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OBJECTIVE: To investigate the relationship between perception of craniofacial deformity, geometric head features, and 3D head shape analyzed by statistical shape modeling (SSM). PATIENTS: A total of 18 unoperated patients with scaphocephaly (age = 5.2 ± 1.1m)-6 were followed-up after spring-assisted cranioplasty (SAC) (age = 9.6 ± 1.5m)-and 6 controls (age = 6.7 ± 2.5m). MAIN OUTCOME MEASURES: 3D head shapes were retrieved from 3D scans or computed tomography (CTs). Various geometrical features were measured: anterior and posterior prominence, take-off angle, average anterior and posterior lateral and horizontal curvatures, cranial index (CI) (cranial width over length), and turricephaly index (TI) (cranial height over length). SSM and principal component analysis (PCA) described shape variability. All models were 3D printed; the perception of deformity was blindly scored by 9 surgeons and 1 radiologist in terms of frontal bossing (FB), occipital bulleting (OB), biparietal narrowing (BN), low posterior vertex (LPV), and overall head shape (OHS). RESULTS: A moderate correlation was found between FB and anterior prominence (r = 0.56, P < .01) and take-off angle (r = - 0.57, P < .01). OB correlated with average posterior lateral curvature (r = 0.43, P < 0.01) similarly to BPN (r = 0.55, P < .01) and LPV (r = 0.43, P < .01). OHS showed strong correlation with CI (r = - 0.68, P < .01) and TI (r = 0.63, P< .01). SSM Mode 1 correlated with OHS (r = 0.66, p < .01) while Mode 3 correlated with FB (r = - 0.58, P < .01). CONCLUSIONS: Esthetic cranial appearance in craniofacial patients is correlated to specific geometric parameters and could be estimated using automated methods such as SSM.
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Craneosinostosis , Anomalías Maxilomandibulares , Humanos , Preescolar , Niño , Cefalometría/métodos , Craneosinostosis/diagnóstico por imagen , Craneosinostosis/cirugía , Cráneo/cirugía , Percepción , EstéticaRESUMEN
Endocarditis is a cardiovascular disease caused by the inflammation of the inner tissues of the heart, the endocardium, usually of the valves. Bacteraemia is essential in the development of endocarditis, and there are some findings that the main pathogens of endocarditis are viridans group streptococci: Streptococcus oralis, Streptococcus sanguinis, and Enterococcus faecalis. There is strong evidence that endocarditis bacteria are present in the tonsillar microbiota, so that tonsillar infection is associated with an increased risk of endocarditis. The aim of this manuscript is to investigate the presence of the main pathogens of endocarditis in tonsillar microbiota of an Afghan population group. A sample of 80 tonsil swabs were analyzed by quantitative real time PCR to detect endocarditis pathogens and an estimation of the total bacterial load. The median bacterial load in PCR reaction was 1.4x106 (interquartile range 4,7x105 - 2,9x106). Three species, S. Oralis, S. Sanguinis, and E. Faecalis were found in large amounts in all specimens. On the other hand, S. Mitis was never detected. The S. Aureus was found in 3 samples with a prevalence of 0.04 (C.I. 0.01-0.10). The S. Mutans was found in 33 samples with a prevalence of 0.41 (C.I. 0.31-0.52). Endocarditis bacteria has been found into the tonsillar microbiota, so there is sufficient evidence to justify that the oral cavity is a reservoir of endocarditis bacteria that can have a significant impact on the cardiovascular function.
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Bacterias/aislamiento & purificación , Endocarditis/microbiología , Membrana Mucosa/microbiología , Tonsila Palatina/microbiología , Afganistán/epidemiología , Humanos , Staphylococcus aureus/aislamiento & purificaciónRESUMEN
Some studies have evidenced the role of human polyomaviruses in head and neck squamous cell carcinoma. BK, JC and SV40 human polyoma viruses are widely recognized as etiological agents associated with malignancies. The aim of this study was to analyse the prevalence of BK, IC and SV40 in tonsillar microbiota in a group of Afghan volunteers. A sample of the tonsillar microbiota was taken from a single site using a sterile oral swab paper stick. A fixed volume of purified DNA from each sample was tested by quantitative real-time polymerase chain reactions to evaluate the number of human cells and the number of viral genomes in each sample. The cell number was evaluated via the quantification of a single copy genomic sequence, which is located in the HMBS locus. The median analyzed cell number in each reaction was 4343 (interquartile range 2074-8470). SV40 was never detected, while prevalence rate was 0.11 (C.I. 0.06-0.20) for BK and 0.10 (C.I. 0.05-0.19) for JC. Further studies are necessary to clarify whether polyomaviruses can be considered a risk factor of oral, oropharyngeal and laryngeal malignancies.
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Tonsila Palatina/microbiología , Poliomavirus/aislamiento & purificación , Afganistán/epidemiología , Humanos , Infecciones por Polyomavirus/epidemiología , Infecciones por Polyomavirus/microbiología , Prevalencia , Virus 40 de los Simios/aislamiento & purificaciónRESUMEN
Cancer of the oral cavity is known to have a diverse aetiology that includes infectious agents. Human papilloma virus has been found to be associated with several types of human cancer, inclusive of cervical, vulvar, vaginal, penile, anal, and cancer of tonsil. The aim of this manuscript is to investigate the presence of human papilloma virus in tonsillar microbiota of an Afghan population group. A sample of the tonsillar microbiota was collected by oral swab paper stick from 80 healthy donors. The sample was investigated for the presence of high-risk human papillomavirus types 16, 18, 31 and 45 by real time PCR. Eight samples produced some positive endpoint signals for human papillomaviruses. The human papillomavirus 31 was the unique papillomavirus detected; its calculated prevalence rate was 0.10 (C.I. 0.05-0.19). However, the viral load was always very low, in the order of 10-3 viral genomes per cell. The high prevalence of high-risk human papillomavirus in healthy population suggest a need for further investigation on virus spreading and supports the development of vaccination strategies.
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Microbiota , Tonsila Palatina/microbiología , Poliomavirus/aislamiento & purificación , Afganistán/epidemiología , Femenino , Humanos , Masculino , Infecciones por Papillomavirus/epidemiología , Infecciones por Papillomavirus/microbiología , Poliomavirus/clasificación , Poliomavirus/genética , Infecciones por Polyomavirus/epidemiología , Infecciones por Polyomavirus/microbiología , PrevalenciaRESUMEN
The Ma_MISS miniaturized spectrometer is integrated within the Drilling System of the ExoMars Rosalind Franklin Rover for Mars exploration. Here we focus on the on ground calibration campaign to obtain radiometric and linearity calibrations of the Ma_MISS instrument, while the first paper dealt with the spectral calibration [De Angelis et al., Rev. Sci. Instrum. 93, 123704 (2022)]. The experimental setup used to carry out radiometric calibration is described, as are the methods used for data processing and key parameter retrieval. In particular, the Spectrometer Transfer Function (Responsivity), Signal-to-Noise Ratio, and detector linearity are determined. In a third paper [De Sanctis et al., Planet. Sci. J. 3, 142 (2022)], validation of the Ma_MISS calibration results through spectral measurements performed on rock and synthetic targets during the radiometric calibration campaign is described.
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PURPOSE: Sliding genioplasty is used to surgically correct a retruded or misaligned chin: in this procedure, an osteotomy is performed and the bony segment is repositioned. In this study we investigate the effect of surgical parameters (bony segment movement, osteotomy design) on postop soft tissue changes in a patient cohort. METHODS: Seven patients were retrospectively recruited. Cone beam computed tomography data were obtained and soft tissue and bone shape reconstructions were performed. 3D models were created and surgical cuts were replicated according to postop scans. Each model was imported in ANSYS 2019R1 (Ansys Inc, USA) for simulation: the effect of variation in osteotomy plane as well as extent of bony segment movement were assessed by means of design of experiment: surgical parameters were varied in a surgically acceptable range and the soft tissue predictions were evaluated as displacement output of five craniometric landmarks. RESULTS: Simulation results show the overall changes of the lower third of the face are sensitive to changes in horizontal and vertical displacement of the bony segment as well as segment rotation. No significant changes in the soft tissue response were to attribute to the osteotomy design. CONCLUSIONS: Our results are consistent with experimental findings reported in the literature: when planning genioplasty in orthognathic surgery, particular focus on the segment movement (horizontal translation, vertical translation and rotation), rather than on the design of the osteotomy itself, should be considered.
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Mentoplastia , Procedimientos Quirúrgicos Ortognáticos , Cefalometría , Humanos , Mandíbula , Estudios RetrospectivosRESUMEN
The Ma_MISS spectrometer is integrated within the drilling system of the Rosalind Franklin ExoMars rover. This paper reports the on-ground calibration campaign performed on the spectrometer. Here, we focus on the spectral calibration of the instrument. The experimental setup used to carry out calibration is described, and the methods used for data processing and key parameters retrieval are explained. In particular, the spectral parameters such as (i) pixel central wavelengths, (ii) spectral response function, (iii) spectral resolution, (iv) sampling, and (v) range are determined. In a follow-up paper, the linearity and radiometric calibrations are described, while in De Sanctis et al. [Planet. Sci. J. 3, 142 (2022)], the validation of spectral measurements performed on synthetic and natural rock targets is presented.
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AIM: Early recurrence of atrial fibrillation (AF) is common after electrical cardioversion (ECV). Accurate prediction of AF recurrence might allow more selective use of ECV and the targeted use of antiarrhtyhmic therapy in those at highest risk of recurrence. METHODS: We have screened consecutive patients attending for cardioversion of AF and recruited those without valvular heart disease, heart failure or permanent pacemakers. All patients underwent echocardiography and measurement of serum BNP levels within 24 hours before ECV. Measurement of BNP was repeated at 1, 7, 30 and 90 days after ECV and an ECG recorded on each occasion. RESULTS: We have screened 24 consecutive patients. Five were excluded. All 19 study subjects were succesfully cardioverted to sinus rhythm. AF recurred in nine cases. Recurrence of AF was associated with AF duration, left atrial size, the presence of hypertension and the BNP level before cardioversion. BNP fell significantly after cardioversion. The BNP level after cardioversion was not associated with AF recurrence. CONCLUSION: Even in persons without valvular heart disease or heart failure, an elevated level of BNP predicts recurrence of AF after ECV. The level to which BNP falls after cardioversion is not predictive of AF recurrence.
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Fibrilación Atrial/sangre , Fibrilación Atrial/terapia , Cardioversión Eléctrica , Péptido Natriurético Encefálico/sangre , Anciano , Femenino , Humanos , Masculino , Valor Predictivo de las Pruebas , Estudios Prospectivos , RecurrenciaRESUMEN
BACKGROUND: An objective evaluation of coronavirus disease 2019 in the first days of infection is almost impossible, as affected individuals are generally in home quarantine, and there is limited accessibility for the operator who should perform the test. To overcome this limitation, a recently validated psychophysical self-administered test was used, which can be performed remotely in the assessment of early-stage coronavirus disease 2019 patients. METHODS: Olfactory and gustatory functions were objectively assessed in 300 patients in the first 7 days from coronavirus disease 2019 symptom onset. RESULTS: Seventy per cent of the patients presented olfactory and/or gustatory disorders. The dysfunctions detected were mainly complete anosmia (47 per cent) or ageusia (38 per cent). A significant correlation was found between taste dysfunction and female gender (odds ratio = 1.936, p = 0.014) and fever (odds ratio = 2.132, p = 0.003). CONCLUSION: The psychophysical evaluation protocol proposed is an effective tool for the fast and objective evaluation of patients in the early stages of coronavirus disease 2019. Chemosensitive disorders have been confirmed to be frequent and early symptoms of the coronavirus infection, and, in a significant number of cases, they are the first or only manifestation of coronavirus disease 2019.
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Infecciones por Coronavirus/fisiopatología , Autoevaluación Diagnóstica , Técnicas y Procedimientos Diagnósticos , Trastornos del Olfato/diagnóstico , Neumonía Viral/fisiopatología , Trastornos del Gusto/diagnóstico , Telemedicina , Ácido Acético , Adulto , Betacoronavirus , COVID-19 , Chocolate , Café , Combinación de Medicamentos , Femenino , Jugos de Frutas y Vegetales , Productos Domésticos , Humanos , Italia , Modelos Logísticos , Masculino , Persona de Mediana Edad , Antisépticos Bucales , Trastornos del Olfato/fisiopatología , Pandemias , Extractos Vegetales , SARS-CoV-2 , Autoinforme , Umbral Sensorial , Factores Sexuales , Jabones , Especias , Trastornos del Gusto/fisiopatología , Umbral Gustativo , Terpenos , Pastas de Dientes , VinoRESUMEN
Mutational analyses of genes that encode components of the anchoring complex underlying the basolateral surface of external epithelia indicate that this structure is the major element providing for resistance to external friction. Ultrastructurally, laminin 5 (alpha3beta3gamma2; a component of the anchoring filament) appears as a thin filament bridging the hemidesmosome with the anchoring fibrils. Laminin 5 binds the cell surface through hemidesmosomal integrin alpha6beta4. However, the interaction of laminin 5 with the anchoring fibril (type VII collagen) has not been elucidated. In this study we demonstrate that monomeric laminin 5 binds the NH2-terminal NC-1 domain of type VII collagen. The binding is dependent upon the native conformation of both laminin 5 and type VII collagen NC-1. Laminin 6 (alpha3beta1gamma1) has no detectable affinity for type VII collagen NC-1, indicating that the binding is mediated by the beta3 and/or gamma2 chains of laminin 5. Approximately half of the laminin 5 solubilized from human amnion or skin is covalently complexed with laminins 6 or 7 (alpha3beta2gamma1). The adduction occurs between the NH2 terminus of laminin 5 and the branch point of the short arms of laminins 6 or 7. The results are consistent with the presumed orientation of laminin 5, having the COOH-terminal G domain apposed to the hemidesmosomal integrin, and the NH2-terminal domains within the lamina densa. The results also support a model predicting that monomeric laminin 5 constitutes the anchoring filaments and bridges integrin alpha6beta4 with type VII collagen, and the laminin 5-6/7 complexes are present within the interhemidesmosomal spaces bound at least by integrin alpha3beta1 where they may mediate basement membrane assembly or stability, but contribute less significantly to epithelial friction resistance.
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Moléculas de Adhesión Celular/metabolismo , Colágeno/metabolismo , Antígenos de Superficie/metabolismo , Membrana Basal/metabolismo , Moléculas de Adhesión Celular/análisis , Moléculas de Adhesión Celular/química , Línea Celular , Colágeno/química , Desmosomas/química , Humanos , Integrina alfa6beta4 , Integrinas/metabolismo , Microscopía Electrónica , Conformación Proteica , Piel/química , KalininaRESUMEN
Neurotrophins and tyrosine receptor kinase (Trk) receptors are expressed in skeletal muscle, but it is unclear what functional role Trk-mediated signaling plays during postnatal life. Full-length TrkB (trkB.FL) as well as truncated TrkB (trkB.t1) were found to be localized primarily to the postsynaptic acetylcholine receptor- (AChR-) rich membrane at neuromuscular junctions. In vivo, dominant-negative manipulation of TrkB signaling using adenovirus to overexpress trkB.t1 in mouse sternomastoid muscle fibers resulted in the disassembly of postsynaptic AChR clusters at neuromuscular junctions, similar to that observed in mutant trkB+/- mice. When TrkB-mediated signaling was disrupted in cultured myotubes in the absence of motor nerve terminals and Schwann cells, agrin-induced AChR clusters were also disassembled. These results demonstrate a novel role for neurotrophin signaling through TrkB receptors on muscle fibers in the ongoing maintenance of postsynaptic AChR regions.
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Unión Neuromuscular/metabolismo , Agregación de Receptores/fisiología , Receptor trkB/fisiología , Transducción de Señal/fisiología , Sinapsis/metabolismo , Adenoviridae/genética , Animales , Animales Recién Nacidos , Factor Neurotrófico Derivado del Encéfalo/fisiología , Expresión Génica/fisiología , Genes Dominantes , Ratones , Ratones SCID , Ratones Transgénicos , Músculo Esquelético/fisiología , Factores de Crecimiento Nervioso/fisiología , Células PC12 , Fragmentos de Péptidos/genética , Fragmentos de Péptidos/metabolismo , Ratas , Receptor trkB/química , Receptor trkB/genética , Receptores Colinérgicos/metabolismo , Membranas Sinápticas/metabolismoRESUMEN
Reactive oxygen species (ROS) are considered a key factor in brain aging process. Mitochondrial respiration is an important site of ROS production and hence a potential contributor to brain functional changes with aging. In this study we examined the effect of aging on complex I activity, oxygen consumption, ROS production and phospholipid composition in rat brain mitochondria. The activity of complex I was reduced by 30% in brain mitochondria from 24 months aged rats relative to young animals. These changes in complex I activity were associated with parallel changes in state 3 respiration. H(2)O(2) generation was significantly increased in mitochondria isolated from aged rats. The mitochondrial content of cardiolipin, a phospholipid required for optimal activity of complex I, decreased by 31% as function of aging, while there was a significant increase in the level of peroxidized cardiolipin. The age-related decrease in complex I activity in brain mitochondria could be reversed by exogenously added cardiolipin. This effect of cardiolipin could not be replaced by other phospholipids. It is proposed that aging causes brain mitochondrial complex I dysfunction which can be attributed to ROS-induced cardiolipin oxidation. These findings may prove useful in elucidating the mechanism underlying mitochondrial dysfunction associated with brain aging.
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Envejecimiento/metabolismo , Encéfalo/metabolismo , Cardiolipinas/metabolismo , Complejo I de Transporte de Electrón/metabolismo , Mitocondrias/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Animales , Técnicas In Vitro , Masculino , Oxidación-Reducción , Ratas , Ratas WistarRESUMEN
Reactive oxygen species (ROS) are considered an important factor in ischemia/reperfusion injury to cardiac myocytes. Mitochondrial respiration, mainly at the level of complex I and III, is an important source of ROS generation and hence a potential contributor of cardiac reperfusion injury. Appropriate antioxidant strategies could be particularly useful to limit this ROS generation and associated mitochondrial dysfunction. Melatonin has been shown to effectively protect against ischemic-reperfusion myocardial damage. The mechanism by which melatonin exerts this cardioprotective effect is not well established. In the present study we examined the effects of melatonin on various parameters of mitochondrial bioenergetics in a Langerdoff isolated perfused rat heart model. After isolation of mitochondria from control, ischemic-reperfused and melatonin-treated ischemic-reperfused rat heart, various bioenergetic parameters were evaluated such as rates of mitochondrial oxygen consumption, complex I and complex III activity, H2O2 production as well as the degree of lipid peroxidation, cardiolipin content, and cardiolipin oxidation. We found that reperfusion significantly altered all these mitochondrial parameters, while melatonin treatment had strong protective effect attenuating these alterations. This effect appears to be due, at least in part, to the preservation, by ROS attack, of the content and integrity of cardiolipin molecules which play a pivotal role in mitochondrial bioenergetics. Protection of mitochondrial dysfunction was associated with an improvement of post-ischemic hemodynamic function of the heart. Melatonin had also strong protective effect against oxidative alterations to complex I and III as well as to cardiolipin in isolated mitochondria.
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Cardiolipinas/metabolismo , Corazón/efectos de los fármacos , Melatonina/farmacología , Mitocondrias Cardíacas/efectos de los fármacos , Mitocondrias Cardíacas/fisiología , Daño por Reperfusión Miocárdica/fisiopatología , Animales , Masculino , Mitocondrias Cardíacas/metabolismo , Consumo de Oxígeno , Ratas , Ratas Wistar , Especies Reactivas de Oxígeno/metabolismoRESUMEN
The affine transformation hypothesis is usually adopted in order to link the tissue scale with the fibers scale in structural constitutive models of fibrous tissues. Thanks to the recent advances in imaging techniques, such as multiphoton microscopy, the microstructural behavior and kinematics of fibrous tissues can now be monitored at different stretching within the same sample. Therefore, the validity of the affine hypothesis can be investigated. In this paper, the fiber reorientation predicted by the affine assumption is compared to experimental data obtained during mechanical tests on skin and liver capsule coupled with microstructural imaging using multiphoton microscopy. The values of local strains and the collagen fibers orientation measured at increasing loading levels are used to compute a theoretical estimation of the affine reorientation of collagen fibers. The experimentally measured reorientation of collagen fibers during loading could not be successfully reproduced with this simple affine model. It suggests that other phenomena occur in the stretching process of planar fibrous connective tissues, which should be included in structural constitutive modeling approaches.
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Colágeno/fisiología , Modelos Biológicos , Fenómenos Biomecánicos , Humanos , Hígado/citología , Hígado/metabolismo , Piel/citología , Piel/metabolismo , Estrés MecánicoRESUMEN
Reactive oxygen species (ROS) are considered an important factor in ischemia/reperfusion injury to cardiac myocites. Mitochondrial respiration is an important source of ROS generation and hence a potential contributor to cardiac reperfusion injury. Appropriate treatment strategy could be particularly useful to limit this ROS generation and associated mitochondrial dysfunction. In the present study, we examined the effect of lowering the oxygen tension, at the onset of the reperfusion, on various parameters of mitochondrial bioenergetics in rat heart tissue. After isolation of mitochondria from control, ischemic, normoxic and hypoxic reperfused rat heart, various bioenergetic parameters were evaluated such as rates of mitochondrial oxygen consumption, complex I and complex III activity, H2O2 production and in addition, the degree of lipid peroxidation, cardiolipin content and cardiolipin oxidation. We found that normoxic reperfusion significantly altered all these mitochondrial parameters, while hypoxic reperfusion had a protective effect attenuating these alterations. This effect appears to be due, at least in part, to a reduction of mitochondrial ROS generation with subsequent preservation of cardiolipin integrity, protection of mitochondrial function and improvement of post-ischemic hemodynamic function of the heart.
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Cardiolipinas/metabolismo , Mitocondrias Cardíacas/metabolismo , Daño por Reperfusión Miocárdica/metabolismo , Reperfusión Miocárdica , Especies Reactivas de Oxígeno/metabolismo , Animales , Cardiolipinas/fisiología , Complejo I de Transporte de Electrón/metabolismo , Complejo III de Transporte de Electrones/metabolismo , Radicales Libres/metabolismo , Peróxido de Hidrógeno , Peroxidación de Lípido , Mitocondrias Cardíacas/enzimología , Daño por Reperfusión Miocárdica/enzimología , Daño por Reperfusión Miocárdica/terapia , Oxidación-Reducción , Oxígeno/metabolismo , Consumo de Oxígeno , RatasRESUMEN
The effect of hyperthyroidism on the transport of phosphate in rat-liver mitochondria has been examined. Thyroid hormones administered in vivo increased carrier mediated (mersalyl-sensitive) phosphate transport. Kinetic analysis of the phosphate transport showed that the thyroid hormone affects the Vmax of this process, while having no effect on the Km values. The higher activity of the phosphate carrier was found not to be due to a change in the endogenous content of phosphate nor to a change in the transmembrane delta pH value. Inhibitor titrations with mersalyl showed that mitochondria from both control and hyperthyroid rats required the same concentrations of inhibitor to produce total inhibition of phosphate transport, thus suggesting that the amount of functional translocase present is unaffected. The level of cardiolipin was significantly higher in mitochondrial membranes from hyperthyroid rats as compared to the control rats. The thyroid hormone induced change in the activity of the phosphate carrier appears to be due to a more favorable lipid microenvironment (cardiolipin content) surrounding the carrier molecule in the mitochondrial membrane.
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Hipertiroidismo/metabolismo , Mitocondrias Hepáticas/metabolismo , Fosfatos/metabolismo , Animales , Membranas Intracelulares/fisiología , Cinética , Masculino , Potenciales de la Membrana , Mersalil/farmacología , Mitocondrias Hepáticas/efectos de los fármacos , Mitocondrias Hepáticas/fisiología , Ratas , Ratas Endogámicas , Valores de ReferenciaRESUMEN
A comparative study of the transport of pyruvate in heart mitochondria from normal and triiodothyronine-treated rats has been carried out. It has been found that the rate of carrier-mediated (alpha-cyanocinnamate-sensitive) pyruvate uptake is significantly enhanced in mitochondria from triiodothyronine-treated rats as compared with mitochondria from control rats. The kinetic parameters of the pyruvate uptake indicate that only the Vmax of this process is enhanced whilst there is no change in the Km value. The enhanced rate of pyruvate uptake is not dependent on the increase of the transmembrane delta pH value (both mitochondria from normal and triiodothyronine-treated rats exhibit the same delta pH value) neither does it depend on the increase of the pyruvate carrier molecules (titration of these last with alpha-cyanocinnamate gives the same total number of binding sites). the pyruvate-dependent oxygen uptake is stimulated by 35-40% in mitochondria from hyperthyroid rats when compared with mitochondria from control rats. There is, however, no difference in either the respiratory control ratios or in the ADP/O ratios between these two types of mitochondria. The heart mitochondrial phospholipid composition is altered significantly in hyperthyroid rats; in particular, negatively charged phospholipid such as cardiolipin and phosphatidylserine were found to increase by more than 50%. Minor alterations were found in the pattern of fatty acids with an increase of 20:4/18:2 ratio. It is suggested that the changes in the kinetic parameters of pyruvate transport in mitochondria from hyperthyroid rats involve hormone-mediated changes in the lipid composition of the mitochondrial membranes which in turn modulate the activity of the pyruvate carrier.
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Hipertiroidismo/metabolismo , Proteínas de Transporte de Membrana , Mitocondrias Cardíacas/metabolismo , Piruvatos/metabolismo , Animales , Transporte Biológico/efectos de los fármacos , Proteínas Portadoras/metabolismo , Cinamatos/metabolismo , Ácidos Grasos/metabolismo , Concentración de Iones de Hidrógeno , Hipertiroidismo/fisiopatología , Membranas Intracelulares/metabolismo , Cinética , Masculino , Mitocondrias Cardíacas/efectos de los fármacos , Proteínas Mitocondriales , Transportadores de Ácidos Monocarboxílicos , Fosfolípidos/metabolismo , Ácido Pirúvico , Ratas , Ratas Endogámicas , Receptores de Superficie Celular/análisis , Proteínas Transportadoras de Solutos , Triyodotironina/farmacologíaRESUMEN
The effect of aging on the activity of the pyruvate translocator and on the lipid composition in rat-heart mitochondria has been investigated. It has been found that the rate of pyruvate transport in mitochondria from aged rats (28 months old) is markedly reduced (38%) as compared with that obtained with mitochondria from young adults rats (4 months old). Kinetic analysis of the pyruvate transport shows that only the Vmax of this process is decreased, while there is no change in the Km values. The age-related decrement in the activity of the pyruvate carrier is not due to a decrease in the transmembrane delta pH value, neither does it depend on a decrease in the total number of the pyruvate carrier molecules, titrated with radioactive alpha-cyanocinnamate. The lower activity of the pyruvate translocator in mitochondria from aged rats is associated to a parallel decrement of the rate of pyruvate-dependent oxygen uptake. There is, however no appreciable difference in either the respiratory control ratios or in the ADP/O ratios between these two types of mitochondrion. The Arrhenius plot characteristics differ for pyruvate transport activity in mitochondria from aged rats as compared with young rats in that the break point of the biphasic plot is shifted to a higher temperature. The heart mitochondrial lipid composition is significantly altered in aged rats. The total cholesterol increases (43%), the phospholipids decrease (15%) and the cholesterol/phospholipid molar ratio increases (68%). Among phospholipids, cardiolipin shows the greatest alteration (28% decrease in aged rats). The lower activity of the pyruvate carrier in mitochondria from aged rats may be ascribed to changes in the lipid domain surrounding the carrier molecule in the membrane.
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Envejecimiento/metabolismo , Proteínas Portadoras/metabolismo , Lípidos de la Membrana/metabolismo , Proteínas de Transporte de Membrana , Mitocondrias Cardíacas/metabolismo , Piruvatos/metabolismo , Animales , Cromatografía Líquida de Alta Presión , Cinamatos/metabolismo , Metabolismo Energético/fisiología , Concentración de Iones de Hidrógeno , Membranas Intracelulares/metabolismo , Masculino , Proteínas Mitocondriales , Transportadores de Ácidos Monocarboxílicos , Oxidación-Reducción , Ratas , Proteínas Transportadoras de Solutos , TemperaturaRESUMEN
The effect of pH and substrates on the binding of radiolabelled alpha-cyanocinnamate to mitochondria and submitochondrial particles has been investigated. It has been found that the binding is strongly influenced by the pH of the medium (it decreases on increasing the pH of the medium). The inhibition of pyruvate oxidation by this inhibitor follows the same pH dependence. The pH affects only the affinity of the alpha-cyanocinnamate binding site without changing their total number. A similar pH dependence has been found in inside-out submitochondrial particles where the binding sites are directly accessible. The quantitative parameters of the binding of alpha-cyanocinnamate in submitochondrial particles have been determined. The binding can be prevented or displaced by pyruvate and other substrates of the carrier. The turnover number for pyruvate transport in rat-heart mitochondria has been determined.
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Cinamatos/metabolismo , Mitocondrias Cardíacas/metabolismo , Animales , Sitios de Unión , Ácidos Carboxílicos/metabolismo , Proteínas Portadoras/metabolismo , Concentración de Iones de Hidrógeno , Transportadores de Ácidos Monocarboxílicos , Piruvatos/metabolismo , Ratas , Partículas Submitocóndricas/metabolismoRESUMEN
The influence of hypothyroidism on the transport of phosphate and on the lipid composition in rat-liver mitochondria was examined. It was found that the rate of phosphate transport is reduced (around 40%) in mitochondria from hypothyroid rats compared to that obtained in mitochondria from normal rats. Treatment of hypothyroid rats with thyroid hormone reverses this effect completely. Kinetic analysis of the phosphate transport indicates that only the Vmax of this process is affected, while there is no change in the Km values. The lower rate of phosphate transport in mitochondria from hypothyroid rats is also demonstrated by swelling experiments. There is no significant difference either in the respiratory control ratios or in the ADP/O ratios between these two types of mitochondria. The hepatic mitochondrial lipid composition is altered significantly in hypothyroid rats. The total cholesterol increases, the phospholipids decrease and the cholesterol/phospholipid molar ratio increases (around 40%). Among the phospholipids, cardiolipin shows the greatest alteration (30% decrease in the hypothyroid rats). The phosphatidylethanolamine/phosphatidylcholine ratio also decreases. Alterations were also found in the pattern of fatty acids. These changes in lipid composition may be responsible, at least in part, for the depression of the phosphate carrier activity in mitochondria from hypothyroid rats.