Tego: a new concept of teledentistry for the elderly through a web platform and mobile app in the context of the covid-19 pandemic / Tego: un nuevo concepto de teleodontología para adultos mayores a través de una plataforma web y aplicación móvil en el contexto de la pandemia del covid-19

Objective: To develop a new concept of teledentistry for the elderly through a web platform and associated mobile application in the context of the COVID-19 pandemic. Material and Methods: A new concept for attention via teledentistry of the elderly supported by the web platform/app TEGO (Acronym for Tele-platform of Geriatric and Dental Specialties in Spanish) was developed. Priority and urgent dental care for elderly patients in the context of the COVID-19 pandemic was provided onboard a mobile dental clinic equipped with all the necessary conventional dental care facilities as well as state-of-the-art digital technology. Dental care was carried out in five cities of Chile. For the study, 135 elderly patients were treated. The tele-dental care model includes visit-appointment and remote interconsultation with a staff of specialists. To evaluate patient satisfaction aspects, regarding the service / care provided, a user satisfaction survey was applied. Results: A total of 68 questionnaires were completed by patients. The results showed high levels of patients' satisfaction after the priority or urgent dental care, which reached above 75% in all dimensions of the questionnaire (Access to dental care, user treatment, platform, recommendation). Conclusion: The generation of a technological ecosystem for teledentistry can provide a series of important advantages in the attention of elderly patients, by optimizing the dental care coverage by different specialists who can provide attention to a population that has limited or no access to them.

Objetivo: Desarrollar un nuevo concepto de teleodon-tología para adultos mayores a través de una plataforma web y aplicación móvil asociada en el contexto de la pandemia de COVID-19. Material y Métodos: Se desarrolló un nuevo concepto de atención vía teleodontología del adulto mayor apoyado en la plataforma/app web TEGO (Teleplataforma de Especialidades Geriatricas y Odontológicas). La atención dental prioritaria y urgente para pacientes de edad avanzada en el contexto de la pandemia de COVID-19 se brindó a bordo de una clínica dental móvil equipada con todas las instalaciones de atención dental convencional necesarias, así como con tecnología digital de última generación. La atención odontológica se realizó en cinco ciudades de Chile. Para el estudio, 135 pacientes de edad avanzada fueron atendidos. El modelo de atención teledental incluye visita-cita e inter-consulta remota con un staff de especialistas. Para evaluar los aspectos de satisfacción del paciente, respecto al servicio/atención brindada, se aplicó una encuesta de satisfacción del usuario. Resultados: Los pacientes completaron un total de 68 cuestionarios. Los resultados mostraron altos niveles de satisfacción de los pacientes tras la atención odontológica prioritaria o urgente, que superó el 75% en todas las dimensiones del cuestionario (Acceso a la atención odontológica, trato al usuario, plataforma, recomendación). Conclusión: La generación de un ecosistema tecnológico para la teleodontología puede brindar una serie de ventajas importantes en la atención de pacientes adultos mayores, al optimizar la cobertura de atención odontológica por parte de diferentes especialistas que pueden brindar atención a una población que tiene acceso limitado o nulo.

Development of a teledentistry system for the elderly in the context of the covid-19 pandemic: 3d diagnostic models integration in a web platform / Desarrollo de un sistema de teleodontología para adultos mayores en el contexto de la pandemia de covid-19: integración de modelos de diagnóstico 3d en una plataforma web

Objective: To recognize the usefulness of incorporating Three-Dimensional models of standardized humans in electronic health records, in the context of the development of a teledentistry web platform designed for the attention of the elderly population in COVID-19 pandemic context. Material and Methods: A teledentistry web platform designed with different modules for clinical records. Through a new user-computer interface with a standardized virtual 3D phantom, an extraoral physical examination, an intraoral examination section was modeled. A label-associated marker is allowed to record descriptive aspects of the findings. A 3D odontogram represents multiple patient's conditions for each of the 32 dental positions. Results: From a total of 135 patients registered on the platform, 51 markers and 33 photographs associated with the surface of the virtual 3D phantoms were recorded. For the Location parameter: Hard palate 27.6%, inserted gingiva 15.7%, tongue 15.6%. For the Type of lesion parameter (according to the information entered in the pathology selector): unidentified 35.3%, sub-prosthetic stomatitis 23.5%, irritative fibroma 9.8%. Through the registration of the exact location of the finding in the virtual phantom by a 3D marker, the 3D modeling of the oral pathologies contributed to a better diagnosis, improving the remote communication between the attending dentist and specialists. Conclusion: The combination of the 3D modeling and anatomical-referencing in a teledentistry platform can become a powerful tool for the dental practice, due to their utility and specificity.

Objetivo: Reconocer la utilidad de incorporar modelos tridimensionales de humanos estandarizados en registros electrónicos de salud, en el contexto del desarrollo de una plataforma web de teleodontología diseñada para la atención de la población adulta mayor en contexto de pandemia por COVID-19. Material y Métodos: Una plataforma web de teleodontología diseñada con diferentes módulos para historias clínicas. A través de una nueva interfaz usuario-computadora con un fantoma 3D virtual estandarizado, se modeló un examen físico extraoral, una sección de examen intraoral. Se permite un marcador asociado a la etiqueta para registrar aspectos descriptivos de los hallazgos. Un odontograma 3D representa múltiples condiciones del paciente para cada una de las 32 posiciones dentales.Resultados: De un total de 135 pacientes registrados en la plataforma, se registraron 51 marcadores y 33 fotografías asociadas a la superficie de los fantomas virtuales 3D. Para el parámetro Ubicación: Paladar duro 27,6%, encía insertada 15,7%, lengua 15,6%. Para el parámetro Tipo de lesión (según la información ingresada en el selector de patología): no identificado 35,3%, estomatitis subprotésica 23,5%, fibroma irritativo 9,8%. A través del registro de la ubicación exacta del hallazgo en el fantoma virtual mediante un marcador 3D, el modelado 3D de las patologías orales contribuyó a un mejor diagnóstico, mejorando la comunicación remota entre el odontólogo tratante y los especialistas. Conclusión: La combinación del modelado 3D y la referenciación anatómica en una plataforma de teleodontología puede convertirse en una poderosa herramienta para la práctica odontológica, debido a su utilidad y especificidad.

Implementation of a Teledentistry Platform for Dental Emergencies for the Elderly in the Context of the COVID-19 Pandemic in Chile.

Objectives: To develop and implement a "semi-presential" technology platform to support urgent and priority dental care for the elderly in the context of the COVID-19 pandemic among the Chilean population. Methods: A dental mobile clinic was implemented along with the development of a technological platform designed to support emergency and priority dental procedures, including teleconsultation with specialists. Under strict biosafety protocols, dental care was provided in five Chilean regions between February and May 2021. Sociodemographic, medical, and dental data were recorded. Results: A total of 135 patients over sixty years old, with a mean age of 72 years, were treated, 48 males and 87 females were attended between February and May 2021 in five different regions of Chile. 53.3% required immediate or urgent treatment, and 24.4% were derived to specialists from whom 60.6% needed immediate or urgent treatment. 74.3% of teleconsultations were derived to an oral pathology specialist. Conclusion: It was shown that a "semi-presential" technology platform implemented in a mobile dental clinic can help elderly people who are impeded to look for traditional dental assistance during a pandemic.

In situ endoscopic analysis of bone microstructure and vascularization in post-extraction sites immediately after a minimally invasive vertical tooth extraction in teeth with different periodontal status / Análisis endoscópico in situ de la microestructura ósea y vascularización en alvéolos post-extracción inmediatamente después de una extracción dental mínimamente invasiva en dientes con diferente estado periodontal

SUMMARY: The aim of this study was to perform an in situ endoscopic analysis of the vascularization of post-extraction sites immediately after a non-traumatic extraction in terms of the number of blood vessels per field (NBV), relative area of blood vessels (RABV) and relative area of unmineralized bone (RAUB) in teeth with different periodontal status (PS). This assessment was performed using short distance support immersion endoscopy (SD-SIE). Ten patients (4 men/ 6 women, aged between 25 and 44) were selected. From them, 10 teeth were extracted due to periodontal reasons or other motives. These teeth were then categorized into 2 groups according to their PS, either as periodontally compromised (PC) (clinical attachment loss (CAL) > 7 mm and probing depth (PD) > 5 mm) or periodontally healthy (PH) (CAL < 7 mm and PD < 5 mm, without bleeding or suppuration during periodontal probing), and mobile (M) (> 1 mm horizontally) or immobile (I) (< 1 mm horizontally). The minimally invasive vertical tooth extractions were performed using the Benex ® extractor. Immediately after extraction, a rigid immersion endoscope with a diameter of 2.7 mm was introduced, and a video-alveoloscopy was carried out. This video was analyzed by ImageJ software for the quantification of NBV, RABV and RAUB per field of the post-extraction sites with different PS (PC, PH, M, I) were quantified. In the PC group, significantly greater values for RAUB were observed (33.45 %) compared to those from the PH group (19.65 %). Compared with the M group, the I group did not show significant differences in terms of RAUB or RABV. There were also no differences in NBV in both groups (Means: 33.8 vs. 30.5, respectively).

RESUMEN: El objetivo de este estudio fue realizar un análisis endoscópico in situ de la vascularización de los alvéolos post-extracción inmediatamente después de una extracción atraumática en términos de número de vasos sanguíneos por campo de observación (NBV), área relativa de vasos sanguíneos (RABV) y el área relativa de espacios no mineralizados (RAUB) en dientes con diferente estado periodontal (PS). Esta evaluación se realizó mediante endoscopía de inmersión de corta distancia (SD-SIE). Se seleccionaron diez pacientes (4 hombres / 6 mujeres, con edades comprendidas entre 25 y 44). De ellos, se extrajeron 10 dientes debido a razones periodontales u otros motivos. Estos dientes se clasificaron en 2 grupos según su PS, ya sea como periodontalmente comprometidos (PC), los que presentaban un nivel de inserción clínica (CAL) ≥ 7 mm y una profundidad de sondaje (PD) ≥ 5 mm; o periodontalmente sanos (PH) (CAL <7 mm y PD <5 mm, sin sangramiento o supuración durante el sondaje periodontal). También se categorizaron según su movilidad como móvil (M) (≥ 1 mm horizontalmente) o inmóvil (I) (<1 mm horizontalmente). Las extracciones verticales mínimamente invasivas se realizaron con el extractor Benex ®. Inmediatamente después de la extracción, se introdujo un endoscopio rígido de inmersión con un diámetro de 2.7 mm, con el cual se realizó una video-alveoloscopía. Este video fue analizado por el software ImageJ para la cuantificación de NBV, RABV y RAUB por campo, de los alvéolos post-extracción con diferente estado periodontal. En el grupo de dientes PC, se observaron valores significativamente mayores para RAUB (33.45%) en comparación con los del grupo PH (19.65 %). En comparación con el grupo M, el grupo I no mostró diferencias significativas en términos de RAUB o RABV. Tampoco hubo diferencias en el NBV en ambos grupos (Media: 33.8 frente a 30.5, respectivamente).

Biology and pathological implications of brown adipose tissue: promises and caveats for the control of obesity and its associated complications.

The discovery of metabolically active brown adipose tissue (BAT) in adult humans has fuelled the research of diverse aspects of this previously neglected tissue. BAT is solely present in mammals and its clearest physiological role is non-shivering thermogenesis, owing to the capacity of brown adipocytes to dissipate metabolic energy as heat. Recently, a number of other possible functions have been proposed, including direct regulation of glucose and lipid homeostasis and the secretion of a number of factors with diverse regulatory actions. Herein, we review recent advances in general biological knowledge of BAT and discuss the possible implications of this tissue in human metabolic health. In particular, we confront the claimed thermogenic potential of BAT for human energy balance and body mass regulation, mostly based on animal studies, with the most recent quantifications of human BAT.

Mystery solved: Trehalose kickstarts autophagy by blocking glucose transport.

Although vertebrates cannot synthesize the natural disaccharide trehalose, exogenous administration of trehalose to mammalian cells may be beneficial for protein misfolding disorders. In this issue, DeBosch et al. show that trehalose may also be useful in treating nonalcoholic fatty liver disease and identify inhibition of cellular glucose import through SLC2A (also known as GLUT) transporters as a mechanism by which trehalose stimulates autophagy through the adenosine monophosphate-activated protein kinase (AMPK).

Regulation of Memory Formation by the Transcription Factor XBP1.

Contextual memory formation relies on the induction of new genes in the hippocampus. A polymorphism in the promoter of the transcription factor XBP1 was identified as a risk factor for Alzheimer's disease and bipolar disorders. XBP1 is a major regulator of the unfolded protein response (UPR), mediating adaptation to endoplasmic reticulum (ER) stress. Using a phenotypic screen, we uncovered an unexpected function of XBP1 in cognition and behavior. Mice lacking XBP1 in the nervous system showed specific impairment of contextual memory formation and long-term potentiation (LTP), whereas neuronal XBP1s overexpression improved performance in memory tasks. Gene expression analysis revealed that XBP1 regulates a group of memory-related genes, highlighting brain-derived neurotrophic factor (BDNF), a key component in memory consolidation. Overexpression of BDNF in the hippocampus reversed the XBP1-deficient phenotype. Our study revealed an unanticipated function of XBP1 in cognitive processes that is apparently unrelated to its role in ER stress.

Peroxisomes Get Loud: A Redox Antidote to Hearing Loss.

Pejvakin (PJVK), a protein originally identified in Persian families with sensorineural hearing loss, regulates peroxisomal dynamics and the antioxidant defense triggered by noise exposure in hair cells and auditory neurons of the inner ear. These findings bring peroxisomes to the forefront of noise-induced hearing loss research.

Control of systemic proteostasis by the nervous system.

Maintenance of organismal homeostasis depends on the integration of intracellular and external signals, involving the ability to detect molecular perturbations. An explosion of studies in model organisms indicates the occurrence of dynamic communication between alarm pathways engaged by protein-folding stress in neurons that activate adaptive programs in peripheral organs to control cellular proteostasis. Here we review emerging concepts that highlight the contribution of the proteostasis network to the regulation of several aspects of animal physiology through central integration of signals spanning multiple tissues and organs. These recent findings uncover a new layer of functional interrelation between cells that handle and orchestrate the global maintenance of the proteome at the organismal level in a cell-nonautonomous manner.

Cell-nonautonomous control of the UPR: mastering energy homeostasis.

Endoplasmic reticulum (ER) stress and activation of the unfolded protein response (UPR) in hypothalamic neurons are common features of obesity, resulting in leptin and insulin resistance. In this issue, Williams et al. (2014) demonstrate, for the first time, cell-nonautonomous UPR signaling between brain and liver in the context of glucoregulation.

Cyclic AMP and alkaline pH downregulate carbonic anhydrase 2 in mouse fibroblasts.

BACKGROUND: The hydration of CO2 catalyzed by the ubiquitous carbonic anhydrase 2 (Ca2) is central for bicarbonate transport, bone metabolism and acid-base homeostasis in metazoans. There is evidence that in some tissues Ca2 expression can be acutely induced by cAMP, whereas in other cell types it is unresponsive to cAMP-mediated transcriptional activation. METHODS: We isolated fibroblasts from wild type and mice lacking the ubiquitous chloride/bicarbonate exchanger (Ae2a,b(-/-) mice). In these cells the regulation of carbonic anhydrase 2 by cAMP was studied. RESULTS: We show that Ca2 expression is strongly inhibited by chronic incubation with dibutyryl-cAMP, forskolin or alkaline pH in cultured mouse fibroblasts. Furthermore, fibroblasts obtained from anion exchanger 2 deficient (Ae2a,b(-/-)) mice, which display intracellular alkalosis and increased cAMP production, express less than 10% of control Ca2 mRNA and protein. Surprisingly, inhibition of the bicarbonate-sensitive soluble adenylyl cyclase (sAC) was found to reduce CA2 expression instead of increasing it. CONCLUSIONS: CA2 expression is strongly regulated by intracellular pH and by cAMP, suggesting a role for soluble adenylyl cyclase. Regulation occurs in opposite directions which may be explained by an incoherent feedforward loop consisting of activation by pCREB and repression by ICER.

Retracted: Advances in the physiological and pathological implications of cholesterol.

Cholesterol has evolved to fulfill sophisticated biophysical, cell signalling, and endocrine functions in animal systems. At the cellular level, cholesterol is found in membranes where it increases both bilayer stiffness and impermeability to water and ions. Furthermore, cholesterol is integrated into specialized lipid-protein membrane microdomains with critical topographical and signalling functions. At the organismal level, cholesterol is the precursor of all steroid hormones, including gluco- and mineralo-corticoids, sex hormones, and vitamin D, which regulate carbohydrate, sodium, reproductive, and bone homeostasis, respectively. This sterol is also the immediate precursor of bile acids, which are important for intestinal absorption of dietary lipids as well as energy homeostasis and glucose regulation. Complex mechanisms maintain cholesterol within physiological ranges and the dysregulation of these mechanisms results in embryonic or adult diseases, caused by either excessive or reduced tissue cholesterol levels. The causative role of cholesterol in these conditions has been demonstrated by genetic and pharmacological manipulations in animal models of human disease that are discussed herein. Importantly, the understanding of basic aspects of cholesterol biology has led to the development of high-impact pharmaceutical therapies during the past century. The continuing effort to offer successful treatments for prevalent cholesterol-related diseases, such as atherosclerosis and neurodegenerative disorders, warrants further interdisciplinary research in the coming decades.

Ae2(a,b)-deficient mice exhibit osteopetrosis of long bones but not of calvaria.

Extracellular acidification by osteoclasts is essential to bone resorption. During proton pumping, intracellular pH (pH(i)) is thought to be kept at a near-neutral level by chloride/bicarbonate exchange. Here we show that the Na(+)-independent chloride/bicarbonate anion exchanger 2 (Ae2) is relevant for this process in the osteoclasts from the long bones of Ae2(a,b)(-/-) mice (deficient in the main isoforms Ae2a, Ae2b(1), and Ae2b(2)). Although the long bones of these mice had normal numbers of multinucleated osteoclasts, these cells lacked a ruffled border and displayed impaired bone resorption activity, resulting in an osteopetrotic phenotype of long bones. Moreover, in vitro osteoclastogenesis assays using long-bone marrow cells from Ae2(a,b)(-/-) mice suggested a role for Ae2 in osteoclast formation, as fusion of preosteoclasts for the generation of active multinucleated osteoclasts was found to be slightly delayed. In contrast to the abnormalities observed in the long bones, the skull of Ae2(a,b)(-/-) mice showed no alterations, indicating that calvaria osteoclasts may display normal resorptive activity. Microfluorimetric analysis of osteoclasts from normal mice showed that, in addition to Ae2 activity, calvaria osteoclasts--but not long-bone osteoclasts--possess a sodium-dependent bicarbonate transporting activity. Possibly, this might compensate for the absence of Ae2 in calvaria osteoclasts of Ae2(a,b)(-/-) mice.

Activation of cyclic AMP Signaling in Ae2-deficient mouse fibroblasts.

Anion exchanger 2 (AE2, SLC4A2) is a ubiquitously expressed membrane solute carrier that regulates intracellular pH (pH(i)) by exchanging cytosolic bicarbonate for extracellular chloride. We used fibroblasts from Ae2-deficient (Ae2(a,b)(-/-)) mice to study the effects of an alkaline shift in resting intracellular pH (pH(i)) on the activation of cAMP signaling and gene expression. Ae2(a,b)(-/-) fibroblasts show increased pH(i) (by 0.22 +/- 0.03 unit) compared with wild type cells at extracellular pH (pH(o)) 7.4 and 37 degrees C. This shift in resting pH(i) is associated with an up-regulation of bicarbonate-activated soluble adenylyl cyclase expression, increased cAMP production, Creb phosphorylation, inducible cAMP early repressor 1 mRNA expression, and impaired activation of c-Fos transcription by forskolin. These results highlight the importance of bicarbonate transport via Ae2 in maintaining pH(i) homeostasis in cultured mouse fibroblasts and unveil the role of cAMP in the cellular response to chronic alkalization, which putatively includes an inducible cAMP early repressor 1-mediated attenuation of phosphorylated Creb activity.

Inefficient chronic activation of parietal cells in Ae2a,b(-/-) mice.

In parietal cells, basolateral Ae2 Cl(-)/HCO(3)(-) exchanger (Slc4a2) appears to compensate for luminal H(+) pumping while providing Cl(-) for apical secretion. In mouse and rat, mRNA variants Ae2a, Ae2b1, Ae2b2, and Ae2c2 are all found in most tissues (although the latter at very low levels), whereas Ae2c1 is restricted to the stomach. We studied the acid secretory function of gastric mucosa in mice with targeted disruption of Ae2a, Ae2b1, and Ae2b2 (but not Ae2c) isoforms. In the oxyntic mucosa of Ae2(a,b)(-/-) mice, total Ae2 protein was nearly undetectable, indicating low gastric expression of the Ae2c isoforms. In Ae2(a,b)(-/-) mice basal acid secretion was normal, whereas carbachol/histamine-stimulated acid secretion was impaired by 70%. These animals showed increased serum gastrin levels and hyperplasia of G cells. Immunohistochemistry and electron microscopy revealed baseline activation of parietal cells with fusion of intracellular H(+)/K(+)-ATPase-containing vesicles with the apical membrane and degenerative changes (but not substantial apoptosis) in a subpopulation of these cells. Increased expression of proliferating cell nuclear antigen in the oxyntic glands suggested enhanced Ae2(a,b)(-/-) parietal cell turnover. These data reveal a critical role of Ae2a-Ae2b1-Ae2b2 isoforms in stimulated gastric acid secretion whereas residual Ae2c isoforms could account to a limited extent for basal acid secretion.

Cellular mechanisms of vitamin E uptake: relevance in alpha-tocopherol metabolism and potential implications for disease.

alpha-Tocopherol is an essential micronutrient involved in various oxidative stress-related processes. Because of its hydrophobic nature, alpha-tocopherol is transported in plasma lipoproteins, and the pathways involved in its cellular uptake are closely related to the lipoprotein metabolism. alpha-Tocopherol transfer from plasma to cells can occur by different mechanisms such as uptake facilitated by lipid transfer proteins and lipases, receptor-mediated lipoprotein endocytosis, and selective lipid uptake. Here we discuss recent progress in understanding the physiological and pathophysiological relevance of these different pathways for cellular uptake of vitamin E in vivo. This review is mainly focused on the role of the scavenger receptor class B type I (SR-BI) on alpha-tocopherol metabolism and its potential implications for disease conditions.

Biliary lipid secretion, bile acid metabolism, and gallstone formation are not impaired in hepatic lipase-deficient mice.

Whereas hepatic lipase (HL) has been implicated in lipoprotein metabolism and atherosclerosis, its role in controlling biliary lipid physiology has not been reported. This work characterizes plasma lipoprotein cholesterol, hepatic cholesterol content, bile acid metabolism, biliary cholesterol secretion, and gallstone formation in HL-deficient mice and C57BL/6 controls fed standard chow, a cholesterol-supplemented diet, or a lithogenic diet. Compared with C57BL/6 controls, HL knockout mice exhibited increased basal plasma high-density lipoprotein (HDL) cholesterol as well as reduced cholesterol levels transported in large lipoproteins in response to cholesterol-enriched diets. Hepatic cholesterol content and biliary cholesterol secretion of chow-fed HL knockout and wild-type mice were not different and increased similarly in both strains after feeding dietary cholesterol or a lithogenic diet. There were no differences in biliary bile acid secretion, bile acid pool size and composition, or fecal bile acid excretion between HL-deficient and control mice. HL knockout mice had a similar prevalence of gallstone formation as compared with control mice when both strains were fed with a lithogenic diet. In conclusion, the deficiency of HL has no major impact on the availability of lipoprotein-derived hepatic cholesterol for biliary secretion; HL expression is not essential for diet-induced gallstone formation in mice.

Fibrates down-regulate hepatic scavenger receptor class B type I protein expression in mice.

Fibrates are normolipidemic drugs used in atherogenic dyslipidemia because of their ability to raise high density lipoprotein (HDL) and decrease triglyceride levels. They exert multiple effects on lipid metabolism by activating the peroxisome proliferator-activated receptor-alpha (PPAR-alpha), which controls the transcriptional regulation of genes involved in hepatic fatty acid, cholesterol, and lipoprotein metabolism. The hepatic expression of the scavenger receptor class B type I (SR-BI) plays a critical role in lipoprotein metabolism, mainly due to its ability to mediate selective cholesterol uptake. Because fibrates and PPAR-alpha agonists up-regulate SR-BI expression in human and murine macrophages, we tested whether fibrates raised a similar regulatory response on hepatic SR-BI expression in mice. Surprisingly, fibrate treatment suppressed SR-BI protein expression in the liver without changing steady state SR-BI mRNA levels. Decreased hepatic SR-BI protein expression correlated with enlarged HDL particle size. This effect was concomitant with down-regulation of CLAMP, a putative SR-BI-stabilizing protein found in the hepatic plasma membrane, which was also not associated to changes in CLAMP mRNA levels. The post-transcriptional regulatory effect of fibrates over hepatic SR-BI protein levels was dependent on PPAR-alpha expression, because it was absent in PPAR-alpha-deficient mice. Restoring hepatic SR-BI expression in fibrate-treated mice by recombinant adenoviral gene transfer abolished fibrate-mediated HDL particle size enlargement. This study describes a novel effect of fibrates on hepatic SR-BI expression providing an alternative mechanism by which this drug family modulates HDL metabolism in vivo.

Alpha-tocopherol metabolism is abnormal in scavenger receptor class B type I (SR-BI)-deficient mice.

Despite the physiologic importance of vitamin E, in particular its alpha-tocopherol (alpha-T) isoform, the molecular mechanisms involved in the cellular uptake of this antioxidant from plasma lipoproteins have not been well-defined. Recent studies have suggested that selective lipid uptake, rather than endocytosis, is important for alpha-T delivery to cells. Here we show that the scavenger receptor class B type I (SR-BI), which mediates cellular selective cholesteryl ester uptake from lipoproteins, facilitates efficient transfer of alpha-T from HDL to cultured cells. In SR-BI-deficient mutant mice, relative to wild-type control animals, there was a significant increase in plasma alpha-T levels (1.1- to 1.4-fold higher) that was mostly due to the elevated alpha-T content of their abnormally large plasma HDL-like particles. This increase in plasma alpha-T in SR-BI knockout mice was accompanied by a significant decrease (65-80%) in the alpha-T concentrations in bile and several tissues including ovary, testis, lung and brain. SR-BI deficiency did not alter the alpha-T concentrations of the liver, spleen, kidney or white fat. These data show that SR-BI plays an important role in transferring alpha-T from plasma lipoproteins to specific tissues. Also, in the case of the liver as was previously shown for SR-BI-dependent hepatic cholesterol transport, SR-BI-mediated uptake of alpha-T was primarily coupled to biliary excretion rather than to tissue accumulation. Defective tissue uptake of lipoprotein alpha-T in SR-BI-deficient mice may contribute to the reproductive and cardiovascular pathologies exhibited by these animals.