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BACKGROUND: Rheumatoid arthritis (RA) is chronically persistent synovitis and systemic inflammation. Although multiple contributors are detected, only one is pivotal in the neonatal period: the negative selection of autoimmune naïve T-cells by the autoimmune regulator (AIRE) transcriptional factor. METHODS: Single-nucleotide polymorphisms (SNPs) in the DNA-binding site of AIRE may determine its function and expression. We intended to analyse site-specific allelic polymorphisms in two exon (rs878081 and rs1055311) and three intron (rs1003853, rs2075876, and rs1003854) loci with an RA risk. Our analytical case-control study analysed 270 RA patients and 322 control subjects in five different genetic models using quantitative real-time PCR (qPCR) with TaqMan® assays. RESULTS: Statistically significant differences were found between the odds of allelic polymorphisms in the loci of rs878081, rs1003854, and rs1003853 among the controls and RA patients, and the disease activity seemed to be significantly associated with the genotypic subgroups of rs878081 and rs1055311. Our in silico analysis supported this, suggesting that allele-specific alterations in the binding affinity of transcriptional factor families might determine RA activity. CONCLUSION: Our findings highlight the involvement of neonatal self-tolerance in RA pathogenesis, providing novel insights into disease development and paving the way for an analysis of further site-specific genetic polymorphisms in AIRE to expand the intervention time for RA.
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Background - Leukodystrophies, a heterogeneous group of brain and spinal cord disorders, often pose challenges in establishing molecular etiology. Vanishing White Matter Disease (VWMD) is a rare subtype of leukodystrophies presenting with characteristic clinical and MRI features, nevertheless, achieving diagnostic certainty requires genetic studies.
Case presentation - Our patient is a nine year old girl, who developed progressive gait difficulties at around 3-4 years of age. Her brain MRI showed confluent lesions with increased signal intensity in the cerebral and cerebellar white matter on T2/FLAIR sequences, within which hypointense regions appeared with signal intensity resembling that of the cerebrospinal fluid on T1 sequences. Whole exome sequencing identified a homozygous likely pathogenic variant within the EIF2B5 gene in the proband, which was present in a heterozygous state in both asymptomatic parents. Having the clinical and molecular genetic diagnosis established, we explored therapeutic possibilities for the patient.
Conclusion - VWMD is a severe form of leukodystrophies with little or no disease modifying therapy available until recently. A better understanding of its molecular pathogenesis offers some hope for new inventive therapies.
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Factor 2B Eucariótico de Iniciación , Leucoencefalopatías , Mutación , Humanos , Leucoencefalopatías/genética , Leucoencefalopatías/diagnóstico por imagen , Leucoencefalopatías/patología , Femenino , Factor 2B Eucariótico de Iniciación/genética , Niño , Imagen por Resonancia Magnética , Sustancia Blanca/diagnóstico por imagen , Sustancia Blanca/patologíaAsunto(s)
Feto , Diagnóstico Prenatal , Embarazo , Femenino , Humanos , Secuenciación del Exoma , Hungría , Análisis por MicromatricesRESUMEN
Background: Midwifery practice in Hungary is characterized by chronic stress, which may in turn lead to burnout and impaired perinatal care. However, little is known about the degree and potential stressors of burnout, which hinder the development of strategies to promote well-being among midwives in Hungary. Aim: To assess the prevalence of burnout and identify persistent individual and occupational stressors among midwives in Hungary over the past decade to inform prevention. Methods: We conducted two cross-sectional studies among midwives in 2014 and 2022. We used the Maslach Burnout Inventory to assess burnout (emotional exhaustion, depersonalization, and personal accomplishment) over time. We also collected data on individual and work characteristics. We performed a multivariate regression analysis to explore associations between burnout and respondents' characteristics. Findings: The degree and prevalence of emotional exhaustion among midwives increased significantly between 2014 (N = 224) and 2022 (N = 152). High workload, not feeling valued at work, poorly perceived health status and work dissatisfaction emerged as a significant positive correlate of emotional exhaustion or depersonalization in both studies. Living alone showed both a positive and inverse association with burnout in 2014 and 2022, respectively. Work satisfaction was a positive correlate of personal accomplishment in both studies. Conclusions: Our results add to and confirm the growing body of evidence about the high prevalence of burnout among midwives in Hungary. We identified potential risk factors and outcomes of burnout, which remained unchanged over time. To prevent or reduce burnout among midwives, future interventions should focus on addressing these potential persistent risk factors. However, the time-varying role of factors influencing burnout makes it advisable to review preventive interventions from time to time.
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INTRODUCTION: The healthcare sector is the most studied area of burnout, as the mental health of healthcare workers has a significant impact on the mental health of the people they care for. OBJECTIVE: The aim of our study was to investigate whether there have been changes in the dimensions of burnout among midwives, and how the relationships between burnout and the individual factors and working conditions that influence it have evolved, using national data from 2014 and 2022. METHOD: An anonymous, voluntary, questionnaire-based survey of midwives working exclusively in maternity units was conducted using the Maslach Burnout Inventory questionnaire, which measures burnout, and questions on respondents' demographic characteristics and working conditions. Multivariate ordinal logistic regression was used to explore associations between burnout and respondent characteristics, and associations were characterized by odds ratios. RESULTS: Among the dimensions of burnout, no change in depersonalization was observed in 2022, but both emotional exhaustion and personal ineffectiveness were significantly more common in 2022 than in 2014. Responses from 224 midwives in 2014 and 152 midwives in 2022 were analyzed. Looking at the influencing factors, higher levels of burnout in 2014 were significantly associated with poorer perceived health, lack of a partner, smoking, shorter time in healthcare, having a job in a larger city, feeling overworked and dissatisfied. In 2022, on the other hand, younger age, smoking, shorter time in healthcare, feeling overworked, dissatisfied and unvalued were associated with higher levels of burnout. Looking at the combined effect of these factors, willingness to attend a health promotion lecture and having a second job also showed a significant effect on burnout in 2022. DISCUSSION: The authors discuss the change in burnout among midwives and the possible reasons for the correlations shown. CONCLUSION: The results of the first study on burnout among midwives in Hungary show that improving the working conditions of midwives is essential for the functioning of family-friendly midwifery. In addition, to prevent burnout, more emphasis should be placed on the prevention of the risk factors identified in the study in education and training. Orv Hetil. 2023; 164(40): 1592-1599.
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Partería , Embarazo , Femenino , Humanos , Hungría/epidemiología , Agotamiento Psicológico , Fumar , EmocionesRESUMEN
INTRODUCTION: Despite the more than 100-year history of the Hungarian Health Visitor Service, no study has yet been carried out that looked back at the cooperation between health visitors and physicians. OBJECTIVE: Our aim was 1) to explore the professional advances of the health visitor service and the cooperation between health visitor and physician by examining historical documents, legal and professional regulations governing the work of health visitor, furthermore, 2) to investigate whether there are compulsory training elements in today's training for health visitors that prepare students for health visitor and physician collaboration, moreover, 3) to search for old tools and documents used by health visitors and doctors in the North-West of Transdanubia. METHOD: A literature search was carried out to identify documents relating to the development of the work of health visitors, the cooperation between health visitors and physicians, past and current legal and professional regulations, the current regulation on training of health visitors. Through field research, we tracked down old tools and documents of health visitors and physicians. RESULTS: The establishment of the Hungarian Health Visitor Service is associated with the names of professors of medicine. The historical documents and regulations testify the development of the work of the health visitor, the expansion of her competences and the importance of the health visitor and physician cooperation. The training competences required for the cooperation between health visitors and physicians, health visitors and specialists are regulated by the regulation on training of health visitors. We have found many old objects and documents used in the work of the health visitor and doctor. DISCUSSION: The documents that have preserved almost invariably describe the health visitor as a person working alongside the physician, in cooperation with the physician. Nowadays, the regulation of cooperation covers for all specialties in the field of health visitor. CONCLUSION: Based on our research, it is fair to say that the health visitor-physician cooperation is an important pillar of the 108-year-old Hungarian Health Visitor Service. Orv Hetil. 2023; 164(33): 1311-1318.
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Medicina , Enfermeros de Salud Comunitaria , Médicos , Humanos , Femenino , Anciano de 80 o más Años , Hungría , Servicios de SaludRESUMEN
Background: With the increase of cyberbullying, several intervention programmes have been created that aim at reducing cyber-victimisation and perpetration. Objective: Our study presents the effects of the STAnD anti-cyberbullying programme with peer-education both on the short and the long run among lower and upper primary school students, with a focus on the participants' cyberbullying roles. Method: The sample comprised of 536 students who participated in the intervention programme, involving 36% lower and 64% upper primary school students. Participants were measured by a self-reported questionnaire before and right after the programme, then six months later. Results: The main effect of the STAnD programme was a positive change in the participants' willingness to engage in help-seeking and their active-defending reaction, although this effect decreased after six months. The changes were larger among lower primary school students compared to upper primary school participants. Conclusion: Our results imply that long-lasting and intensive health promotion programmes are necessary to reach a long-term intervention effect. Anti-cyberbullying programmes should take into consideration participants' involvement and roles in cyberbullying. As our study was a non-randomised uncontrolled study design, thus interpretation of the effectiveness of the programme is limited. Supplementary Information: The online version contains supplementary material available at 10.1007/s10566-022-09714-9.
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Introduction: Burnout syndrome among healthcare workers is a well-known problem. Its occurrence and the roots have been addressed in several studies. The daily work of the specialist employees in the neonatal intensive care units is extremely stressful physically and mentally. Objective: The study assessed the frequency and intensity of burnout phenomenon among healthcare professionals working in neonatal intensive care units and examined the relations between institutional levels, occupation, and work experience. Method: Data were collected in 2019 using the Maslach Burnout Inventory (MBI) questionnaire compiled by
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Agotamiento Profesional , Agotamiento Psicológico , Agotamiento Profesional/psicología , Agotamiento Psicológico/psicología , Personal de Salud , Humanos , Recién Nacido , Encuestas y Cuestionarios , Lugar de Trabajo/psicologíaRESUMEN
The use of non-Saccharomyces yeasts for alcoholic beverage improvement and diversification has gained considerable attention in recent years. The effect of pure and mixed inocula (of Torulaspora delbrueckii, Lachancea thermotolerans, and Saccharomyces cerevisiae) on apple mash fermentation has been determined for the production of Hungarian fruit spirit (Pálinka), with a special emphasis on the chemical, volatile, and sensory attributes. The enological parameters were followed during the fermentation process. Sugar consumption and organic acid production were determined by HPLC, whereas the aromatic profile of the distillates was characterized by GC-FID. According to the results, single and mixed cultures showed similar characteristics during mash fermentation. The identified volatile compounds included aldehydes, esters, and higher alcohols. Mixed culture fermentation trials revealed a significantly higher concentration of volatile compounds and better sensorial attributes compared to those exhibited by the pure culture of S. cerevisiae.
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INTRODUCTION: Osteoarthritis (OA) as the most common joint disease is a major public health concern. AIM: To investigate the effect of multimorbidity on functional and quality of life outcomes in women with generalized osteoathritis (hand and knee arthritis, GOA). METHOD: In this cross-sectional study, patients according to the American College of Rheumatology (ACR) criteria for OA were invited. The control group consisted of subjects without any musculoskeletal symptoms, osteoarthritis or inflammatory rheumatic disease. Comorbidity count was calculated from the investigated comorbidities. In the GOA group, the function was assessed by Western Ontario and McMaster Universities Arthritis Index (WOMAC), Cochin Hand Scale, Knee Injury and Osteoarthritis Outcome Score (KOOS), Health Assessment Questionnaire (HAQ), while quality of life was measured in both groups with the EuroQol-5D Scale. Interaction between summarized comorbidity count, age, body mass index (BMI) and scores were analysed. Descriptive statistics, two-sample t-test and Pearson's correlation test were used for data analysis. RESULTS: The study groups included 200-200 participants with a similar age spread. Significant correlation was demonstrated in both study groups between higher comorbidity count and older age (0.37, p<0.001, and 0.24, p<0.001 in the GOA and the control group, respectively) and higher BMI (0.18, p: 0.01, and 0.45, p<0.001 in the GOA and the control group, respectively). In GOA, the increasing comorbidity number had a negative effect on the measured outcomes. CONCLUSIONS: Age and BMI showed strong correlation with multimorbidity in both groups. The lower correlation between BMI and comorbidity count in the GOA group requires further investigation and may suggest different interactions. Orv Hetil. 2020; 161(32): 1332-1340.
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Actividades Cotidianas , Osteoartritis de la Rodilla/psicología , Calidad de Vida , Factores de Edad , Anciano , Índice de Masa Corporal , Estudios de Casos y Controles , Comorbilidad , Estudios Transversales , Femenino , Humanos , Multimorbilidad , Dolor/epidemiologíaRESUMEN
BACKGROUND: Congenital chloride diarrhea (CCD, OMIM 214700) is a rare autosomal recessively inherited condition characterized by watery diarrhea, hypochloremia and metabolic alkalosis. Mutations of the solute carrier family 26, member 3 (SLC26A3, OMIM 126650) gene are responsible for the disease. The gene encodes a transmembrane protein, which is essential for intestinal chloride absorption. CASE PRESENTATION: Here we report a Hungarian boy, presenting the clinical phenotype of CCD. The patient born at 32 weeks of gestation and underwent surgery for abdominal distension and intestinal obstruction related to malrotation. After recovery, electrolyte replacement therapy was necessary due to several periods of diarrhea. After exclusion of other possible causes, increased chloride concentration in the feces supported the diagnosis of CCD. The diagnosis was confirmed by molecular genetic testing. Direct sequencing revealed compound-heterozygosity for a frameshift mutation c.1295delT (p.Leu432Argfs*11) and the known Polish founder mutation c.2024_2026dupTCA (p.Ile675_Arg676insLeu). CONCLUSIONS: Here we present the clinical symptoms of the first patient in Hungary diagnosed with CCD. Based on the clinical symptoms, stool analysis and genetic testing, the diagnosis of CCD was established. Our study provides expansion for the mutation spectrum of the SLC26A3 gene and the genetic background of CCD.
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Diarrea/congénito , Errores Innatos del Metabolismo/genética , Diarrea/diagnóstico , Diarrea/genética , Humanos , Hungría , Recién Nacido , Masculino , Errores Innatos del Metabolismo/diagnóstico , Linaje , FenotipoRESUMEN
Until recently, the diagnosis of spinal muscular atrophy (SMA) has been associated with severe life-long motor disability in adults and with early death in infants. The new experimental therapeutic approaches of the last few years have become more and more promising, while nusinersen was approved for the treatment of SMA in December 2016 in the USA, and in May 2017 in Hungary. Our paper presents mechanisms and clinical benefits of this new medication, and highlights some of the other therapeutic strategies still in experimental stages.
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Atrofia Muscular Espinal/tratamiento farmacológico , Fármacos Neuroprotectores/uso terapéutico , Oligonucleótidos/uso terapéutico , HumanosRESUMEN
INTRODUCTION: A survey that investigates the situation of physicians working at neonatal intensive care (NIC) centres has not been made since 1997. AIM: To give an overview of the sociodemographic characteristics; personal and professional problems; the satisfaction with their job and family roles; their levels of healthy lifestyle; resources in the families of physicians working at NIC. METHOD: We have made an examination in Hungary at NIC among physicians from April 2015 till January 2016, with an anonym self-fill-in questionnaire. RESULTS: The physicians involved in the research (n = 111) are representatively middle-aged people. They are well-qualified and hold a subordinate post. Most of them have second jobs. The manager and deputy-manager positions are characteristic for the men. Most of them live in family. The main problems for them are financial and professional difficulties, not the family or personal problems. They have conflicts in families because of finding partners and having children as well as job problems. They are satisfied with their parenting, partnership and professional roles but they are not contented with their family role as a financial safety provider person and as a person living a healthy life. In difficult situations in their life, they can count on friends and family members, furthermore they can rely on their workmates and superiors. CONCLUSION: It is the first research that focuses on the general situation of physicians working at level 3 NIC centres. This is the first time when a survey investigates their professional-personal-family life. Orv Hetil. 2018; 159(16): 628-635.
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Agotamiento Profesional/epidemiología , Estado de Salud , Cuidado Intensivo Neonatal , Satisfacción en el Trabajo , Neonatólogos/normas , Actitud del Personal de Salud , Femenino , Humanos , Hungría , Recién Nacido , Masculino , Salud Mental/estadística & datos numéricos , Persona de Mediana Edad , Neonatólogos/psicología , Encuestas y Cuestionarios , Equilibrio entre Vida Personal y Laboral/estadística & datos numéricosRESUMEN
Determination of the oligosaccharide composition in different wort samples is important to monitor their change during the brewing process with different yeast types. In our work, the concentration of fermentable and non-fermentable sugars were monitored by capillary electrophoresis to observe the effect of two different types of yeasts, Saccharomyces pastorianus and Saccharomycodes ludwigii. The former first ferments the monosaccharides, then the higher sugar oligomers, such as maltose and maltotriose, to ethanol, while the latter fully ferments the monosaccharides, but ferments only very low percentages of the oligosaccharides. Therefore, breweries use Saccharomycodes ludwigii to produce beers with low alcohol content. The CE-LIF traces of the wort samples represented unique oligosaccharide signatures.
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Cerveza/análisis , Electroforesis Capilar , Rayos Láser , Oligosacáridos/química , Fermentación , Oligosacáridos/aislamiento & purificación , Saccharomyces/metabolismo , Espectrometría de FluorescenciaRESUMEN
INTRODUCTION: Health-related attitudes can be encouraged most effectively at young ages. Young generations would require more interactive methods in programs engaged in health promotion. AIM: The aim of the authors was to get an insight into the attitudes, experience and motivation of youngsters in connection with health promotion programs and the community service work. METHOD: The questionnaires were filled in by high school students studying in Budapest and in the countryside (N = 898). RESULTS: 44.4% of the students did not have lessons or extracurricular activities dealing with health promotion. Concerning health promotion programs, youngsters in Budapest had more positive experience, while female students showed a more adoptive attitude. CONCLUSIONS: It was concluded that in one of the most susceptible life stages, many youngsters either do not participate in programs dealing with health promotion, or participate in programs that are within the framework of school subjects or extracurricular activities building on traditional teaching methods.
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Actitud Frente a la Salud , Promoción de la Salud , Motivación , Servicios de Salud Escolar/estadística & datos numéricos , Estudiantes/estadística & datos numéricos , Adolescente , Femenino , Humanos , Hungría/epidemiología , Masculino , Evaluación de Programas y Proyectos de Salud , Opinión Pública , Autoinforme , Estudiantes/psicologíaRESUMEN
In eukaryotes the TFIID complex is required for preinitiation complex assembly which positions RNA polymerase II around transcription start sites. On the other hand, histone acetyltransferase complexes including SAGA and ATAC, modulate transcription at several steps through modification of specific core histone residues. In this study we investigated the function of Drosophila melanogaster proteins TAF10 and TAF10b, which are subunits of dTFIID and dSAGA, respectively. We generated a mutation which eliminated the production of both Drosophila TAF10 orthologues. The simultaneous deletion of both dTaf10 genes impaired the recruitment of the dTFIID subunit dTAF5 to polytene chromosomes, while binding of other TFIID subunits, dTAF1 and RNAPII was not affected. The lack of both dTAF10 proteins resulted in failures in the larval-pupal transition during metamorphosis and in transcriptional reprogramming at this developmental stage. Surprisingly, unlike dSAGA mutations, dATAC subunit mutations resulted in very similar changes in the steady state mRNA levels of approximately 5000 genes as did ablation of both dTaf10 genes, indicating that dTAF10- and/or dTAF10b-containing complexes and dATAC affect similar pathways. Importantly, the phenotype resulting from dTaf10+dTaf10b mutation could be rescued by ectopically added ecdysone, suggesting that dTAF10- and/or dTAF10b-containing complexes are involved in the expression of ecdysone biosynthetic genes. Indeed, in dTaf10+dTaf10b mutants, cytochrome genes, which regulate ecdysone synthesis in the ring gland, were underrepresented. Therefore our data support the idea that the presence of dTAF10 proteins in dTFIID and/or dSAGA is required only at specific developmental steps. We propose that distinct forms of dTFIID and/or dSAGA exist during Drosophila metamorphosis, wherein different TAF compositions serve to target RNAPII at different developmental stages and tissues.
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Proteínas de Drosophila/metabolismo , Drosophila melanogaster/fisiología , Ecdisona/metabolismo , Larva/fisiología , Metamorfosis Biológica/fisiología , Pupa/fisiología , Factores Asociados con la Proteína de Unión a TATA/metabolismo , Factor de Transcripción TFIID/metabolismo , Animales , Proteínas de Drosophila/genética , Ecdisona/genética , Mutación , Factores Asociados con la Proteína de Unión a TATA/genética , Factor de Transcripción TFIID/genéticaRESUMEN
Cardiovascular disease is the biggest challenge in terms of life expectancy in developed countries. Adenosine contributes to the adaptation of the heart to ischemia and hypoxia, because adenosine, in addition to its metabolite role in the nucleic acid metabolism, is the endogenous agonist of the ubiquitous adenosine receptor family. Adenosine receptor activation is beneficial in most cases, it improves the balance between energy supply and consumption, reduces injury caused by stressors and inhibits the unfavorable tissue remodeling. Pharmacological manipulation of cardioprotective effects evoked by adenosine is an important, although to date not sufficiently utilized endeavor that may have therapeutic and preventive implications in cardiovascular diseases. As the ligand binding site of adenosine receptors is accessible from the extracellular space, it is especially important to know the adenosine concentration of the interstitial fluid ([Ado](ISF)). However, in the functioning heart, [Ado](ISF) values range in an extremely wide interval, spanning from nano- to micromolar concentrations, as estimated by the commonly used methods. Our recently developed procedure, the receptorial responsiveness method (RRM), may resolve this problem in certain cases. RRM enables quantification of an acute increase in the concentration of a pharmacological agonist, uniquely in the microenvironment of the receptors of the given agonist. As a limitation, concentration of agonists with short half-life (just like adenosine) at their receptors can only be quantified with the equieffective concentration of a stable agonist exerting the same action. In a previous study using RRM, inhibition of the transmembrane nucleoside transport in the euthyroid guinea pig atrium produced an increase in [Ado](ISF) that was equieffective with 18.8 +/- 3 nM CPA (N6-cyclopentyladenosine, a stable, selective A1 adenosine receptor agonist). This finding is consistent with observations of others, i.e., in the normoxic heart, adenosine flow is directed into the cell interior, and thus transport blockade elevates the extracellular adenosine level. In turn, nucleoside transport inhibition in the hyperthyroid guinea pig atrium caused a rise in [Ado](ISF) equieffective with 46.5 +/- 13.7 nM CPA. In sum, our work team was the first to demonstrate that adenosine transport in the hyperthyroid atrium has the same direction but is more intense as/than that in the euthyroid one.
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Adenosina/agonistas , Adenosina/metabolismo , Miocardio/metabolismo , Sustancias Protectoras/metabolismo , Receptores Purinérgicos P1/metabolismo , Adenosina/uso terapéutico , Enfermedades Cardiovasculares/metabolismo , Enfermedades Cardiovasculares/prevención & control , Humanos , Sustancias Protectoras/uso terapéuticoRESUMEN
Although the A1 adenosine receptor (A1 receptor), the main adenosine receptor type in cardiac muscle, is involved in powerful cardioprotective processes such as ischemic preconditioning, the atrial A1 receptor reserve has not yet been quantified for the direct negative inotropic effect of adenosine. In the present study, adenosine concentration-effect (E/c) curves were constructed before and after pretreatment with FSCPX (8-cyclopentyl-N3-[3-(4-(fluorosulfonyl)benzoyloxy)propyl]-N1-propylxanthine), an irreversible A1 receptor antagonist, in isolated guinea pig atria. To prevent the intracellular elimination of the administered adenosine, NBTI (S-(2-hydroxy-5-nitrobenzyl)-6-thioinosine), a nucleoside transport inhibitor, was used. As expected, NBTI alone and FSCPX-pretreatment alone shifted the adenosine E/c curve to the left and right, respectively. However, in the presence of NBTI, FSCPX-pretreatment appeared to increase the maximal response to adenosine. By means of the receptorial responsiveness method (RRM), our recently developed procedure, adenosine E/c curves generated in the presence of NBTI were corrected for the bias caused by the endogenous adenosine accumulated by NBTI. The corrected curves indicate a substantial A1 receptor reserve for the direct negative inotropy evoked by adenosine. In addition, our results suggest that accumulation of an endogenous agonist may bias the E/c curve constructed with the same or similar agonist that can lead to seemingly paradoxical results.
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Adenosina/farmacología , Función Atrial/efectos de los fármacos , Atrios Cardíacos/efectos de los fármacos , Atrios Cardíacos/metabolismo , Contracción Miocárdica/efectos de los fármacos , Receptor de Adenosina A1/metabolismo , Adenosina/análogos & derivados , Antagonistas del Receptor de Adenosina A1/farmacología , Animales , Relación Dosis-Respuesta a Droga , Cobayas , Técnicas In Vitro , Masculino , Tioinosina/análogos & derivados , Tioinosina/farmacología , Xantinas/farmacologíaRESUMEN
A1 adenosine receptors (A1 receptors) are widely expressed in mammalian tissues; therefore attaining proper tissue selectivity is a cornerstone of drug development. The fact that partial agonists chiefly act on tissues with great receptor reserve can be exploited to achieve an appropriate degree of tissue selectivity. To the best of our knowledge, the A1 receptor reserve has not been yet quantified for the atrial contractility. A1 receptor reserve was determined for the direct negative inotropic effect of three A1 receptor full agonists (NECA, CPA and CHA) in isolated, paced guinea pig left atria, with the use of FSCPX, an irreversible A1 receptor antagonist. FSCPX caused an apparently pure dextral displacement of the concentration-response curves of A1 receptor agonists. Accordingly, the atrial A1 receptor function converging to inotropy showed a considerably great, approximately 80-92 % of receptor reserve for a near maximal (about 91-96 %) effect, which is greater than historical atrial A1 receptor reserve data for any effects other than inotropy. Consequently, the guinea pig atrial contractility is very sensitive to A1 receptor stimulation. Thus, it is worthwhile considering that even partial A1 receptor agonists, given in any indication, might decrease the atrial contractile force, as an undesirable side effect, in humans.
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Atrios Cardíacos/efectos de los fármacos , Contracción Muscular/efectos de los fármacos , Agonistas del Receptor Purinérgico P1/farmacología , Antagonistas de Receptores Purinérgicos P1/farmacología , Receptor de Adenosina A1 , Xantinas/farmacología , Animales , Relación Dosis-Respuesta a Droga , Cobayas , Masculino , Contracción Muscular/fisiología , Técnicas de Cultivo de Órganos , Agonistas del Receptor Purinérgico P1/química , Antagonistas de Receptores Purinérgicos P1/química , Distribución Aleatoria , Receptor de Adenosina A1/fisiología , Resultado del Tratamiento , Xantinas/químicaRESUMEN
The Gram-positive soil-borne streptomycetes exhibit a complex life cycle that is controlled by extracellular regulatory molecules. One interesting autoregulator is the protein factor C, originally isolated from the culture fluid of S. albidoflavus 45H. Southern hybridizations and database searches revealed that although homologues of factor C are not present in most Streptomyces strains, an exception is the plant pathogenic S. scabies , which causes common scab disease on potato. In S. scabies and related strains pathogenicity involves a large pathogenicity island that carries thaxtomin biosynthetic genes, the nec1 necrogenic factor and other putative virulence genes. Extracellular enzymes, including extracellular esterases, that attack the surface of the tubers and disintegrate the external protective layer are also known to be involved in pathogenicity. In S. albidoflavus 45H, factor C coordinates the expression of many secreted hydrolases. To find out whether esterase is also regulated by factor C, we made a factor C null mutant of strain 45H. The mutant showed a bald phenotype and was impaired in pathogenicity and esterase activity. This is a first indication that extracellular regulatory factors may play a role in the development of potato scab.