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Background: Mechanical neck pain (MNP) is one of the most prevalent musculoskeletal pathologies in the present time. Physiotherapy management strategies comprising manual therapy and exercise therapy are routinely administered in patients with MNP. Objective: To compare the immediate effect of craniocervical flexion (CCF) exercise and Mulligan mobilisation on pain, active cervical range of motion (CROM) and CCF test performance in patients with MNP. Methods: This prospective, randomised, single-blinded study involved 26 patients with MNP (16 females; mean age; 31.12±8.40 years) randomised to a single session of active CCF exercise (3 sets of 10 repetitions) or Mulligan mobilisation (3 sets of 6-10 repetitions). Pain intensity was measured on a numerical pain rating scale (NPRS), active CROM was measured using CROM device, and CCF test performance with surface electromyography (EMG) from bilateral sternocleidomastoid (SCM) and anterior scalene (AS) muscles recorded pre- and immediately post-intervention by an assessor blinded to the treatment groups. Mann-Whitney U test was used to analyse between groups and Wilcoxon signed rank test was used to analyse within-group significance for pain and CROM, Cochran-Mantel-Haenszel correlation test was used to analyse the CCF test performance on EMG from the bilateral SCM and AS muscles. Results: Comparison between pre- and post-intervention readings revealed statistically significant within-group (p<0.05) and no between-group significant difference for pain, ROM, and CCF test performance, indicating both interventions were equally effective. Conclusion: Patients with MNP who received active CCF exercise or Mulligan mobilisation exhibited similar reduction in pain intensity and increased CROM and CCF test performance post-intervention. Surprisingly, AS surface EMG amplitudes were increased post-intervention in both groups warranting further exploration of its role in neck pain.
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BACKGROUND: Local anaesthesia (LA) administration provokes dental anxiety in children. BrightHearts is a biofeedback relaxation application designed to reduce anxiety in children during painful procedural interventions. AIM: To compare the effectiveness of biofeedback relaxation (BR) and audio-visual (AV) distraction on dental anxiety among 7- to 12-year-old children while administering LA. DESIGN: A total of 70 children requiring dental treatment under LA for three visits were recruited for this single-blinded randomized control trial. They were randomly divided into two equal groups. Group A received BR and Group B received AV distraction during LA delivery in the first two visits, and both groups did not receive any intervention during LA in third visit. Outcomes were measured using heart rate and a cartoon-based anxiety measuring scale (Chotta Bheem-Chutki (CBC) scale). RESULTS: AV group had statistically significant higher mean heart rates than BR group (P < .001) during needle penetration and post-intervention, respectively. CBC scale showed no statistical differences between the groups. CONCLUSION: Both the interventions are effective in reducing dental anxiety during LA administration. Based on objective measures, BR is found to be better than AV distraction. Subjective scores, however, show no differences between the two.
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Anestesia Local , Ansiedade ao Tratamento Odontológico , Biorretroalimentação Psicológica , Criança , Ansiedade ao Tratamento Odontológico/prevenção & controle , Humanos , DorRESUMO
PURPOSE: To examine whether a structured neonatal physical therapy program (SNP) improves neurobehavior and general movements in moderate to late preterm (MLP) infants. METHODS: Sixty MLP infants participated in this clinical trial. After baseline assessment using the Neurobehavioral Assessment of Preterm Infant (NAPI) and Prechtl General Movements (GMs) Assessment, infants were randomly allocated to a usual care (n = 30) or an SNP group (n = 30) and continued receiving usual care. The SNP group received intervention for 90 minutes/day, 6 days/week until discharge. Changes in neurobehavior and GMs were assessed at hospital discharge. RESULTS: Changes in scores on scarf sign and motor development and vigor clusters of NAPI document an improvement in the SNP group. The proportion of infants with poor repertoire GMs also decreased more in the SNP group than in the usual care group. CONCLUSION: The SNP may be effective in improving some aspects of neurobehavior and quality of GMs in MLP infants. WHAT THIS ADDS TO THE EVIDENCE: The addition of a structured neonatal physical therapy program to usual care can promote neurobehavioral organization and improve the quality of general movements in moderate and late preterm infants in India.
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Recém-Nascido Prematuro , Movimento , Humanos , Índia , Lactente , Recém-NascidoRESUMO
The spectrum of presentation of airway foreign body can vary from having mild symptoms to sudden death. Smaller foreign body in distal airways, especially if the patient is unaware of aspiration can result in chronic symptoms mimicking asthma. Clove, has been used traditionally for its medicinal values and commonly used as a cough remedy. In this case series, we report four cases of this unusual airway foreign body which were essentially consumed with an intention to prevent cough, but unfortunately became the reason for their cough.
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Patient and public involvement (PPI) in every aspect of research will add valuable insights from patients' experiences, help to explore barriers and facilitators to their compliance/adherence to assessment and treatment methods, bring meaningful outcomes that could meet their expectations, needs and preferences, reduce health care costs, and improve dissemination of research findings. It is essential to ensure competence of the research team by capacity building with available resources on PPI. This review summarizes practical resources for PPI in various stages of research projects-conception, co-creation, design (including qualitative or mixed methods), execution, implementation, feedback, authorship, acknowledgement and remuneration of patient research partners, and dissemination and communication of research findings with PPI. We have briefly summarized the recommendations and checklists, amongst others, for PPI in rheumatic and musculoskeletal research (e.g. the European Alliance of Associations for Rheumatology (EULAR) recommendations, the Core Outcome Measures in Effectiveness Trials (COMET) checklist and the Guidance for Reporting Involvement of Patients and the Public (GRIPP) checklist). Various tools that could be used to facilitate participation, communication and co-creation of research projects with PPI are highlighted in the review. We shed light on the opportunities and challenges for young investigators involving PPI in their research projects, and have summarized various resources that could be used to enhance PPI in various phases/aspects of research. A summary of web links to various tools and resources for PPI in various stages of research is provided in Additional file 1.
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The anxiety of the mother influences the child's behaviour in a dental setting. Objectives: The study aimed at evaluating the mother's anxiety and a child's fear of first and second dental visits in two different age groups. Study Design: The cross-sectional study design consisted of a total of 100 mother-child pairs attending Pediatric Dental clinics was included in the study. Group I consisted of 50 mother-child pairs of 6-8 years of age. Group II consisted of another 50 mother-child pairs between 12-15 years of age. Short Form of the Dental Subscale of the Children's Fear Survey Schedule (DFSS-SF) was administered to the child. Corah's Dental anxiety scale was administered to the mother. The Tell-Show-Do (TSD) technique was used in all children before the treatment. Statistical Analysis Used: SPSS software 21 was used for descriptive and inferential statistics. Pearson's correlation coefficient was used for bivariate correlation between variables in the study. Results: The anxiety level of mothers on both appointment days in both age groups was found to be highly significant. The correlation of maternal anxiety to the gender of the child in both groups was found to be highly significant. Conclusion: The fear of dental treatment was commonly found in children irrespective of gender in both age groups. The TSD technique was found to reduce fear in the subsequent appointment.
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Ansiedade ao Tratamento Odontológico , Mães , Criança , Comportamento Infantil , Estudos Transversais , Medo , Feminino , HumanosRESUMO
AIM: Behaviour management is one of the essential skills of paediatric dentists. Appropriate use of behavioural principles helps the child in developing the skills and behaviours necessary to willingly undergo dental care, not hindered by undue anxiety or fear. However, very little is known about the knowledge of principles regarding behaviour management among paediatric dentists. Contingency management which is based on the principles of behaviour analysis is a widely accepted behavioural management technique and it includes reinforcement and punishment. The aim and objective of this study was to assess the knowledge of paediatric dentists regarding behavioural management principles related to contingency management. MATERIALS AND METHODS: A cross- sectional survey was conducted among paediatric dental professionals and post-graduate students pursuing masters in paediatric dentistry across Tamil Nadu, India using Knowledge of Behavioural Principles as Applied to Children (KBPAC) questionnaire modified for the dental setting. The data were obtained, tabulated and statistically analysed using SPSS. RESULTS: Responses were obtained from 130 participants, comprising 67 paediatric dental professionals and 63 post-graduate students. The overall average knowledge score was 40.72%. The mean knowledge level of paediatric dental professionals was (0.4378) versus (0.3597) among post-graduate students (p <0.05). CONCLUSION: Knowledge of behavioural management principles related to contingency management among paediatric dentists in Tamil Nadu, India is low.
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Odontólogos , Odontopediatria , Criança , Estudos Transversais , Humanos , Índia , Inquéritos e QuestionáriosRESUMO
CONTEXT: In-vitro studies of microleakage are an initial screening method to assess the maximum theoretical loss of sealing ability in-vivo. AIMS: Our objective was to determine and compare microleakage patterns of conventional glass ionomer cement (GIC) and resin-modified GIC (RMGIC) for band cementation. METHODS: Forty caries-free second primary molars were randomly divided into two groups of 20 teeth each. Preformed molar bands in the two groups were cemented to enamel with one of two types of cement: Conventional GIC (Fuji I, GC Corporation; Tokyo, Japan) and RMGIC (Fuji Plus, GC Corporation; Tokyo, Japan). A dye penetration method was used for microleakage evaluation. Microleakage was determined by a stereomicroscope for the cement-band and cement-enamel interfaces. STATISTICAL ANALYSIS USED: Statistical analysis was performed with Kruskal-Wallis and Mann-Whitney U tests. RESULTS: The mean microleakage value for conventional GIC (Fuji I) at cement-band and cement-enamel interfaces was 2.41 mm and 2.15 mm, respectively. The mean microleakage value for RMGIC (Fuji Plus) at cement-band and cement-enamel interfaces was 0.44 mm and 0.46 mm, respectively. Compared to conventional GIC, RMGIC showed less microleakage at both cement-band and cement-enamel interfaces. P < 0.001 and it was statistically highly significant. CONCLUSIONS: Bands cemented with RMGIC had significantly less microleakage between the cement-band and cement-enamel interfaces than conventional GIC.
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Infiltração Dentária , Cimentos Dentários , Esmalte Dentário , Cimentos de Ionômeros de Vidro , Humanos , Cimentos de Resina , Dente DecíduoRESUMO
BACKGROUND: Placement of full-coverage restorations such as stainless steel crowns (SSCs) for pulpectomy treated primary molars is essential for successful outcomes. The tooth preparation process for SSCs can cause discomfort to gingival tissues since the crown should be seated 1 mm subgingivally. The purpose of this prospective trial was to compare the effectiveness of subgingival and transmucosal application of topical anesthetics on dental pain during SSC tooth preparation among 6- to 8-year-old children. METHODS: A consecutive sample of 27 children, aged 6-8 years, who required an SSC after pulp therapy in primary molars were randomly divided into three groups. Group A received infiltration anesthesia before tooth preparation for SSC placement, whereas in Group B and C, only topical anesthesia was applied subgingivally and transmucosally. Wong-Bakers Faces pain rating scale (WBFPS) scores were recorded after tooth preparation. Faces, Legs, Activity, Cry and Consolability (FLACC) scores were evaluated by two blinded and calibrated investigators through video recordings of the patient during tooth preparation. Data were tabulated, and inter-group comparisons were performed using the Kruskal-Wallis and analysis of variance tests. RESULTS: Out of the 27 participants, 48% were boys and 52% were girls, with an overall mean age of 6.83 years. Group A showed the least pain scores according to both the scales, followed by Group B and Group C. The pain intensity was statistically significant on both the pain scales with P = 0.003 for FLACC and P < 0.001 for WBFPS. CONCLUSION: Subgingival application of topical anesthesia reduced pain to a certain extent but not as effectively as infiltration anesthesia during SSC tooth preparation in primary molars. Transmucosal application of topical anesthesia did not reduce discomfort when compared to the other two interventions.
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Atherosclerosis is the leading cause of death in the United States, and human cytomegalovirus (HCMV), a member of the herpes virus family, may play a role in the development of the disease. We previously showed that HCMV regulated endothelial apoptosis. In this study, we investigated the induction of apoptosis and signal transduction pathways regulating this process in HCMV-infected endothelial cells. As observed previously, HCMV induced a typical cytopathic effect in human aortic endothelial cells (HAECs), ie, the formation of single nucleated or multinucleated giant cells. Although infected HAECs were resistant to apoptosis at earlier stages of infection, they became apoptotic with prolonged infection as demonstrated by positive staining using terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL). This apoptotic process was mediated by the caspase-dependent mitochondrial apoptotic pathway as indicated by increased expression and cleavage of caspases 3 and 9 as well as increased expressions of pro-apoptotic molecules Bax and Bak. Blocking caspases 3 or 9 significantly inhibited the HCMV-induced apoptosis. Further exploration of the upstream pathway demonstrated upregulation of the tumor suppressor p53 gene and activation of the ataxia telangiectasia mutant (ATM) pathway in the infected cells. Blocking p53 inhibited HCMV-stimulated Bax and Bak expression as well as caspase-3 activation and blocking the ATM pathway inhibited HCMV-stimulated p53 activation. Although early infection may render cells antiapoptotic, prolonged infection, however, induced endothelial apoptosis through ATM and p53-dependent activation of the mitochondrial death pathway. This proapoptotic effect may be relevant to endothelial dysfunction and HCMV-associated vascular diseases.
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Apoptose , Citomegalovirus/patogenicidade , Endotélio Vascular/virologia , Proteínas Serina-Treonina Quinases/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Proteínas Mutadas de Ataxia Telangiectasia , Caspases/metabolismo , Proteínas de Ciclo Celular , Dano ao DNA , Proteínas de Ligação a DNA , Endotélio Vascular/citologia , Endotélio Vascular/metabolismo , Humanos , Proteínas Serina-Treonina Quinases/fisiologia , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Transdução de Sinais , Proteínas Supressoras de TumorRESUMO
BACKGROUND: Nitric oxide (NO), a highly reactive radical, participates in the nonspecific natural defense mechanism of the oral cavity. The present study was attempted to evaluate the salivary NO levels in 4-5 year-old children with early childhood caries (ECC). The objective of the present study was to assess the salivary NO concentration in children with different caries activity. MATERIALS AND METHODS: The study included 120 healthy 4.5 year-old children and they were equally divided into three groups based on decayed, missing, filled surfaces (dmfs) score; forty caries-free children (control group), forty children with dmfs 1.5 (ECC group), and forty with dmfs ⩾6 (severe ECC group). Saliva collected was measured for NO concentration by Griess reaction method. The obtained data were analyzed by ANOVA and Pearson's correlation coefficient. RESULTS: The mean level of NO in the saliva of the control group was 51.2 ± 8.3457 and that of ECC and severe ECC were 47.1 ± 5.2614 and 33.625 ± 4.6942, respectively. The mean salivary NO concentration was significantly higher in healthy controls when compared to children with ECC and severe ECC. Moreover, a negative correlation (r = -0.6658) was observed between the salivary NO level and the mean dmfs, suggesting that as the salivary NO level decreases, the caries incidence increases. CONCLUSION: The obtained results support the antimicrobial activity of salivary NO and also suggest that an increase in NO production might contribute to lower the caries occurrence in children.
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The number of patients living with end-stage renal disease (ESRD) is increasing in our country and demand for renal grafts is ever increasing. Cadaver renal transplantation is being established as a viable supplement to live transplantation. We present a case where a mass lesion was encountered in the donor kidney from a cadaver. Enucleation of the lesion was done and we proceeded with the grafting. Histopathological examination showed a 'Renomedullary interstitial cell tumour', a rare benign lesion. Post transplant, the renal function recovered well and the patient is asymptomatic. Such incidental renal masses present an ethical dilemma to the operating surgeon.
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Proteomic analysis is an important investigative tool used to systematically explore cellular proteins that are responsive to adverse environmental challenges. Tobacco smoking is the second major cause of death in the world. In this study, we utilized two-dimensional electrophoresis (2-DE) and mass spectrometry (MS) technologies to explore protein changes in human aortic endothelial cells (HAECs) in response to cigarette smoke extracts (CSE). Among 389 individual proteins resolved using 2-DE, 43 had a 2- to 3-fold change in levels as measured by spot intensity and 32 had more than a 3-fold change. Sixteen of the 32 spots with sufficient amount of proteins were excised for identification by performing matrix-assisted laser desorption/ionization (MALDI)-MS analysis. Using a peptide mass fingerprinting (PMF) to search the nrNCBI database, we identified all these 16 proteins, which were either increased (n = 9) or decreased (n = 7) after CSE treatment. All these proteins have known functions, however, none have been reported to be altered after CSE treatment. The findings from our study suggest that utilizing a systemic investigative tool, such as the proteomic approach using 2-DE, may play an important role in discovering novel molecular mechanisms for cigarette smoking-induced pathological changes. Further investigation following the systemic discoveries must be further examined as they may potentially lead to new therapeutic approaches to smoking-induced diseases - a health issue affecting everyone in the world.
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Misturas Complexas/farmacologia , Células Endoteliais/efeitos dos fármacos , Nicotiana , Proteoma/efeitos dos fármacos , Fumaça , Aorta/citologia , Arginina/farmacologia , Células Cultivadas , Misturas Complexas/administração & dosagem , Misturas Complexas/química , Regulação para Baixo/efeitos dos fármacos , Eletroforese em Gel Bidimensional , Células Endoteliais/metabolismo , Humanos , Ponto Isoelétrico , Peso Molecular , NG-Nitroarginina Metil Éster/farmacologia , Proteoma/análise , Proteoma/metabolismo , Solubilidade , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Regulação para Cima/efeitos dos fármacos , Água/químicaRESUMO
OBJECTIVE: To study the effect of L-cysteine on urinary risk factors in hyperoxaluric urolithiasis in rats. MATERIALS AND METHODS: Twenty-four rats were divided into four groups of six rats each; those in Group I served as controls, those in Group II had hyperoxaluria induced using sodium glycollate, those in Group III were given cysteine alone and those in Group IV were given sodium glycollate and cysteine. Samples of 24 h urine were collected and analysed to determine the content of calcium, oxalate, phosphorus and magnesium, and the organic acids, glycollic, glyoxylic and citric acid. RESULTS: Hyperoxaluric rats treated with cysteine had significantly lower excretion rates of calcium, oxalate, phosphorus, glycollic and glyoxylic acid than the glycollate fed rats. When cysteine was given, the excretion of urinary citric acid and magnesium were also increased. CONCLUSION: Cysteine may be a useful agent in preventing oxalate urolithiasis.
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Cisteína/farmacologia , Hiperoxalúria/urina , Cálculos Urinários/etiologia , Animais , Cálcio/urina , Oxalato de Cálcio/urina , Citratos/urina , Ácido Cítrico , Glicolatos/urina , Glioxilatos/urina , Masculino , Ratos , Cálculos Urinários/induzido quimicamente , Cálculos Urinários/urinaRESUMO
Oxalate, the major stone-forming constituent induces lipid peroxidation during lithogenesis. In experimental condition oxalate formation was induced by the administration of its precursor glycollate. Glycollate-fed rats showed increased susceptibility to lipid peroxidation in the presence of promoters. In addition, antioxidant enzymes-catalase, superoxide dismutase and glutathione peroxidase also showed decreased activity. Reduced glutathione, total thiols and ascorbic acid were also significantly decreased. On the other hand, an increased xanthine oxidase and decreased glucose-6-phosphate dehydrogenase activity was also observed upon glycollate administration. Cysteine, a sulphydryl compound, is known to inhibit free radical toxicity in various pathologies. Cysteine administration to glycollate-fed rats brought about a significant decrease in the peroxidative level, with an increase in the antioxidant status.
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Cisteína/farmacologia , Peroxidação de Lipídeos/efeitos dos fármacos , Animais , Peso Corporal , Cisteína/administração & dosagem , Glutationa/metabolismo , Glicolatos/administração & dosagem , Rim/enzimologia , Fígado/enzimologia , Masculino , Ratos , Ratos WistarRESUMO
Calcium oxalate crystal growth and aggregation leads to the formation of renal calculi. It is known to be inhibited by several compounds both in vitro and in vivo conditions. The present study highlights the inhibitory potential of sodium pentosan polysulphate (SPP), a semi-synthetic glycosaminoglycan (GAG) on calcium oxalate crystal growth in vitro. Its efficacy was compared with those of known inhibitors like pyrophosphate, heparin and chondroitin-4-sulphate. Of the above compounds pyrophosphate was found to be the most potent inhibitor. Among the GAGs, SPP exhibited 80% inhibitory activity as compared to heparin. A lesser degree of inhibition was observed with chondroitin-4-sulphate.
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Oxalato de Cálcio/química , Poliéster Sulfúrico de Pentosana/farmacologia , Sulfatos de Condroitina/farmacologia , Cristalização , Depressão Química , Difosfatos/farmacologia , Heparina/farmacologia , Cálculos Urinários/prevenção & controleRESUMO
Sodium pentosan polysulphate (SPP) has been shown to inhibit calcium oxalate crystallization in vitro. Here, the effect of SPP was studied on in vivo crystallization. Ammonium oxalate was used as the inducer of calcium oxalate crystallization in rats and the effect of SPP on in vivo crystallization factor is reported. The increased excretions of stone forming constituents associated with urinary marker enzymes are the salient features observed in experimental rats. Sodium pentosan polysulphate administration brought about a significant reduction in urinary stone forming constituents. It also decreased the extent of renal tubular damage as evidenced from the reduced level of marker enzymes in urine. These observations highlight the inhibitory capacity of SPP against in vivo calcium oxalate crystallization.
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Inibidores Enzimáticos/farmacologia , Poliéster Sulfúrico de Pentosana/farmacologia , Cálculos Urinários/prevenção & controle , Animais , Oxalato de Cálcio/urina , Cristalização , Enzimas/urina , Masculino , Ratos , Ratos Wistar , Cálculos Urinários/urinaRESUMO
BACKGROUND: In utero ethanol exposure causes abnormal fetal brain development that may partly be due to enhanced cell death. The mechanisms underlying this remain to be defined, but ethanol-induced oxidative stress may play a role. The following studies investigated the effects of short-term in utero ethanol exposure on fetal brain mitochondrial events that are known to elicit apoptotic cell death. Evidence is presented suggesting that 4-hydroxynonenal (HNE), a toxic product of lipid oxidation, is a causal factor in the observed mitochondrial damage. METHODS: Mitochondria were isolated from control and ethanol-exposed fetal brains (days 17 and 18 of gestation). Permeability transition was determined spectrophotometrically, and cytochrome c and apoptosis-inducing factor (AIF) release were assessed by Western blotting. Caspase-3 activity and DNA fragmentation were determined both as markers for mitochondrially mediated apoptosis and as consequences of cytochrome c and AIF release. RESULTS: Maternal ethanol intake caused an increase in mitochondrial permeability transition, and this was accompanied by cytochrome c and AIF release from fetal brain mitochondria that exceeded control values by 62 and 25%, respectively (p < 0.05). In utero ethanol exposure resulted in a 30% increase in caspase-3 activity and a 25% increase in DNA fragmentation (p < 0.05) in the fetal brain. HNE levels were increased by 23% (p < 0.05) in mitochondria by in vivo ethanol exposure. In vitro treatment of fetal brain mitochondria with HNE (25-100 microM) also caused increases in mitochondrial permeability transition, as well as dose-dependent releases of cytochrome c and AIF. CONCLUSIONS: These studies illustrate that in utero ethanol exposure can elicit a cascade of events in the fetal brain that are consistent with mitochondrially mediated apoptotic cell death. Additionally, the increase in mitochondrial content of HNE after ethanol intake and the ability of HNE added to fetal brain mitochondria to mimic these effects of in vivo ethanol exposure support a potential role for HNE in the proapoptotic responses to ethanol.
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Aldeídos/metabolismo , Apoptose , Encéfalo/embriologia , Encéfalo/ultraestrutura , Etanol/efeitos adversos , Troca Materno-Fetal , Mitocôndrias/efeitos dos fármacos , Aldeídos/análise , Animais , Fator de Indução de Apoptose , Atractilosídeo/farmacologia , Encéfalo/metabolismo , Cálcio/farmacologia , Caspase 3 , Caspases/metabolismo , Grupo dos Citocromos c/metabolismo , Fragmentação do DNA , Inibidores Enzimáticos/farmacologia , Feminino , Flavoproteínas/metabolismo , Proteínas de Membrana/metabolismo , Mitocôndrias/fisiologia , Translocases Mitocondriais de ADP e ATP/antagonistas & inibidores , Permeabilidade , Gravidez , Ratos , Ratos Sprague-DawleyRESUMO
Interaction between angiotensin II, which binds a G-protein-coupled receptor, and insulin, a ligand for receptor tyrosine kinase, was examined in renal proximal tubular epithelial cells. Augmented protein translation by insulin involves activation of eukaryotic initiation factor 4E (eIF4E) which follows the release of the factor from a heterodimeric complex by phosphorylation of its binding protein, 4E-BP1. Angiotensin II (1 nM) or insulin (1 nM) individually stimulated 4E-BP1 phosphorylation. However, pre-incubation with angiotensin II abrogated insulin-induced phosphorylation of 4E-BP1, resulting in persistent binding to eIF4E. Although angiotensin II and insulin individually activated phosphoinositide 3-kinase and extracellular signal-regulated kinase (ERK)-1/-2-type mitogen-activated protein (MAP) kinase, pre-incubation with angiotensin II abolished insulin-induced stimulation of these kinases, suggesting more proximal events in insulin signalling may be intercepted. Pretreatment with angiotensin II markedly inhibited insulin-stimulated tyrosine phosphorylation of insulin-receptor beta-chain and insulin-receptor substrate 1. Losartan prevented angiotensin II inhibition of insulin-induced ERK-1/-2-type MAP kinase activation and 4E-BP1 phosphorylation, suggesting mediation of the effect of angiotensin II by its type 1 receptor. Insulin-stimulated de novo protein synthesis was also abolished by pre-incubation with angiotensin II. These data show that angiotensin II inhibits 4E-BP1 phosphorylation and stimulation of protein synthesis induced by insulin by interfering with proximal events in insulin signalling. Our data provide a mechanistic basis for insulin insensitivity induced by angiotensin II.