos , Sensibilidade e Especificidade , Raios UltravioletaRESUMO
BACKGROUND: Previous studies showed an association between apelin and atrial fibrillation (AF). The aim of this study was to analyse the effect of pulmonary vein isolation (PVI) in patients with paroxysmal AF on plasmatic apelin concentrations. METHODS: Nine consecutive patients (aged from 43 to 69 years, 3 females and 6 males) with documented paroxysmal atrial fibrillation and implanted loop recorders (ILR) for continuous ECG monitoring were included in this study. All the patients underwent a radiofrequency catheter ablation with PVI. RESULTS: The plasmatic concentration of apelin increased after PVI. The average plasmatic concentration of apelin before PVI was 0.299 ng/ml (±0.16), 3 months after PVI 0.462 ng/ml (±0.10) and 9 months after PVI 0.565 ng/ml (±0.146). There was an increase in the concentration of apelin 3 months and 9 months after the PVI by 0.163 ng/ml (p=0.07) and by 0.266 ng/ml (p=0.01), respectively. The concentration of apelin inversely correlated with the AF burden (r=-0.44, p=0.03). CONCLUSIONS: Our study showed a significant increase in apelin levels after the reduction of AF burden via PVI and an inverse correlation with AF burden. Apelin might be a promising marker of AF (Tab. 2, Fig. 2, Ref. 28).
Assuntos
Apelina , Fibrilação Atrial , Biomarcadores , Ablação por Cateter , Adulto , Idoso , Apelina/sangue , Fibrilação Atrial/sangue , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/cirurgia , Biomarcadores/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Veias Pulmonares , Recidiva , Resultado do TratamentoRESUMO
BACKGROUND: Telocytes represent a relatively newly discovered population of cells found within the various tissues and organs, including Fallopian tubes. It is presumed that telocytes could serve as a sensor of hormone levels or regulate activity of muscle peristaltic movement. METHODS: Tissue sections from anatomically different parts of Fallopian tubes of 48 women (age 48.8±9.1) were stained for the expression of five different antigens: c-kit (CD117), CD34, vimentin, podoplanin (D2-40) and Dog-1. RESULTS: Telocytes form a network associated with the smooth muscle cells. From the mentioned antibodies, only anti-c-kit (CD117) seems to be relatively selective specific to the telocytes, others react also with numerous other cells and tissue structures. Our results when using antibodies against podoplanin and Dog-1 are in dissonance with recent literature - with regards to our results, they are not suitable for detection of telocytes. CONCLUSION: Methods of immunohistochemistry are suitable for identification of telocytes in Fallopian tubes. C-kit (CD117) antigens are useful for routine identification of telocytes in histological sections. This antigen can be combined with CD34 or vimentin in cases of double staining immunohistochemistry.
Assuntos
Tubas Uterinas/citologia , Telócitos/citologia , Adulto , Anoctamina-1 , Antígenos CD34/metabolismo , Canais de Cloreto/metabolismo , Tubas Uterinas/metabolismo , Feminino , Humanos , Imuno-Histoquímica , Glicoproteínas de Membrana/metabolismo , Pessoa de Meia-Idade , Proteínas de Neoplasias/metabolismo , Proteínas Proto-Oncogênicas c-kit/metabolismo , Telócitos/metabolismo , Vimentina/metabolismoRESUMO
INTRODUCTION: The current paradigm claims a link between oxidative stress and atrial fibrillation. The aim of our research was to study a relation between the percentage of time spent in atrial fibrillation (AF burden) and concentrations of oxidative stress biomarkers, before and after pulmonary veins isolation (PVI). METHODOLOGY: We included 19 patients (mean age 55±10years, 4 females and 15 males) with implanted loop recorders undergoing PVI. Plasmatic concentrations of advanced glycation end-products (AGEs), fructosamine, advanced oxidation protein products and thiobarbituric-acid reacting substances (TBARS) were measured and AF burden was recorded immediately before and 3months after the PVI. AF burden was also recorded 9months after the PVI. RESULTS: Post procedural AGEs concentration significantly negatively correlated with AF burden after 3months (ρ=-0.63; p<0.01) and 9months (ρ=-0.5; p=0.04), respectively as well as TBARS concentration significantly negatively correlated with AF burden after 9months (ρ=-0.61; p=0.01). CONCLUSION: Our study showed AGEs and TBARS to be potential predictors for AF burden after the PVI. We suppose that the more oxidative stress after the PVI is provoked, the more fibrotic tissue is produced. That means a better electrical isolation of pulmonary veins and consequently a lower AF burden.
Assuntos
Fibrilação Atrial/sangue , Fibrilação Atrial/cirurgia , Produtos Finais de Glicação Avançada/sangue , Sistema de Condução Cardíaco/cirurgia , Veias Pulmonares/cirurgia , Espécies Reativas de Oxigênio/sangue , Substâncias Reativas com Ácido Tiobarbitúrico/análise , Fibrilação Atrial/diagnóstico , Biomarcadores/sangue , Ablação por Cateter , Diagnóstico por Computador/métodos , Eletrocardiografia , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo , Prognóstico , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Resultado do TratamentoRESUMO
Discovery of telocytes has become an important and key challenge in past few years. These cells are interstitial cells extending very long cytoplasmic processes named telopodes, by which they create functional networks in the interstitium of different organs. Telocytes are considered to be connective tissue elements that create contacts among each other, but they also function as intercellular structures, functionally connected with cells of the immune system, neurons and smooth muscle cells. Telocytes can be found also in the different parts of female reproductive system with functions and purpose, which is summarized in our overview. Telocytes regulate for example peristaltic movements in fallopian tubes. The decrease of their number (due to inflammatory disease or endometriosis) causes impairment in transport through fallopian tubes which may result in sterility or tubal gravidity. In uterus they regulate contraction of myometrial smooth muscle (blood expulsion in menstrual phase, childbirth) as well as they contribute in immunological care during embryo implantation. Telocytes probably control also the involution of uterus after delivery. Their function in vagina has not been yet clearly defined; they probably take part in slow muscle contraction movement during sexual intercourse. In mammary glands some scientists suppose their function in control of cell proliferation and apoptosis, that is why, they may play a role in carcinogenesis. In placenta they probably monitor and regulate flow of blood in vessels of chorionic villi and they may be responsible also for etiopathogenesis of pre-eclampsy. All these mentioned functions of telocytes are only in the level of hypothesis and have been published recently. New research and studies will try to answer the questions whether telocytes play a key role in these processes. Our review we completed with some original microphotographs of telocytes in different organs of female reproductive system.
Assuntos
Implantação do Embrião/fisiologia , Tubas Uterinas/fisiopatologia , Contração Muscular/fisiologia , Miométrio/fisiopatologia , Peristaltismo/fisiologia , Telócitos/fisiologia , Contração Uterina/fisiologia , Vagina/fisiopatologia , Endometriose/fisiopatologia , Feminino , Humanos , GravidezRESUMO
OBJECTIVES: The aim of our study was to verify the efficiency of catheter ablation of atrial fibrillation (CA AF) according to the "atrial fibrillation (AF) burden"(time spent in AF) and symptoms related to AF. METHODS: We retrospectively analysed a selected set of 133 patients with atrial fibrillation (81% men, 19% women) who underwent an invasive therapy in the form of CA AF and at the same time had an implanted long-term ECG loop recorder (Reveal XT) in a period of eight years. We investigated AF burden and objective symptoms of AF by data obtained from a long-term implantable ECG loop recorder. Subjective symptoms related to AF were identified during outpatient controls. RESULTS: Firstly, our results demonstrate for the first time a clinically relevant increase in the occurrence of asymptomatic episodes of AF after CA AF. Secondly, when analysing AF symptoms and AF burden at the same time, CA AF in terms of reduction of symptoms and shortening the time in AF had a better effect in patients undergoing 1 procedure (CA AF) compared to patients undergoing repeated procedures (re CA AF). CONCLUSION: The increase in the occurrence of asymptomatic episodes of AF is of considerable importance both for the clinical evaluation of ablation efficacy and for individualized clinical management of patients, especially with respect to antithrombotic therapy (Fig. 10, Ref. 19).
Assuntos
Fibrilação Atrial/cirurgia , Ablação por Cateter/métodos , Fibrilação Atrial/fisiopatologia , Ablação por Cateter/estatística & dados numéricos , Eletrocardiografia Ambulatorial/instrumentação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
OBJECTIVES: Obesity is associated with hyperactivation of the reward system for high-calorie (HC) versus low-calorie (LC) food cues, which encourages unhealthy food selection and overeating. However, the extent to which this hyperactivation can be reversed is uncertain, and to date there has been no demonstration of changes by behavioral intervention. SUBJECTS AND METHODS: We used functional magnetic resonance imaging to measure changes in activation of the striatum for food images at baseline and 6 months in a pilot study of 13 overweight or obese adults randomized to a control group or a novel weight-loss intervention. RESULTS: Compared to controls, intervention participants achieved significant weight loss (-6.3±1.0 kg versus +2.1±1.1 kg, P<0.001) and had increased activation for LC food images with a composition consistent with that recommended in the behavioral intervention at 6 months versus baseline in the right ventral putamen (P=0.04), decreased activation for HC images of typically consumed foods in the left dorsal putamen (P=0.01). There was also a large significant shift in relative activation favoring LC versus HC foods in both regions (P<0.04). CONCLUSIONS: This study provides the first demonstration of a positive shift in activation of the reward system toward healthy versus unhealthy food cues in a behavioral intervention, suggesting new avenues to enhance behavioral treatments of obesity.
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On the basis of experiments at 275 GHz, we reconsider the dependence of the continuous-wave EPR spectra of nitroxide spin-labeled protein sites in sensory- and bacteriorhodopsin on the micro-environment. The high magnetic field provides the resolution necessary to disentangle the effects of hydrogen bonding and polarity. In the gxx region of the 275 GHz EPR spectrum, bands are resolved that derive from spin-label populations carrying no, one or two hydrogen bonds. The gxx value of each population varies hardly from site to site, significantly less than deduced previously from studies at lower microwave frequencies. The fractions of the populations vary strongly, which provides a consistent description of the variation of the average gxx and the average nitrogen-hyperfine interaction Azz from site to site. These variations reflect the difference in the proticity of the micro-environment, and differences in polarity contribute marginally. Concomitant W-band ELDOR-detected NMR experiments on the corresponding nitroxide in perdeuterated water resolve population-specific nitrogen-hyperfine bands, which underlies the interpretation for the proteins.
Assuntos
Ligação de Hidrogênio , Proteínas de Membrana/química , Óxidos de Nitrogênio/química , Marcadores de Spin , Espectroscopia de Ressonância de Spin EletrônicaRESUMO
The clitoris is the female external sexual organ and is composed of erectile bodies. The distal portion of the vagina, clitoris and urethra form an integrated entity sui generis. All these components share a common vasculature and nerve supply and during sexual stimulation they respond as one functional unit. The clitoris is closely linked to the mechanism of sexual arousal in women. Glans has a dense network of receptors, innervated often with a several nerves at the same time - taking care of tactile sensitivity, thus, standing on the beginning of the journey, which culminates in orgasm. Nervus dorsalis clitoridis, which is a branch of n. pudendus, takes care of sensitive innervation. For blood supply is responsible a. clitoridis, which is a branch of a. pudenda interna. The most common congenital developmental anomalies of the clitoris include: clitoromegaly, penis-like clitoris and bifid clitoris. All, however, are among the relatively rare birth defects. Mechanism of orgasm gets attention between both laic and scientific community, although to this date there are speculations about its exact mechanism. There is relevant opinion, influenced by Freuds doctrine, which strictly recognizes two kinds of female orgasms - vaginal and clitoral, and, according to proponents of this theory, only the second mentioned is caused by stimulation of the clitoris. The second school unifies the term orgasm and claims that only clitoral stimulation (digital, penile, cunnilingus) and contraction of striated perineal muscle are responsible for orgasm, whether the glans (external part) or the body of the clitoris from the vaginal approach is stimulated. Therewithal, special term for mythical and still undocumented (despite many attempts and bold claims about its finding) G spot (named after Ernst Gräfenberg, a German doctor who predicted the existence of this place) is redundant. Important role in the regulation of female sexuality and responsiveness play a hormonal influences and varying concentrations of neurotransmitters.
Assuntos
Clitóris/anatomia & histologia , Clitóris/fisiologia , Orgasmo/fisiologia , Feminino , HumanosRESUMO
Carotenoids play an important role in plant adaptation to fluctuating environments as well as in the human diet by contributing to the prevention of chronic diseases. Insights have been gained recently into the way individual factors, genetic, environmental or developmental, control the carotenoid biosynthetic pathway at the molecular level. The identification of the rate-limiting steps of carotenogenesis has paved the way for programmes of breeding, and metabolic engineering, aimed at increasing the concentration of carotenoids in different crop species. However, the complexity that arises from the interactions between the different factors as well as from the coordination between organs remains poorly understood. This review focuses on recent advances in carotenoid responses to environmental stimuli and discusses how the interactions between the modulation factors and between organs affect carotenoid build-up. We develop the idea that reactive oxygen species/redox status and sugars/carbon status can be considered as integrated factors that account for most effects of the major environmental factors influencing carotenoid biosynthesis. The discussion highlights the concept of carotenoids or carotenoid-derivatives as stress signals that may be involved in feedback controls. We propose a conceptual model of the effects of environmental and developmental factors on carotenoid build-up in fruits.
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Carotenoides/fisiologia , Frutas/metabolismo , Estresse Oxidativo , Metabolismo dos Carboidratos , Carotenoides/biossíntese , Carotenoides/metabolismo , Frutas/fisiologia , Peróxido de Hidrogênio/metabolismo , Modelos Biológicos , Oxirredução , Folhas de Planta/metabolismo , Folhas de Planta/fisiologia , Espécies Reativas de Oxigênio/metabolismo , Transdução de SinaisRESUMO
The last decade has witnessed an explosion in novel findings relating to the molecules involved in mediating the sensation of pain in humans. Transient receptor potential (TRP) ion channels emerged as the greatest group of molecules involved in the transduction of various physical stimuli into neuronal signals in primary sensory neurons, as well as, in the development of pain. Here, we review the role of TRP ion channels in primary sensory neurons in the development of pain associated with peripheral pathologies and possible strategies to translate preclinical data into the development of effective new analgesics. Based on available evidence, we argue that nociception-related TRP channels on primary sensory neurons provide highly valuable targets for the development of novel analgesics and that, in order to reduce possible undesirable side effects, novel analgesics should prevent the translocation from the cytoplasm to the cell membrane and the sensitization of the channels rather than blocking the channel pore or binding sites for exogenous or endogenous activators.
Assuntos
Analgésicos/farmacologia , Moduladores de Transporte de Membrana/farmacologia , Nociceptividade/efeitos dos fármacos , Dor Nociceptiva/prevenção & controle , Limiar da Dor/efeitos dos fármacos , Células Receptoras Sensoriais/efeitos dos fármacos , Canais de Potencial de Receptor Transitório/efeitos dos fármacos , Animais , Desenho de Fármacos , Humanos , Terapia de Alvo Molecular , Dor Nociceptiva/metabolismo , Dor Nociceptiva/fisiopatologia , Dor Nociceptiva/psicologia , Células Receptoras Sensoriais/metabolismo , Transdução de Sinais/efeitos dos fármacos , Canais de Potencial de Receptor Transitório/metabolismoRESUMO
We describe the construction and performance of a scanning tunneling microscope capable of taking maps of the tunneling density of states with sub-atomic spatial resolution at dilution refrigerator temperatures and high (14 T) magnetic fields. The fully ultra-high vacuum system features visual access to a two-sample microscope stage at the end of a bottom-loading dilution refrigerator, which facilitates the transfer of in situ prepared tips and samples. The two-sample stage enables location of the best area of the sample under study and extends the experiment lifetime. The successful thermal anchoring of the microscope, described in detail, is confirmed through a base temperature reading of 20 mK, along with a measured electron temperature of 250 mK. Atomically resolved images, along with complementary vibration measurements, are presented to confirm the effectiveness of the vibration isolation scheme in this instrument. Finally, we demonstrate that the microscope is capable of the same level of performance as typical machines with more modest refrigeration by measuring spectroscopic maps at base temperature both at zero field and in an applied magnetic field.
RESUMO
Our measurements of the low frequency ac conductivity in strongly disordered two-dimensional films near the magnetic-field-tuned superconductor-to-insulator transition show a sudden drop in the phase stiffness of superconducting order with either increased temperature or magnetic field. Surprisingly, for two different material systems, the abrupt drop in the superfluid density in a magnetic field has the same universal value as that expected for a Berezinskii-Kosterlitz-Thouless transition in a zero magnetic field. The characteristic temperature at which phase stiffness is suddenly lost can be tuned to zero at a critical magnetic field, following a power-law behavior with a critical exponent consistent with that obtained in previous dc transport studies on the dissipative side of the transition.
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The Fallopian tube has until recently been a neglected structure, bypassed by in vitro fertilization and seen only as a tube that transports the oocyte or early embryo to the uterus. More recently, its role is even more undervalued after the introduction of techniques of assisted reproduction, in which the Fallopian tubes become like unnecessary. The Fallopian tube performs several important functions. It captures the oocyte after ovulation, maintains and controls the migration of spermatozoa to the site of fertilization. It provides the special microenvironment for fertilization; nourishes the early embryo while it is being carried to the uterus and amplifies signals from embryo to the mother. In our article we conducted a systematic review of relevant articles found in PubMed, Scopus and ISI Web of Knowledge, focused on the new insights into the functional morphology of Fallopian tube. We described the possible function of muscle layer motility, ciliary activity and tubal fluid movement on transport of gamets / embryo, as well as we mentioned the negative factors (such as smoking, chlamydial infection or endometriosis) affecting the transport through the Fallopian tube.
Assuntos
Tubas Uterinas/fisiologia , Transporte do Óvulo , Transporte Espermático , Tubas Uterinas/anatomia & histologia , Feminino , Humanos , MasculinoRESUMO
Ventricular fibrillation (VF) is a life-threatening arrhythmia, whose occurrence precedes the development of myocardial arrhythmogenic substrate resulting from either chronic or acute pathophysiological conditions. The authors' previous and current studies suggest that downregulated and/or heterogeneously distributed cell-to-cell coupling protein - connexin-43 (Cx43) - facilitates the development of malignant arrhythmias. It was hypothesized that VF itself deteriorates Cx43, and may hamper cardioversion into sinus rhythm. The purpose of the present study was to examine whether myocardial expression and the phosphorylated status of Cx43 is altered due to VF and during sinus rhythm restoration. Experiments were performed using 10-month-old male and female Wistar rats. Isolated Langendorff-mode-perfused rat hearts were subjected to the following events: basal condition, electrically induced VF lasting 2 min, electrically induced VF lasting 10 min, and sustained VF followed by spontaneous sinus rhythm restoration due to transient stop perfusion. The hearts were snap frozen at each event; ventricular tissue was sent for Cx43 immunoblotting using rabbit antiCx43 polyclonal antibody to detect phosphorylated (P-Cx43) as well as unphosphorylated (noP-Cx43) forms of Cx43, and mouse antiCx43 monoclonal antibody to detect noP-Cx43 only. Compared with basal conditions, total Cx43 expression did not change during experiments in either male or female rat hearts. However, P-Cx43 and the ratio of P-Cx43 to total Cx43 decreased significantly due to VF lasting 2 min and 10 min in male rat hearts only. In parallel, there was a significant increase in noP-Cx43 due to VF lasting 2 min and 10 min in male rat hearts only. Surprisingly, an enhancement of noP-Cx43 linked with suppression of P-Cx43 was detected during stop perfusion-induced termination of VF lasting 2 min, followed by sinus rhythm restoration in both male and female rat hearts. Sinus rhythm was not restored after 10 min of VF, which caused pronounced Cx43 dephosphorylation. In conclusion, there is a downregulation of Cx43 due to sustaining of VF, and it occurs earlier in male rat hearts compared with female rat hearts. It appears that transient no-flow-related inhibition of cell-to-cell coupling, as indicated by an increase in nonP-Cx43, can terminate VF followed by sinus rhythm restoration depending on the degree of previous Cx43 downregulation.
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OBJECTIVES: The aim of the presented study was to evaluate the frequency-domain signal-averaged ECGs (SAECG) abnormalities in childhood and adolescence acute leukemia and lymphoma survivors treated either with or without anthracyclines (ANT) containing chemotherapy in comparison with healthy volunteers. BACKGROUND: The late development of chemotherapy-induced myocardial complications becomes an issue as the number of childhood cancer survivors is increasing. Underlying cardiac impairment may progress to serious cardiac diseases. Therefore, an early identification of myocardial injury is essential. PATIENTS AMD METHODS: Study population was divided into two treatment groups: ANT group (31 patients previously treated with ANT), and non-ANT group (32 patients who underwent chemotherapy without ANT, both more than 5 years ago). SAECG was added to routine cardiology examination in the whole population study and 32 controls. Using the frequency-domain analysis within the QRS complex a ratio (AR) of 20-50 (Hz)/0-20 (Hz) was calculated. RESULTS: AR 20-50/0-20 in SAECG was significantly higher in ANT and non-ANT groups, relative to controls (262.5 p < 0.00001 vs. 135.9 p < 0.001 vs. 74.7). The difference between both patient groups was also evident p < 0.01. CONCLUSION: Significant differences in frequency-domain SAECG parameters between patients (with or without anthracyclines) and controls might indicate the increased risk of electrical instability particularly in anthracycline-treated patients (Tab. 2, Fig. 1, Ref. 34).
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Antraciclinas/uso terapêutico , Antibióticos Antineoplásicos/uso terapêutico , Eletrocardiografia , Leucemia/fisiopatologia , Linfoma/fisiopatologia , Processamento de Sinais Assistido por Computador , Doença Aguda , Adolescente , Antraciclinas/efeitos adversos , Antibióticos Antineoplásicos/efeitos adversos , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Leucemia/tratamento farmacológico , Linfoma/tratamento farmacológico , MasculinoRESUMO
Late cardiac complications in cancer survivors may develop from subclinical myocardial damage. Biochemical correlates of minimal myocardial changes can be analyzed using a commercially available rapid assay. Biomarkers are considered more sensitive markers of subclinical cardiotoxicity than conventional electrocardiographic and echocardiographic methods. The aim of this study was to determine the values of plasma N-terminal pro brain natriuretic peptide (NT-pro-BNP) and cardiac troponin T (cTnT) in asymptomatic childhood leukemia survivors after anthracycline therapy in comparison with healthy volunteers. The survivors also underwent a detailed echocardiography. Twenty six survivors of leukemia previously treated with anthracyclines with total cumulative dose 95-600 (median 221) mg/m(2) were evaluated. Analyses of cTnT and NT-proBNP from blood samples and echocardiography were performed 5-25 years after completion of therapy for childhood leukemia. Control group for biochemical analyses consisted of 22 age- and gender- matched apparently healthy volunteers. Values of NT-proBNP were significantly elevated in ANT group compared to controls (35.1 +/- 37.8 vs. 9.6 +/- 6.7 pg/ml, P<0.010). CTnT remained below the diagnostic cut-off values in both groups. All echocardiographic parameters of patients remained normal. In conclusion, differences in NT-proBNP values between patients treated with anthracyclines and healthy volunteers might signal an initial stage of anthracycline-induced myocardial damage. The potential of this biomarker to detect subclinical anthracycline-induced myocardial alterations before development of echocardiographic and clinical changes is promising.